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Sample records for d2 na morbidade

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

    PubMed

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

    2016-09-03

    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.

  2. 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

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

    PubMed

    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

  4. Formation of NaCl-type monodeuteride LaD by the disproportionation reaction of LaD2.

    PubMed

    Machida, A; Honda, M; Hattori, T; Sano-Furukawa, A; Watanuki, T; Katayama, Y; Aoki, K; Komatsu, K; Arima, H; Ohshita, H; Ikeda, K; Suzuya, K; Otomo, T; Tsubota, M; Doi, K; Ichikawa, T; Kojima, Y; Kim, D Y

    2012-05-18

    Previous x-ray diffraction measurements revealed the pressure-induced decomposition of an fcc LaH2.3 into H-rich and H-poor fcc phases around 11 GPa. The present neutron diffraction measurements on LaD2 confirm the formation of NaCl-type LaD as a counterpart of the D-rich LaD2+δ by disproportionation. First-principles enthalpy and lattice dynamic calculations demonstrate that the NaCl-type LaH is stabilized at high pressures and can be recovered at ambient conditions. Finding the NaCl-type LaH will pave the way for investigations on the site-dependent nature of hydrogen-metal interactions.

  5. Interstellar Lines NaI 5890 (D2), NaI 5896 (D1) in the Spectra of the Wolf-Rayet Type Star HD 192163

    NASA Astrophysics Data System (ADS)

    Rustamov, J. N.; Abdulkerimova, A. F.

    2012-08-01

    Results of spectral investigations of the interstellar absorption lines NaI 5890 (D2) and NaI 5896 (D1) in a spectrum of a Wolf-Rayet type star HD 192163 are presented. Observations carried out at Cassegrain focus of 2- meter "Zeiss-2000" telescope of N.Tusi Shamakhy Astrophysical observatory (ShAO) of NAS Azerbaijan in 2005-2010. 46 eshelle-spectrograms of star HD 192163, and also 4 eshelle-spectrograms of star HD 191765 and standard star HD 18947 for the purpose of comparative research of lines of doublet NaI 5890 (D2) and NaI 5896 (D1) were investigated. The asymmetry of profiles of these interstellar absorption lines had been revealed only in the spectra of HD 192163 and this asymmetry is interpreted by the contribution of genetic associated with the star HD 192163 ring nebula NGC 6888, in formation of these lines.

  6. Striatal D2/3 Binding Potential Values in Drug-Naïve First-Episode Schizophrenia Patients Correlate With Treatment Outcome

    PubMed Central

    Wulff, Sanne; Pinborg, Lars Hageman; Svarer, Claus; Jensen, Lars Thorbjørn; Nielsen, Mette Ødegaard; Allerup, Peter; Bak, Nikolaj; Rasmussen, Hans; Frandsen, Erik; Rostrup, Egill; Glenthøj, Birte Yding

    2015-01-01

    One of best validated findings in schizophrenia research is the association between blockade of dopamine D2 receptors and the effects of antipsychotics on positive psychotic symptoms. The aim of the present study was to examine correlations between baseline striatal D2/3 receptor binding potential (BPp) values and treatment outcome in a cohort of antipsychotic-naïve first-episode schizophrenia patients. Additionally, we wished to investigate associations between striatal dopamine D2/3 receptor blockade and alterations of negative symptoms as well as functioning and subjective well-being. Twenty-eight antipsychotic-naïve schizophrenia patients and 26 controls were included in the study. Single-photon emission computed tomography (SPECT) with [123I]iodobenzamide ([123I]-IBZM) was used to examine striatal D2/3 receptor BPp. Patients were examined before and after 6 weeks of treatment with the D2/3 receptor antagonist amisulpride. There was a significant negative correlation between striatal D2/3 receptor BPp at baseline and improvement of positive symptoms in the total group of patients. Comparing patients responding to treatment to nonresponders further showed significantly lower baseline BPp in the responders. At follow-up, the patients demonstrated a negative correlation between the blockade and functioning, whereas no associations between blockade and negative symptoms or subjective well-being were observed. The results show an association between striatal BPp of dopamine D2/3 receptors in antipsychotic-naïve first-episode patients with schizophrenia and treatment response. Patients with a low BPp have a better treatment response than patients with a high BPp. The results further suggest that functioning may decline at high levels of dopamine receptor blockade. PMID:25698711

  7. Striatal D(2/3) Binding Potential Values in Drug-Naïve First-Episode Schizophrenia Patients Correlate With Treatment Outcome.

    PubMed

    Wulff, Sanne; Pinborg, Lars Hageman; Svarer, Claus; Jensen, Lars Thorbjørn; Nielsen, Mette Ødegaard; Allerup, Peter; Bak, Nikolaj; Rasmussen, Hans; Frandsen, Erik; Rostrup, Egill; Glenthøj, Birte Yding

    2015-09-01

    One of best validated findings in schizophrenia research is the association between blockade of dopamine D2 receptors and the effects of antipsychotics on positive psychotic symptoms. The aim of the present study was to examine correlations between baseline striatal D(2/3) receptor binding potential (BP(p)) values and treatment outcome in a cohort of antipsychotic-naïve first-episode schizophrenia patients. Additionally, we wished to investigate associations between striatal dopamine D(2/3) receptor blockade and alterations of negative symptoms as well as functioning and subjective well-being. Twenty-eight antipsychotic-naïve schizophrenia patients and 26 controls were included in the study. Single-photon emission computed tomography (SPECT) with [(123)I]iodobenzamide ([(123)I]-IBZM) was used to examine striatal D(2/3) receptor BP(p). Patients were examined before and after 6 weeks of treatment with the D(2/3) receptor antagonist amisulpride. There was a significant negative correlation between striatal D(2/3) receptor BP(p) at baseline and improvement of positive symptoms in the total group of patients. Comparing patients responding to treatment to nonresponders further showed significantly lower baseline BP(p) in the responders. At follow-up, the patients demonstrated a negative correlation between the blockade and functioning, whereas no associations between blockade and negative symptoms or subjective well-being were observed. The results show an association between striatal BP(p) of dopamine D(2/3) receptors in antipsychotic-naïve first-episode patients with schizophrenia and treatment response. Patients with a low BP(p) have a better treatment response than patients with a high BP(p). The results further suggest that functioning may decline at high levels of dopamine receptor blockade.

  8. 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.

  9. 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

    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

  10. 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

  11. Possible role of dopamine D1-like and D2-like receptors in behavioural activation and "contingent" reward evaluation in sodium-replete and sodium-depleted rats licking for NaCl solutions.

    PubMed

    D'Aquila, Paolo S; Rossi, Roberta; Rizzi, Antonella; Galistu, Adriana

    2012-03-01

    Based on the different effects of the dopamine D1-like and D2-like receptor antagonists SCH 23390 and raclopride on the measures of licking microstructure in rats, we suggested that the level of activation of reward-associated responses depends on dopamine D1-like receptor stimulation, and is updated, or "reboosted", on the basis of a dopamine D2-like receptor-mediated reward evaluation. To further test this hypothesis, we examined the effects of the dopamine D2-like receptor antagonist raclopride (0, 25, 125, 250μg/kg) and of the dopamine D1-like receptor antagonist SCH 23390 (0, 10, 20 and 40μg/kg) on the microstructure of licking for two different NaCl solutions (0.9% and 2.7%) in rats in sodium-replete status and in the sodium-depleted status induced by the diuretic drug furosemide. Rats were exposed to each solution for 180 seconds after the first lick. Both in sodium-replete and in sodium-depleted status, SCH 23390 produced a decrease of burst number, a measure of behavioural activation, without affecting their size, a measure of reward evaluation. Raclopride reduced burst number but appeared also to exert some effects on burst size. Sodium depletion resulted in an increased intake for both NaCl solutions due to an increase in burst number and size, and in a reduced sensitivity to the effect of raclopride on lick number. These results are not in contrast with the proposed hypothesis and are consistent with previous evidence suggesting a role for dopamine D2-like receptors in the increased NaCl appetite induced by sodium depletion.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  17. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 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...

  18. 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...

  19. 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...

  20. 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...

  1. CERES ISCCP-D2like Legacy

    Atmospheric Science Data Center

    2014-07-24

    ... fluxes and clouds. Description : CERES-MODIS and GEO cloud properties stratified by ISCCP cloud types and in the similar D2 ... geostationary cloud retrievals for daytime only.  GEO : 3-hourly geostationary-only cloud retrievals for daytime only.  ...

  2. Anthrorack on the Spacelab D2 mission

    NASA Technical Reports Server (NTRS)

    Perry, Michael (Editor)

    1997-01-01

    The Anthrorack facility, launched on the German Spacelab D2 mission, and the experiments performed, are described. The Anthrorack was developed in order to investigate the physiological effects of microgravity on human beings. In particular, the following topics are reported on: cardiovascular system responses; body fluid shifts; pulmonary responses; human endocrinology and metabolism.

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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.

  9. Dopamine D2 receptor signaling dynamics of dopamine D2-neurotensin 1 receptor heteromers.

    PubMed

    Borroto-Escuela, Dasiel O; Ravani, Annalisa; Tarakanov, Alexander O; Brito, Ismel; Narvaez, Manuel; Romero-Fernandez, Wilber; Corrales, Fidel; Agnati, Luigi F; Tanganelli, Sergio; Ferraro, Luca; Fuxe, Kjell

    2013-05-24

    Biochemical, histochemical and coimmunoprecipitation experiments have indicated the existence of antagonistic dopamine D2 (D2R) and neurotensin 1 (NTS1R) receptor-receptor interactions in the dorsal and ventral striatum indicating a potential role of these receptor-receptor interactions in Parkinson's disease and schizophrenia. By means of Bioluminiscence Resonance energy transfer (BRET(2)) evidence has for the first time been obtained in the current study for the existence of both D2LR/NTS1R and D2SR/NTS1R heteromers in living HEK293T cells. Through confocal laser microscopy the NTS1R(GFP2) and D2R(YFP) were also shown to be colocated in the plasma membrane of these cells. A bioinformatic analysis suggests the existence of a basic set of three homology protriplets (TVM, DLL and/or LRA) in the two participating receptors which may contribute to the formation of the D2R/NTS1R heteromers by participating in guide-clasp interactions in the receptor interface. The CREB reporter gene assay indicated that the neurotensin receptor agonist JMV 449 markedly reduced the potency of the D2R like agonist quinpirole to inhibit the forskolin induced increase of the CREB signal. In contrast, the neurotensin agonist was found to markedly increase the quinpirole potency to activate the MAPK pathway as also studied with luciferase reporter gene assay measuring the degree of SRE activity as well as with ERK1/2 phosphorylation assays. These dynamic changes in D2R signaling produced by the neurotensin receptor agonist may involve antagonistic allosteric receptor-receptor interactions in the D2LR-NTS1R heteromers at the plasma membrane level (CREB pathway) and synergistic interactions in PKC activation at the cytoplasmatic level (MAPK pathway).

  10. Thz Spectroscopy of D_2H^+

    NASA Astrophysics Data System (ADS)

    Yu, Shanshan; Pearson, John; Amano, Takayoshi

    2015-06-01

    Pure rotational transitions of D_2H^+ observed by high-resolution spectroscopy have been limited so far to the J = 110-101 transition at 691.7 GHz, J=220-211 at 1.370 THz, and J=111-000 at 1.477 THz. As this ion is a light asymmetric-top molecule, spectroscopic characterization and prediction of other rotational transition frequencies are not straightforward. In this presentation, we extended the measurements up to 2 THz by using the JPL frequency multiplier chains, and observed three new THz lines and re-measured the three known transitions. D_2H^+ was generated in an extended negative glow discharge cell cooled to liquid nitrogen temperature. Six rotational transition frequencies together with the combination differences derived from 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. T. Hirao and T. Amano, Ap. J.,597, L85 (2003) K. M. Evenson et al cited by O. L. Polyansky and A. R. W. McKellar, J. Chem. Phys., 92, 4039 (1990) O. Asvany et al, Phys. Rev. Lett., 100, 233004 (2008)

  11. 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.

  12. 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:...

  13. 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...

  14. 26 CFR 1.337(d)-2 - Loss limitation rules.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... § 1.337(d)-2T as contained in the 26 CFR part 1 in effect on March 2, 2005. ... 26 Internal Revenue 4 2012-04-01 2012-04-01 false Loss limitation rules. 1.337(d)-2 Section 1.337... (CONTINUED) INCOME TAXES (Continued) Effects on Corporation § 1.337(d)-2 Loss limitation rules. (a)...

  15. 26 CFR 1.337(d)-2 - Loss limitation rules.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... § 1.337(d)-2T as contained in the 26 CFR part 1 in effect on March 2, 2005. ... 26 Internal Revenue 4 2013-04-01 2013-04-01 false Loss limitation rules. 1.337(d)-2 Section 1.337... (CONTINUED) INCOME TAXES (CONTINUED) Effects on Corporation § 1.337(d)-2 Loss limitation rules. (a)...

  16. 26 CFR 1.337(d)-2 - Loss limitation rules.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 4 2014-04-01 2014-04-01 false Loss limitation rules. 1.337(d)-2 Section 1.337(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Effects on Corporation § 1.337(d)-2 Loss limitation rules. (a) Loss disallowance—(1) General rule. No deduction...

  17. 26 CFR 1.337(d)-2 - Loss limitation rules.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 4 2011-04-01 2011-04-01 false Loss limitation rules. 1.337(d)-2 Section 1.337(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Effects on Corporation § 1.337(d)-2 Loss limitation rules. (a) Loss disallowance—(1) General rule. No deduction is allowed...

  18. 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...

  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 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...

  1. 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...

  2. 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...

  3. D2 to M2 procedure for D2-brane DBI effective action

    NASA Astrophysics Data System (ADS)

    Klusoň, J.

    2009-02-01

    We apply the procedure that was suggested in [B. Ezhuthachan, S. Mukhi, C. Papageorgakis, arxiv:/0806.1639] to the case of abelian D2-brane Dirac-Born-Infeld effective action and discuss its limitation. Then we suggest an alternative form of this procedure that is based on an existence of interpolating action proposed in [T. Ortin, hep-th/9707113, Y. Lozano, hep-th/9707011].

  4. IDH2 mutations in patients with D-2-hydroxyglutaric aciduria.

    PubMed

    Kranendijk, Martijn; Struys, Eduard A; van Schaftingen, Emile; Gibson, K Michael; Kanhai, Warsha A; van der Knaap, Marjo S; Amiel, Jeanne; Buist, Neil R; Das, Anibh M; de Klerk, Johannis B; Feigenbaum, Annette S; Grange, Dorothy K; Hofstede, Floris C; Holme, Elisabeth; Kirk, Edwin P; Korman, Stanley H; Morava, Eva; Morris, Andrew; Smeitink, Jan; Sukhai, Rám N; Vallance, Hilary; Jakobs, Cornelis; Salomons, Gajja S

    2010-10-15

    Heterozygous somatic mutations in the genes encoding isocitrate dehydrogenase-1 and -2 (IDH1 and IDH2) were recently discovered in human neoplastic disorders. These mutations disable the enzymes' normal ability to convert isocitrate to 2-ketoglutarate (2-KG) and confer on the enzymes a new function: the ability to convert 2-KG to d-2-hydroxyglutarate (D-2-HG). We have detected heterozygous germline mutations in IDH2 that alter enzyme residue Arg(140) in 15 unrelated patients with d-2-hydroxyglutaric aciduria (D-2-HGA), a rare neurometabolic disorder characterized by supraphysiological levels of D-2-HG. These findings provide additional impetus for investigating the role of D-2-HG in the pathophysiology of metabolic disease and cancer. PMID:20847235

  5. ISCCP-D2like-GEO Ed3A

    Atmospheric Science Data Center

    2016-10-12

    ISCCP-D2like-GEO Ed3A Project Title:  CERES Discipline:  ... Order Data Guide Documents:  GEO Description/Abstract Detailed CERES ISCCP-D2like Product ... Data Products Catalog:  DPC_ISCCP-D2like-GEO_R5V3  (PDF) Readme Files:  Readme GEO R5-987 ...

  6. ISCCP-D2like-GEO Ed2A

    Atmospheric Science Data Center

    2014-07-24

    ISCCP-D2like-GEO Ed2A Project Title:  CERES Discipline:  ... Order Data Guide Documents:  GEO Description/Abstract Detailed CERES ISCCP-D2like Product ... Data Products Catalog:  DPC_ISCCP-D2like-GEO_R5V3  (PDF) Readme Files:  Readme GEO R5-909 ...

  7. Memantine agonist action at dopamine D2High receptors.

    PubMed

    Seeman, Philip; Caruso, Carla; Lasaga, Mercedes

    2008-02-01

    Memantine is reported to improve symptoms in moderate cases of Alzheimer's disease and Parkinson's disease, but is also known to trigger psychosis in some Parkinson patients. Because these clinical features suggested a possible dopamine component of memantine action, we measured the potency of memantine on the functional high-affinity state of dopamine D2 receptors, or D2(High). Using [(3)H]domperidone to label D2 receptors, the memantine dissociation constant at D2(High) was 917 +/- 23 nM for rat striatal D2 receptors and 137 +/- 19 nM for human cloned D2Long receptors. The memantine dissociation constant for striatal N-methyl-D-aspartate (NMDA) receptors labeled by [(3)H]MK 801 was 2200 +/- 400 nM. Memantine stimulated the incorporation of [(35)S]GTP-gamma-S into D2-expressing Chinese Hamster Ovary cells with a dissociation constant of 1200 +/- 400 nM. Memantine, between 200 and 2000 nM, directly acted on D2(High) to inhibit the release of prolactin from isolated anterior pituitary cells in culture. Because the memantine potencies at NMDA receptors and dopamine D2(High) receptors are of a similar order of magnitude, it is likely that the clinical features of memantine can be attributed to its action at both types of receptors.

  8. Investigation of Solid D 2 for UCN Sources.

    PubMed

    Atchison, F; Bodek, K; van den Brandt, B; Bryś, T; Daum, M; Fierlinger, P; Geltenbort, P; Giersch, M; Hautle, P; Hino, M; Henneck, R; Kasprzak, M; Kirch, K; Kohlbrecher, J; Konter, J A; Kühne, G; Kuźniak, M; Mishima, K; Pichlmaier, A; Rätz, D; Serebrov, A; Utsuro, M; Wokaun, A; Zmeskal, J

    2005-01-01

    Solid deuterium (sD2) will be used for the production of ultra-cold neutrons (UCN) in a new generation of UCN sources. Scattering cross sections of UCN in sD2 determine the source yield but until now have not been investigated. We report first results from transmission and scattering experiments with cold, very cold and ultra-cold neutrons on sD2 along with light transmission and Raman scattering studies showing the influence of the sD2 crystal properties.

  9. D-2-hydroxyglutaric aciduria: case report and biochemical studies.

    PubMed

    Chalmers, R A; Lawson, A M; Watts, R W; Tavill, A S; Kamerling, J P; Hey, E; Ogilvie, D

    1980-01-01

    A patient with protein-losing gastroenteropathy and egg allergy has been shown to have a previously unrecognized organic aciduria, D-2-hydroxyglutaric aciduria. The observations made are consistent with an inherited metabolic disorder in the catabolism of 5-aminolaevulinate possibly due to deficient activity of a specific D-2-hydroxyglutarate dehydrogenase.

  10. Effect of age on extrastriatal dopamine D2 receptor availability

    SciTech Connect

    Wang, G.J.; Volkow, N.D.; Fowler, J.S. |

    1996-05-01

    It is known that dopamine (DA) D2 receptor availability in basal ganglia decreases with age. This study was done to assess the effects of age on extrastriatal DA D2 receptors. DA D2 receptor availability was evaluated in 42 healthy male subjects (age mean 41 {plus_minus} 16, range 21 -86 year old) using positron emission tomography (PET) and [C-11]raclopride. DA D2 receptor availability was measured using the ratio of the distribution volume in the region of interest (caudate, putamen, thalamus, frontal, occipital cortices, temporal insula, cingulate and orbitofrontal gyri) to that in the cerebellum which is a function of B{sub max.}/K{sub d}. Pearson product-moment correlation was used to evaluate the correlation between age and D2 receptor availability. DA D2 receptor availability in putamen (r {le} 0.0001), caudate (r {le} 0.0002), thalamus (r {le} 0.03), and temporal insula (r {le} 0.01) were significantly correlated with age. The decrements in D2 receptors with age were lower in extrastriatal than in striatal regions and corresponded to a decrease of 4.7% per decade in caudate, 6.2% in putamen, 2.1% in thalamus and 2.5% in temporal insula. This study documents age related decrement of DA D2 receptor availability in striatal and extrastriatal regions.

  11. 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.

  12. A droplet-to-digital (D2D) microfluidic device for single cell assays.

    PubMed

    Shih, Steve C C; Gach, Philip C; Sustarich, Jess; Simmons, Blake A; Adams, Paul D; Singh, Seema; Singh, Anup K

    2015-01-01

    We have developed a new hybrid droplet-to-digital microfluidic platform (D2D) that integrates droplet-in-channel microfluidics with digital microfluidics (DMF) for performing multi-step assays. This D2D platform combines the strengths of the two formats-droplets-in-channel for facile generation of droplets containing single cells, and DMF for on-demand manipulation of droplets including control of different droplet volumes (pL-μL), creation of a dilution series of ionic liquid (IL), and parallel single cell culturing and analysis for IL toxicity screening. This D2D device also allows for automated analysis that includes a feedback-controlled system for merging and splitting of droplets to add reagents, an integrated Peltier element for parallel cell culture at optimum temperature, and an impedance sensing mechanism to control the flow rate for droplet generation and preventing droplet evaporation. Droplet-in-channel is well-suited for encapsulation of single cells as it allows the careful manipulation of flow rates of aqueous phase containing cells and oil to optimize encapsulation. Once single cell containing droplets are generated, they are transferred to a DMF chip via a capillary where they are merged with droplets containing IL and cultured at 30 °C. The DMF chip, in addition to permitting cell culture and reagent (ionic liquid/salt) addition, also allows recovery of individual droplets for off-chip analysis such as further culturing and measurement of ethanol production. The D2D chip was used to evaluate the effect of IL/salt type (four types: NaOAc, NaCl, [C2mim] [OAc], [C2mim] [Cl]) and concentration (four concentrations: 0, 37.5, 75, 150 mM) on the growth kinetics and ethanol production of yeast and as expected, increasing IL concentration led to lower biomass and ethanol production. Specifically, [C2mim] [OAc] had inhibitory effects on yeast growth at concentrations 75 and 150 mM and significantly reduced their ethanol production compared to cells grown

  13. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Federal Register approves this incorporation by reference in accordance with 5 U.S.C 552(a) and 1 CFR part... isolated from yeast and is purified by crystallization. (b) Vitamin D2 meets the specifications of the...

  14. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Federal Register approves this incorporation by reference in accordance with 5 U.S.C 552(a) and 1 CFR part... isolated from yeast and is purified by crystallization. (b) Vitamin D2 meets the specifications of the...

  15. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Federal Register approves this incorporation by reference in accordance with 5 U.S.C 552(a) and 1 CFR part... isolated from yeast and is purified by crystallization. (b) Vitamin D2 meets the specifications of the...

  16. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Federal Register approves this incorporation by reference in accordance with 5 U.S.C 552(a) and 1 CFR part... isolated from yeast and is purified by crystallization. (b) Vitamin D2 meets the specifications of the...

  17. 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

  18. Jet spectroscopy of benzyl and benzyl-α-d2

    NASA Astrophysics Data System (ADS)

    Fukushima, Masaru; Obi, Kinichi

    1992-03-01

    Benzyl and benzyl-α-d2 radicals are produced by the ArF laser (193 nm) photolysis of benzylchloride and benzylchloride-α-d2, respectively, in a supersonic free jet. The spectroscopy of the D1 1 2A2-D0 1 2B1 transition of these radicals is studied by means of the laser induced fluorescence (LIF) method. LIF excitation spectra show well resolved but unusual vibrational structure. The assignments of vibronic bands have been carried out on the basis of dispersed spectra from the single vibronic level (SVL) and transition band types derived from rotational analysis of high resolution LIF excitation spectra. The intensity anomaly of the vibronic bands in the excitation spectra is interpreted as the breakdown of the accidental forbidden character of the D1-D0 and D2-D0 electronic transitions, whose mechanism will be discussed in terms of vibronic coupling.

  19. Evidence against dopamine D1/D2 receptor heteromers

    PubMed Central

    Frederick, Aliya L.; Yano, Hideaki; Trifilieff, Pierre; Vishwasrao, Harshad D.; Biezonski, Dominik; Mészáros, József; Sibley, David R.; Kellendonk, Christoph; Sonntag, Kai C.; Graham, Devon L.; Colbran, Roger J.; Stanwood, Gregg D.; Javitch, Jonathan A.

    2014-01-01

    Hetero-oligomers of G-protein-coupled receptors have become the subject of intense investigation because their purported potential to manifest signaling and pharmacological properties that differ from the component receptors makes them highly attractive for the development of more selective pharmacological treatments. In particular, dopamine D1 and D2 receptors have been proposed to form hetero-oligomers that couple to Gαq proteins, and SKF83959 has been proposed to act as a biased agonist that selectively engages these receptor complexes to activate Gαq and thus phospholipase C. D1/D2 heteromers have been proposed as relevant to the pathophysiology and treatment of depression and schizophrenia. We used in vitro bioluminescence resonance energy transfer (BRET), ex vivo analyses of receptor localization and proximity in brain slices, and behavioral assays in mice to characterize signaling from these putative dimers/oligomers. We were unable to detect Gαq or Gα11 protein coupling to homomers or heteromers of D1 or D2 receptors using a variety of biosensors. SKF83959-induced locomotor and grooming behaviors were eliminated in D1 receptor knockout mice, verifying a key role for D1-like receptor activation. In contrast, SKF83959-induced motor responses were intact in D2 receptor and Gαq knockout mice, as well as in knock-in mice expressing a mutant Ala286-CaMKIIα, that cannot autophosphorylate to become active. Moreover, we found that in the shell of the nucleus accumbens, even in neurons in which D1 and D2 receptor promoters are both active, the receptor proteins are segregated and do not form complexes. These data are not compatible with SKF83959 signaling through Gαq or through a D1–D2 heteromer and challenge the existence of such a signaling complex in the adult animals that we used for our studies. PMID:25560761

  20. 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.

  1. 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

  2. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... this incorporation by reference in accordance with 5 U.S.C. 552(a) and 1 CFR part 51. You may obtain... at NARA, call 202-741-6030 or go to: http://www.archives.gov/federal-register/cfr/ibr-locations.html... crystallization. (b) Vitamin D2 meets the specifications of the Food Chemicals Codex, 7th ed. (2010), pp....

  3. CERES ISCCP-D2like Data Products

    Atmospheric Science Data Center

    2014-07-24

    ... fluxes and clouds. Description : CERES-MODIS and GEO cloud properties stratified by ISCCP cloud types and in the similar D2 ... geostationary cloud retrievals for daytime only.  GEO : 3-hourly geostationary-only cloud retrievals for daytime only.  ...

  4. Stripping lead from D2EHPA by direct displacement reactions

    SciTech Connect

    Chia, L.M.; O`Keefe, T.J.

    1995-07-01

    The direct removal of lead ions from D2EHPA-kerosene using metallic zinc as the reducing agent was evaluated. The electrochemical process, called galvanic stripping, is a potential alternative stripping technique when standard chemical methods are not adequate. Four parameters found to be important in the rate of lead removal were studied in a factorially designed experiment. The variable evaluated included D2EHPA concentration, temperature, zinc surface area and solution agitation. Temperature and surface area were found to be the most significant, while agitation and D2EHPA concentration had less influence on the reaction. An activation energy of 22.5 Kcal/mole was calculated indicating a chemically-controlled process. The reaction was also sensitive to the concentration of oxygen in the system. The zinc required was considerably in excess of stoichiometry, possibly due to the dissolution and redeposition of lead. In general, the results were encouraging and demonstrated that lead impurities could be removed from D2EHPA using cementation type reactions.

  5. 26 CFR 1.337(d)-2 - Loss limitation rules.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... § 1.337(d)-2T as contained in the 26 CFR part 1 in effect on March 2, 2005. ... differences between the approach of this section and that of § 1.1502-20. (4) Netting. Paragraph (a)(1) of... means fair market value. (4) Netting. Paragraph (b)(1) of this section does not apply to reduce...

  6. Attenuated D2 16681-PDK53 vaccine: defining humoral and cell-mediated immunity.

    PubMed

    Rabablert, J; Yoksan, S

    2009-01-01

    Dengue viruses cause 50-100 million cases of acute febrile disease every year, including more than 500000 reported cases of the severe forms of the disease-dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Attempts to create conventional vaccines have been hampered by the lack of suitable experimental models, the need to provide protection against all four serotypes simultaneously and the possible involvement of virus-specific immune responses in severe disease. Live attenuated D2 16681-PDK53 vaccine was first developed from Mahidol University, Thailand. This vaccine induced both humoral and cell-mediated immunity and lack of reactogeneticity in humans. Infectious cDNA clones of the virulent D2 16681 virus and its attenuated D2 16681-PDK53 were constructed. The attenuated virus elicited neutralizing antibodies in mice and monkeys and developed viremia in monkeys. At molecular level, patterns of cytokines which are immunological mediators released from human mononuclear cells obtained from dengue naïve and immune donors infected with this attenuated virus compared with virulent virus were studied. In dengue naïve PBMC, the virulent and attenuated clones induced alternation in expression of 25 and 24 versus 13 and 18 genes out of 268 genes on day 1 and 3. In dengue immune PBMC, the virulent and attenuated clones induced alternation in expression of 33 and 38 versus 25 and 29 genes on days 1 and 3. Up-regulation of IL-1beta, IL-6, IL-8, IL-10, IFN-alpha, IFNgammaR, MIP-1alpha, MIP-1beta, MIP-2alpha, VEGF and down-regulation of IL-4, IL-4R, IL-RII, MIF, RANTES, IGF-1, GM-CSF-2 were shown. This review pointed out the infectious clones of the attenuated D2 16681-PDK53 was safe and induced both neutralizing antibodies in vivo and cytokine gene expression in vitro at molecular level. Furthermore, the phenotypic markers of ideal dengue vaccine could be included the alteration of cytokine gene expression and cytokine production in human mononuclear cells.

  7. Romans-mass-driven flows on the D2-brane

    NASA Astrophysics Data System (ADS)

    Guarino, Adolfo; Tarrío, Javier; Varela, Oscar

    2016-08-01

    The addition of supersymmetric Chern-Simons terms to N=8 super-Yang-Mills theory in three-dimensions is expected to make the latter flow into infrared super-conformal phases. We address this problem holographically by studying the effect of the Romans mass on the D2-brane near-horizon geometry. Working in a consistent, effective four-dimensional setting provided by D = 4 N=8 supergravity with a dyonic ISO(7) gauging, we verify the existence of a rich web of supersymmetric domain walls triggered by the Romans mass that interpolate between the (four-dimensional description of the) D2-brane and various superconformal phases. We also construct domain walls for which both endpoints are superconformal. While most of our results are numerical, we provide analytic results for the SU(3) × U(1)-invariant flow into an N=2 conformal phase recently discovered.

  8. Dopamine D2/D3 receptor availability and venturesomeness.

    PubMed

    Bernow, Nina; Yakushev, Igor; Landvogt, Christian; Buchholz, Hans-Georg; Smolka, Michael N; Bartenstein, Peter; Lieb, Klaus; Gründer, Gerhard; Vernaleken, Ingo; Schreckenberger, Mathias; Fehr, Christoph

    2011-08-30

    The construct of impulsivity is considered as a major trait of personality. There is growing evidence that the mesolimbic dopamine system plays an important role in the modulation of impulsivity and venturesomeness, the two key components within the impulsivity-construct. The aim of the present study was to explore an association between trait impulsivity measured with self-assessment and the dopaminergic neurotransmission as measured by positron emission tomography (PET) in a cohort of healthy male subjects. In vivo D2/D3 receptor availability was determined with [(18)F]fallypride PET in 18 non-smoking healthy subjects. The character trait impulsivity was measured using the Impulsiveness-Venturesomeness-Empathy questionnaire (I7). Image processing and statistical analysis was performed on a voxel-by-voxel basis using statistical parametric mapping (SPM) software. The I7 subscale venturesomeness correlated positively with the D2/D3 receptor availability within the left temporal cortex and the thalamus. Measures on the I7 subscale impulsiveness and empathy did not correlate with the D2/D3 receptor availability in any brain region investigated. Our results suggest the involvement of extrastriatal dopaminergic neurotransmission in venturesomeness, a component of impulsivity. PMID:21689908

  9. Dopamine D2 receptor-mediated Akt/PKB signalling: initiation by the D2S receptor and role in quinpirole-induced behavioural activation.

    PubMed

    Chen, Han-Ting; Ruan, Nan-Yu; Chen, Jin-Chung; Lin, Tzu-Yung

    2012-09-24

    The short and long isoforms of the dopamine D2 receptor (D2S and D2L respectively) are highly expressed in the striatum. Functional D2 receptors activate an intracellular signalling pathway that includes a cAMP-independent route involving Akt/GSK3 (glycogen synthase kinase 3). To investigate the Akt/GSK3 response to the seldom-studied D2S receptor, we established a rat D2S receptor-expressing cell line [HEK (human embryonic kidney)-293/rD2S]. We found that in HEK-293/rD2S cells, the D2/D3 agonists bromocriptine and quinpirole significantly induced Akt and GSK3 phosphorylation, as well as ERK1/2 (extracellular-signal-regulated kinase 1/2) activation. The D2S receptor-induced Akt signals were profoundly inhibited by the internalization blockers monodansyl cadaverine and concanavalin A. Activation of the D2S receptor in HEK-293/rD2S cells appeared to trigger Akt/phospho-Akt translocation to the cell membrane. In addition to our cell culture experiments, we studied D2 receptor-dependent Akt in vivo by systemic administration of the D2/D3 agonist quinpirole. The results show that quinpirole evoked Akt-Ser473 phosphorylation in the ventral striatum. Furthermore, intra-accumbens administration of wortmannin, a PI3K (phosphoinositide 3-kinase) inhibitor, significantly suppressed the quinpirole-evoked behavioural activation. Overall, we demonstrate that activation of the dopamine D2S receptor stimulates Akt/GSK3 signalling. In addition, in vivo Akt activity in the ventral striatum appears to play an important role in systemic D2/D3 agonist-induced behavioural activation.

  10. Dopamine D2 receptor-mediated Akt/PKB signalling: initiation by the D2S receptor and role in quinpirole-induced behavioural activation

    PubMed Central

    Chen, Han-Ting; Ruan, Nan-Yu; Chen, Jin-Chung; Lin, Tzu-Yung

    2012-01-01

    The short and long isoforms of the dopamine D2 receptor (D2S and D2L respectively) are highly expressed in the striatum. Functional D2 receptors activate an intracellular signalling pathway that includes a cAMP-independent route involving Akt/GSK3 (glycogen synthase kinase 3). To investigate the Akt/GSK3 response to the seldom-studied D2S receptor, we established a rat D2S receptor-expressing cell line [HEK (human embryonic kidney)-293/rD2S]. We found that in HEK-293/rD2S cells, the D2/D3 agonists bromocriptine and quinpirole significantly induced Akt and GSK3 phosphorylation, as well as ERK1/2 (extracellular-signal-regulated kinase 1/2) activation. The D2S receptor-induced Akt signals were profoundly inhibited by the internalization blockers monodansyl cadaverine and concanavalin A. Activation of the D2S receptor in HEK-293/rD2S cells appeared to trigger Akt/phospho-Akt translocation to the cell membrane. In addition to our cell culture experiments, we studied D2 receptor-dependent Akt in vivo by systemic administration of the D2/D3 agonist quinpirole. The results show that quinpirole evoked Akt-Ser473 phosphorylation in the ventral striatum. Furthermore, intra-accumbens administration of wortmannin, a PI3K (phosphoinositide 3-kinase) inhibitor, significantly suppressed the quinpirole-evoked behavioural activation. Overall, we demonstrate that activation of the dopamine D2S receptor stimulates Akt/GSK3 signalling. In addition, in vivo Akt activity in the ventral striatum appears to play an important role in systemic D2/D3 agonist-induced behavioural activation. PMID:22909302

  11. 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.

  12. Improvements of AIMS D2DB matching for product patterns

    NASA Astrophysics Data System (ADS)

    Nishiguchi, Masaharu; Kanno, Koichi; Miyashita, Hiroyuki; Ohara, Kana; Son, Donghwan; Tolani, Vikram; Satake, Masaki

    2015-07-01

    AIMSTM is mainly used in photomask industry for verifying the print impact of mask defects on wafer CD in DUV lithography process. AIMS verification is typically used in D2D configuration, wherein two AIMS images, reference and defect, are captured and compared. Criticality of defects is then analyzed off these images using a number of criteria. As photomasks with aggressive OPC, sub-resolution assist features (SRAFs), and single-die are being routinely manufactured in production environment, it is required to improve cycle time through the AIMS step by saving time in searching for and capturing an adequate reference AIMS image. One solution is to use AIMS D2DB methodology which compares AIMS defect image with a reference image simulated from the corresponding mask design data. In general, such simulation needs calibration with the native images captured on the AIMS tool. In our previous paper we evaluated a calibration procedure directly using the defect AIMS image and compared the analysis results with a D2D capture using AIA (Aerial Image Analyzer) software product from Luminescent Technologies (now part of KLA-Tencor Corporation). The results showed that calibration using defect AIMS image does not influence AIMS judgment as long as the defect size is less than 100nm in case of typical basic patterns. When applying this methodology to product patterns, it was found that there were differences between reference AIMS image and simulation image. These differences influenced AIMS verification. Then new method to compensate would be needed. Our approach to compensate the difference between AIMS image and simulated image is examination with some factors likely to cause the difference.

  13. 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.

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

    NASA Astrophysics Data System (ADS)

    Ćaǧlar, 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 .

  15. The dissolution of metallic zinc in D2EHPA

    SciTech Connect

    Chia, L.M.; Neira, M.P.; O`Keefe, T.J.

    1995-07-01

    The direct dissolution of zinc in an organic solution of di-(2-ethylhexyl) phosphoric acid (D2EHPA) and kerosene was studied. The objective was to gain a better understanding of the fundamentals involved in the anodic step of the galvanic stripping process. Results showed that metallic zinc does dissolve spontaneously at ambient temperature by an electrochemical mechanism and the presence of additional oxygen activated the process. When oxygen was removed by prior nitrogen sparging, dissolution did not occur indicating a depolarizing cathodic reaction is necessary. The concentration of water in the organic also affected the rate of dissolution. A factorially designed experiment was made using four variables at two levels selected by evaluating results from previous screening tests. D2EHPA concentration, surface area and agitation were all found to be significant for the values chosen. Temperature was less significant and it was found that zinc dissolution is probably a diffusion or mixed controlled process, as indicated by the calculated activation energy of 6 kcal/mole.

  16. Neptune's Dark Spot (D2) at High Resolution

    NASA Technical Reports Server (NTRS)

    1989-01-01

    This bulls-eye view of Neptune's small dark spot (D2) was obtained by Voyager 2's narrow-angle camera on Aug. 24, 1989, when Voyager 2 was within 1.1 million km (680,000 miles) of the planet. The smallest structures that can be seen are 20 km (12 miles) across. This unplanned photograph was obtained when the infrared spectrograph was mapping the planet, and is the highest resolution view of the feature taken during the flyby. 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.

  17. 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...

  18. 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.

  19. 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. PMID:21803530

  20. On relating multiple M2 and D2-branes

    NASA Astrophysics Data System (ADS)

    Gran, U.; Nilsson, B. E. W.; Petersson, C.

    2008-10-01

    Due to the difficulties of finding superconformal Lagrangian theories for multiple M2-branes, we will in this paper instead focus on the field equations. By relaxing the requirement of a Lagrangian formulation we can explore the possibility of having structure constants fABCD satisfying the fundamental identity but which are not totally antisymmetric. We exemplify this discussion by making use of an explicit choice of a non-antisymmetric fABCD constructed from the Lie algebra structure constants fabc of an arbitrary gauge group. Although this choice of fABCD does not admit an obvious Lagrangian description, it does reproduce the correct SYM theory for a stack of N D2-branes to leading order in gYM-1 upon reduction and, moreover, it sheds new light on the centre of mass coordinates for multiple M2-branes.

  1. Striatal dopamine (D2) receptor availability predicts socially desirable responding.

    PubMed

    Reeves, Suzanne J; Mehta, Mitul A; Montgomery, Andrew J; Amiras, Dimitri; Egerton, Alice; Howard, Robert J; Grasby, Paul M

    2007-02-15

    Research in non-human primates has implicated striatal dopamine (D2) receptor function in the expression of social dominance--a fundamental component of social extraversion. We predicted that trait extraversion - indexed by the revised Eysenck Personality Questionnaire (EPQ-R) - would correlate with striatal DA (D2) receptor measures - indexed by [(11)C]-Raclopride binding potential (BP) - in 28 healthy post-menopausal females (mean age=75 years; range=58-91 years). Region of interest (ROI) and voxel-based statistical parametric mapping (SPM) analyses were performed, using a reference tissue model for [(11)C]-Raclopride. ROI analysis showed moderately significant negative correlations between extraversion and BP measures in the left caudate and between psychoticism scores and BP in the right putamen. Unexpectedly, scores on the Lie scale, a measure of socially desirable responding, were significantly and negatively correlated with BP measures in the putamen and survived Bonferroni correction on the right side. After controlling for the potential confounding of self-report bias in high Lie scorers, only the correlation between Lie scores and BP measures in the right putamen remained significant. Voxel-based analysis showed only Lie scores to be significantly and negatively correlated with BP measures in the right putamen. We explored this association further by applying an ROI-based approach to data on a previously scanned sample of young adults (n=13) and found a similar pattern of association, which achieved trend level significance in the right putamen. Although unanticipated, the relationship observed between BP measures in the right putamen and Lie scores is consistent with dopaminergic involvement in socially rewarding behaviour. How this relates to dopaminergic tone will need to be further explored.

  2. D2-receptor upregulation is dependent upon temporal course of D2-occupancy: a longitudinal [11C]-raclopride PET study in cats.

    PubMed

    Ginovart, Nathalie; Wilson, Alan A; Hussey, Doug; Houle, Sylvain; Kapur, Shitij

    2009-02-01

    Long-term occupancy of dopamine D(2)-receptors, as achieved by chronic treatment with antipsychotics, leads to D(2)-receptor upregulation, and this upregulation is thought to be responsible for loss of efficacy and development of tardive dyskinesia. However, little is known about the parameters of D(2)-receptor blockade (duration and percentage of blockade) that lead to upregulation. In this study, we investigated the effects of different degrees (60 vs >80%) and durations (a transient peak vs 24 h/day) of D(2)-receptor blockade on inducing this upregulation. These different patterns of D(2)-receptor occupancy kinetics were produced in cats using bolus vs constant infusion of haloperidol for 4 weeks. D(2)-receptors were measured using positron emission tomography and Scatchard analyses of [(11)C]raclopride binding, before and after withdrawal of treatment. Continuously high (80% for 24 h/day) D(2)-receptor blockade led to a robust upregulation of striatal D(2)-receptors that was maximal at 1-week withdrawal (35+/-5%) and still detectable at 2-week withdrawal (20+/-3%). This pattern of D(2)-receptor blockade also induced behavioral tolerance to the effect of haloperidol on spontaneous locomotor activity. Continuously moderate (60% for 24 h/day) or transiently high (80% for a few hours/day) D(2)-receptor blockade did not produce any of these effects. The long-term effect of haloperidol on D(2)-receptor density and behavioral tolerance thus appears to be dependent not only on a critical threshold of D(2)-receptor blockade but also on the daily duration of D(2)-receptors blockade. This suggests that as far as antipsychotics are concerned, not only dose but disbursment throughout the day have an impact on eventual pharmacodynamic and behavioral outcomes.

  3. Superconductivity in epitaxial thin films of NaxCoO2•yD2O

    NASA Astrophysics Data System (ADS)

    Krockenberger, Y.; Fritsch, I.; Christiani, G.; Habermeier, H.-U.; Yu, Li; Bernhard, C.; Keimer, B.; Alff, L.

    2006-04-01

    The observation of superconductivity in the layered transition metal oxide NaxCoO2•yH2O [K. Takada et al., Nature (London) 422, 53 (2003)] has caused a tremendous upsurge of scientific interest due to its similarities and its differences to the copper based high-temperature superconductors. Two years after the discovery, we report the fabrication of single-phase superconducting epitaxial thin films of Na0.3CoO2•1.3D2O grown by pulsed laser deposition technique. This opens additional roads for experimental research exploring the superconducting state and the phase diagram of this unconventional material.

  4. Schizophrenia thalamus imaging: low benzamide binding to dopamine D2 receptors suggests fewer D2Short receptors and fewer presynaptic terminals.

    PubMed

    Seeman, Philip

    2013-12-30

    The dopamine D2 receptor continues to be the major target for the treatment of schizophrenia and is one of many genes genetically associated with this disease. Recent data show that fewer short forms of the D2 receptor protein are synthesized if there is a genetic variant in the D2 receptor (with a T in rs 1076560 in intron 6). At the same time, at least six publications report that the binding of radioactive benzamides is reduced in the schizophrenia thalamus. A review of the benzamide pharmacology of the short and long forms of the D2 receptor shows that benzamides have a 2.4-fold higher affinity for the D2Short receptor relative to the D2Long form. Hence, the reduced amount of benzamide binding to the D2 receptors in the schizophrenia thalamus suggests that there is a reduced amount of D2Short receptors in this diseased region, and may possibly also mean fewer presynaptic terminals because that is where D2Short receptors mostly reside. If so, fewer presynaptic dopamine terminals in various brain regions may be the basis of the known behavioural dopamine supersensitivity in schizophrenia.

  5. Control of lactotrop proliferation by dopamine: Essential role of signaling through D2 receptors and ERKs

    PubMed Central

    Iaccarino, Ciro; Samad, Tarek A.; Mathis, Carole; Kercret, Henri; Picetti, Roberto; Borrelli, Emiliana

    2002-01-01

    Dopamine is thought to exert a negative control on lactotrop cell proliferation and prolactin production. Indeed, mice lacking the D2 receptor develop pituitary tumors of lactotrop origin. Because lactotrops express two isoforms of D2R, D2L, and D2S, in a specific ratio, we decided to explore the physiological importance of their relative abundance in vivo. Thus, we generated transgenic animals overexpressing either D2L or D2S in lactotrops. Increased expression of D2S, but not of D2L, leads to mitogen-activated protein kinase (MAPK) induction, which results in pituitary hypoplasia. On the other hand, levels of phosphorylated MAPKs are drastically reduced in pituitary tumors generated by the absence of D2-dependent signaling. These results underline a critical role of D2-mediated MAPK activation in lactotrop proliferation. Furthermore, whereas D2S overexpression results to a drastic reduction of prolactin, D2L overexpression elevates it. Our findings underscore a different role of the two D2R isoforms in the pituitary gland physiology. PMID:12391292

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

    PubMed

    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

  7. Cryogenic DT and D2 targets for inertial confinement fusiona)

    NASA Astrophysics Data System (ADS)

    Sangster, T. C.; Betti, R.; Craxton, R. S.; Delettrez, J. A.; Edgell, D. H.; Elasky, L. M.; Glebov, V. Yu.; Goncharov, V. N.; Harding, D. R.; Jacobs-Perkins, D.; Janezic, R.; Keck, R. L.; Knauer, J. P.; Loucks, S. J.; Lund, L. D.; Marshall, F. J.; McCrory, R. L.; McKenty, P. W.; Meyerhofer, D. D.; Radha, P. B.; Regan, S. P.; Seka, W.; Shmayda, W. T.; Skupsky, S.; Smalyuk, V. A.; Soures, J. M.; Stoeckl, C.; Yaakobi, B.; Frenje, J. A.; Li, C. K.; Petrasso, R. D.; Séguin, F. H.; Moody, J. D.; Atherton, J. A.; MacGowan, B. D.; Kilkenny, J. D.; Bernat, T. P.; Montgomery, D. S.

    2007-05-01

    Ignition target designs for inertial confinement fusion on the National Ignition Facility (NIF) [W. J. Hogan et al., Nucl. Fusion 41, 567 (2001)] are based on a spherical ablator containing a solid, cryogenic-fuel layer of deuterium and tritium. The need for solid-fuel layers was recognized more than 30 years ago and considerable effort has resulted in the production of cryogenic targets that meet most of the critical fabrication tolerances for ignition on the NIF. At the University of Rochester's Laboratory for Laser Energetics (LLE), the inner-ice surface of cryogenic DT capsules formed using β-layering meets the surface-smoothness requirement for ignition (<1-μm rms in all modes). Prototype x-ray-drive cryogenic targets being produced at the Lawrence Livermore National Laboratory are nearing the tolerances required for ignition on the NIF. At LLE, these cryogenic DT (and D2) capsules are being imploded on the direct-drive 60-beam, 30-kJ UV OMEGA laser [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)]. The designs of these cryogenic targets for OMEGA are energy scaled from the baseline direct-drive-ignition design for the NIF. Significant progress with the formation and characterization of cryogenic targets for both direct and x-ray drive will be described. Results from recent cryogenic implosions will also be presented.

  8. 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.

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

    NASA Astrophysics Data System (ADS)

    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 O2 at 157 nm provides a clean source of fast-moving O(1D2) 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.

  10. Proteomics and lipids of lipoproteins isolated at low salt concentrations in D2O/sucrose or in KBr.

    PubMed

    Ståhlman, Marcus; Davidsson, Pia; Kanmert, Ida; Rosengren, Birgitta; Borén, Jan; Fagerberg, Björn; Camejo, Germán

    2008-02-01

    There is much interest in the significance of apolipoproteins and proteins that are noncovalently associated with lipoproteins. It is possible that the high ionic strength used for isolation of lipoproteins with KBr and NaI could alter the pattern of associated exchangeable proteins. Here we describe lipoprotein classes fractionation from up to 0.5 ml of serum or plasma with buffers of physiological ionic strength and pH prepared with deuterium oxide (D(2)O) and sucrose. An advantage of the D(2)O/sucrose procedure was that the lipoproteins could be directly analyzed by the techniques described without need for desalting. We compared the isolated lipoproteins with those obtained using ultracentrifugation in KBr from the same plasma pool. Electrophoretic homogeneity of the lipoproteins was very similar using the two methods, as well as their lipid composition evaluated by HPLC. Two-dimensional electrophoresis and surface-enhanced laser adsorption/ionization time-of-flight mass spectrometry indicated that the patterns of exchangeable proteins of VLDL isolated using with the two procedures were very similar. However, significant differences were found in the profiles of LDL and HDL, indicating that the D(2)O/sucrose method allowed a more complete characterization of its exchangeable apolipoproteins and proteins. PMID:18025001

  11. Phosphorylation and palmitoylation of the human D2L dopamine receptor in Sf9 cells.

    PubMed

    Ng, G Y; O'Dowd, B F; Caron, M; Dennis, M; Brann, M R; George, S R

    1994-11-01

    We have expressed and biochemically characterized the human D2long (D2L) dopamine receptor isoform using the baculovirus/Sf9 cell system. The expressed receptor bound ligands with a pharmacological profile similar to that reported for neuronal and cloned D2L receptors expressed in mammalian cell lines. Dopamine binding to D2L receptor was sensitive to guanine nucleotides, indicating receptor coupling to endogenous G proteins. A D2L receptor-specific antibody identified two major protein species at approximately 44 kDa and at approximately 93 kDa in immunoblots, suggesting the presence of D2L receptor monomers and dimers. Both species were purified by immunoprecipitation from digitonin-solubilized preparation of cells expressing D2L receptor prelabeled with 32P(i) or [3H]-palmitate. These results constitute the first direct evidence for D2L receptor phosphorylation and palmitoylation.

  12. 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.

  13. Opposing roles of Prostaglandin D2 receptors in ulcerative colitis

    PubMed Central

    Sturm, Eva M.; Radnai, Balazs; Jandl, Katharina; Stančić, Angela; Parzmair, Gerald P.; Högenauer, Christoph; Kump, Patrizia; Wenzl, Heimo; Petritsch, Wolfgang; Pieber, Thomas R.; Schuligoi, Rufina; Marsche, Gunther; Ferreirós, Nerea; Heinemann, Akos; Schicho, Rudolf

    2014-01-01

    Pro-resolution functions were reported for Prostaglandin D2 (PGD2) in colitis, but the role of its two receptors, DP and in particular CRTH2 are less well defined. We investigated DP and CRTH2 expression and function during human and murine ulcerative colitis (UC). Expression of receptors was measured by flow cytometry on peripheral blood leukocytes, and by immunohistochemistry and immunoblotting in colon biopsies of patients with active UC and healthy individuals. Receptor involvement in UC was evaluated in a mouse model of DSS colitis. DP and CRTH2 expression changed in leukocytes of patients with active UC in a differential manner. In UC patients, DP showed higher expression in neutrophils but lower in monocytes as compared to control subjects. In contrast, CRTH2 was decreased in eosinophils, NK and CD3+ T cells but not in monocytes and CD3+/CD4+ T cells. The decrease of CRTH2 on blood eosinophils clearly correlated with disease activity. DP correlated positively with disease activity in eosinophils but inversely in neutrophils. CRTH2 internalized upon treatment with PGD2 and 11-dehydroTXB2 in eosinophils of controls. Biopsies of UC patients revealed an increase of CRTH2-positive cells in the colonic mucosa and high CRTH2 protein content. The CRTH2 antagonist CAY10595 improved while the DP antagonist MK0524 worsened inflammation in murine colitis. DP and CRTH2 play differential roles in UC. Although expression of CRTH2 on blood leukocytes is downregulated in UC, CRTH2 is present in colon tissue where it may contribute to inflammation whereas DP likely promotes anti-inflammatory actions. PMID:24929001

  14. 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...

  15. 17 CFR 270.27d-2 - Insurance company undertaking in lieu of segregated trust account.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Insurance company undertaking in lieu of segregated trust account. 270.27d-2 Section 270.27d-2 Commodity and Securities Exchanges....27d-2 Insurance company undertaking in lieu of segregated trust account. (a) Any depositor of...

  16. 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... 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...

  17. 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...

  18. 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... 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...

  19. Hypothyroidism Stimulates D2 Receptor-mediated Breathing in Response to Acute Hypoxia and alters D2 Receptors Levels in Carotid Bodies & Brain

    PubMed Central

    Schlenker, Evelyn H.; Schultz, Harold D.

    2011-01-01

    Hypothyroidism can depress breathing and alter dopamine D2 receptor expression and function. We hypothesized that relative to euthyroid hamsters (EH), hypothyroid hamsters (HH) contain increased D2 receptors in brain regions associated with breathing and carotid bodies (CB), and that stimulation of D2 receptors would decease ventilation more in the HH compared to the EH. Hamsters were treated with vehicle, carmoxirile (peripherally acting D2 receptor agonist), or bromocriptine (central and peripherally acting D2 receptor agonist) and breathing was evaluated during exposure to air, hypoxia, and then air. HH exhibited increased D2 receptor protein levels in the striatum and CB’s, but decreased levels in the paraventricular hypothalamic nucleus. Relative to vehicle, carmoxirole and bromocriptine stimulated ventilation in the HH during and following exposure to hypoxia. Only bromocriptine depressed ventilation in the EH during and after exposure to hypoxia. Thus,, hypothyroidism impacts the expression of D2 receptors in the carotid body, PVN and striatum, and D2 stimulation affects ventilation remarkably differently than in EH. PMID:22051191

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

    PubMed

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

    2016-02-01

    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)/Ca(2+)/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.

  1. 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. PMID:26214036

  2. 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

  3. Isotope effect on adsorbed quantum phases: diffusion of H2 and D2 in nanoporous carbon.

    PubMed

    Contescu, Cristian I; Zhang, Hongxin; Olsen, Raina J; Mamontov, Eugene; Morris, James R; Gallego, Nidia C

    2013-06-01

    Quasielastic neutron scattering of H(2) and D(2) in the same nanoporous carbon at 10-40 K demonstrates extreme quantum sieving, with D(2) diffusing up to 76 times faster. D(2) also shows liquidlike diffusion while H(2) exhibits Chudley-Elliott jump diffusion, evidence of their different relationships with the local lattice of adsorption sites due to quantum effects on intermolecular interactions. The onset of diffusion occurs at 22-25 K for H(2) and 10-13 K for D(2). At these temperatures, H(2) and D(2) have identical thermal de Broglie wavelengths that correlate with the dominant pore size. PMID:25167516

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

    PubMed

    Trifilieff, P; Feng, B; Urizar, E; Winiger, V; Ward, R D; Taylor, K M; Martinez, D; Moore, H; Balsam, P D; Simpson, E H; Javitch, J A

    2013-09-01

    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. As 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 postsynaptic 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

  5. Absence of cyclin D2 expression is associated with promoter hypermethylation in gastric cancer.

    PubMed

    Yu, J; Leung, W K; Ebert, M P A; Leong, R W L; Tse, P C H; Chan, M W Y; Bai, A H C; To, K F; Malfertheiner, P; Sung, J J Y

    2003-05-19

    Expression of cyclin D2 is absent in 30-70% of gastric cancers. We investigated the role of promoter hypermethylation in the transcriptional silencing of cyclin D2 in five gastric cell lines and 47 primary gastric carcinomas. CpG island methylation status of the cyclin D2 gene was studied by methylation-specific polymerase chain reaction and bisulphite sequencing. RNA and protein expression was analysed by reverse transcription-PCR and Western blot, respectively. Dense methylation of cyclin D2 was detected in three cell lines (KATOIII, AGS and NCI-N87), which also lacked cyclin D2 mRNA and protein expression. Bisulphite DNA sequencing revealed that loss of cyclin D2 expression was closely associated with the density of methylation in the promoter region. Treatment with DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, restored the cyclin D2 expression level in methylated gastric cells. Among the 47 primary gastric cancers, cyclin D2 hypermethylation was detected in 23 (48.9%) cases. None of the 23 normal gastric biopsies from noncancer patients showed hypermethylation. Hypermethylation was associated with loss of mRNA (P&<0.001) and protein (P=0.006) expressions. Our study showed that cyclin D2 hypermethylation is associated with loss of cyclin D2 expression in a subset of gastric cancers, which may suggest an alternative gastric carcinogenesis pathway in the absence of cyclin D2 expression. PMID:12771922

  6. Dopamine responsiveness is regulated by targeted sorting of D2 receptors.

    PubMed

    Bartlett, Selena E; Enquist, Johan; Hopf, Frederic W; Lee, Josephine H; Gladher, Fredrik; Kharazia, Viktor; Waldhoer, Maria; Mailliard, William S; Armstrong, Randall; Bonci, Antonello; Whistler, Jennifer L

    2005-08-01

    Aberrant dopaminergic signaling is a critical determinant in multiple psychiatric disorders, and in many disease states, dopamine receptor number is altered. Here we identify a molecular mechanism that selectively targets D2 receptors for degradation after their activation by dopamine. The degradative fate of D2 receptors is determined by an interaction with G protein coupled receptor-associated sorting protein (GASP). As a consequence of this GASP interaction, D2 responses in rat brain fail to resensitize after agonist treatment. Disruption of the D2-GASP interaction facilitates recovery of D2 responses, suggesting that modulation of the D2-GASP interaction is important for the functional down-regulation of D2 receptors.

  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. Aripiprazole has functionally selective actions at dopamine D2 receptor-mediated signaling pathways.

    PubMed

    Urban, Jonathan D; Vargas, Gabriel A; von Zastrow, Mark; Mailman, Richard B

    2007-01-01

    Aripiprazole is a unique atypical antipsychotic drug with an excellent side-effect profile presumed, in part, to be due to lack of typical D(2) dopamine receptor antagonist properties. Whether aripiprazole is a typical D(2) partial agonist, or a functionally selective D(2) ligand, remains controversial (eg D(2)-mediated inhibition of adenylate cyclase is system dependent; aripiprazole antagonizes D(2) receptor-mediated G-protein-coupled inwardly rectifying potassium channels and guanosine triphosphate nucleotide (GTP)gammaS coupling). The current study examined the D(2L) receptor binding properties of aripiprazole, as well as the effects of the drug on three downstream D(2) receptor-mediated functional effectors: mitogen-activated protein kinase (MAPK) phosphorylation, potentiation of arachidonic acid (AA) release, and D(2) receptor internalization. Unlike quinpirole (a full D(2) agonist) or (-)3PPP (S(-)-3-(3-hydroxyphenyl)-N-propylpiperidine hydrochloride, a D(2) partial agonist), the apparent D(2) affinity of aripiprazole was not decreased significantly by GTP. Moreover, full or partial agonists are expected to have Hill slopes <1.0, yet that of aripiprazole was significantly >1.0. Whereas aripiprazole partially activated both the MAPK and AA pathways, its potency vs MAPK phosphorylation was much lower relative to potencies in assays either of AA release or inhibition of cyclic adenosine 3',5'-cyclic monophosphate accumulation. In addition, unlike typical agonists, neither aripiprazole nor (-)3PPP produced significant internalization of the D(2L) receptor. These data are clear evidence that aripiprazole affects D(2L)-mediated signaling pathways in a differential manner. The results are consistent with the hypothesis that aripiprazole is a functionally selective D(2) ligand rather than a simple partial agonist. Such data may be useful in understanding the novel clinical actions of this drug.

  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

    2014-01-01

    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. 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

  11. Dopamine D2 receptor availability is linked to hippocampal-caudate functional connectivity and episodic memory.

    PubMed

    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; Lindenberger, Ulman; Bäckman, Lars

    2016-07-12

    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 [(11)C]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

  12. 17 CFR 270.12d2-1 - Definition of insurance company for purposes of sections 12(d)(2) and 12(g) of the Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., INVESTMENT COMPANY ACT OF 1940 § 270.12d2-1 Definition of insurance company for purposes of sections 12(d)(2... include a foreign insurance company as that term is used in rule 3a-6 under the Act (17 CFR 270.3a-6). ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Definition of...

  13. 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.

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

    PubMed

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

    2016-04-01

    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 pathological

  15. 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

  16. 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.

  17. Increased baseline occupancy of D2 receptors by dopamine in schizophrenia

    PubMed Central

    Abi-Dargham, Anissa; Rodenhiser, Janine; Printz, David; Zea-Ponce, Yolanda; Gil, Roberto; Kegeles, Lawrence S.; Weiss, Richard; Cooper, Thomas B.; Mann, J. John; Van Heertum, Ronald L.; Gorman, Jack M.; Laruelle, Marc

    2000-01-01

    The classical dopamine hypothesis of schizophrenia postulates a hyperactivity of dopaminergic transmission at the D2 receptor. We measured in vivo occupancy of striatal D2 receptors by dopamine in 18 untreated patients with schizophrenia and 18 matched controls, by comparing D2 receptor availability before and during pharmacologically induced acute dopamine depletion. Acute depletion of intrasynaptic dopamine resulted in a larger increase in D2 receptor availability in patients with schizophrenia (19% ± 11%) compared with control subjects (9% ± 7%, P = 0.003). The increased occupancy of D2 receptors by dopamine occurred both in first-episode neuroleptic-naive patients and in previously treated chronic patients experiencing an episode of illness exacerbation. In addition, elevated synaptic dopamine was predictive of good treatment response of positive symptoms to antipsychotic drugs. This finding provides direct evidence of increased stimulation of D2 receptors by dopamine in schizophrenia, consistent with increased phasic activity of dopaminergic neurons. PMID:10884434

  18. 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

  19. 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

    2016-01-01

    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

  20. 40 CFR 721.10270 - [5,6]Fullerene-C84-D2d.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fullerene-C84-D2d. 721.10270 Section... Substances § 721.10270 Fullerene-C84-D2d. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as Fullerene-C84-D2d (PMN P-09-57; CAS No. 145809-20-7)...

  1. 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…

  2. TSC22D2 interacts with PKM2 and inhibits cell growth in colorectal cancer.

    PubMed

    Liang, Fang; Li, Qiao; Li, Xiayu; Li, Zheng; Gong, Zhaojian; Deng, Hao; Xiang, Bo; Zhou, Ming; Li, Xiaoling; Li, Guiyuan; Zeng, Zhaoyang; Xiong, Wei

    2016-09-01

    We previously identified TSC22D2 (transforming growth factor β-stimulated clone 22 domain family, member 2) as a novel cancer-associated gene in a rare multi-cancer family. However, its role in tumor development remains completely unknown. In this study, we found that TSC22D2 was significantly downregulated in colorectal cancer (CRC) and that TSC22D2 overexpression inhibited cell growth. Using a co-immunoprecipitation (co-IP) assay combined with mass spectrometry analysis to identify TSC22D2-interacting proteins, we demonstrated that TSC22D2 interacts with pyruvate kinase isoform M2 (PKM2). These findings were confirmed by the results of immunoprecipitation and immunofluorescence assays. Moreover, overexpression of TSC22D2 reduced the level of nuclear PKM2 and suppressed cyclin D1 expression. Collectively, our study reveals a growth suppressor function of TSC22D2 that is at least partially dependent on the TSC22D2-PKM2-cyclinD1 regulatory axis. In addition, our data provide important clues that might contribute to future studies evaluating the role of TSC22D2. PMID:27573352

  3. Immunohistochemical localization of dopamine D2 receptor in the rat carotid body.

    PubMed

    Wakai, Jun; Takayama, Anna; Yokoyama, Takuya; Nakamuta, Nobuaki; Kusakabe, Tatsumi; Yamamoto, Yoshio

    2015-10-01

    Dopamine modulates the chemosensitivity of arterial chemoreceptors, and dopamine D2 receptor (D2R) is expected to localize in the glomus cells and/or sensory nerve endings of the carotid body. In the present study, the localization of D2R in the rat carotid body was examined using double immunofluorescence for D2R with various cell markers. D2R immunoreactivity was mainly localized in glomus cells immunoreactive to tyrosine hydroxylase or dopamine β-hydroxylase (DBH), but not in S100B-immunoreactive sustentacular cells. Furthermore, D2R immunoreactivity was observed in petrosal ganglion cells and nerve bundles in the carotid body, but not in the nerve endings with P2X2 immunoreactivity. In the carotid ganglion, a few punctate D2R-immunoreactive products were detected in DBH-immunoreactive nerve cell bodies. These results showed that D2R was mainly distributed in glomus cells, and suggested that D2R plays a role in the inhibitory modulation of chemosensory activity in a paracrine and/or autocrine manner. PMID:26272445

  4. STS-55 German payload specialists pose in front of SL-D2 module at KSC

    NASA Technical Reports Server (NTRS)

    1992-01-01

    STS-55 Columbia, Orbiter Vehicle (OV) 102, German payload specialists pose in front of the Spacelab Deutsche 2 (SL-D2) science module at a Kennedy Space Center (KSC) processing facility. These two Germans have been assigned to support the STS-55/SL-D2 mission. They are Payload Specialist 2 Hans Schlegel (left) and Payload Specialist 1 Ulrich Walter. Walter and Schlegel are scheduled to fly aboard OV-102 for the mission, joining five NASA astronauts. Clearly visible on the SL-D2 module are the European Space Agency (ESA) insignia, the feedthrough plate, and the D2 insignia.

  5. Dual Control of Dopamine Synthesis and Release by Presynaptic and Postsynaptic Dopamine D2 Receptors

    PubMed Central

    Anzalone, Andrea; Lizardi-Ortiz, José E.; Ramos, Maria; De Mei, Claudia; Hopf, F. Woodward; Iaccarino, Ciro; Halbout, Briac; Jacobsen, Jacob; Kinoshita, Chisato; Welter, Marc; Caron, Marc G.; Bonci, Antonello; Sulzer, David

    2012-01-01

    Dysfunctions of dopaminergic homeostasis leading to either low or high dopamine (DA) levels are causally linked to Parkinson's disease, schizophrenia, and addiction. Major sites of DA synthesis are the mesencephalic neurons originating in the substantia nigra and ventral tegmental area; these structures send major projections to the dorsal striatum (DSt) and nucleus accumbens (NAcc), respectively. DA finely tunes its own synthesis and release by activating DA D2 receptors (D2R). To date, this critical D2R-dependent function was thought to be solely due to activation of D2Rs on dopaminergic neurons (D2 autoreceptors); instead, using site-specific D2R knock-out mice, we uncover that D2 heteroreceptors located on non-DAergic medium spiny neurons participate in the control of DA levels. This D2 heteroreceptor-mediated mechanism is more efficient in the DSt than in NAcc, indicating that D2R signaling differentially regulates mesolimbic- versus nigrostriatal-mediated functions. This study reveals previously unappreciated control of DA signaling, shedding new light on region-specific regulation of DA-mediated effects. PMID:22745501

  6. Synthesis and SAR of aminothiazole fused benzazepines as selective dopamine D2 partial agonists.

    PubMed

    Urbanek, Rebecca A; Xiong, Hui; Wu, Ye; Blackwell, William; Steelman, Gary; Rosamond, Jim; Wesolowski, Steven S; Campbell, James B; Zhang, Minli; Brockel, Becky; Widzowski, Daniel V

    2013-01-15

    Dopamine (D(2)) partial agonists (D2PAs) have been regarded as a potential treatment for schizophrenia patients with expected better side effect profiles than currently marketed antipsychotics. Herein we report the synthesis and SAR of a series of aminothiazole fused benzazepines as selective D(2) partial agonists. These compounds have good selectivity, CNS drug-like properties and tunable D(2) partial agonism. One of the key compounds, 8h, has good in vitro/in vivo ADME characteristics, and is active in a rat amphetamine-induced locomotor activity model. PMID:23237836

  7. Mutational analysis of Agrobacterium tumefaciens virD2: tyrosine 29 is essential for endonuclease activity.

    PubMed Central

    Vogel, A M; Das, A

    1992-01-01

    Agrobacterium tumefaciens VirD2 polypeptide, in the presence of VirD1, catalyzes a site- and strand-specific nicking reaction at the T-DNA border sequences. VirD2 is found tightly attached to the 5' end of the nicked DNA. The protein-DNA complex is presumably formed via a tyrosine residue of VirD2 (F. Durrenberger, A. Crameri, B. Hohn, and Z. Koukolikova-Nicola, Proc. Natl. Acad. Sci. USA 86:9154-9158, 1989). A mutational approach was used to study whether a tyrosine residue(s) of VirD2 is required for its activity. By site-specific mutagenesis, a tyrosine (Y) residue at position 29, 68, 99, 119, 121, 160, or 195 of the octopine Ti plasmid pTiA6 VirD2 was altered to phenylalanine (F). The Y-29-F or Y-121-F mutation completely abolished nicking activity of VirD2 in vivo in Escherichia coli. Two other substitutions, Y-68-F and Y-160-F, drastically reduced VirD2 activity. A substitution at position 99, 119, or 195 had no effect on VirD2 activity. Additional mutagenesis experiments showed that at position 29, no other amino acid could substitute for tyrosine without destroying VirD2 activity. At position 121, only a tryptophan (W) residue could be substituted. This, however, yielded a mutant protein with significantly reduced VirD2 activity. The nicked DNA from strains bearing a Y-68-F, Y-99-F, Y-119-F, Y-160-F, Y-195-F, or Y-121-W mutation in VirD2 was always found to contain a tightly linked protein. Images PMID:1309520

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

    PubMed

    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 [(11)C]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

  9. 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

  10. Receptor, Ligand and Transducer Contributions to Dopamine D2 Receptor Functional Selectivity

    PubMed Central

    Peterson, Sean M.; Pack, Thomas F.; Caron, Marc G.

    2015-01-01

    Functional selectivity (or biased agonism) is a property exhibited by some G protein-coupled receptor (GPCR) ligands, which results in the modulation of a subset of a receptor’s signaling capabilities and more precise control over complex biological processes. The dopamine D2 receptor (D2R) exhibits pleiotropic responses to the biogenic amine dopamine (DA) to mediate complex central nervous system functions through activation of G proteins and β-arrestins. D2R is a prominent therapeutic target for psychological and neurological disorders in which DA biology is dysregulated and targeting D2R with functionally selective drugs could provide a means by which pharmacotherapies could be developed. However, factors that determine GPCR functional selectivity in vivo may be multiple with receptors, ligands and transducers contributing to the process. We have recently described a mutagenesis approach to engineer biased D2R mutants in which G protein-dependent ([Gprot]D2R) and β-arrestin-dependent signaling ([βarr]D2R) were successfully separated (Peterson, et al. PNAS, 2015). Here, permutations of these mutants were used to identify critical determinants of the D2R signaling complex that impart signaling bias in response to the natural or synthetic ligands. Critical residues identified in generating [Gprot]D2R and [βarr]D2R conferred control of partial agonism at G protein and/or β-arrestin activity. Another set of mutations that result in G protein bias was identified that demonstrated that full agonists can impart unique activation patterns, and provided further credence to the concept of ligand texture. Finally, the contributions and interplay between different transducers indicated that G proteins are not aberrantly activated, and that receptor kinase and β-arrestin activities are inextricably linked. These data provide a thorough elucidation of the feasibility and malleability of D2R functional selectivity and point to means by which novel in vivo therapies

  11. 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…

  12. Recent Progress in Understanding the Sodium Nightglow D2/D1 Ratio, and Future Prospects for Measuring the Mesopause [O]/[O2] Ratio

    NASA Astrophysics Data System (ADS)

    She, C. Y.; Plane, J. M. C.; Yuan, T.

    2014-12-01

    The mechanism for sodium nightglow was proposed by Chapman in 1939, in which the emitting sodium atoms in the Na(2P) state were produced by the reaction of NaO and O in the mesopause region. Laboratory experiments in the early 1990s have shown that the NaO produced by the reaction Na + O3 are in the low-lying NaO(A2S+) excited electronic state, rather than the NaO(X2P) ground state, suggesting that the intensity ratio RD between the D2 line and the D1 line should be 2.0, in accord with their statistical spin-orbit weights. However, observed high resolution airglow spectra during the past decade clearly showed, surprisingly, that RD is quite variable. This led Slanger et al. (2005) to propose a modified Champman model, based on the fact that the ground state, NaO(X2P), resulting from quenching of NaO(A2S+) by atmospheric O2, provides a competitive pathway for the production of Na(2P). The paper also published a laboratory measured relationship between RD and [O]/[O2]. Harrell et al. (2010) then noted that the Na(2P) atoms produced from NaO(A2S+) and NaO(X2P) will have different kinetic energies and hence emission linewidths, so that the D line ratio arising from each state, RA and RX respectively, should be separately measurable. They developed a Faraday-filter-based sodium spectrometer which in addition to RD measures RA and RX: values of RA = 2.22 ± 0.72 and RX = 1.44 ± 0.48 were reported from 5 nights of data. They also showed that the ratio R2 (the ratio of the D2 emission intensity from NaO(A2S+) to that from NaO(X2P)), and similarly R1 for the D1 emission ratio, are directly proportional to [O]/[O2]. Plane et al. (2012) then showed by considering correlation of the electronic potential energy surfaces connecting the reactants NaO(A2S+)+O and NaO(X2P) +O with the products Na+O2 through the NaO2 intermediate that the theoretical values of RA and RX should be 2.0 and 1.5, respectively, in good agreement with the observations. In this paper, we will provide a

  13. 12 CFR Appendix D-2 to Part 208 - Interagency Guidelines Establishing Information Security Standards

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... their obligations as required by paragraph D.2. As part of this monitoring, a bank should review audits... (OTS). 2 12 CFR part 30, app. B (OCC); 12 CFR part 208, app. D-2 and part 225, app. F (Board); 12 CFR part 364, app. B (FDIC); and 12 CFR part 570, app. B (OTS). The “Interagency Guidelines...

  14. Striatal Dopamine D2/3 Receptor Availability in Treatment Resistant Depression

    PubMed Central

    Ruhé, Eric H. G.; van Wingen, Guido A.; Booij, Jan; Denys, Damiaan

    2014-01-01

    Several studies demonstrated improvement of depressive symptoms in treatment resistant depression (TRD) after administering dopamine agonists which suggest abnormal dopaminergic neurotransmission in TRD. However, the role of dopaminergic signaling through measurement of striatal dopamine D2/3 receptor (D2/3R) binding has not been investigated in TRD subjects. We used [123I]IBZM single photon emission computed tomography (SPECT) to investigate striatal D2/3R binding in TRD. We included 6 severe TRD patients, 11 severe TRD patients on antipsychotics (TRD AP group) and 15 matched healthy controls. Results showed no significant difference (p = 0.75) in striatal D2/3R availability was found between TRD patients and healthy controls. In the TRD AP group D2/3R availability was significantly decreased (reflecting occupancy of D2/3Rs by antipsychotics) relative to TRD patients and healthy controls (p<0.001) but there were no differences in clinical symptoms between TRD AP and TRD patients. This preliminary study therefore does not provide evidence for large differences in D2/3 availability in severe TRD patients and suggests this TRD subgroup is not characterized by altered dopaminergic transmission. Atypical antipsychotics appear to have no clinical benefit in severe TRD patients who remain depressed, despite their strong occupancy of D2/3Rs. PMID:25411966

  15. 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..., AND RECORDKEEPING BY POLITICAL COMMITTEES (2 U.S.C. 433) § 102.4 Administrative termination (2 U.S.C. 433(d)(2)). (a) The Commission, on its own initiative or upon the request of the political...

  16. 11 CFR 102.4 - Administrative termination (2 U.S.C. 433(d)(2)).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 11 Federal Elections 1 2014-01-01 2014-01-01 false Administrative termination (2 U.S.C. 433(d)(2..., AND RECORDKEEPING BY POLITICAL COMMITTEES (2 U.S.C. 433) § 102.4 Administrative termination (2 U.S.C. 433(d)(2)). (a) The Commission, on its own initiative or upon the request of the political...

  17. 11 CFR 102.4 - Administrative termination (2 U.S.C. 433(d)(2)).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 11 Federal Elections 1 2013-01-01 2012-01-01 true Administrative termination (2 U.S.C. 433(d)(2..., AND RECORDKEEPING BY POLITICAL COMMITTEES (2 U.S.C. 433) § 102.4 Administrative termination (2 U.S.C. 433(d)(2)). (a) The Commission, on its own initiative or upon the request of the political...

  18. 11 CFR 102.4 - Administrative termination (2 U.S.C. 433(d)(2)).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 11 Federal Elections 1 2012-01-01 2012-01-01 false Administrative termination (2 U.S.C. 433(d)(2..., AND RECORDKEEPING BY POLITICAL COMMITTEES (2 U.S.C. 433) § 102.4 Administrative termination (2 U.S.C. 433(d)(2)). (a) The Commission, on its own initiative or upon the request of the political...

  19. 11 CFR 102.4 - Administrative termination (2 U.S.C. 433(d)(2)).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 11 Federal Elections 1 2011-01-01 2011-01-01 false Administrative termination (2 U.S.C. 433(d)(2..., AND RECORDKEEPING BY POLITICAL COMMITTEES (2 U.S.C. 433) § 102.4 Administrative termination (2 U.S.C. 433(d)(2)). (a) The Commission, on its own initiative or upon the request of the political...

  20. The Dopamine D2 Receptor Gene in Lamprey, Its Expression in the Striatum and Cellular Effects of D2 Receptor Activation

    PubMed Central

    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. PMID:22563388

  1. 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

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

    PubMed Central

    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

    2015-01-01

    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. PMID:25735756

  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. 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

  5. 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

    2015-03-01

    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.

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

    PubMed

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

    2015-08-04

    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-HT(2A/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.

  7. 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. PMID:25735756

  8. 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

    2015-03-01

    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. PMID:25740537

  9. 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

  10. Melanocortin 4 Receptor and Dopamine D2 Receptor Expression in Brain Areas Involved in Food Intake

    PubMed Central

    Yoon, Ye Ran

    2015-01-01

    Background The melanocortin 4 receptor (MC4R) is involved in the regulation of homeostatic energy balance by the hypothalamus. Recent reports showed that MC4R can also control the motivation for food in association with a brain reward system, such as dopamine. We investigated the expression levels of MC4R and the dopamine D2 receptor (D2R), which is known to be related to food rewards, in both the hypothalamus and brain regions involved in food rewards. Methods We examined the expression levels of D2R and MC4R by dual immunofluorescence histochemistry in hypothalamic regions and in the bed nucleus of the stria terminalis (BNST), the central amygdala, and the ventral tegmental area of transgenic mice expressing enhanced green fluorescent protein under the control of the D2R gene. Results In the hypothalamic area, significant coexpression of MC4R and D2R was observed in the arcuate nucleus. We observed a significant coexpression of D2R and MC4R in the BNST, which has been suggested to be an important site for food reward. Conclusion We suggest that MC4R and D2R function in the hypothalamus for control of energy homeostasis and that within the brain regions related with rewards, such as the BNST, the melanocortin system works synergistically with dopamine for the integration of food motivation in the control of feeding behaviors. PMID:26790386

  11. Targeting Dopamine D2 and Cannabinoid-1 (CB1) Receptors in Rat Nucleus Accumbens

    PubMed Central

    PICKEL, VIRGINA M.; CHAN, JANE; KEARN, CHRISTOPHER S.; MACKIE, KENNETH

    2006-01-01

    The nucleus accumbens (Acb) shell and core are essential components of neural circuitry mediating the reward and motor effects produced by activation of dopamine D2 or cannabinoid-1 (CB1) receptors. D2 receptors can form heterodimeric complexes with cannabinoid-1 (CB1) receptors and are also involved in control of the availability of both dopamine and endocannabinoids. Thus, the subcellular locations of D2 and CB1 receptors with respect to each other are implicit to their physiological actions in the Acb. We used electron microscopic immunocytochemistry to determine these locations in the Acb shell and core of rat brain. In each region, many neuronal profiles showed endomembrane and plasmalemmal distributions of one or both receptors. Approximately one-third of the labeled profiles were somata and dendrites, some of which showed overlapping subcellular distributions of D2 and CB1 immunoreactivities. The remaining labeled profiles were small axons and axon terminals containing CB1 and/or D2 receptors. Of the labeled terminals forming recognizable synapses, ~20% of those containing CB1 receptors contacted D2-labeled dendrites, while conversely, almost 15% of those containing D2 receptors contacted CB1-labeled dendrites. These results provide the first ultrastructural evidence that D2 and CB1 receptors in the Acb shell and core have subcellular distributions supporting both intracellular associations and local involvement of D2 receptors in making available endocannabinoids that are active on CB1 receptors in synaptic neurons. These distributions have direct relevance to the rewarding and euphoric as well as motor effects produced by marijuana and by addictive drugs enhancing dopamine levels in the Acb. PMID:16440297

  12. Impact of D2 Receptor Internalization on Binding Affinity of Neuroimaging Radiotracers

    PubMed Central

    Guo, Ningning; Guo, Wen; Kralikova, Michaela; Jiang, Man; Schieren, Ira; Narendran, Raj; Slifstein, Mark; Abi-Dargham, Anissa; Laruelle, Marc; Javitch, Jonathan A; Rayport, Stephen

    2010-01-01

    Synaptic dopamine (DA) levels seem to affect the in vivo binding of many D2 receptor radioligands. Thus, release of endogenous DA induced by the administration of amphetamine decreases ligand binding, whereas DA depletion increases binding. This is generally thought to be due to competition between endogenous DA and the radioligands for D2 receptors. However, the temporal discrepancy between amphetamine-induced increases in DA as measured by microdialysis, which last on the order of 2 h, and the prolonged decrease in ligand binding, which lasts up to a day, has suggested that agonist-induced D2 receptor internalization may contribute to the sustained decrease in D2 receptor-binding potential seen following a DA surge. To test this hypothesis, we developed an in vitro system showing robust agonist-induced D2 receptor internalization following treatment with the agonist quinpirole. Human embryonic kidney 293 (HEK293) cells were stably co-transfected with human D2 receptor, G-protein-coupled receptor kinase 2 and arrestin 3. Agonist-induced D2 receptor internalization was demonstrated by fluorescence microscopy, flow cytometry, and radioligand competition binding. The binding of seven D2 antagonists and four agonists to the surface and internalized receptors was measured in intact cells. All the imaging ligands bound with high affinity to both surface and internalized D2 receptors. Affinity of most of the ligands to internalized receptors was modestly lower, indicating that internalization would reduce the binding potential measured in imaging studies carried out with these ligands. However, between-ligand differences in the magnitude of the internalization-associated affinity shift only partly accounted for the data obtained in neuroimaging experiments, suggesting the involvement of mechanisms beyond competition and internalization. PMID:19956086

  13. 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.

  14. Interactive effect of histamine and prostaglandin D2 on nasal allergic symptoms in rats.

    PubMed

    Rahman, Ashequr; Inoue, Toshio; Ago, Jun; Ishikawa, Takashi; Kamei, Chiaki

    2007-01-12

    This study was undertaken to investigate the interactive effect of histamine and prostaglandin D(2) in nasal allergic symptoms in rats. The intranasal application of histamine at doses lower than 10 mumol/site caused no sneezing or nasal rubbing. In addition, prostaglandin D(2) also showed no significant increase in these responses, even at a dose of 10 nmol/site. On the other hand, the simultaneous instillation of histamine and prostaglandin D(2) resulted in a 1000 times more potent effect in inducing nasal symptoms than the administration of histamine alone. Thus, prostaglandin D(2) enhanced the actions of histamine in inducing sneezing and nasal rubbing in a dose-dependent manner, and significant effects were observed at doses higher than 1 nmol/site. The responses induced by the simultaneous application of histamine and prostaglandin D(2) were inhibited by chlorpheniramine, cyproheptadine, BW A868C and ramatroban. Chlorpheniramine and cyproheptadine showed the dose-related inhibition of nasal symptoms induced by the combined administration of histamine (10 nmol) and prostaglandin D(2) (10 nmol), but the effect of cyproheptadine was relatively weak compared with chlorpheniramine. Moreover, BW A868C and ramatroban also showed the inhibition of nasal symptoms induced by the simultaneous administration of histamine and prostaglandin D(2) in a dose-dependent manner. BW A868C was more potent in inhibiting the nasal symptoms than ramatroban. These results clearly indicate that prostaglandin D(2) showed a synergistic effect on sneezing and nasal rubbing induced by histamine in rats, and its effect occurred through both prostaglandin D(2) and CRTH2 (chemoattractant receptor-homologous molecule expressed on TH2 cells) receptors.

  15. Sweet Dopamine: Sucrose Preferences Relate Differentially to Striatal D2 Receptor Binding and Age in Obesity.

    PubMed

    Pepino, Marta Y; Eisenstein, Sarah A; Bischoff, Allison N; Klein, Samuel; Moerlein, Stephen M; Perlmutter, Joel S; Black, Kevin J; Hershey, Tamara

    2016-09-01

    Alterations in dopaminergic circuitry play a critical role in food reward and may contribute to susceptibility to obesity. Ingestion of sweets releases dopamine in striatum, and both sweet preferences and striatal D2 receptors (D2R) decline with age and may be altered in obesity. Understanding the relationships between these variables and the impact of obesity on these relationships may reveal insight into the neurobiological basis of sweet preferences. We evaluated sucrose preferences, perception of sweetness intensity, and striatal D2R binding potential (D2R BPND) using positron emission tomography with a D2R-selective radioligand insensitive to endogenous dopamine, (N-[(11)C] methyl)benperidol, in 20 subjects without obesity (BMI 22.5 ± 2.4 kg/m(2); age 28.3 ± 5.4 years) and 24 subjects with obesity (BMI 40.3 ± 5.0 kg/m(2); age 31.2 ± 6.3 years). The groups had similar sucrose preferences, sweetness intensity perception, striatal D2R BPND, and age-related D2R BPND declines. However, both striatal D2R BPND and age correlated with sucrose preferences in subjects without obesity, explaining 52% of their variance in sucrose preference. In contrast, these associations were absent in the obese group. In conclusion, the age-related decline in D2R was not linked to the age-related decline in sweetness preferences, suggesting that other, as-yet-unknown mechanisms play a role and that these mechanisms are disrupted in obesity. PMID:27307220

  16. Functional variants of the dopamine receptor D2 gene modulate prefronto-striatal phenotypes in schizophrenia

    PubMed Central

    Fazio, Leonardo; Caforio, Grazia; Blasi, Giuseppe; Rampino, Antonio; Romano, Raffaella; Di Giorgio, Annabella; Taurisano, Paolo; Papp, Audrey; Pinsonneault, Julia; Wang, Danxin; Nardini, Marcello; Popolizio, Teresa; Sadee, Wolfgang

    2009-01-01

    Dopamine D2 receptor signalling is strongly implicated in the aetiology of schizophrenia. We have recently characterized the function of three DRD2 SNPs: rs12364283 in the promoter affecting total D2 mRNA expression; rs2283265 and rs1076560, respectively in introns 5 and 6, shifting mRNA splicing to two functionally distinct isoforms, the short form of D2 (D2S) and the long form (D2L). These two isoforms differentially contribute to dopamine signalling in prefrontal cortex and in striatum. We performed a case–control study to determine association of these variants and of their main haplotypes with several schizophrenia-related phenotypes. We demonstrate that the minor allele in the intronic variants is associated with reduced expression of %D2S of total mRNA in post-mortem prefrontal cortex, and with impaired working memory behavioural performance, both in patients and controls. However, the fMRI results show opposite effects in patients compared with controls: enhanced engagement of prefronto-striatal pathways in controls and reduced activity in patients. Moreover, the promoter variant is also associated with working memory activity in prefrontal cortex and striatum of patients, and less robustly with negative symptoms scores. Main haplotypes formed by the three DRD2 variants showed significant associations with these phenotypes consistent with those of the individual SNPs. Our results indicate that the three functional DRD2 variants modulate schizophrenia phenotypes possibly by modifying D2S/D2L ratios in the context of different total D2 density. PMID:18829695

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

    PubMed Central

    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. PMID:27014623

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

    PubMed

    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

    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

  19. 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

  20. 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. PMID:26484605

  1. Caspase-resistant VirD2 protein provides enhanced gene delivery and expression in plants.

    PubMed

    Reavy, Brian; Bagirova, Svetlana; Chichkova, Nina V; Fedoseeva, Svetlana V; Kim, Sang Hyon; Vartapetian, Andrey B; Taliansky, Michael E

    2007-08-01

    Agrobacterium tumefaciens VirD2 protein is one of the key elements of Agrobacterium-mediated plant transformation, a process of transfer of T-DNA sequence from the Agrobacterium tumour inducing plasmid into the nucleus of infected plant cells and its integration into the host genome. The VirD2 protein has been shown to be a substrate for a plant caspase-like protease activity (PCLP) in tobacco. We demonstrate here that mutagenesis of the VirD2 protein to prevent cleavage by PCLP increases the efficiency of reporter gene transfer and expression. These results indicate that PCLP cleavage of the Agrobacterium VirD2 protein acts to limit the effectiveness of T-DNA transfer and is a novel resistance mechanism that plants utilise to combat Agrobacterium infection. PMID:17370074

  2. Expression of D2 dopamine receptor mRNA in the arterial chemoreceptor afferent pathway.

    PubMed

    Czyzyk-Krzeska, M F; Lawson, E E; Millhorn, D E

    1992-11-01

    Dopamine is a major neurotransmitter in the arterial chemoreceptor pathway. In the present study we wished to determine if messenger RNAs for dopamine D1 and D2 receptor are expressed in carotid body (type I cells), in sensory neurons of the petrosal ganglion which innervate the carotid body and in sympathetic neurons of the superior cervical ganglion. We failed to detect D1 receptor mRNA in any of these tissues. However, we found that D2 receptor mRNA was expressed by dopaminergic carotid body type I cells. D2 receptor mRNA was also found in petrosal ganglion neurons that innervated the carotid sinus and carotid body. In addition, a large number of sympathetic postganglionic neurons in the superior cervical ganglion expressed D2 receptor mRNA. PMID:1362730

  3. 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.

  4. Resolvin D1 and Resolvin D2 Govern Local Inflammatory Tone in Obese Fat1

    PubMed Central

    Clària, Joan; Dalli, Jesmond; Yacoubian, Stephanie; Gao, Fei; Serhan, Charles N.

    2012-01-01

    The unprecedented rise in the prevalence of obesity and obesity-related disorders is causally linked to a chronic state of low-grade inflammation in adipose tissue. Timely resolution of inflammation and return of this tissue to homeostasis are key to reducing obesity-induced metabolic dysfunctions. Here, with inflamed adipose, we investigated the biosynthesis, conversion and actions of Resolvin (Rv) D1 and RvD2, potent anti-inflammatory and pro-resolving lipid mediators (LM), and their ability to regulate monocyte interactions with adipocytes. LM-metabololipidomics identified RvD1 and RvD2 from endogenous sources in human and mouse adipose tissues. We also identified pro-resolving receptors (i.e. ALX/FPR2, ChemR23 and GPR32) in these tissues. Compared to lean tissue, obese adipose showed a deficit of these endogenous anti-inflammatory signals. With inflamed obese adipose tissue, RvD1 and RvD2 each rescued impaired expression and secretion of adiponectin in a time- and concentration-dependent manner while decreasing pro-inflammatory adipokine production including leptin, TNFα, IL-6 and IL-1β. RvD1 and RvD2 each reduced MCP-1 and leukotriene B4-stimulated monocyte adhesion to adipocytes and their transadipose migration. Adipose tissue rapidly converted both resolvins to novel oxo-resolvins. RvD2 was enzymatically converted to 7-oxo-RvD2 as its major metabolic route that retained adipose-directed RvD2 actions. These results indicate, in adipose, D-series resolvins (RvD1 and RvD2) are potent pro-resolving mediators that counteract both local adipokine production and monocyte accumulation in obesity-induced adipose inflammation. PMID:22844113

  5. Vitamin D2 is much less effective than vitamin D3 in humans.

    PubMed

    Armas, Laura A G; Hollis, Bruce W; Heaney, Robert P

    2004-11-01

    Vitamins D(2) and D(3) are generally considered to be equivalent in humans. Nevertheless, physicians commonly report equivocal responses to seemingly large doses of the only high-dose calciferol (vitamin D(2)) available in the U.S. market. The relative potencies of vitamins D(2) and D(3) were evaluated by administering single doses of 50,000 IU of the respective calciferols to 20 healthy male volunteers, following the time course of serum vitamin D and 25-hydroxyvitamin D (25OHD) over a period of 28 d and measuring the area under the curve of the rise in 25OHD above baseline. The two calciferols produced similar rises in serum concentration of the administered vitamin, indicating equivalent absorption. Both produced similar initial rises in serum 25OHD over the first 3 d, but 25OHD continued to rise in the D(3)-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D(2)-treated subjects and was not different from baseline at 14 d. Area under the curve (AUC) to d 28 was 60.2 ng.d/ml (150.5 nmol.d/liter) for vitamin D(2) and 204.7 (511.8) for vitamin D(3) (P < 0.002). Calculated AUC(infinity) indicated an even greater differential, with the relative potencies for D(3):D(2) being 9.5:1. Vitamin D(2) potency is less than one third that of vitamin D(3). Physicians resorting to use of vitamin D(2) should be aware of its markedly lower potency and shorter duration of action relative to vitamin D(3).

  6. 26 CFR 53.4941(d)-2 - Specific acts of self-dealing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Specific acts of self-dealing. 53.4941(d)-2...) MISCELLANEOUS EXCISE TAXES (CONTINUED) FOUNDATION AND SIMILAR EXCISE TAXES Taxes on Self-Dealing § 53.4941(d)-2 Specific acts of self-dealing. Except as provided in § 53.4941(d)-3 or § 53.4941(d)-4: (a) Sale or...

  7. Dopaminergic isoquinolines with hexahydrocyclopenta[ij]-isoquinolines as D2-like selective ligands.

    PubMed

    Párraga, Javier; Andujar, Sebastián A; Rojas, Sebastián; Gutierrez, Lucas J; El Aouad, Noureddine; Sanz, M Jesús; Enriz, Ricardo D; Cabedo, Nuria; Cortes, Diego

    2016-10-21

    Dopamine receptors (DR) ligands are potential drug candidates for treating neurological disorders including schizophrenia or Parkinson's disease. Three series of isoquinolines: (E)-1-styryl-1,2,3,4-tetrahydroisoquinolines (series 1), 7-phenyl-1,2,3,7,8,8a-hexahydrocyclopenta[ij]-IQs (HCPIQs) (series 2) and (E)-1-(prop-1-en-1-yl)-1,2,3,4- tetrahydroisoquinolines (series 3), were prepared to determine their affinity for both D1 and D2-like DR. The effect of different substituents on the nitrogen atom (methyl or allyl), the dioxygenated function (methoxyl or catechol), the substituent at the β-position of the THIQ skeleton, and the presence or absence of the cyclopentane motif, were studied. We observed that the most active compounds in the three series (2c, 2e, 3a, 3c, 3e, 5c and 5e) possessed a high affinity for D2-like DR and these remarkable features: a catechol group in the IQ-ring and the N-substitution (methyl or allyl). The series showed the following trend to D2-RD affinity: HCPIQs > 1-styryl > 1-propenyl. Therefore, the substituent at the β-position of the THIQ and the cyclopentane ring also modulated this affinity. Among these dopaminergic isoquinolines, HCPIQs stood out for unexpected selectivity to D2-DR since the Ki D1/D2 ratio reached values of 2465, 1010 and 382 for compounds 3a, 3c and 3e, respectively. None of the most active THIQs in D2 DR displayed relevant cytotoxicity in human neutrophils and HUVEC. Finally, and in agreement with the experimental data, molecular modeling studies on DRs of the most characteristic ligands of the three series revealed stronger molecular interactions with D2 DR than with D1 DR, which further supports to the encountered enhanced selectivity to D2 DR. PMID:27343851

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

    DOE PAGES

    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 [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

  9. 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. PMID:27495973

  10. 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

    2015-01-01

    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. PMID:25871974

  11. 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.

  12. Dopaminergic isoquinolines with hexahydrocyclopenta[ij]-isoquinolines as D2-like selective ligands.

    PubMed

    Párraga, Javier; Andujar, Sebastián A; Rojas, Sebastián; Gutierrez, Lucas J; El Aouad, Noureddine; Sanz, M Jesús; Enriz, Ricardo D; Cabedo, Nuria; Cortes, Diego

    2016-10-21

    Dopamine receptors (DR) ligands are potential drug candidates for treating neurological disorders including schizophrenia or Parkinson's disease. Three series of isoquinolines: (E)-1-styryl-1,2,3,4-tetrahydroisoquinolines (series 1), 7-phenyl-1,2,3,7,8,8a-hexahydrocyclopenta[ij]-IQs (HCPIQs) (series 2) and (E)-1-(prop-1-en-1-yl)-1,2,3,4- tetrahydroisoquinolines (series 3), were prepared to determine their affinity for both D1 and D2-like DR. The effect of different substituents on the nitrogen atom (methyl or allyl), the dioxygenated function (methoxyl or catechol), the substituent at the β-position of the THIQ skeleton, and the presence or absence of the cyclopentane motif, were studied. We observed that the most active compounds in the three series (2c, 2e, 3a, 3c, 3e, 5c and 5e) possessed a high affinity for D2-like DR and these remarkable features: a catechol group in the IQ-ring and the N-substitution (methyl or allyl). The series showed the following trend to D2-RD affinity: HCPIQs > 1-styryl > 1-propenyl. Therefore, the substituent at the β-position of the THIQ and the cyclopentane ring also modulated this affinity. Among these dopaminergic isoquinolines, HCPIQs stood out for unexpected selectivity to D2-DR since the Ki D1/D2 ratio reached values of 2465, 1010 and 382 for compounds 3a, 3c and 3e, respectively. None of the most active THIQs in D2 DR displayed relevant cytotoxicity in human neutrophils and HUVEC. Finally, and in agreement with the experimental data, molecular modeling studies on DRs of the most characteristic ligands of the three series revealed stronger molecular interactions with D2 DR than with D1 DR, which further supports to the encountered enhanced selectivity to D2 DR.

  13. Colony-stimulating Factor-1 Receptor Utilizes Multiple Signaling Pathways to Induce Cyclin D2 Expression

    PubMed Central

    Dey, Arunangsu; She, Hongyun; Kim, Leopold; Boruch, Allan; Guris, Deborah L.; Carlberg, Kristen; Sebti, Saïd M.; Woodley, David T.; Imamoto, Akira; Li, Wei

    2000-01-01

    Colony-stimulating factor-1 (CSF-1) induces expression of immediate early gene, such as c-myc and c-fos and delayed early genes such as D-type cyclins (D1 and D2), whose products play essential roles in the G1 to S phase transition of the cell cycle. Little is known, however, about the cytoplasmic signal transduction pathways that connect the surface CSF-1 receptor to these genes in the nucleus. We have investigated the signaling mechanism of CSF-1-induced D2 expression. Analyses of CSF-1 receptor autophosphorylation mutants show that, although certain individual mutation has a partial inhibitory effect, only multiple combined mutations completely block induction of D2 in response to CSF-1. We report that at least three parallel pathways, the Src pathway, the MAPK/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, and the c-myc pathway, are involved. Induction of D2 is partially inhibited in Src−/− bone marrow-derived macrophages and by Src inhibitor PP1 and is enhanced in v-Src-overexpressing cells. Activation of myc's transactivating activity selectively induces D2 but not D1. Blockade of c-myc expression partially blocks CSF-1-induced D2 expression. Complete inhibition of the MEK/ERK pathway causes 50% decrease of D2 expression. Finally, simultaneous inhibition of Src, MEK activation, and c-myc expression additively blocks CSF-1-induced D2 expression. This study indicates that multiple signaling pathways are involved in full induction of a single gene, and this finding may also apply broadly to other growth factor-inducible genes. PMID:11071910

  14. 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.

  15. 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. PMID:18632953

  16. 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.

  17. Agrobacterium VirD2 protein interacts with plant host cyclophilins.

    PubMed

    Deng, W; Chen, L; Wood, D W; Metcalfe, T; Liang, X; Gordon, M P; Comai, L; Nester, E W

    1998-06-01

    Agrobacterium tumefaciens induces crown gall tumors on plants by transferring a nucleoprotein complex, the T-complex, from the bacterium to the plant cell. The T-complex consists of T-DNA, a single-stranded DNA segment of the tumor-inducing plasmid, VirD2, an endonuclease covalently bound to the 5' end of the T-DNA, and perhaps VirE2, a single-stranded DNA binding protein. The yeast two-hybrid system was used to screen for proteins interacting with VirD2 and VirE2 to identify components in Arabidopsis thaliana that interact with the T-complex. Three VirD2- and two VirE2-interacting proteins were identified. Here we characterize the interactions of VirD2 with two isoforms of Arabidopsis cyclophilins identified by using this analysis. The VirD2 domain interacting with the cyclophilins is distinct from the endonuclease, omega, and the nuclear localization signal domains. The VirD2-cyclophilin interaction is disrupted in vitro by cyclosporin A, which also inhibits Agrobacterium-mediated transformation of Arabidopsis and tobacco. These data strongly suggest that host cyclophilins play a role in T-DNA transfer. PMID:9618535

  18. 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

  19. 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.

  20. Decreased striatal dopamine receptor binding in primary focal dystonia: a D2 or D3 defect?

    PubMed Central

    Karimi, Morvarid; Moerlein, Stephen M.; Videen, Tom O.; Luedtke, Robert R.; Taylor, Michelle; Mach, Robert H.; Perlmutter, Joel S.

    2010-01-01

    Dystonia is an involuntary movement disorder characterized by repetitive patterned or sustained muscle contractions causing twisting or abnormal postures. Several lines of evidence suggest that abnormalities of dopaminergic pathways contribute to the pathophysiology of dystonia. In particular dysfunction of D2-like receptors that mediate function of the indirect pathway in the basal ganglia may play a key role. We have demonstrated with positron emission tomography (PET) that patients with primary focal cranial or hand dystonia have reduced putamenal specific binding of [18F]spiperone a non-selective D2-like radioligand with nearly equal affinity for serotonergic 5-HT(2A) sites. We then repeated the study with [18F]N-methyl-benperidol (NMB), a more selective D2-like receptor radioligand with minimal affinity for 5-HT(2A). Surprisingly, there was no decrease in NMB binding in the putamen of subjects with dystonia. Our findings excluded reductions of putamenal uptake greater than 20% with 95% confidence intervals. Following analysis of the in vitro selectivity of NMB and spiperone demonstrated that NMB was highly selective for D2 receptors relative to D3 receptors (200-fold difference in affinity), whereas spiperone has similar affinity for all three of the D2-like receptor subtypes. These findings coupled with other literature suggest that a defect in D3, rather than D2, receptor expression may be associated with primary focal dystonia. PMID:20960437

  1. PET imaging of dopamine D2 receptors during chronic cocaine self-administration in monkeys.

    PubMed

    Nader, Michael A; Morgan, Drake; Gage, H Donald; Nader, Susan H; Calhoun, Tonya L; Buchheimer, Nancy; Ehrenkaufer, Richard; Mach, Robert H

    2006-08-01

    Dopamine neurotransmission is associated with high susceptibility to cocaine abuse. Positron emission tomography was used in 12 rhesus macaques to determine if dopamine D2 receptor availability was associated with the rate of cocaine reinforcement, and to study changes in brain dopaminergic function during maintenance of and abstinence from cocaine. Baseline D2 receptor availability was negatively correlated with rates of cocaine self-administration. D2 receptor availability decreased by 15-20% within 1 week of initiating self-administration and remained reduced by approximately 20% during 1 year of exposure. Long-term reductions in D2 receptor availability were observed, with decreases persisting for up to 1 year of abstinence in some monkeys. These data provide evidence for a predisposition to self-administer cocaine based on D2 receptor availability, and demonstrate that the brain dopamine system responds rapidly following cocaine exposure. Individual differences in the rate of recovery of D2 receptor function during abstinence were noted. PMID:16829955

  2. 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

  3. 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.

  4. Dopamine D2 receptors and striatopallidal transmission in addiction and obesity.

    PubMed

    Kenny, Paul J; Voren, George; Johnson, Paul M

    2013-08-01

    Drug addiction and obesity share the core feature that those afflicted by the disorders express a desire to limit drug or food consumption yet persist despite negative consequences. Emerging evidence suggests that the compulsivity that defines these disorders may arise, to some degree at least, from common underlying neurobiological mechanisms. In particular, both disorders are associated with diminished striatal dopamine D2 receptor (D2R) availability, likely reflecting their decreased maturation and surface expression. In striatum, D2Rs are expressed by approximately half of the principal medium spiny projection neurons (MSNs), the striatopallidal neurons of the so-called 'indirect' pathway. D2Rs are also expressed presynaptically on dopamine terminals and on cholinergic interneurons. This heterogeneity of D2R expression has hindered attempts, largely using traditional pharmacological approaches, to understand their contribution to compulsive drug or food intake. The emergence of genetic technologies to target discrete populations of neurons, coupled to optogenetic and chemicogenetic tools to manipulate their activity, have provided a means to dissect striatopallidal and cholinergic contributions to compulsivity. Here, we review recent evidence supporting an important role for striatal D2R signaling in compulsive drug use and food intake. We pay particular attention to striatopallidal projection neurons and their role in compulsive responding for food and drugs. Finally, we identify opportunities for future obesity research using known mechanisms of addiction as a heuristic, and leveraging new tools to manipulate activity of specific populations of striatal neurons to understand their contributions to addiction and obesity.

  5. Characterization of D2 receptors and dopamine levels in the thalamus of the rat

    SciTech Connect

    Young, K.A.; Wilcox, R.E. Univ. of Texas, Austin )

    1991-01-01

    The authors kinetically characterized D2 receptors in thalami pooled from a group of Sprague-Dawley rats and then determined thalamic levels of dopamine (DA), homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), and norepinephrine (NE) in relation to a measure of thalamic DA D2 receptor densities in another group of rats. The equilibrium dissociation constant (kd) was estimated as 0.1 nM by three independent methods, while the Bmax for thalamic D2 receptors was found to be 6.4 fmol/mg p using {sup 3}H-spiperone as ligand and ketanserin to occlude 5HT2 binding. Kinetic constants were in agreement with previously reported kinetic data from rodent caudate-putamen. This suggests that thalamic D2 receptors are similar to D2 receptors from other brain areas. Mean thalamic levels of DA, DOPAC, and HVA concur with previous reports of a sparse distribution of thalamic DA neurons. D2 receptor densities were positively correlated with DA metabolites DOPAC and HVA, but not DA or NE. These results establish fundamental characteristics of thalamic DA neurotransmission to assist in the investigation of behavioral pharmacology of this area.

  6. Magnetization of AN S=1/2 and 1 Ferrimagnetic Chain NiCu(pba)(D2O)32D2O in High Magnetic Fields

    NASA Astrophysics Data System (ADS)

    Hagiwara, M.; Narumi, Y.; Tatani, K.; Kindo, K.; Minami, K.

    2004-11-01

    We report the results of high field magnetization measurements on a powder sample of NiCu (pba)(D2O)32D2O (pba = 1,3-propylenebis(oxamato), C7H6N2O6) which is regarded as a ferrimagnetic chain composed of spins S = 1/2 and 1. From a fit of the susceptibility of this compound to numerical calculations (exact diagonalization for ten sites), we evaluated the exchange constant J/kB = 121 K. In the magnetization measurements at 10 K up to 50 T, we observed a magnetization plateau of about 1.1 μB/(formula unit) corresponding to about one-third of the saturated magnetization. The increase of the magnetization at low magnetic fields is discussed and compared with some calculations.

  7. Region-specific activation of the AMPK system by cocaine: The role of D1 and D2 receptors.

    PubMed

    Xu, Shijie; Kang, Ung Gu

    2016-01-01

    The 5' adenosine monophosphate-activated protein kinase (AMPK) functions as an intracellular energy sensor that regulates and maintains energy balance. The psychostimulant drug cocaine has profound effects on behavior that are accentuated with repeated use, which is a process termed sensitization. Thus, the present study examined whether the sensitizing effects of cocaine could be observed in the AMPK system and aimed to determine whether these effects were mediated by dopamine (DA) D1 or D2 receptors. In the first set of experiments, rats were injected daily for 5days with either cocaine (15mg/kg, intraperitoneal [IP]) or saline. On the day 6, each group was divided into two subgroups and given either cocaine or saline. In the second set of experiments, rats were pretreated with SCH23390 (0.5mg/kg, IP), haloperidol (1mg/kg, IP), or both agents in combination, followed by cocaine or saline treatment. In the drug-naïve state, acute treatment with cocaine produced an increase in locomotor activity and increased AMPK phosphorylation in the frontal cortex but decreased it in the dorsal striatum. In the drug-sensitized state (following repeated treatment), the behavioral responsiveness to cocaine was augmented and accompanied by alterations in AMPK activity. The phosphorylation levels of the upstream kinases Ser-431-LKB1 and Thr-196-CaMK4 were congruent with the changes in AMPK activity. Thr-184/187-TAK1 was phosphorylated after chronic cocaine treatment in the dorsal striatum but not in the frontal cortex. The opposite effects induced by cocaine in the AMPK system in the dorsal striatum and frontal cortex may be explained by the differential activations of DA D1 and D2 receptors in these brain regions. PMID:27132751

  8. 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.

  9. 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

  10. Specific induction of a functional endogenous D2 short dopamine receptor in GH4C1 cells.

    PubMed

    Allard, S; Lapointe, S; Falardeau, P

    1993-06-15

    In contrast to lactotrophs, tumoral pituitary cells like GH3 and GH4C1 lack expression of dopamine D2short and D2long receptors. In GH4C1 cells, we observed that the expression of only the short isoform of D2 receptor can be induced after transfection with a plasmid which confers resistance to neomycin (pRSVNeo). High levels of fully functional D2short receptor were obtained in GH4C1 following transfection (528fmol/mg protein). Sequence, pharmacology and coupling of the induced-D2 receptor do not show any difference with the cloned rat D2 short receptor.

  11. Excitation of sodium D-line radiation in collisions of sodium atoms with internally excited H2, D2 and N2.

    NASA Technical Reports Server (NTRS)

    Krause, H. F.; Fricke, J.; Fite, W. L.

    1972-01-01

    Excitation of D-line radiation in collisions of Na atoms with vibrationally excited N2, H2, and D2 was studied in two modulated crossed-beam experiments. In both experiments, the molecular excitation was provided by heating the molecular beam to temperatures which were assumed to give populations corresponding to the Boltzmann distribution. In the first experiment, a total rate coefficient was measured as a function of molecular beam temperature. The second experiment achieved partial separation of internal vs kinetic energy transfer effects by using a velocity-selected molecular beam. The data from both experiments were used to determine parameters for the dependence of the transfer cross section upon the kinetic energy for a given change in the vibrational quantum number. Results indicate that most of the Na excitation energy comes from internal vibrational energy, with the remainder coming from kinetic energy.

  12. 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.

  13. 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.

  14. Progress in Understanding the Infrared Spectra of He- and Ne-C_2D_2

    NASA Astrophysics Data System (ADS)

    Moazzen-Ahmadi, Nasser; McKellar, Bob

    2014-06-01

    Infrared spectra of He-C_2H_2 were recorded around 1990 in Roger Miller's lab, but detailed rotational assignment was apparently not possible even with the help of theoretical predictions. So there were no published experimental spectra of helium-acetylene van der Waals complexes until our recent work on He-C_2D_2 in the νb{3} region (˜2440 wn). The problem is that this complex lies close to the free rotor limit, so that most of the intensity in the spectrum piles up in tangles of closely spaced lines located close to the monomer rotational transitions, R(0), P(1), etc. Our previous He-C_2D_2 assignments were limited to the R(0) region, that is, the j = 1 ← 0 subband, where j represents C_2D_2 rotation. Here, we extend the analysis to j = 0 ← 1 and 2 ← 1 transitions with the help of new spectra obtained using a tunable OPO laser probe and a cooled supersonic jet nozzle. These subbands are weaker, not only because of the Boltzmann factor, but also the 2:1 nuclear spin statistics of j" = even:odd C_2D_2 levels. Moreover, the j = 0 ← 1 subband is overlapped by strong (C_2D_2)_2 transitions. We use a term value approach, obtaining a self-consistent set of ``experimental" energy levels which can be directly compared with theory or fitted in terms of a Coriolis model. Challenges also arise with Ne-C_2D_2, which is not quite so close to the free rotor limit, but still has many overlapping lines. Insights gained here help in assigning the tricky R(1) region for Ne-C_2D_2. M. Rezaei, N. Moazzen-Ahmadi, A.R.W. McKellar, B. Fernández, and D. Farrelly, Mol. Phys. 110, 2743 (2012).

  15. 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. PMID:27476435

  16. Origins, distribution and expression of the Duarte-2 (D2) allele of galactose-1-phosphate uridylyltransferase

    PubMed Central

    Carney, Amanda E.; Sanders, Rebecca D.; Garza, Kerry R.; McGaha, Lee Anne; Bean, Lora J. H.; Coffee, Bradford W.; Thomas, James W.; Cutler, David J.; Kurtkaya, Natalie L.; Fridovich-Keil, Judith L.

    2009-01-01

    Duarte galactosemia is a mild to asymptomatic condition that results from partial impairment of galactose-1-phosphate uridylyltransferase (GALT). Patients with Duarte galactosemia demonstrate reduced GALT activity and carry one profoundly impaired GALT allele (G) along with a second, partially impaired GALT allele (Duarte-2, D2). Molecular studies reveal at least five sequence changes on D2 alleles: a p.N314D missense substitution, three intronic base changes and a 4 bp deletion in the 5′ proximal sequence. The four non-coding sequence changes are unique to D2. The p.N314D substitution, however, is not; it is found together with a silent polymorphism, p.L218(TTA), on functionally normal Duarte-1 alleles (D1, also called Los Angeles or LA alleles). The HapMap database reveals that p.N314D is a common human variant, and cross-species comparisons implicate D314 as the ancestral allele. The p.N314D substitution is also functionally neutral in mammalian cell and yeast expression studies. In contrast, the 4 bp 5′ deletion characteristic of D2 alleles appears to be functionally impaired in reporter gene transfection studies. Here we present allele-specific qRT–PCR evidence that D2 alleles express less mRNA in vivo than their wild-type counterparts; the difference is small but statistically significant. Furthermore, we characterize the prevalence of the 4 bp deletion in GG, NN and DG populations; the deletion appears exclusive to D2 alleles. Combined, these data strongly implicate the 4 bp 5′ deletion as a causal mutation in Duarte galactosemia and suggest that direct tests for this deletion, as proposed here, could enhance or supplant current tests, which define D2 alleles on the basis of the presence and absence of linked coding sequence polymorphisms. PMID:19224951

  17. Resolvin D1 and resolvin D2 govern local inflammatory tone in obese fat.

    PubMed

    Clària, Joan; Dalli, Jesmond; Yacoubian, Stephanie; Gao, Fei; Serhan, Charles N

    2012-09-01

    The unprecedented increase in the prevalence of obesity and obesity-related disorders is causally linked to a chronic state of low-grade inflammation in adipose tissue. Timely resolution of inflammation and return of this tissue to homeostasis are key to reducing obesity-induced metabolic dysfunctions. In this study, with inflamed adipose, we investigated the biosynthesis, conversion, and actions of Resolvins D1 (RvD1, 7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid) and D2 (RvD2, 7S,16R,17S-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid), potent anti-inflammatory and proresolving lipid mediators (LMs), and their ability to regulate monocyte interactions with adipocytes. Lipid mediator-metabololipidomics identified RvD1 and RvD2 from endogenous sources in human and mouse adipose tissues. We also identified proresolving receptors (i.e., ALX/FPR2, ChemR23, and GPR32) in these tissues. Compared with lean tissue, obese adipose showed a deficit of these endogenous anti-inflammatory signals. With inflamed obese adipose tissue, RvD1 and RvD2 each rescued impaired expression and secretion of adiponectin in a time- and concentration-dependent manner as well as decreasing proinflammatory adipokine production including leptin, TNF-α, IL-6, and IL-1β. RvD1 and RvD2 each reduced MCP-1 and leukotriene B₄-stimulated monocyte adhesion to adipocytes and their transadipose migration. Adipose tissue rapidly converted both resolvins (Rvs) to novel oxo-Rvs. RvD2 was enzymatically converted to 7-oxo-RvD2 as its major metabolic route that retained adipose-directed RvD2 actions. These results indicate, in adipose, D-series Rvs (RvD1 and RvD2) are potent proresolving mediators that counteract both local adipokine production and monocyte accumulation in obesity-induced adipose inflammation.

  18. Intracellular Na+ regulates epithelial Na+ channel maturation.

    PubMed

    Heidrich, Elisa; Carattino, Marcelo D; Hughey, Rebecca P; Pilewski, Joseph M; Kleyman, Thomas R; Myerburg, Mike M

    2015-05-01

    Epithelial Na(+) channel (ENaC) function is regulated by the intracellular Na(+) concentration ([Na(+)]i) through a process known as Na(+) feedback inhibition. Although this process is known to decrease the expression of proteolytically processed active channels on the cell surface, it is unknown how [Na(+)]i alters ENaC cleavage. We show here that [Na(+)]i regulates the posttranslational processing of ENaC subunits during channel biogenesis. At times when [Na(+)]i is low, ENaC subunits develop mature N-glycans and are processed by proteases. Conversely, glycan maturation and sensitivity to proteolysis are reduced when [Na(+)]i is relatively high. Surface channels with immature N-glycans were not processed by endogenous channel activating proteases, nor were they sensitive to cleavage by exogenous trypsin. Biotin chase experiments revealed that the immature surface channels were not converted into mature cleaved channels following a reduction in [Na(+)]i. The hypothesis that [Na(+)]i regulates ENaC maturation within the biosynthetic pathways is further supported by the finding that Brefeldin A prevented the accumulation of processed surface channels following a reduction in [Na(+)]i. Therefore, increased [Na(+)]i interferes with ENaC N-glycan maturation and prevents the channel from entering a state that allows proteolytic processing. PMID:25767115

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Terahertz Spectroscopy and Global Analysis of the Bending Vibrations of Acetylene 12C2D2

    NASA Astrophysics Data System (ADS)

    Yu, Shanshan; Drouin, Brian J.; Pearson, John C.; Pickett, Herbert M.; Lattanzi, Valerio; Walters, Adam

    2009-06-01

    Two hundred and fifty-one 12C2D2 transitions have been measured in the 0.2-1.6 THz region of its ν5-ν4 difference band and 202 of them were observed for the first time. The accuracy of these measurements is estimated to be ranging from 50 kHz to 100 kHz. The 12C2D2 molecules were generated under room temperature by passing 120-150 mTorr D2O vapor through calcium carbide (CaC2) powder. A multistate analysis was carried out for the bending vibrational modes ν4 and ν5 of 12C2D2, which includes the lines observed in this work and prior microwave, far-infrared and infrared data on the pure bending levels. Significantly improved molecular parameters were obtained for 12C2D2 by adding the new measurements to the old data set, which had only 10 lines with microwave measurement precision. New frequency and intensity predictions have been made based on the obtained molecular parameters. The more precise measurements and new predictions reported here will support the analyses of astronomical observations by the future high-resolution spectroscopy telescopes such as Herschel, SOFIA, and ALMA, which will work in the terahertz spectral region.

  4. 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.

  5. Synthesis and characterization of selective dopamine D2 receptor ligands using aripiprazole as the lead compound

    PubMed Central

    Vangveravong, Suwanna; Zhang, Zhanbin; Taylor, Michelle; Bearden, Melissa; Xu, Jinbin; Cui, Jinquan; Wang, Wei; Luedtke, Robert R.; Mach, Robert H.

    2011-01-01

    A series of compounds structurally related to aripiprazole (1), an atypical antipsychotic and antidepressant used clinically for the treatment of schizophrenia, bipolar disorder, and depression, have been prepared and evaluated for affinity at D2-like dopamine receptors. These compounds also share structural elements with the classical D2-like dopamine receptor antagonists, haloperidol, N-methylspiperone, domperidone and benperidol. Two new compounds, 7-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one oxalate (6) and 7-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one oxalate (7) were found to (a) bind to the D2 receptor subtype with high affinity (Ki values <0.3 nM), (b) exhibit >50-fold D2 versus D3 receptor binding selectivity and (c) be partial agonists at both the D2 and D3 receptor subtype. PMID:21536445

  6. 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.

  7. Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs

    SciTech Connect

    Farde, L.; Wiesel, F.A.; Halldin, C.; Sedvall, G.

    1988-01-01

    Using positron emission tomography and the carbon 11-labeled ligand raclopride, central D2-dopamine receptor occupancy in the putamen was determined in psychiatric patients treated with clinical doses of psychoactive drugs. Receptor occupancy in drug-treated patients was defined as the percent reduction of specific carbon 11-raclopride binding in relation to the expected binding in the absence of drug treatment. Clinical treatment of schizophrenic patients with 11 chemically distinct antipsychotic drugs (including both classic and atypical neuroleptics such as clozapine) resulted in a 65% to 85% occupancy of D2-dopamine receptors. In a depressed patient treated with the tricyclic antidepressant nortriptyline, no occupancy was found. The time course for receptor occupancy and drug levels was followed after withdrawal of sulpiride or haloperidol. D2-dopamine receptor occupancy remained above 65% for many hours despite a substantial reduction of serum drug concentrations. In a sulpiride-treated patient, the dosage was reduced in four steps over a nine-week period and a curvilinear relationship was demonstrated between central D2-dopamine receptor occupancy and serum drug concentrations. The results demonstrate that clinical doses of all the currently used classes of antipsychotic drugs cause a substantial blockade of central D2-dopamine receptors in humans. This effect appears to be selective for the antipsychotics, since it was not induced by the antidepressant nortriptyline.

  8. Decreased D2-40 immunoreactivity in stored paraffin sections and methods for preserving it.

    PubMed

    Sasaki, T; Kawabata, Y; Suzuki, N; Tanaka, H; Sano, M; Kato, S; Takemura, A; Unno, N; Kojima, T; Sato, K

    2014-08-01

    D2-40, a monoclonal antibody against podoplanin, is a selective marker of lymphatic endothelium and is widely used for research on and diagnosis of pathology of lymphatic vessels. We examined the relation between the duration of tissue section storage and changes in immunostaining by D2-40 antibody; we evaluated also the effects of preservation methods on changes in immunostaining during storage. Staining by D2-40 was attenuated by long-term preservation of scalp skin and lymph node sections at room temperature. The attenuation of D2-40 staining in stored sections was improved by preservation at low temperature, i.e., 4° or - 30° C. We investigated also the immunostaining of preserved tissue sections using NZ-1 and Lyve-1, which are antibodies against lymphatic endothelium markers. Staining by NZ-1 or Lyve-1 antibody was detected clearly in sections that had been stored for 16 weeks. Our study suggests that either long-term storage of D2-40 immunostained tissue sections should be avoided or the section should be preserved at low temperature.

  9. 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.

  10. 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.

  11. 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. PMID:12654668

  12. UV photoreaction cross sections of CO and D2O on NiAl(110)

    NASA Astrophysics Data System (ADS)

    Nagai, Kenta; Watanabe, Kazuo

    2016-01-01

    Adsorption states and photoreactions of CO and D2O adsorbed on NiAl(110) at 90 K were studied by temperature-programmed desorption (TPD). Coverage dependence of TPD spectra showed growth behavior of adlayers of these molecules consistent with the literature, but a new path of thermal dissociation of D2O upon adsorption at 90 K was found. The photoreaction cross sections of CO and D2O at 4.7 eV were estimated in the order of 10- 21 cm2 and 10- 20 cm2, respectively. This result suggests that photoexcitation of the NiAl(110) substrate itself, a typical substrate used in supported model catalyst studies, will induce only negligible photoreactions of molecules adsorbed at surfaces of metal nanoparticles supported on ultrathin alumina films formed on NiAl(110).

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

    PubMed

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

    2014-03-26

    The development of deuterated biomass is essential for effective neutron scattering studies on biomass, which can provide key insights into the complex biomass conversion processes. A method for optimized production of deuterated annual ryegrass (Lolium multiflorum) was developed by growing the plants in 50% D2O in perfused hydroponic chambers. Deuterium incorporation of 36.9% was found in the annual rye grown in 50% D2O. Further, deuterium incorporation of 60% was achieved by germinating the rye seedlings in H2O and growing in 50% D2O inside the perfusion chambers. The characteristics related to enzymatic hydrolysis such as biomass composition, degree of polymerization, and cellulose crystallinity were compared with its control protiated counterpart. The cellulose molecular weight indicated slight variation while hemicellulose molecular weights and cellulose crystallinity remain unaffected with the deuteration.

  14. Reappraising striatal D1- and D2-neurons in reward and aversion.

    PubMed

    Soares-Cunha, Carina; Coimbra, Barbara; Sousa, Nuno; Rodrigues, Ana J

    2016-09-01

    The striatum has been involved in complex behaviors such as motor control, learning, decision-making, reward and aversion. The striatum is mainly composed of medium spiny neurons (MSNs), typically divided into those expressing dopamine receptor D1, forming the so-called direct pathway, and those expressing D2 receptor (indirect pathway). For decades it has been proposed that these two populations exhibit opposing control over motor output, and recently, the same dichotomy has been proposed for valenced behaviors. Whereas D1-MSNs mediate reinforcement and reward, D2-MSNs have been associated with punishment and aversion. In this review we will discuss pharmacological, genetic and optogenetic studies that indicate that there is still controversy to what concerns the role of striatal D1- and D2-MSNs in this type of behaviors, highlighting the need to reconsider the early view that they mediate solely opposing aspects of valenced behaviour. PMID:27235078

  15. 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.

  16. 3D/2D convertible projection-type integral imaging using concave half mirror array.

    PubMed

    Hong, Jisoo; Kim, Youngmin; Park, Soon-gi; Hong, Jong-Ho; Min, Sung-Wook; Lee, Sin-Doo; Lee, Byoungho

    2010-09-27

    We propose a new method for implementing 3D/2D convertible feature in the projection-type integral imaging by using concave half mirror array. The concave half mirror array has the partially reflective characteristic to the incident light. And the reflected term is modulated by the concave mirror array structure, while the transmitted term is unaffected. With such unique characteristic, 3D/2D conversion or even the simultaneous display of 3D and 2D images is also possible. The prototype was fabricated by the aluminum coating and the polydimethylsiloxane molding process. We could experimentally verify the 3D/2D conversion and the display of 3D image on 2D background with the fabricated prototype.

  17. Synthesis and binding profile of haloperidol-based bivalent ligands targeting dopamine D(2)-like receptors.

    PubMed

    Salama, Ismail; Löber, Stefan; Hübner, Harald; Gmeiner, Peter

    2014-08-15

    Homodimers of dopamine D2-like receptors are suggested to be of particular importance in the pathophysiology of schizophrenia and, thus, serve as promising targets for the discovery of atypical antipsychotics. This study describes the development of a series of novel bivalent molecules with a pharmacophore derived from the dopamine receptor antagonist haloperidol. These dimers were investigated in comparison to their monomeric analogues for their D2long, D2short, D3, and D4 receptor binding and the ability to bridge two neighboring receptor protomers. Radioligand binding studies provided diagnostic insights when Hill slopes close to two for the bivalent ligand 13 incorporating 22 spacer atoms and a comparative analysis with monovalent control ligands indicated a bivalent binding mode with a simultaneous occupancy of two neighboring binding sites. PMID:25047579

  18. Structure-guided development of dual β2 adrenergic/dopamine D2 receptor agonists.

    PubMed

    Weichert, Dietmar; Stanek, Markus; Hübner, Harald; Gmeiner, Peter

    2016-06-15

    Aiming to discover dual-acting β2 adrenergic/dopamine D2 receptor ligands, a structure-guided approach for the evolution of GPCR agonists that address multiple targets was elaborated. Starting from GPCR crystal structures, we describe the design, synthesis and biological investigation of a defined set of compounds leading to the identification of the benzoxazinone (R)-3, which shows agonist properties at the adrenergic β2 receptor and substantial G protein-promoted activation at the D2 receptor. This directed approach yielded molecular probes with tuned dual activity. The congener desOH-3 devoid of the benzylic hydroxyl function was shown to be a β2 adrenergic antagonist/D2 receptor agonist with Ki values in the low nanomolar range. The compounds may serve as a promising starting point for the investigation and treatment of neurological disorders. PMID:27132867

  19. Satellite studies of N/D-2/ emission and ion chemistry in aurorae

    NASA Technical Reports Server (NTRS)

    Rusch, D. W.; Gerard, J.-C.

    1980-01-01

    The incident particle flux ion and neutral composition data taken on the AE-D satellite have been used to investigate the quantal emission of N2(plus) at 4278 A, N(D-2) at 5200 A, and the ion chemistry in aurorae. The results of a time dependent auroral model have been compared to the data. The calculated 4278 A emission of N2(plus), the 5200 A emission of N(D-2), the densities of O2(plus), NO(plus), N2(plus), O(plus), and the electron density are generally in agreement with the measured values. These results are consistent with the branching ratios and quenching rates deduced from previous studies of the N(D-2) densities in the day-time, mid-latitude ionosphere. It is found that in an auroral arc, the measured atomic oxygen density is lower than predicted by the MSIS model.

  20. 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.

  1. 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.

  2. 75 FR 18915 - Program for Allocation of Regulatory Responsibilities Pursuant to Rule 17d-2; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-13

    .... 12352 (April 20, 1976), 41 FR 18808 (May 7, 1976). To address regulatory duplication in these and other... paragraph (c) of Rule 17d-2, the Commission may declare such a plan effective if, after providing for...), 41 FR 49091 (November 8, 1976). II. Proposed 17d-2 Plan The proposed 17d-2 Plan is intended to...

  3. 75 FR 18920 - Program for Allocation of Regulatory Responsibilities Pursuant to Rule 17d-2; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-13

    .... 12352 (April 20, 1976), 41 FR 18808 (May 7, 1976). To address regulatory duplication in these and other... paragraph (c) of Rule 17d- 2, the Commission may declare such a plan effective if, after providing for...), 41 FR 49091 (November 8, 1976). II. Proposed 17d-2 Plan The proposed 17d-2 Plan is intended to...

  4. 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. PMID:26864127

  5. 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.

  6. 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

  7. 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

  8. N-allyl epiderpride: An extremely potent SPECT radioligand for the dopamine D2 receptor

    SciTech Connect

    Kessler, R.M.; Mason, N.S.; Ansari, M.S.

    1994-05-01

    We have previously reported that epidepride is a potent (K{sub D} 24pM) and specific SPECT radioligand for the dopamine D2 receptor which can be used to study striatal and extrastriatal dopamine D2 receptors in man. We have synthesized and evaluated the N-allyl analogue of epiderpride (APID) as a potential SPECT radioligand for the dopamine D2 receptor. In comparison to epidepride it is even more potent at the dopamine D2 receptor, the K{sub D} for APID being 11 frontal cortical homogenate. The lipophilicity, evaluated using the log kw pH 7.5, was 2.9 versus 2.05 for epidepride. Competitive binding studies using rat striatal, hippocampal and frontal cortical homogenates showed high affinity for only dopamine D2 like cerebellar ratio of 275:1 at 320 minutes post injection-similar to that seen with epidepride, but with nearly four times higher brain uptake. Of interest was the off-rate from the dopamine D2 receptor; it was 0.0046 min{sup -1} in vitro at 25{degrees}C-corresponding to an t 1/2 of 150 minutes. Studies in rhesus monkeys show an in vivo off rate (following 2.5 mg/kg raclopride IV) of about 0.0082 min{sup -1} seen that with epidepride. SPECT studies in rhesus monkeys reveal APID is a promising SPECT radioligand that appears to be similar to epidepride, but with higher brain uptake due to its more optimal lipophilicity for entry into brain.

  9. 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.

  10. 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. PMID:26882987

  11. 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.

  12. Melittin stimulates liver glycogenolysis and the release of prostaglandin D2 and thromboxane B2.

    PubMed Central

    García-Sáinz, J A; Hernández-Sotomayor, S M; Macías-Silva, M

    1990-01-01

    Melittin stimulates glycogenolysis and induces vasoconstriction in perfused rat liver. The effect was rapid and associated with production and release of prostaglandin D2 and thromboxane B2. Indomethacin blocked the release of these eicosanoids and the stimulation of glycogenolysis induced by melittin. Ibuprofen blocked the release of prostaglandin D2 induced by melittin and markedly attenuated that of thromboxane B2. Interestingly, the initial burst of glucose output induced by melittin was not inhibited by ibuprofen, although the duration of the glycogenolytic action of the peptide was greatly diminished. PMID:2375756

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

    PubMed

    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

  14. Identification of Dopamine D2 Receptors in Gill of Crassostrea virginica

    PubMed Central

    Anador, Samuel; Brown, Cherryle; Adebesin, Damilola; Cilli, Noelia; Fleming, Renee; Carroll, Margaret A.; Catapane, Edward J.

    2011-01-01

    The lateral epithelial cells of gill of Crassostrea virginica are innervated by dopamine and serotonin nerves that regulate the beating rate of their lateral cilia. Terminal release of dopamine slows down the beating rate of the cilia, while serotonin release increases the beating rate. Previously, we showed that the dopaminergic, but not the serotonergic, mechanism regulating the beating rate of the lateral cilia was disrupted by manganese treatments and that this disruption was occurring postsynaptically, at the level of the dopamine receptor or further downstream in the signal transduction pathway. In humans manganese toxicity causes Manganism, a neurological disorder with clinical symptoms similar to Parkinson s disease. In this study we utilized pharmacological agents and an immunohistofluorescence technique to characterize the dopamine receptor type present on the lateral ciliated cells of C. virginica gill. Agonists and antagonists to dopamine D1 or dopamine D2 receptors were applied to gill sections and beating rates of the lateral cilia were measured by stroboscopic microscopy. The D2 agonists and D2 antagonists were effective in mimicking or blocking, respectively, the inhibitory actions of dopamine on lateral cilia beating, while application of either D1 agonists or D1 antagonists had no significant effect. In other experiments we used an epilume fluorescence microscopic fitted with FITC filters to view gill sections treated with a primary antibody against D2 receptors and a FITC-linked secondary antibody. Control gill sections without primary antibody exposure were similarly treated and viewed. The D2 antibody treated sections showed bright fluorescent receptor-antibody complexes present at the lateral ciliated cells and other areas of gill, when compared to controls. The results of our immunofluorescence study identify the presence of D2-like receptors on the lateral ciliated cells of C. virginica gill and our pharmacological results indicate that D2

  15. MIE Lidar proposed for the German Space Shuttle Mission D2

    NASA Technical Reports Server (NTRS)

    Renger, W.; Endemann, M.; Quenzel, H.; Werner, C.

    1986-01-01

    Firm plans for a second German Spacelab mission (D2-mission), originally scheduled for late 1988 is basically a zero-g mission, but will also include earth observation experiments. On board the D2-facility will allow performance of a number of different measurements with the goal to obtain performance data (cloud top heights, height of the planetary boundary layer, optical thickness, and cloud base height of thin and medium thick clouds, ice/water phase discriminatin for clouds, tropopause height, tropaspheric height, tropospheric aerosols, and stratospheric aerosols.

  16. Identification of dopamine D2 receptors in gill of Crassostrea virginica.

    PubMed

    Anador, Samuel; Brown, Cherryle; Adebesin, Damilola; Cilli, Noelia; Fleming, Renee; Carroll, Margaret A; Catapane, Edward J

    2011-01-01

    The lateral epithelial cells of gill of Crassostrea virginica are innervated by dopamine and serotonin nerves that regulate the beating rate of their lateral cilia. Terminal release of dopamine slows down the beating rate of the cilia, while serotonin release increases the beating rate. Previously, we showed that the dopaminergic, but not the serotonergic, mechanism regulating the beating rate of the lateral cilia was disrupted by manganese treatments and that this disruption was occurring postsynaptically, at the level of the dopamine receptor or further downstream in the signal transduction pathway. In humans manganese toxicity causes Manganism, a neurological disorder with clinical symptoms similar to Parkinson s disease. In this study we utilized pharmacological agents and an immunohistofluorescence technique to characterize the dopamine receptor type present on the lateral ciliated cells of C. virginica gill. Agonists and antagonists to dopamine D1 or dopamine D2 receptors were applied to gill sections and beating rates of the lateral cilia were measured by stroboscopic microscopy. The D2 agonists and D2 antagonists were effective in mimicking or blocking, respectively, the inhibitory actions of dopamine on lateral cilia beating, while application of either D1 agonists or D1 antagonists had no significant effect. In other experiments we used an epilume fluorescence microscopic fitted with FITC filters to view gill sections treated with a primary antibody against D2 receptors and a FITC-linked secondary antibody. Control gill sections without primary antibody exposure were similarly treated and viewed. The D2 antibody treated sections showed bright fluorescent receptor-antibody complexes present at the lateral ciliated cells and other areas of gill, when compared to controls. The results of our immunofluorescence study identify the presence of D2-like receptors on the lateral ciliated cells of C. virginica gill and our pharmacological results indicate that D2

  17. 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

  18. Synthesis of 25-hydroxy-(26,27-/sup 3/H)vitamin D2, 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D2 and their (24R)-epimers

    SciTech Connect

    Sicinski, R.R.; Tanaka, Y.; Phelps, M.; Schnoes, H.K.; DeLuca, H.F.

    1987-02-15

    Synthesis of a C-24-epimeric mixture of 25-hydroxy-(26,27-/sup 3/H)vitamin D2 and a C-24-epimeric mixture of 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D2 by the Grignard reaction of the corresponding 25-keto-27-nor-vitamin D2 and 1 alpha-acetoxy-25-keto-27-nor-vitamin D3 with tritiated methyl magnesium bromide is described. Separation of epimers by high-performance liquid chromatography afforded pure radiolabeled vitamins of high specific activity (80 Ci/mmol). The identities and radiochemical purities of 25-hydroxy-(26,27-/sup 3/H(vitamin D2 and 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D2 D2 were established by cochromatography with synthetic 25-hydroxyvitamin D2 or 1,25-dihydroxyvitamin D2. Biological activity of 25-hydroxy-(26,27-/sup 3/H)vitamin D2 was demonstrated by its binding to the rat plasma binding protein for vitamin D compounds, and by its in vitro conversion to 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D2 by kidney homogenate prepared from vitamin D-deficient chickens. The biological activity of 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D2 was demonstrated by its binding to the chick intestinal receptor for 1,25-dihydroxyvitamin D3.

  19. 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

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

    PubMed

    Newton, Claire L; 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

  1. Proresolving lipid mediators resolvin D1, resolvin D2, and maresin 1 are critical in modulating T cell responses.

    PubMed

    Chiurchiù, Valerio; Leuti, Alessandro; Dalli, Jesmond; Jacobsson, Anders; Battistini, Luca; Maccarrone, Mauro; Serhan, Charles N

    2016-08-24

    Resolution of inflammation is a finely regulated process mediated by specialized proresolving lipid mediators (SPMs), including docosahexaenoic acid (DHA)-derived resolvins and maresins. The immunomodulatory role of SPMs in adaptive immune cells is of interest. We report that D-series resolvins (resolvin D1 and resolvin D2) and maresin 1 modulate adaptive immune responses in human peripheral blood lymphocytes. These lipid mediators reduce cytokine production by activated CD8(+) T cells and CD4(+) T helper 1 (TH1) and TH17 cells but do not modulate T cell inhibitory receptors or abrogate their capacity to proliferate. Moreover, these SPMs prevented naïve CD4(+) T cell differentiation into TH1 and TH17 by down-regulating their signature transcription factors, T-bet and Rorc, in a mechanism mediated by the GPR32 and ALX/FPR2 receptors; they concomitantly enhanced de novo generation and function of Foxp3(+) regulatory T (Treg) cells via the GPR32 receptor. These results were also supported in vivo in a mouse deficient for DHA synthesis (Elovl2(-/-)) that showed an increase in TH1/TH17 cells and a decrease in Treg cells compared to wild-type mice. Additionally, either DHA supplementation in Elovl2(-/-) mice or in vivo administration of resolvin D1 significantly reduced cytokine production upon specific stimulation of T cells. These findings demonstrate actions of specific SPMs on adaptive immunity and provide a new avenue for SPM-based approaches to modulate chronic inflammation. PMID:27559094

  2. 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. PMID:26446938

  3. 17 CFR 240.12d2-1 - Suspension of trading.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Suspension of trading. 240... Securities Exchange Act of 1934 Suspension of Trading, Withdrawal, and Striking from Listing and Registration § 240.12d2-1 Suspension of trading. (a) A national securities exchange may suspend from trading...

  4. Chemical sputtering of ATJ graphite induced by low-energy D2+ bombardment

    NASA Astrophysics Data System (ADS)

    Vergara, L. I.; Meyer, F. W.; Krause, H. F.

    2005-12-01

    Results of chemical sputtering of ATJ graphite by impact of D2+ in the energy range 10-250 eV/D are presented. Our experimental approach is based on the use of a quadrupole mass spectrometer (QMS) which samples the partial pressures of selected mass species in the scattering chamber resulting from the incident ion beam. Based on in situ measurements of cracking patterns and QMS sensitivities using calibrated leaks, sputtering yields are presented for the production of methane and acetylene for sample temperatures of 300 K and 800 K. In the energy range 10-60 eV/D, CD 4 appears to be the dominant light stable hydrocarbon detected at room temperature. With increasing D2+ energy, its contribution is found to decrease, while the contribution of C 2D 2 is virtually unchanged. In contrast to what is observed for the sample at room temperature, at 800 K a dramatic increase in the CD 4 production is observed with increasing beam energy, which is also manifested in the production of C 2D 2, although to a smaller degree.

  5. 26 CFR 53.4941(d)-2 - Specific acts of self-dealing.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) MISCELLANEOUS EXCISE TAXES (CONTINUED) FOUNDATION AND SIMILAR EXCISE TAXES Taxes on Self-Dealing § 53.4941(d)-2... of property—(1) In general. The sale or exchange of property between a private foundation and a... disqualified person to a private foundation shall be an act of self-dealing regardless of the amount paid...

  6. 26 CFR 53.4941(d)-2 - Specific acts of self-dealing.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) MISCELLANEOUS EXCISE TAXES (CONTINUED) FOUNDATION AND SIMILAR EXCISE TAXES Taxes on Self-Dealing § 53.4941(d)-2... of property—(1) In general. The sale or exchange of property between a private foundation and a... disqualified person to a private foundation shall be an act of self-dealing regardless of the amount paid...

  7. Podoplanin (D2-40) is a reliable marker of urinary bladder myofibroblasts (telocytes).

    PubMed

    Povýšil, C; Kaňa, M; Zámečník, L; Vaľová, Z; Hanuš, T

    2014-01-01

    Podoplanin, D2-40, has been described in a variety of normal and neoplastic tissues. It is often used for highlighting lymphatics. We evaluated the expression of podoplanin in α-smooth muscle actinpositive myofibroblasts producing the suburothelial layer in tunica propria of the urinary bladder that have some similar features with telocytes. Our results showed that these cells demonstrate distinct D2-40 immunoreactivity from telocytes occurring in the renal pelvis and ureter. We observed positive reaction not only in bioptic specimens from women with interstitial cystitis, but also in a control group of women and men treated for pathological bladder lesion different from interstitial cystitis. It is interesting that identical staining reaction was observed in the ureters only exceptionally. In addition, we examined samples from myofibroblastic tumoriform lesions of soft tissue such as nodular fascitis and fibromatosis (desmoid) and we obtained negative results. It means that the so-called myofibroblasts of urinary bladder tunica propria have a unique immunophenotype that has probably not been described until now. Our findings suggest that D2-40 can be used as a complementary immunostainer to α-smooth muscle actin on urinary bladder biopsies from patients with interstitial cystitis. The role of D2-40 as an immunohistochemical marker is still being investigated. PMID:25629270

  8. AIMS D2DB simulation for DUV and EUV mask inspection

    NASA Astrophysics Data System (ADS)

    Peng, Danping; Li, Ying; Satake, Masaki; Hu, Peter; Chen, Jerry; Hsu, S. C.; Lai, Rick; Lin, C. S.; Tuo, Laurent C. C.

    2012-02-01

    AIMS™ Die-to-Die (D2D) is widely used in checking the wafer printability of mask defects for DUV lithography. Two AIMS images, a reference and a defect image, are captured and compared with differences larger than certain tolerances identified as real defects. Since two AIMS images are needed, and since AIMS system time is precious, it is desirable to save image search and capture time by simulating reference images from the OPC mask pattern and AIMS optics. This approach is called Die-to-Database (D2DB). Another reason that D2DB is desirable is in single die mask, where the reference image from another die does not exist. This paper presents our approach to simulate AIMS optics and mask 3D effects. Unlike OPC model, whose major concern is predicting printed CD, AIMS D2DB model must produce simulated images that match measured images across the image field. This requires a careful modeling of all effects that impact the final image quality. We present a vector-diffraction theory that is based on solid theoretical foundations and a general formulation of mask model that are applicable to both rigorous Maxwell solver and empirical model that can capture the mask 3D-effects. We demonstrated the validity of our approach by comparing our simulated image with AIMS machine measured images. We also briefly discuss the necessary changes needed to model EUV optics. Simulation is particularly useful while the industry waits for an actinic EUV-AIMS tool.

  9. Cerebellar LTD vs. motor learning-lessons learned from studying GluD2.

    PubMed

    Yuzaki, Michisuke

    2013-11-01

    Synaptic plasticity, such as long-term potentiation and long-term depression (LTD), is believed to underlie learning and memory processes in vivo. The cerebellum is an ideal brain region to obtain definitive proof for this hypothesis. The current belief is that the acquisition of motor learning is stored by LTD at the parallel fiber (PF)-Purkinje cell synapse in the cerebellar cortex. Recently, however, several lines of mutant mice that display normal motor learning in the absence of cerebellar LTD have been reported. A similar dichotomy between synaptic plasticity at the circuitry level and learning at the behavioral level has also been reported in the hippocampus. One possible explanation for this dichotomy is that compensatory pathways at the molecular and circuitry levels play an important role in mice that have been genetically modified for their entire lives. Mice that are genetically modified to be deficient in or to express mutant versions of the δ2 glutamate receptor (GluD2) serve as an interesting model due to the predominant expression of GluD2 at PF-Purkinje cell synapses. Furthermore, two major functions of GluD2-PF synapse formation and LTD induction-can be mechanistically dissociated so that the role of LTD in motor learning can be investigated in the absence of morphological abnormalities caused by altered synapse formation. Therefore, genetic manipulations of GluD2 will help to clarify the relationship between LTD and motor learning in the cerebellum.

  10. 26 CFR 301.6104(d)-2 - Making applications and returns widely available.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 18 2014-04-01 2014-04-01 false Making applications and returns widely... Returns and Records § 301.6104(d)-2 Making applications and returns widely available. (a) In general. A... must correct or replace the document. (c) Discretion to prescribe other methods for making...

  11. 26 CFR 301.6104(d)-2 - Making applications and returns widely available.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 18 2012-04-01 2012-04-01 false Making applications and returns widely... Returns and Records § 301.6104(d)-2 Making applications and returns widely available. (a) In general. A... must correct or replace the document. (c) Discretion to prescribe other methods for making...

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

    PubMed Central

    Guo, Juen; Simmons, W. Kyle; Herscovitch, Peter; Martin, Alex; Hall, Kevin D.

    2014-01-01

    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 due to 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 (PET) with [18F]fallypride in 43 human subjects with body mass indices (BMI) ranging from 18–45 kg/m2. 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. PMID:25199919

  13. 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.

  14. Roles of Dopamine D2 Receptor Subregions in Interactions with β-Arrestin2

    PubMed Central

    Zhang, Xiaohan; Choi, Bo-Gil; Kim, Kyeong-Man

    2016-01-01

    β-Arrestins are one of the protein families that interact with G protein-coupled receptors (GPCRs). The roles of β-arrestins are multifaceted, as they mediate different processes including receptor desensitization, endocytosis, and G protein-independent signaling. Thus, determining the GPCR regions involved in the interactions with β-arrestins would be a preliminary step in understanding the molecular mechanisms involved in the selective direction of each function. In the current study, we determined the roles of the N-terminus, intracellular loops, and C-terminal tail of a representative GPCR in the interaction with β-arrestin2. For this, we employed dopamine D2 and D3 receptors (D2R and D3R, respectively), since they display distinct agonist-induced interactions with β-arrestins. Our results showed that the second and third intracellular loops of D2R are involved in the agonist-induced translocation of β-arrestins toward plasma membranes. In contrast, the N- and C-termini of D2R exerted negative effects on the basal interaction with β-arrestins. PMID:27068263

  15. Resolvin D2 prevents secondary thrombosis and necrosis in a mouse burn wound model.

    PubMed

    Bohr, Stefan; Patel, Suraj J; Sarin, Dhruv; Irimia, Daniel; Yarmush, Martin L; Berthiaume, Francois

    2013-01-01

    Deep partial thickness burns are subject to delayed necrosis of initially viable tissues surrounding the primary zone of thermally induced coagulation, which results in an expansion of the burn wound, both in area and depth, within 48 hours postburn. Neutrophil sequestration and activation leading to microvascular damage is thought to mediate this secondary tissue damage. Resolvins, a class of endogenous mediators derived from omega-3 polyunsaturated fatty acids, have been shown to regulate the resolution of inflammation. We hypothesized that exogenous resolvins could mitigate the deleterious impact of the inflammatory response in burn wounds. Using two different mouse burn injury models involving significant partial thickness injuries, we found that a systemically administered single dose of resolvin D2 (RvD2) as low as 25 pg/g bw given within an interval of up to 4 hours postburn effectively prevented thrombosis of the deep dermal vascular network and subsequent dermal necrosis. By preserving the microvascular network, RvD2 enhanced neutrophil access to the dermis, but prevented neutrophil-mediated damage through other anti-inflammatory actions, including inhibition of tumor necrosis factor-α, interleukin-1β, and neutrophil platelet-endothelial cell adhesion molecule-1. In a clinical context, RvD2 may be therapeutically useful by reducing the need for surgical debridement and the area requiring skin grafting. PMID:23110665

  16. Resolvin D2 prevents secondary thrombosis and necrosis in a mouse burn wound model.

    PubMed

    Bohr, Stefan; Patel, Suraj J; Sarin, Dhruv; Irimia, Daniel; Yarmush, Martin L; Berthiaume, Francois

    2013-01-01

    Deep partial thickness burns are subject to delayed necrosis of initially viable tissues surrounding the primary zone of thermally induced coagulation, which results in an expansion of the burn wound, both in area and depth, within 48 hours postburn. Neutrophil sequestration and activation leading to microvascular damage is thought to mediate this secondary tissue damage. Resolvins, a class of endogenous mediators derived from omega-3 polyunsaturated fatty acids, have been shown to regulate the resolution of inflammation. We hypothesized that exogenous resolvins could mitigate the deleterious impact of the inflammatory response in burn wounds. Using two different mouse burn injury models involving significant partial thickness injuries, we found that a systemically administered single dose of resolvin D2 (RvD2) as low as 25 pg/g bw given within an interval of up to 4 hours postburn effectively prevented thrombosis of the deep dermal vascular network and subsequent dermal necrosis. By preserving the microvascular network, RvD2 enhanced neutrophil access to the dermis, but prevented neutrophil-mediated damage through other anti-inflammatory actions, including inhibition of tumor necrosis factor-α, interleukin-1β, and neutrophil platelet-endothelial cell adhesion molecule-1. In a clinical context, RvD2 may be therapeutically useful by reducing the need for surgical debridement and the area requiring skin grafting.

  17. 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.

  18. 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.

  19. Repumping of ultracold strontium atoms using the ^3P2 - ^3D2 transition

    NASA Astrophysics Data System (ADS)

    Mickelson, P. G.; Martinez de Escobar, Y. N.; Traverso, A. J.; Killian, T. C.

    2008-05-01

    We discuss recent experiments involving ultracold strontium. Using a commercially-available 3 micron laser, we repump atoms out of the ^3P2 level via the ^3D2 state and gain almost a factor of 10 in the number of atoms in our system. This increase in the signal-to-noise ratio enables improved spectroscopy of strontium in our optical trap.

  20. Introducing the R2D2 Model: Online Learning for the Diverse Learners of This World

    ERIC Educational Resources Information Center

    Bonk, Curtis J.; Zhang, Ke

    2006-01-01

    The R2D2 method--read, reflect, display, and do--is a new model for designing and delivering distance education, and in particular, online learning. Such a model is especially important to address the diverse preferences of online learners of varied generations and varied Internet familiarity. Four quadrants can be utilized separately or as part…

  1. On principal finite W-algebras for the Lie superalgebra D(2, 1; α)

    NASA Astrophysics Data System (ADS)

    Poletaeva, Elena

    2016-05-01

    We study finite W-algebras associated to even regular (principal) nilpotent elements for the family of simple exceptional Lie superalgebras D(2, 1; α) and for the universal central extension of 𝔭𝔰𝔩(2|2). We give a complete description of these finite W-algebras in terms of generators and relations.

  2. STS-55 German Payload Specialist Walter freefloats inside the SL-D2 module

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 German Payload Specialist 1 Ulrich Walter demonstrates the microgravity aboard the Spacelab Deutsche 2 (SL-D2) science module in Columbia's, Orbiter Vehicle (OV) 102's, payload bay (PLB). The module served as his space laboratory and that of his six crewmates for 10 days. Walter represents the German Aerospace Research Establishment (DLR).

  3. Determination of the D2 parameter for (d,t) reactions

    NASA Astrophysics Data System (ADS)

    Knutson, L. D.; Colby, P. C.; Hichwa, B. P.

    1981-08-01

    Measurements of the tensor analyzing powers have been obtained for (d-->,t) reactions on 91Zr, 118Sn, 119Sn, and 208Pb for deuteron energies both above and below the Coulomb barrier. The measurements are sensitive to the presence of D-state components in the triton wave function and allow the determination of a parameter D2. This parameter is a measure of the importance of triton wave function components in which one neutron moves with orbital angular momentum L=2 relative to the deuteron center of mass. Values of D2 are extracted from the tensor analyzing power measurements by making use of distorted-wave Born approximation calculations. Analysis of the sub-Coulomb measurements leads to D2=-0.279+/-0.012 fm2, which is somewhat larger in magnitude than recent theoretical predictions. [NUCLEAR REACTIONS 91Zr(d,t), Ed=6.0,7.5 MeV, 118Sn(d,t), Ed=12.0 MeV, 119Sn(d,t), Ed=6.0,7.5,9.0 MeV, 208Pb(d,t), Ed=10.0,12.3 MeV; measured polarization parameters T20(θ), T21(θ), T22(θ) deduced D2. Enriched targets, DWBA analysis.

  4. 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.

  5. 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. PMID:10989281

  6. 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…

  7. 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

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

    PubMed

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

    2016-09-13

    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

  9. Hydron transfer catalyzed by triosephosphate isomerase. Products of isomerization of dihydroxyacetone phosphate in D2O.

    PubMed

    O'Donoghue, Annmarie C; Amyes, Tina L; Richard, John P

    2005-02-22

    The product distributions for the reactions of dihydroxyacetone phosphate (DHAP) in D(2)O at pD 7.9 catalyzed by triosephosphate isomerase (TIM) from chicken and rabbit muscle were determined by (1)H NMR spectroscopy using glyceraldehyde 3-phosphate dehydrogenase to trap the first-formed products of the thermodynamically unfavorable isomerization reaction, (R)-glyceraldehyde 3-phosphate (GAP) and [2(R)-(2)H]-GAP (d-GAP). Three products were observed from the reactions catalyzed by TIM: GAP from isomerization with intramolecular transfer of hydrogen (18% of the enzymatic products), d-GAP from isomerization with incorporation of deuterium from D(2)O into C-2 of GAP (43% of the enzymatic products), and [1(R)-(2)H]-DHAP (d-DHAP) from incorporation of deuterium from D(2)O into C-1 of DHAP (40% of the enzymatic products). The ratios of the yields of the deuterium-labeled products d-DHAP and d-GAP from partitioning of the intermediate of the TIM-catalyzed reactions of GAP and DHAP in D(2)O are 1.48 and 0.93, respectively. This provides evidence that the reaction of these two substrates does not proceed through a single, common, reaction intermediate but, rather, through distinct intermediates that differ in the bonding and arrangement of catalytic residues at the enediolate O-1 and O-2 oxyanions formed on deprotonation of GAP and DHAP, respectively.

  10. 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

  11. Initial D2 Dopamine Receptor Sensitivity Predicts Cocaine Sensitivity and Reward in Rats

    PubMed Central

    Merritt, Kathryn E.; Bachtell, Ryan K.

    2013-01-01

    The activation of dopamine receptors within the mesolimbic dopamine system is known to be involved in the initiation and maintenance of cocaine use. Expression of the D2 dopamine receptor subtype has been implicated as both a predisposing factor and consequence of chronic cocaine use. It is unclear whether there is a predictive relationship between D2 dopamine receptor function and cocaine sensitivity that would enable cocaine abuse. Therefore, we exploited individual differences in behavioral responses to D2 dopamine receptor stimulation to test its relationship with cocaine-mediated behaviors. Outbred, male Sprague-Dawley rats were initially characterized by their locomotor responsiveness to the D2 dopamine receptor agonist, quinpirole, in a within-session ascending dose-response regimen (0, 0.1, 0.3 & 1.0 mg/kg, sc). Rats were classified as high or low quinpirole responders (HD2 and LD2, respectively) by a median split of their quinpirole-induced locomotor activity. Rats were subsequently tested for differences in the psychostimulant effects of cocaine by measuring changes in cocaine-induced locomotor activity (5 and 15 mg/kg, ip). Rats were also tested for differences in the development of conditioned place preference to a low dose of cocaine (7.5 mg/kg, ip) that does not reliably produce a cocaine conditioned place preference. Finally, rats were tested for acquisition of cocaine self-administration and maintenance responding on fixed ratio 1 and 5 schedules of reinforcement, respectively. Results demonstrate that HD2 rats have enhanced sensitivity to the locomotor stimulating properties of cocaine, display greater cocaine conditioned place preference, and self-administer more cocaine compared to LD2 animals. These findings suggest that individual differences in D2 dopamine receptor sensitivity may be predictive of cocaine sensitivity and reward. PMID:24223783

  12. 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).

  13. 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.

  14. 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

  15. 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.

  16. 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. PMID:26501177

  17. Topographical evaluation of behavioural phenotype in a line of mice with targeted gene deletion of the D2 dopamine receptor.

    PubMed

    Clifford, J J; Usiello, A; Vallone, D; Kinsella, A; Borrelli, E; Waddington, J L

    2000-01-28

    The phenotype of spontaneous and dopamine D2-like agonist-induced behaviour was assessed topographically in a line of mice with targeted gene deletion of the D1 receptor. An ethologically-based, rapid time-sampling behavioural check-list technique was used to resolve and quantify all behaviours in the natural repertoire of the mouse. Relative to wildtypes [D2+/+], D2-null [D2-/-] mice evidenced over a 1 h period of initial exploration modest but significant reductions in locomotion, grooming, rearing free and rearing to wall; rearing seated, sniffing, sifting and stillness were not altered. Individual elements of behaviour habituated similarly over a 6 h period for both genotypes. The dose-dependent induction of stereotyped sniffing and ponderous locomotion by the D2-like agonist RU 24213 (0.1-12.5 mg/kg) in wildtypes was essentially absent in D2-null mice. The ethogram of spontaneous behaviour in D2-null mice was characterised by only modest reductions in, and topographical shifts between, certain individual elements of behaviour. Essential abolition of D2-like agonist responsivity in D2-null mice vis-à-vis considerable preservation of spontaneous behavioural topography suggests compensatory processes subsequent to developmental absence of the D2 receptor that are able to sustain function under naturalistic, tonic conditions but not during phasic challenge. PMID:10698004

  18. Sub-Doppler Electronic Spectrum of the BENZENE-D2 Complex

    NASA Astrophysics Data System (ADS)

    Hayashi, Masato; Ohshima, Yasuhiro

    2014-06-01

    Excitation spectrum of the benzene-D2 van der Waals (vdW) complex in the vicinity of the S1 ← S0 601 vibronic transition of the monomer was recorded by utilizing mass-selective two-color resonance-enhanced two-photon ionization. Extensive adiabatic cooling with the rotational temperature of ěrb|<| 0.5 K was conducted by the high-pressure pulsed expansion, and sub-Doppler resolution yielding the line width of 250 MHz was realized in a collimated molecular beam by employing Fourier-transform-limited ultraviolet pulses for the excitation. In contrast to our previous study on the benzene-H2 complex, weaker binding ortho nuclear-spin isomer, correlating to the j = 0 state of a freely rotating D2, was observed in addition to the stronger binding para isomer (with j = 1), by using a gas sample of normal D2. Three and two vibronic bands involving vdW-mode excitation were observed for the para and ortho isomers, respectively. By comparing the present results with those of the benzene-H2 complex, we made unambiguous assignments on the vdW modes involved in each observed band, and obtained complete sets of vibrational frequencies of all the three vdW modes for the both H2 and D2 isotopomers in the S1 61 manifold. One of the vdW frequency correlates to the splitting between the m = 0 and ± 1 sublevels in the j = 1 state of a freely rotating H2/D2 molecule, and the potential barrier for the hindered internal rotation has been evaluated to be ca. 60 cm-1 from the values. Ratio of the vdW frequencies between the H2 and D2 species deviate significantly from the value for the harmonic vibration (i.e., √{2} ≈ 1.4), indicating substantial anharmonic character of the vdW modes in the complex. M. Hayashi and Y. Ohshima, Chem. Phys. 419, 131-137 (2013). M. Hayashi and Y. Ohshima, J. Phys. Chem. A 117, 9819-9830 (2013).

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

    DOE PAGES

    Flay, D.; Posik, M.; Parno, D. S.; Allada, K.; Armstrong, W. R.; Averett, T.; Benmokhtar, F.; Bertozzi, W.; Camsonne, A.; Canan, M.; et al

    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

  20. Mutation of lysine 317 in the D2 subunit of photosystem II alters chloride binding and proton transport.

    PubMed

    Pokhrel, Ravi; Service, Rachel J; Debus, Richard J; Brudvig, Gary W

    2013-07-16

    The role of chloride in photosystem II (PSII) is unclear. Using structural information from PSII and a careful comparison with other chloride-activated enzymes, we proposed a role for chloride at the D2-K317 site in PSII [Pokhrel, R., et al. (2011) Biochemistry 50, 2725-2734]. To probe the role of chloride at this site, the D2-K317R, D2-K317A, D2-K317Q, and D2-K317E mutations were created in the cyanobacterium Synechocystis sp. PCC 6803. Purified PSII from the mutants was probed with Fourier transform infrared difference spectroscopy, demonstrating that compared to PSII from wild-type Synechocystis, PSII from all four mutants exhibit changes in the conformations of the polypeptide backbone and carboxylate groups. However, D2-K317R PSII exhibits minor changes, whereas D2-K317A, D2-K317Q, and D2-K317E PSII exhibit more substantial changes in polypeptide conformations. Steady-state oxygen-evolution measurements of purified PSII core complexes show that the oxygen-evolution activity of D2-K317A is independent of chloride. This is consistent with the loss of the chloride requirement when the charged K residue is replaced with an uncharged residue that no longer binds to an essential carboxylate (D1-D61) in the absence of chloride, analogous to observations in other chloride-activated enzymes. In contrast, the oxygen-evolution activity of D2-K317R is sensitive to the chloride concentration in the assay buffer; the effective KD for chloride binding is higher in D2-K317R than in wild-type PSII, possibly because of a less optimal binding site in the mutant. The S2 states of wild-type, D2-K317A, and D2-K317R PSII were probed using electron paramagnetic resonance spectroscopy. A g = 2 multiline signal, similar to the wild-type signal, was observed for D2-K317A and D2-K317R. However, a g = 4 signal was also observed for D2-K317R. Measurements of flash-dependent O2 yields showed that D2-K317A and D2-K317R have a higher miss factor than wild-type PSII. The oxygen

  1. 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

  2. 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).

  3. STS-55 Pilot Henricks with baroreflex collar in 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, STS-55 Pilot Terence T. Henricks, shirtless and wearing the baroreflex (BA) collar, conducts a space adaptation experiment at Rack 12, an experiment rack. The BA experiment is designed to investigate the theory that light-headedness and a reduction in blood pressure behaves differently after having adapted to a microgravity environment. These space-based measurements of the baroreflex will be compared to ground measurements to determine if microgravity affects the reflex. The SL-D2 module is located in the payload bay (PLB) of the Earth-orbiting Columbia, Orbiter Vehicle (OV) 102.

  4. 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.

  5. Does Prostaglandin D2 hold the cure to male pattern baldness?

    PubMed Central

    Nieves, Ashley; Garza, Luis A.

    2014-01-01

    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 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 androgenetic alopecia 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 androgenetic alopecia. PMID:24521203

  6. PRECO-D2: program for calculating preequilibrium and direct reaction double differential cross sections

    SciTech Connect

    Kalbach, C.

    1985-02-01

    The code PRECO-D2 uses the exciton model for preequilibrium nuclear reactions to describe the emission of particles with mass numbers of 1 to 4 from an equilibrating composite nucleus. A distinction is made between open and closed configurations in this system and between the multi-step direct (MSD) and multi-step compound (MSC) components of the preequilibrium cross section. Additional MSD components are calculated semi-empirically to account for direct nucleon transfer reactions and direct knockout processes involving cluster degrees of freedom. Evaporation from the equilibrated composite nucleus is included in the full MSC cross section. Output of energy differential and double differential cross sections is provided for the first particle emitted from the composite system. Multiple particle emission is not considered. This report describes the reaction models used in writing PRECO-D2 and explains the organization and utilization of the code. 21 refs.

  7. STS-55 German Payload Specialist Schlegel manipulates ROTEX controls in SL-D2

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 German Payload Specialist 2 Hans Schlegel, wearing goggles (eye glasses) and positioned in front of Spacelab Deutsche 2 (SL-D2) Rack 4 System Rack controls, operates Robotics Technology Experiment (ROTEX) arm. ROTEX is a robotic arm that operates within an enclosed workcell in Rack 6 (partially visible in the foreground) and uses teleoperation from both an onboard station located nearby in Rack 4 and from a station on the ground. The device uses teleprogramming and artificial intelligence to look at the design, verification and operation of advanced autonomous systems for use in future applications. Schlegel represents the German Aerospace Research Establishment (DLR). SL-D2, a German-managed payload, is aboard Columbia, Orbiter Vehicle (OV) 102, for this science research mission.

  8. STS-55 crew poses for portrait in front of SL-D2 module at KSC

    NASA Technical Reports Server (NTRS)

    1992-01-01

    STS-55 Columbia, Orbiter Vehicle (OV) 102, crewmembers pose for group portrait in front of Spacelab Deutsche 2 (SL-D2) science module at a Kennedy Space Center (KSC) processing facility. These five Americans and two Germans have been assigned as prime crewmembers to support the STS-55/SL-D2 mission. Left to right (front) are Commander Steven R. Nagel, Payload Specialist 2 Hans Schlegel, Mission Specialist 3 (MS3) Bernard A. Harris, Jr, Payload Specialist 1 Ulrich Walter, and MS2 Charles J. Precourt; and (back) Pilot Terence T. Henricks and MS1 and Payload Commander (PLC) Jerry L. Ross. Walter and Schlegel are scheduled to represent the DLR as payload specialists for the mission.

  9. [Ribonuclease hydration and its heat stability in solutions of H2O and D2O].

    PubMed

    Mrevlishvili, G M; Lobyshev, V I; Dzhaparidze, G Sh; Sokhadze, V M; Tatishvili, D A

    1980-01-01

    Ribonuclease hydration in wide concentration and temperature range using differential scanning microcalorimetry and NMR technique was studied. The temperature- concentration equilibrium diagram for H2O--ribonuclease system was suggested. Protein hydration in D2O was shown to be higher than in ordinary water. NMR measurements in dilute protein solutions showed that cooperative temperature denaturation was followed by solvation changes. Models of globular protein hydration are discussed. PMID:6245723

  10. Scalar field theory at finite temperature in D =2+1

    NASA Astrophysics Data System (ADS)

    Añaños, G. N. J.

    2006-01-01

    We discuss the φ6 theory defined in D =2+1-dimensional space-time and assume that the system is in equilibrium with a thermal bath at temperature β-1. We use the 1/N expansion and the method of the composite operator (Cornwall, Jackiw, and Tomboulis) for summing a large set of Feynman graphs. We demonstrate explicitly the Coleman-Mermin-Wagner theorem at finite temperature.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Assignment of laser lines in optically pumped submillimeter lasers - HDCO, D2CO

    NASA Astrophysics Data System (ADS)

    Dangoisse, D.; Duterage, B.; Glorieux, P.

    1980-03-01

    Respectively, three and eight laser lines have been precisely measured and assigned in asymmetric-top molecules HDCO and D2CO. Frequency calculations of rotational transitions use parameters obtained from microwave studies. For frequency calculations of rovibrational transitions, vibrational energies derived from infrared band analysis have been also taken into account. The assignment is confirmed by infrared radio frequency double resonance experiments inside the submillimeter laser cavity.

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

    PubMed Central

    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

    2015-01-01

    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. PMID:25550518

  17. Absolute measurement of the ultrafast nonlinear electronic and rovibrational response in H2 and D2

    NASA Astrophysics Data System (ADS)

    Wahlstrand, J. K.; Zahedpour, S.; Cheng, Y.-H.; Palastro, J. P.; Milchberg, H. M.

    2015-12-01

    The electronic, rotational, and vibrational components of the ultrafast optical nonlinearity in H2 and D2 are measured directly and absolutely at intensities up to the ionization threshold of ˜1014W/cm 2 . As the most basic nonlinear interactions of the simplest molecules exposed to high fields, these results constitute a benchmark for high-field laser-matter theory and simulation.

  18. STS-55 German Payload Specialist Walter at the SL-D2 Fluid Physics Module

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 German Payload Specialist 1 Ulrich Walter conducts an experiment using the advanced fluid physics module located in Spacelab Deutsche 2 (SL-D2) Rack 8 Werkstofflabor (WL) (Material Sciences Laboratory) aboard Earth-orbiting Columbia, Orbiter Vehicle (OV) 102. Walter uses intravehicular activity (IVA) foot restraints to position himself in front of the rack. Walter represents the German Aerospace Research Establishment (DLR) on the 10-day mission.

  19. STS-55 German payload specialists Walter and Schlegel work in SL-D2 module

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 German Payload Specialist 1 Ulrich Walter, wearing special head gear, conducts Tissue Thickness and Compliance Along Body Axis salt-water balance experiment in the Spacelab Deutsche 2 (SL-D2) science module aboard the Earth-orbiting Columbia, Orbiter Vehicle (OV) 102. Walter's activities in front of Rack 9 Anthrorack (AR) are monitored by German Payload Specialist 2 Hans Schlegel. Walter uses intravehicular activity (IVA) foot restraints. Walter and Schlegel represent the German Aerospace Research Establishment (DLR).

  20. STS-55 German Payload Specialist Schlegel works at SL-D2 Biolabor microscope

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 German Payload Specialist 2 Hans Schlegel loads sample into a microscope at the Spacelab Deutsche 2 (SL-D2) Rack 7 Biolabor (BB) workstation. The BB facility is a life sciences and biotechnology research device developed by Germany (MBB/ERNO) for use aboard Spacelab. Schlegel represents the German Aerospace Research Establishment (DLR) during this 10-day mission aboard Columbia, Orbiter Vehicle (OV) 102.

  1. Raman spectroscopy of gases with a Fourier transform spectrometer - The spectrum of D2

    NASA Technical Reports Server (NTRS)

    Jennings, D. E.; Weber, A.; Brault, J. W.

    1986-01-01

    Fourier transform spectrometry (FTS) is presently used to record the spontaneous incoherent laser Raman spectra of gases. The high resolution, sensitivity, calibration accuracy and spectral coverage achieved demonstrate the viability of FTS for Raman spectroscopy. Attention is given to the coefficients obtained by fitting measurements obtained from the spectrum of D2, containing both v = 0-0 and 1-0 transitions, to the Dunham (1932) expansion of the vibration-rotation energy levels.

  2. 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.

  3. 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.

  4. Line shapes in sub-Doppler DAVLL in the 87Rb-D2 line

    NASA Astrophysics Data System (ADS)

    Choi, Gyeong-Won; Noh, Heung-Ryoul

    2016-05-01

    We present a theoretical and experimental study of the sub-Doppler dichroic atomic vapor laser lock (DAVLL) for the D2 transition line of 87Rb atoms. The experimental results of the sub-Doppler DAVLL spectra are compared with calculated results using both accurate density matrix equations and approximate rate equations. We find good agreement between the experimental and calculated results. In particular, the coherence effect must be included in the signal for the cycling transition line.

  5. Rovibrational molecular populations, atoms, and negative ions in H2 and D2 magnetic multicusp discharges

    NASA Astrophysics Data System (ADS)

    Pealat, M.; Taran, J.-P. E.; Bacal, M.; Hillion, F.

    1985-06-01

    Coherent anti-Stokes Raman scattering is applied to the study of rovibrational populations in magnetic multicusp H2 and D2 discharges. This subject is of interest to negative hydrogen-ion formation by volume plasma processes. The populations of high-lying rotational states (J greater than 5) in the vibrational levels v = 0, 1, and 2 are found to be significantly higher than expected from the Boltzmann law. In H2 the net populations of the first four vibrational levels follow approximately the Boltzmann law, with the vibrational temperature of 2390 K (in a 90 V-10 A discharge at 55 micro bar). In similar discharge conditions, the population of the state v = 3 in D2 is higher than expected from the Boltzmann law. In the presence of the discharge a deficiency in H2 and D2 molecule density was observed and was attributed to the possible presence of H and D atoms. This was verified by an independent measurement of the atomic fraction and temperature. The density of negative ions, measured by the photodetachment technique, is also reported.

  6. Consumption of vitamin D2 enhanced mushrooms is associated with improved bone health.

    PubMed

    Chen, Shin-Yu; Yu, Hui-Tzu; Kao, Ju-Po; Yang, Chung-Chun; Chiang, Shen-Shih; Mishchuk, Darya O; Mau, Jeng-Leun; Slupsky, Carolyn M

    2015-07-01

    Mushrooms are the best nonanimal food source of vitamin D2. Pulsed irradiation can enhance vitamin D2 in mushrooms quickly. We investigated the effect of supplementing high vitamin D2Pleurotus ferulae mushrooms in a mouse model of osteoporosis. Thirty-two female C57BL/6JNarl mice were divided into four groups including sham, ovariectomized (OVX), OVX+nonpulsed mushroom (NPM) and OVX+pulsed mushroom (PM). After 23 weeks of treatment, serum samples were analyzed for osteoblast and osteoclast indicators, as well as metabolites using NMR spectroscopy. To examine bone density, femurs were analyzed using micro-computed tomography. The NPM and PM treatment mice showed increased bone density in comparison with OVX mice. In addition, the PM mice showed higher osteoblast and lower osteoclast indicators in comparison with OVX mice. Serum metabolomics analysis indicated several metabolites that were different in PM mice, some of which could be correlated with bone health. Taken together, these results suggest that pulsed irradiated mushrooms are able to increase bone density in osteoporotic mice possibly through enhanced bone metabolism. Further studies in humans are needed to show their efficacy in preventing osteoporosis.

  7. 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

  8. Analysis of the CIA Spectra of the Second Overtone Band of D2 at 77 K

    NASA Astrophysics Data System (ADS)

    Abu-Kharma, M.; Shawagfeh, Naseem; Gillard, P.

    2010-10-01

    Quantitative measurements of the collision induced absorption (CIA) spectra of pure D2 gas in the second overtone (v = 3←0) region were made for gas densities in the range 500 to 950 amagat at 77 K for the first time. The observed spectra were modeled with a synthetic profiles; which are composed of the superposition of an overlap-induced profile Q3(overlap)(J = 0 to 3) and a quadrupolar induced profile. The quadrupolar profile is formed of three profiles: a single vibrational transitions of the type X3(J)+X0(J), where X is O(ΔJ = -2), Q(ΔJ = 0) and S(ΔJ = 2) transition, a double vibrational transitions of the type X2(J)+X1(J) and a triple vibrational transitions Q1(J1)+Q1(J2)+Q1(J3) of D2; resulting from simultaneous collision of three D2 molecules. Profile analysis of the spectra was carried out using the Birnbaum—Cohen (BC) line shape function for the quadrupolar transitions and the Levine—Birnbaum (LB) line shape function for the overlap transitions. The fitting parameters were determined from the analysis. The agreement between the experimental and the calculated profiles is satisfactory.

  9. Separation of H2, HD and D2 using Low Temperature Gas Chromatography

    NASA Astrophysics Data System (ADS)

    Whisnant, C. Steven; Kelley, Travis; Burke, Ryan; Hansen, Patrick

    2008-10-01

    The frozen spin HD target developed for the study of photonuclear physics by the LEGS collaboration at Brookhaven National Laboratory (and now moved to JLab) requires high purity HD gas to produce targets with spin relaxation times on the order of months. Since this purity is not available commercially, the gas is distilled at low temperature to reduce the residual H2 and D2 contamination. Quantifying the remaining amount of these contaminants is important for preparing a target that obtains the desired polarization and spin relaxation time. To measure the relative concentrations of H2 and D2, a gas chromatography system has been developed that separates the isotopes of hydrogen. The system uses a 50 meter porous-layer open-tabular (PLOT) 5å carbon molsieve column with an inner diameter of 0.53 mm held at temperatures near 150K. The carrier gas is neon. The signal is produced by measuring differences in thermal conductivity between hydrogen and neon. Under these conditions, not only are H2 and D2 separated from HD, but o-H2 and p-H2 are also well separated from one another. The resulting chromatograms are fit to extract areas and corrected for isotopic differences in thermal conductivity to produce relative concentrations. The analysis of several gas samples will be presented and the status of the method discussed.

  10. Role of prostaglandin D2/CRTH2 pathway on asthma exacerbation induced by Aspergillus fumigatus

    PubMed Central

    Liu, Haixia; Zheng, Mingrui; Qiao, Jianou; Dang, Yajie; Zhang, Pengyu; Jin, Xianqiao

    2014-01-01

    Aspergillus fumigatus is often associated in asthmatic patients with the exacerbation of asthma symptoms. The pathomechanism of this phenomenon has not been fully understood. Here, we evaluated the immunological mechanisms and the role of the prostaglandin D2/ Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells (CRTH2) pathway in the development of Aspergillus-associated asthma exacerbation. We studied the effects of A. fumigatus on airway inflammation and bronchial hyper-responsiveness in a rat model of chronic asthma. Inhalation delivery of A. fumigatus conidia increased the airway eosinophilia and bronchial hyper-responsiveness in ovalbumin-sensitized, challenged rats. These changes were associated with prostaglandin D2 synthesis and CRTH2 expression in the lungs. Direct inflammation occurred in ovalbumin-sensitized, challenged animals, whereas pre-treatment with an antagonist against CRTH2 nearly completely eliminated the A. fumigatus-induced worsening of airway eosinophilia and bronchial hyper-responsiveness. Our data demonstrate that production of prostaglandin D2 followed by eosinophil recruitment into the airways via a CRTH2 receptor are the major pathogenic factors responsible for the A. fumigatus-induced enhancement of airway inflammation and responsiveness. PMID:24329550

  11. The Elevation of Boiling Points in H_2O and D_2O Electrolytes

    NASA Astrophysics Data System (ADS)

    Miles, M. H.; Arman, H. D.; Carrick, J. D.; Gren, C. K.; Haggerty, K. A.; Kim, H. Y.; Ky, A. G.; Markham, J. E.; Meeks, C. F.; Noga, D. E.

    2002-03-01

    The excess enthalpy effect in cold fusion experiments for Pd/D_2O systems is subject to positive feedback, i.e., increasing the cell temperature increases the excess enthalpy . Therefore, the largest excess enthalpy effects are often observed near or at the boiling point corresponding to that of the electrolyte solution in the cell(M.H. Miles, M. Fleischmann and M.A. Imam, "Calorimetric Analysis of a Heavy Water Electrolysis Experiment Using a Pd-B Alloy Cathode", Naval Research Lab Mem. Rep.,#6320-01-8526, pp. 27-30 (2001).). However, the actual boiling point increases as the D_2O content of the cell decreases. The purpose of this project will be to compare experimental values of the change in temperature ΔT obtained using H_2O and D_2O solutions with theoretical values of ΔT calculated by assuming ideal solutions. The emphasis will be on higher concentrations as well as on saturated solutions where ΔT values may be quite large. Preliminary results for LiOH in H_2O show reasonable agreement with ideal solution ΔT values up to LiOH concentrations of 1.0 molal (m).

  12. Consumption of vitamin D2 enhanced mushrooms is associated with improved bone health.

    PubMed

    Chen, Shin-Yu; Yu, Hui-Tzu; Kao, Ju-Po; Yang, Chung-Chun; Chiang, Shen-Shih; Mishchuk, Darya O; Mau, Jeng-Leun; Slupsky, Carolyn M

    2015-07-01

    Mushrooms are the best nonanimal food source of vitamin D2. Pulsed irradiation can enhance vitamin D2 in mushrooms quickly. We investigated the effect of supplementing high vitamin D2Pleurotus ferulae mushrooms in a mouse model of osteoporosis. Thirty-two female C57BL/6JNarl mice were divided into four groups including sham, ovariectomized (OVX), OVX+nonpulsed mushroom (NPM) and OVX+pulsed mushroom (PM). After 23 weeks of treatment, serum samples were analyzed for osteoblast and osteoclast indicators, as well as metabolites using NMR spectroscopy. To examine bone density, femurs were analyzed using micro-computed tomography. The NPM and PM treatment mice showed increased bone density in comparison with OVX mice. In addition, the PM mice showed higher osteoblast and lower osteoclast indicators in comparison with OVX mice. Serum metabolomics analysis indicated several metabolites that were different in PM mice, some of which could be correlated with bone health. Taken together, these results suggest that pulsed irradiated mushrooms are able to increase bone density in osteoporotic mice possibly through enhanced bone metabolism. Further studies in humans are needed to show their efficacy in preventing osteoporosis. PMID:25792284

  13. Homology Modeling of Dopamine D2 and D3 Receptors: Molecular Dynamics Refinement and Docking Evaluation

    PubMed Central

    Platania, Chiara Bianca Maria; Salomone, Salvatore; Leggio, Gian Marco; Drago, Filippo; Bucolo, Claudio

    2012-01-01

    Dopamine (DA) receptors, a class of G-protein coupled receptors (GPCRs), have been targeted for drug development for the treatment of neurological, psychiatric and ocular disorders. The lack of structural information about GPCRs and their ligand complexes has prompted the development of homology models of these proteins aimed at structure-based drug design. Crystal structure of human dopamine D3 (hD3) receptor has been recently solved. Based on the hD3 receptor crystal structure we generated dopamine D2 and D3 receptor models and refined them with molecular dynamics (MD) protocol. Refined structures, obtained from the MD simulations in membrane environment, were subsequently used in molecular docking studies in order to investigate potential sites of interaction. The structure of hD3 and hD2L receptors was differentiated by means of MD simulations and D3 selective ligands were discriminated, in terms of binding energy, by docking calculation. Robust correlation of computed and experimental Ki was obtained for hD3 and hD2L receptor ligands. In conclusion, the present computational approach seems suitable to build and refine structure models of homologous dopamine receptors that may be of value for structure-based drug discovery of selective dopaminergic ligands. PMID:22970199

  14. VORFFIP-driven dock: V-D2OCK, a fast and accurate protein docking strategy.

    PubMed

    Segura, Joan; Marín-López, Manuel Alejandro; Jones, Pamela F; Oliva, Baldo; Fernandez-Fuentes, Narcis

    2015-01-01

    The experimental determination of the structure of protein complexes cannot keep pace with the generation of interactomic data, hence resulting in an ever-expanding gap. As the structural details of protein complexes are central to a full understanding of the function and dynamics of the cell machinery, alternative strategies are needed to circumvent the bottleneck in structure determination. Computational protein docking is a valid and valuable approach to model the structure of protein complexes. In this work, we describe a novel computational strategy to predict the structure of protein complexes based on data-driven docking: VORFFIP-driven dock (V-D2OCK). This new approach makes use of our newly described method to predict functional sites in protein structures, VORFFIP, to define the region to be sampled during docking and structural clustering to reduce the number of models to be examined by users. V-D2OCK has been benchmarked using a validated and diverse set of protein complexes and compared to a state-of-art docking method. The speed and accuracy compared to contemporary tools justifies the potential use of VD2OCK for high-throughput, genome-wide, protein docking. Finally, we have developed a web interface that allows users to browser and visualize V-D2OCK predictions from the convenience of their web-browsers.

  15. 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

  16. [Corynebacterium group D2. Clinical study, biochemical identification and antibiotic sensitivity].

    PubMed

    Marty, N; Clave, D; Cancet, B; Henry-Ferry, S; Didier, J

    1988-05-01

    The comparative study of 44 isolates of Corynebacterium group D2, from urine, most frequently, shows the pathogenic role of these bacteria in urinary tract infection, with or without urinary stones. These microorganisms have an opportunistic behaviour in other non-urinary sites, and become pathogen in immunosuppressed conditions. The rapid tests as urease, glucose acidification, nitrate reductase, associated with multiple resistance to antibiotics (beta-lactams and aminosides) identify easily Corynebacterium group D2, from 48 h cultures under CO2 conditions. The results of MIC determination of 10 antibiotics, show the high activity (100% sensitivity) of vancomycin and pristinamycin, with MIC modes, respectively, 0.5 and 0.03 mg/l. These antibiotics are the most useful for the treatment of non-urinary infections. Among quinolones, the most active agents are ciprofloxacin and ofloxacin (MIC modes: 4 and 2 mg/l), so these antimicrobials could be used for the treatment of urinary tract infections caused by Corynebacterium group D2.

  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. PMID:24520350

  18. 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.

  19. Dopamine D2 gene expression interacts with environmental enrichment to impact lifespan and behavior.

    PubMed

    Thanos, Panayotis K; Hamilton, John; O'Rourke, Joseph R; Napoli, Anthony; Febo, Marcelo; Volkow, Nora D; Blum, Kenneth; Gold, Mark

    2016-04-12

    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.

  20. Design Study of the High Luminosity LHC Recombination Dipole (D2)

    SciTech Connect

    Sabbi, GianLuca; Wang, Xiaorong

    2014-05-26

    The interaction region design of the high-luminosity LHC requires replacing the recombination dipole magnets (D2) with new ones. The preliminary specifications include an aperture of 105 mm, with 186 mm separation between the twin-aperture axes, and an operating field in the range of 3.5 to 4.5 T. The main design challenge is to decouple the magnetic field in the two apertures and ensure good field quality. The approach adopted for the present D2 magnets, using the iron yoke as a shield between the two apertures, leads to large saturation effects. In this study, we propose an alternative approach where the iron yoke is designed primarily for low saturation, and the resulting large but current-independent cross-talk between the apertures is corrected with an asymmetric arrangement of the conductor blocks. A preliminary solution based on the LHC dipole cable is presented, and the expected harmonics for geometric, saturation and persistent current effects are provided. Finally, the feasibility of an operating field at the high end of the range considered is discussed, to minimize the D2 magnet length and facilitate the space allocation for other components.

  1. 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.

  2. 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.

  3. Chronic Cocaine Dampens Dopamine Signaling during Cocaine Intoxication and Unbalances D1 over D2 Receptor Signaling

    PubMed Central

    Park, Kicheon; Pan, Yingtian

    2013-01-01

    Dopamine increases triggered by cocaine and consequent stimulation of dopamine receptors (including D1 and D2) are associated with its rewarding effects. However, while facilitation of D1 receptor (D1R) signaling enhances the rewarding effects of cocaine, facilitation of D2R signaling decreases it, which indicates that for cocaine to be rewarding it must result in a predominance of D1R over D2R signaling. Moreover, the transition to compulsive cocaine intake might result from an imbalance between D1R and D2R signaling. To test the hypothesis that chronic cocaine use unbalances D1R over D2R signaling during cocaine intoxication, we used microprobe optical imaging to compare dynamic changes in intracellular calcium ([Ca2+]i, marker of neuronal activation) to acute cocaine in striatal D1R-EGFP and D2R-EGFP-expressing neurons between control and chronically treated mice. Chronic cocaine attenuated responses to acute cocaine in D1R (blunting Ca2+ increases by 67 ± 16%) and D2R (blunting Ca2+ decrease by 72 ± 17%) neurons in most D1R and D2R neurons (∼75%). However, the dynamics of this attenuation during cocaine intoxication was longer lasting for D2R than for D1R. Thus, whereas control mice showed a fast but short-lasting predominance of D1R over D2R signaling (peaking at ∼8 min) during acute cocaine intoxication, in chronically treated mice D1R predominance was sustained for >30 min (throughout the measurement period). Thus, chronic cocaine use dramatically reduced cocaine-induced DA signaling, shifting the balance between D1R and D2R signaling during intoxication to a predominance of D1R (stimulatory) over D2R (inhibitory) signaling, which might facilitate compulsive intake in addiction. PMID:24089490

  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. PMID:27184782

  5. Melanoma antigen-D2: A nucleolar protein undergoing delocalization during cell cycle and after cellular stress.

    PubMed

    Pirlot, Céline; Thiry, Marc; Trussart, Charlotte; Di Valentin, Emmanuel; Piette, Jacques; Habraken, Yvette

    2016-04-01

    Melanoma antigen D2 (MAGE-D2) is recognized as a cancer diagnostic marker; however, it has poorly characterized functions. Here, we established its intracellular localization and shuttling during cell cycle progression and in response to cellular stress. In normal conditions, MAGE-D2 is present in the cytoplasm, nucleoplasm, and nucleoli. Within the latter, MAGE-D2 is mostly found in the granular and the dense fibrillar components, and it interacts with nucleolin. Transfection of MAGE-D2 deletion mutants demonstrated that Δ203-254 leads to confinement of MAGE-D2 to the cytoplasm, while Δ248-254 prevents its accumulation in nucleoli but still allows its presence in the nucleoplasm. Consequently, this short sequence belongs to a nucleolar localization signal. MAGE-D2 deletion does not alter the nucleolar organization or rRNA levels. However, its intracellular localization varies with the cell cycle in a different kinetic than nucleolin. After genotoxic and nucleolar stresses, MAGE-D2 is excluded from nucleoli and concentrates in the nucleoplasm. We demonstrated that its camptothecin-related delocalization results from two distinct events: a rapid nucleolar release and a slower phospho-ERK-dependent cytoplasm to nucleoplasm translocation, which results from an increased flux from the cytoplasm to nucleoplasm. In conclusion, MAGE-D2 is a dynamic protein whose shuttling properties could suggest a role in cell cycle regulation. PMID:26705694

  6. Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer

    PubMed Central

    Bonaventura, Jordi; Navarro, Gemma; Casadó-Anguera, Verònica; Azdad, Karima; Rea, William; Moreno, Estefanía; Brugarolas, Marc; Mallol, Josefa; Canela, Enric I.; Lluís, Carme; Cortés, Antoni; Volkow, Nora D.; Schiffmann, Serge N.; Ferré, Sergi; Casadó, Vicent

    2015-01-01

    Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R. We describe novel unsuspected allosteric mechanisms within the heteromer by which not only A2AR agonists, but also A2AR antagonists, decrease the affinity and intrinsic efficacy of D2R agonists and the affinity of D2R antagonists. Strikingly, these allosteric modulations disappear on agonist and antagonist coadministration. This can be explained by a model that considers A2AR-D2R heteromers as heterotetramers, constituted by A2AR and D2R homodimers, as demonstrated by experiments with bioluminescence resonance energy transfer and bimolecular fluorescence and bioluminescence complementation. As predicted by the model, high concentrations of A2AR antagonists behaved as A2AR agonists and decreased D2R function in the brain. PMID:26100888

  7. Isotopic exchange processes in cold plasmas of H2/D2 mixtures.

    PubMed

    Jiménez-Redondo, Miguel; Carrasco, Esther; Herrero, Víctor J; Tanarro, Isabel

    2011-05-28

    Isotope exchange in low pressure cold plasmas of H(2)/D(2) mixtures has been investigated by means of mass spectrometric measurements of neutrals and ions, and kinetic model calculations. The measurements, which include also electron temperatures and densities, were performed in a stainless steel hollow cathode reactor for three discharge pressures: 1, 2 and 8 Pa, and for mixture compositions ranging from 100% H(2) to 100% D(2). The data are analyzed in the light of the model calculations, which are in good global agreement with the experiments. Isotope selective effects are found both in the surface recombination and in the gas-phase ionic chemistry. The dissociation of the fuel gas molecules is followed by wall recycling, which regenerates H(2) and D(2) and produces HD. Atomic recombination at the wall is found to proceed through an Eley-Rideal mechanism, with a preference for reaction of the adsorbed atoms with gas phase D atoms. The best fit probabilities for Eley-Rideal abstraction with H and D are: γ(ER H) = 1.5 × 10(-3), γ(ER D) = 2.0 × 10(-3). Concerning ions, at 1 Pa the diatomic species H(2)(+), D(2)(+) and HD(+), formed directly by electron impact, prevail in the distributions, and at 8 Pa, the triatomic ions H(3)(+), H(2)D(+), HD(2)(+) and D(3)(+), produced primarily in reactions of diatomic ions with molecules, dominate the plasma composition. In this higher pressure regime, the formation of the mixed ions H(2)D(+) and HD(2)(+) is favoured in comparison with that of H(3)(+) and D(3)(+), as expected on statistical grounds. The model results predict a very small preference, undetectable within the precision of the measurements, for the generation of triatomic ions with a higher degree of deuteration, which is probably a residual influence at room temperature of the marked zero point energy effects (ZPE), relevant for deuterium fractionation in interstellar space. In contrast, ZPE effects are found to be decisive for the observed distribution of

  8. Prediction of striatal D2 receptor binding by DRD2/ANKK1 TaqIA allele status.

    PubMed

    Eisenstein, Sarah A; Bogdan, Ryan; Love-Gregory, Latisha; Corral-Frías, Nadia S; Koller, Jonathan M; Black, Kevin J; Moerlein, Stephen M; Perlmutter, Joel S; Barch, Deanna M; Hershey, Tamara

    2016-10-01

    In humans, the A1 (T) allele of the dopamine (DA) D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) TaqIA (rs1800497) single nucleotide polymorphism has been associated with reduced striatal DA D2/D3 receptor (D2/D3R) availability. However, radioligands used to estimate D2/D3R are displaceable by endogenous DA and are nonselective for D2R, leaving the relationship between TaqIA genotype and D2R specific binding uncertain. Using the positron emission tomography (PET) radioligand, (N-[(11) C]methyl)benperidol ([(11) C]NMB), which is highly selective for D2R over D3R and is not displaceable by endogenous DA, the current study examined whether DRD2/ANKK1 TaqIA genotype predicts D2R specific binding in two independent samples. Sample 1 (n = 39) was composed of obese and nonobese adults; sample 2 (n = 18) was composed of healthy controls, unmedicated individuals with schizophrenia, and siblings of individuals with schizophrenia. Across both samples, A1 allele carriers (A1+) had 5 to 12% less striatal D2R specific binding relative to individuals homozygous for the A2 allele (A1-), regardless of body mass index or diagnostic group. This reduction is comparable to previous PET studies of D2/D3R availability (10-14%). The pooled effect size for the difference in total striatal D2R binding between A1+ and A1- was large (0.84). In summary, in line with studies using displaceable D2/D3R radioligands, our results indicate that DRD2/ANKK1 TaqIA allele status predicts striatal D2R specific binding as measured by D2R-selective [(11) C]NMB. These findings support the hypothesis that DRD2/ANKK1 TaqIA allele status may modify D2R, perhaps conferring risk for certain disease states. PMID:27241797

  9. Association between striatal dopamine D2/D3 receptors and brain activation during visual attention: effects of sleep deprivation.

    PubMed

    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 [(11)C]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:27244237

  10. 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

  11. 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.

  12. Structural and functional characterization of the Staphylococcus aureus virulence factor and vaccine candidate FhuD2.

    PubMed

    Mariotti, Paolo; Malito, Enrico; Biancucci, Marco; Lo Surdo, Paola; Mishra, Ravi P N; Nardi-Dei, Vincenzo; Savino, Silvana; Nissum, Mikkel; Spraggon, Glen; Grandi, Guido; Bagnoli, Fabio; Bottomley, Matthew J

    2013-02-01

    Staphylococcus aureus is a human pathogen causing globally significant morbidity and mortality. The development of antibiotic resistance in S. aureus highlights the need for a preventive vaccine. In the present paper we explore the structure and function of FhuD2 (ferric-hydroxamate uptake D2), a staphylococcal surface lipoprotein mediating iron uptake during invasive infection, recently described as a promising vaccine candidate. Differential scanning fluorimetry and calorimetry studies revealed that FhuD2 is stabilized by hydroxamate siderophores. The FhuD2-ferrichrome interaction was of nanomolar affinity in surface plasmon resonance experiments and fully iron(III)-dependent. We determined the X-ray crystallographic structure of ligand-bound FhuD2 at 1.9 Å (1 Å=0.1 nm) resolution, revealing the bilobate fold of class III SBPs (solute-binding proteins). The ligand, ferrichrome, occupies a cleft between the FhuD2 N- and C-terminal lobes. Many FhuD2-siderophore interactions enable the specific recognition of ferrichrome. Biochemical data suggest that FhuD2 does not undergo significant conformational changes upon siderophore binding, supporting the hypothesis that the ligand-bound complex is essential for receptor engagement and uptake. Finally, immunizations with FhuD2 alone or FhuD2 formulated with hydroxamate siderophores were equally protective in a murine staphylococcal infection model, confirming the suitability and efficacy of apo-FhuD2 as a protective antigen, and suggesting that other class III SBPs might also be exploited as vaccine candidates.

  13. 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...

  14. 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...

  15. Pretreatment d-2-hydroxyglutarate serum levels negatively impact on outcome in IDH1-mutated acute myeloid leukemia.

    PubMed

    Balss, J; Thiede, C; Bochtler, T; Okun, J G; Saadati, M; Benner, A; Pusch, S; Ehninger, G; Schaich, M; Ho, A D; von Deimling, A; Krämer, A; Heilig, C E

    2016-04-01

    Mutations in isocitrate dehydrogenases (IDHs) 1 and 2 frequently occur in acute myeloid leukemia (AML) and result in the production of the oncometabolite d-2-hydroxyglutarate (D2HG). D2HG has been shown to promote leukemogenesis even in the absence of mutated IDH, but the prognostic significance of pretreatment serum D2HG levels in patients with IDH-mutated AML is unclear. We measured D2HG serum levels in 84 patients with IDH-mutated AML treated in the prospective, randomized multicenter AML2003 trial of the German Study Alliance Leukemia. Multivariate Cox regression showed D2HG levels to negatively impact on event-free survival (EFS) as a continuous variable in the entire IDH(mut) cohort (P=0.04), with no effect on overall survival (OS). In a subgroup analysis, the negative impact of D2HG on EFS was found to be restricted to patients with mutations in IDH1 (P=0.003), adjusted for age, leukocyte count, serum lactate dehydrogenase and European LeukemiaNet risk score. We thus conclude that pretreatment D2HG serum levels may yield prognostic information in patients with IDH1-mutated, but not in IDH2-mutated AML, possibly due to different subcellular localizations of IDH1 and IDH2.

  16. Optogenetics reveals a role for accumbal medium spiny neurons expressing dopamine D2 receptors in cocaine-induced behavioral sensitization

    PubMed Central

    Song, Shelly Sooyun; Kang, Byeong Jun; Wen, Lei; Lee, Hyo Jin; Sim, Hye-ri; Kim, Tae Hyong; Yoon, Sehyoun; Yoon, Bong-June; Augustine, George J.; Baik, Ja-Hyun

    2014-01-01

    Long-lasting, drug-induced adaptations within the nucleus accumbens (NAc) have been proposed to contribute to drug-mediated addictive behaviors. Here we have used an optogenetic approach to examine the role of NAc medium spiny neurons (MSNs) expressing dopamine D2 receptors (D2Rs) in cocaine-induced behavioral sensitization. Adeno-associated viral vectors encoding channelrhodopsin-2 (ChR2) were delivered into the NAc of D2R-Cre transgenic mice. This allowed us to selectively photostimulate D2R-MSNs in NAc. D2R-MSNs form local inhibitory circuits, because photostimulation of D2R-MSN evoked inhibitory postsynaptic currents (IPSCs) in neighboring MSNs. Photostimulation of NAc D2R-MSN in vivo affected neither the initiation nor the expression of cocaine-induced behavioral sensitization. However, photostimulation during the drug withdrawal period attenuated expression of cocaine-induced behavioral sensitization. These results show that D2R-MSNs of NAc play a key role in withdrawal-induced plasticity and may contribute to relapse after cessation of drug abuse. PMID:25352792

  17. Optogenetics reveals a role for accumbal medium spiny neurons expressing dopamine D2 receptors in cocaine-induced behavioral sensitization.

    PubMed

    Song, Shelly Sooyun; Kang, Byeong Jun; Wen, Lei; Lee, Hyo Jin; Sim, Hye-Ri; Kim, Tae Hyong; Yoon, Sehyoun; Yoon, Bong-June; Augustine, George J; Baik, Ja-Hyun

    2014-01-01

    Long-lasting, drug-induced adaptations within the nucleus accumbens (NAc) have been proposed to contribute to drug-mediated addictive behaviors. Here we have used an optogenetic approach to examine the role of NAc medium spiny neurons (MSNs) expressing dopamine D2 receptors (D2Rs) in cocaine-induced behavioral sensitization. Adeno-associated viral vectors encoding channelrhodopsin-2 (ChR2) were delivered into the NAc of D2R-Cre transgenic mice. This allowed us to selectively photostimulate D2R-MSNs in NAc. D2R-MSNs form local inhibitory circuits, because photostimulation of D2R-MSN evoked inhibitory postsynaptic currents (IPSCs) in neighboring MSNs. Photostimulation of NAc D2R-MSN in vivo affected neither the initiation nor the expression of cocaine-induced behavioral sensitization. However, photostimulation during the drug withdrawal period attenuated expression of cocaine-induced behavioral sensitization. These results show that D2R-MSNs of NAc play a key role in withdrawal-induced plasticity and may contribute to relapse after cessation of drug abuse. PMID:25352792

  18. Cocaine-Induced Behavioral Sensitization in Mice: Effects of Microinjection of Dopamine D2 Receptor Antagonist into the Nucleus Accumbens

    PubMed Central

    Jung, Eun-Sol; Lee, Hyo Jin; Sim, Hye-Ri

    2013-01-01

    To determine the role of dopamine D2 receptor (D2R) in the nucleus accumbens (NAc) core in cocaine-induced behavioral sensitization, D2R antagonist, raclopride was bilaterally microinjected (2.5 or 5 nmol) into the NAc core of WT and D2R-/- mice and the initiation and expression phase of cocaine-mediated locomotor sensitization were analyzed. WT and D2R knockout (D2R-/-) mice received bilateral injections of either saline, or raclopride at the NAc core 30 min before each of five daily repeated injections of saline or cocaine (15 mg/kg i.p.). Following 2 weeks of withdrawal after repeated exposure to cocaine, the animals were pre-treated with an intra-accumbal injection of vehicle or raclopride before receiving a systemic cocaine challenge for the expression of sensitization. Animals which had been microinjected raclopride into NAc core displayed the enhancement of cocaine-induced behavioral response for the initiation but also for the expression of sensitization in WT as well as in D2R-/- mice, which was thus unaltered as compared to vehicle-injected control group. These results suggest that D2R in NAc core is not involved in cocaine-induced behavioral sensitization. PMID:24167417

  19. 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.

  20. 26 CFR 20.2056(d)-2 - Marital deduction; effect of disclaimers of post-December 31, 1976 transfers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 14 2011-04-01 2010-04-01 true Marital deduction; effect of disclaimers of post-December 31, 1976 transfers. 20.2056(d)-2 Section 20.2056(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES ESTATE TAX; ESTATES OF DECEDENTS DYING...

  1. 26 CFR 20.2056(d)-2 - Marital deduction; effect of disclaimers of post-December 31, 1976 transfers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 14 2014-04-01 2013-04-01 true Marital deduction; effect of disclaimers of post-December 31, 1976 transfers. 20.2056(d)-2 Section 20.2056(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES ESTATE TAX; ESTATES OF DECEDENTS DYING...

  2. 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

  3. 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

  4. Optogenetics reveals a role for accumbal medium spiny neurons expressing dopamine D2 receptors in cocaine-induced behavioral sensitization.

    PubMed

    Song, Shelly Sooyun; Kang, Byeong Jun; Wen, Lei; Lee, Hyo Jin; Sim, Hye-Ri; Kim, Tae Hyong; Yoon, Sehyoun; Yoon, Bong-June; Augustine, George J; Baik, Ja-Hyun

    2014-01-01

    Long-lasting, drug-induced adaptations within the nucleus accumbens (NAc) have been proposed to contribute to drug-mediated addictive behaviors. Here we have used an optogenetic approach to examine the role of NAc medium spiny neurons (MSNs) expressing dopamine D2 receptors (D2Rs) in cocaine-induced behavioral sensitization. Adeno-associated viral vectors encoding channelrhodopsin-2 (ChR2) were delivered into the NAc of D2R-Cre transgenic mice. This allowed us to selectively photostimulate D2R-MSNs in NAc. D2R-MSNs form local inhibitory circuits, because photostimulation of D2R-MSN evoked inhibitory postsynaptic currents (IPSCs) in neighboring MSNs. Photostimulation of NAc D2R-MSN in vivo affected neither the initiation nor the expression of cocaine-induced behavioral sensitization. However, photostimulation during the drug withdrawal period attenuated expression of cocaine-induced behavioral sensitization. These results show that D2R-MSNs of NAc play a key role in withdrawal-induced plasticity and may contribute to relapse after cessation of drug abuse.

  5. 75 FR 49005 - Program for Allocation of Regulatory Responsibilities Pursuant to Rule 17d-2; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-12

    ... an Amended 17d-2 Plan Between the Financial Industry Regulatory Authority, Inc. and the Chicago Stock... Industry Regulatory Authority, Inc. (``FINRA'') and the Chicago Stock Exchange, Inc. (``CHX'') (together... 240.17d-2, respectively. \\8\\ See Securities Exchange Act Release No. 12352 (April 20, 1976), 41...

  6. Cp2TiCl/D2O/Mn, a formidable reagent for the deuteration of organic compounds.

    PubMed

    Rosales, Antonio; Rodríguez-García, Ignacio

    2016-01-01

    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

  7. 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.

  8. Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making.

    PubMed

    Zalocusky, Kelly A; Ramakrishnan, Charu; Lerner, Talia N; Davidson, Thomas J; Knutson, Brian; Deisseroth, Karl

    2016-03-31

    A marked bias towards risk aversion has been observed in nearly every species tested. A minority of individuals, however, instead seem to prefer risk (repeatedly choosing uncertain large rewards over certain but smaller rewards), and even risk-averse individuals sometimes opt for riskier alternatives. It is not known how neural activity underlies such important shifts in decision-making--either as a stable trait across individuals or at the level of variability within individuals. Here we describe a model of risk-preference in rats, in which stable individual differences, trial-by-trial choices, and responses to pharmacological agents all parallel human behaviour. By combining new genetic targeting strategies with optical recording of neural activity during behaviour in this model, we identify relevant temporally specific signals from a genetically and anatomically defined population of neurons. This activity occurred within dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens (NAc), signalled unfavourable outcomes from the recent past at a time appropriate for influencing subsequent decisions, and also predicted subsequent choices made. Having uncovered this naturally occurring neural correlate of risk selection, we then mimicked the temporally specific signal with optogenetic control during decision-making and demonstrated its causal effect in driving risk-preference. Specifically, risk-preferring rats could be instantaneously converted to risk-averse rats with precisely timed phasic stimulation of NAc D2R cells. These findings suggest that individual differences in risk-preference, as well as real-time risky decision-making, can be largely explained by the encoding in D2R-expressing NAc cells of prior unfavourable outcomes during decision-making. PMID:27007845

  9. Half a century of antipsychotics and still a central role for dopamine D2 receptors.

    PubMed

    Kapur, Shitij; Mamo, David

    2003-10-01

    A review of the history of antipsychotics reveals that while the therapeutic effects of chlorpromazine and reserpine were discovered and actively researched almost concurrently, subsequent drug development has been restricted to drugs acting on postsynaptic receptors rather than modulation of dopamine release. The fundamental property of atypical antipsychotics is their ability to produce an antipsychotic effect in the absence of extrapyramidal side effects (EPS) or prolactin elevation. Modulation of the dopamine D2 receptor remains both necessary and sufficient for antipsychotic drug action, with affinity to the D2-receptor being the single most important discriminator between a typical and atypical drug profile. Most antipsychotics, including atypical antipsychotics, show a dose-dependent threshold of D2 receptor occupancy for their therapeutic effects, although the precise threshold is different for different drugs. Some atypical antipsychotics do not appear to reach the threshold for EPS and prolactin elevation, possibly accounting for their atypical nature. To link the biological theories of antipsychotics to their psychological effects, a hypothesis is proposed wherein psychosis is a state of aberrant salience of stimuli and ideas, and antipsychotics, via modulation of the mesolimbic dopamine system, dampen the salience of these symptoms. Thus, antipsychotics do not excise psychosis: they provide the neurochemical platform for the resolution of symptoms. Future generations of antipsychotics may need to move away from a "one-size-fits-all polypharmacy-in-a-pill" approach to treat all the different aspects of schizophrenia. At least in theory a preferred approach would be the development of specific treatments for the different dimensions of schizophrenia (e.g., positive, negative, cognitive, and affective) that can be flexibly used and titrated in the service of patients' presenting psychopathology. PMID:14642968

  10. 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.

  11. 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

  12. Defluorination of organofluorine sulfur compounds by Pseudomonas sp. strain D2

    SciTech Connect

    Key, B.D.; Criddle, C.S.; Howell, R.D.

    1998-08-01

    Little is known of the potential for biodegradation of fluorinated sulfonates. Because of the apparent stability of fluorinated organics, their bioactivity, and their potential for accumulation in the environment, it is important to understand their environmental fate and the mechanisms by which they might be degraded. To evaluate this potential, the following model compounds were selected: difluoromethane sulfonate (DFMS), trifluoromethane sulfonate (TFMS), 2,2,2-trifluoroethane sulfonate (TES), perfluorooctane sulfonate (PFOS), and 1H,1H,2H,2H-perfluorooctane sulfonate (H-PFOS). A laboratory isolate designated Pseudomonas sp. strain D2 completely defluorinated DFMS under aerobic sulfur-limiting conditions in a defined mineral medium. Strain D2 utilized DFMS as the sole source of sulfur, but not as a source of carbon or energy. DFMS utilization was inhibited by other forms of sulfur, and noncompetitive inhibition kinetics were observed, with K{sub i}-values of 3--4 {micro}M for sulfate, sulfite, methane sulfonate, and cystine. Strain D2 was subsequently used to evaluate degradation of other fluorinated sulfonates. Growth and defluorination were only observed for those compounds containing hydrogen (TES and H-PFOS). TFMS and PFOS were not degraded. TES was completely defluorinated, and H-PFOS was partially defluorinated. No volatile transformation products were detected for TES or DFMS, but six volatile products were detected for H-PFOS. All of the volatile products contained oxygen and fluorine, but not sulfur. This is the first report of defluorination of fluorinated sulfonates, a linkage between sulfur assimilation and defluorination, and generation of volatile fluorinated biotransformation products.

  13. Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making.

    PubMed

    Zalocusky, Kelly A; Ramakrishnan, Charu; Lerner, Talia N; Davidson, Thomas J; Knutson, Brian; Deisseroth, Karl

    2016-03-31

    A marked bias towards risk aversion has been observed in nearly every species tested. A minority of individuals, however, instead seem to prefer risk (repeatedly choosing uncertain large rewards over certain but smaller rewards), and even risk-averse individuals sometimes opt for riskier alternatives. It is not known how neural activity underlies such important shifts in decision-making--either as a stable trait across individuals or at the level of variability within individuals. Here we describe a model of risk-preference in rats, in which stable individual differences, trial-by-trial choices, and responses to pharmacological agents all parallel human behaviour. By combining new genetic targeting strategies with optical recording of neural activity during behaviour in this model, we identify relevant temporally specific signals from a genetically and anatomically defined population of neurons. This activity occurred within dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens (NAc), signalled unfavourable outcomes from the recent past at a time appropriate for influencing subsequent decisions, and also predicted subsequent choices made. Having uncovered this naturally occurring neural correlate of risk selection, we then mimicked the temporally specific signal with optogenetic control during decision-making and demonstrated its causal effect in driving risk-preference. Specifically, risk-preferring rats could be instantaneously converted to risk-averse rats with precisely timed phasic stimulation of NAc D2R cells. These findings suggest that individual differences in risk-preference, as well as real-time risky decision-making, can be largely explained by the encoding in D2R-expressing NAc cells of prior unfavourable outcomes during decision-making.

  14. Half a century of antipsychotics and still a central role for dopamine D2 receptors.

    PubMed

    Kapur, Shitij; Mamo, David

    2003-10-01

    A review of the history of antipsychotics reveals that while the therapeutic effects of chlorpromazine and reserpine were discovered and actively researched almost concurrently, subsequent drug development has been restricted to drugs acting on postsynaptic receptors rather than modulation of dopamine release. The fundamental property of atypical antipsychotics is their ability to produce an antipsychotic effect in the absence of extrapyramidal side effects (EPS) or prolactin elevation. Modulation of the dopamine D2 receptor remains both necessary and sufficient for antipsychotic drug action, with affinity to the D2-receptor being the single most important discriminator between a typical and atypical drug profile. Most antipsychotics, including atypical antipsychotics, show a dose-dependent threshold of D2 receptor occupancy for their therapeutic effects, although the precise threshold is different for different drugs. Some atypical antipsychotics do not appear to reach the threshold for EPS and prolactin elevation, possibly accounting for their atypical nature. To link the biological theories of antipsychotics to their psychological effects, a hypothesis is proposed wherein psychosis is a state of aberrant salience of stimuli and ideas, and antipsychotics, via modulation of the mesolimbic dopamine system, dampen the salience of these symptoms. Thus, antipsychotics do not excise psychosis: they provide the neurochemical platform for the resolution of symptoms. Future generations of antipsychotics may need to move away from a "one-size-fits-all polypharmacy-in-a-pill" approach to treat all the different aspects of schizophrenia. At least in theory a preferred approach would be the development of specific treatments for the different dimensions of schizophrenia (e.g., positive, negative, cognitive, and affective) that can be flexibly used and titrated in the service of patients' presenting psychopathology.

  15. 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

    2016-01-01

    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

  16. Precision Measurement of the Ionization and Dissociation Energies of H_2, HD and D_2

    NASA Astrophysics Data System (ADS)

    Sprecher, Daniel; Liu, Jinjun; Merkt, Frédéric; Jungen, Christian; Ubachs, Wim

    2010-06-01

    The ionization and dissociation energies of H_2, HD and D_2 are benchmark quantities in molecular quantum mechanics. Comparison between experimental and theoretical values for these quantities has a long history starting with the early measurement of Beutler and the calculations of James and Coolidge. Transition wave numbers from the EF ^1Σ g^+ (v=0,N=0,1) state to selected np Rydberg states (n ≈ 60) below the X+ ^2Σ^+u (v^+=0,N^+=0,1)} ionization threshold have been measured in H_2, HD and D_2 at a precision better than 10 MHz (0.0003 cm-1). Combining the results with previous experimental and theoretical data for other energy level intervals, the ionization and dissociation energies of H_2, HD and D_2 could be determined at an absolute accuracy of better than 20 MHz. These new results represent an improvement over previous experimental results by more than one order of magnitude and the most precise values of dissociation and ionization energies measured to date in a molecular system. The results therefore offer the opportunity of a comparison with theoretical values. In particular they will be compared to the latest ab initio calculations which include nonadiabatic, relativistic and radiative effects. The comparison indicates that relativistic and radiative quantum electrodynamics corrections of order up to α^4 are needed to account for the experimental results. H. Beutler, Z. Phys. Chem. 29, 315 (1935) H. M. James and A. S. Coolidge, J. Chem. Phys. 1, 825 (1933) J. Liu, E. J. Salumbides, U. Hollenstein, J. C. J. Koelemeij, K. S. E. Eikema, W. Ubachs, and F. Merkt, J. Chem. Phys. 130, 174306 (2009) J. Liu, D. Sprecher, Ch. Jungen, W. Ubachs, and F. Merkt, submitted to J. Chem. Phys. K. Piszczatowski, G. Łach, M. Przybytek, J. Komasa, K. Pachucki, and B. Jeziorski, J. Chem. Theory Comput. 5, 3039 (2009)

  17. Intramolecular allosteric communication in dopamine D2 receptor revealed by evolutionary amino acid covariation

    PubMed Central

    Sung, Yun-Min; Wilkins, Angela D.; Rodriguez, Gustavo J.; Wensel, Theodore G.; Lichtarge, Olivier

    2016-01-01

    The structural basis of allosteric signaling in G protein-coupled receptors (GPCRs) is important in guiding design of therapeutics and understanding phenotypic consequences of genetic variation. The Evolutionary Trace (ET) algorithm previously proved effective in redesigning receptors to mimic the ligand specificities of functionally distinct homologs. We now expand ET to consider mutual information, with validation in GPCR structure and dopamine D2 receptor (D2R) function. The new algorithm, called ET-MIp, identifies evolutionarily relevant patterns of amino acid covariations. The improved predictions of structural proximity and D2R mutagenesis demonstrate that ET-MIp predicts functional interactions between residue pairs, particularly potency and efficacy of activation by dopamine. Remarkably, although most of the residue pairs chosen for mutagenesis are neither in the binding pocket nor in contact with each other, many exhibited functional interactions, implying at-a-distance coupling. The functional interaction between the coupled pairs correlated best with the evolutionary coupling potential derived from dopamine receptor sequences rather than with broader sets of GPCR sequences. These data suggest that the allosteric communication responsible for dopamine responses is resolved by ET-MIp and best discerned within a short evolutionary distance. Most double mutants restored dopamine response to wild-type levels, also suggesting that tight regulation of the response to dopamine drove the coevolution and intramolecular communications between coupled residues. Our approach provides a general tool to identify evolutionary covariation patterns in small sets of close sequence homologs and to translate them into functional linkages between residues. PMID:26979958

  18. 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

  19. Increase of vitamin D2 by UV-B exposure during the growth phase of white button mushroom (Agaricus bisporus)

    PubMed Central

    Kristensen, Hanne L.; Rosenqvist, Eva; Jakobsen, Jette

    2012-01-01

    Background Mushrooms are the only non-animal food source of vitamin D. Wild mushrooms have naturally high vitamin D2 content, and cultivated mushrooms produce vitamin D2 from ergosterol when exposed to supplementary UV-B during the post-harvest phase. Objectives This study investigated the effects of providing supplementary UV-B during the growth phase on vitamin D2 formation and the interactions with growth of mushrooms, as compared to supplementary UV-B during the post-harvest phase or exposure to sunlight for both cultivated and wild mushrooms. Methods Experiments were carried out with exposure to supplementary UV-B just prior to harvest in the range of 0–2,400 mJ cm−2. Mushrooms grew for 2 days with or without repeated UV-B exposure each day. Vitamin D2 and growth rate were determined. In addition, some mushrooms were post-harvest treated by exposure at 200 mJ cm−2 supplementary UV-B or natural sunlight, prior to vitamin D2 determination. Results The content of vitamin D2 was 0.2–164 µg 100 g−1 fresh weight, and there was a linear relationship between UV-dose up to 1,000 mJ cm−2 and vitamin D2 content. The fast growth rate of the mushrooms diluted the vitamin D2 from 24 to 3 µg 100 g−1 within 2 days of exposure at 200 mJ cm−2. Following repeated UV-B exposure, vitamin D2 increased to 33 µg vitamin D2 100 g−1. Growth was unaffected by UV-B. Post-harvest exposure to supplementary UV-B resulted in a higher vitamin D2 content of 32 µg 100 g−1 compared to the 24 µg 100 g−1 obtained from exposure to UV-B during the growth phase. In contrast, wild and cultivated mushrooms with and without exposure to sunlight had vitamin D2 content in the range of 0.2–1.5 µg vitamin D2 100 g−1. Conclusions This study showed that mushrooms with a well-defined content of vitamin D2 can be obtained by exposure to supplementary UV-B just prior to harvest. PMID:22489222

  20. Production of excited atomic hydrogen and deuterium from H2 and D2 photodissociation

    NASA Astrophysics Data System (ADS)

    Bozek, J. D.; Furst, J. E.; Gay, T. J.; Gould, H.; Kilcoyne, A. L. D.; Machacek, J. R.; Martín, F.; McLaughlin, K. W.; Sanz-Vicario, J. L.

    2006-12-01

    We have measured the production of both Lyα and Hα fluorescence from atomic H and D for the photodissociation of H2 and D2 by linearly polarized photons with energies between 24 and 60 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. Our data are compared with ab initio calculations of the dissociation process, in which both doubly excited state production and prompt ionization (non-resonant) channels are considered. Agreement between our experimental data and that of earlier work, and with our theoretical calculations, is qualitative at best.

  1. 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.

  2. 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).

  3. Ruthenium Catalyzed Selective α- and α,β-Deuteration of Alcohols Using D2O.

    PubMed

    Chatterjee, Basujit; Gunanathan, Chidambaram

    2015-10-01

    Highly selective ruthenium catalyzed α-deuteration of primary alcohols and α,β-deuteration of secondary alcohols are achieved using deuterium oxide (D2O) as a source of deuterium and reaction solvent. Minimal loading of catalyst (Ru-macho), base (KO(t)Bu), and low temperature heating provided efficient selective deuteration of alcohols making the process practically attractive and environmentally benign. Mechanistic studies indicate the D-O(D/R) bond activations by metal-ligand cooperation and intermediacy of carbonyl compounds resulting from dehydrogenation of alcohols. PMID:26381108

  4. Production of excited atomic hydrogen and deuterium from H2 and D2photodissociation

    SciTech Connect

    Bozek, J.D.; Furst, J.E.; Gay, T.J.; Gould, H.; Kilcoyne, A.L.D.; Machacek, J.R.; Martin, F.; McLaughlin, K.W.; Sanz-Vicario, J.L.

    2006-09-17

    We have measured the production of both Ly alpha and H alphafluorescence from atomic H and D for the photodissociation of H2 and D2by linearly polarized photons with energies between 24 and 60 eV. In thisenergy range, excited photofragments result primarily from the productionof doubly excited molecular species which promptly autoionize ordissociate into two neutrals. Our data are compared with ab initiocalculations of the dissociation process, in which both doubly excitedstate production and prompt ionization (nonresonant) channels areconsidered. Agreement between our experimental data and that of earlierwork, and with our theoretical calculations, is qualitative atbest.

  5. Dual descriptions of massive spin-3 particles in D =2 +1 via Noether gauge embedment

    NASA Astrophysics Data System (ADS)

    Mendonça, E. L.; Dalmazi, D.

    2015-03-01

    We present here a relationship among massive self-dual models for spin-3 particles in D =2 +1 via the Noether gauge embedment (NGE) procedure. Starting with a first-order model (in derivatives) SSD (1 ) we have obtained a sequence of four self-dual models SSD (i ) where i =1 ,2 ,3 ,4 . We demonstrate that the NGE procedure generates the correct action for the auxiliary fields automatically. We obtain the whole action for the fourth-order self-dual model including all the needed auxiliary fields to get rid of the ghosts of the theory.

  6. Narrowing of Doppler and hyperfine line shapes of Rb - D2 transition using a Vortex beam

    NASA Astrophysics Data System (ADS)

    Das, Bankim Chandra; Bhattacharyya, Dipankar; De, Sankar

    2016-01-01

    We performed an experimental and theoretical study on saturation absorption spectroscopy on 87Rb and 85Rb atoms in D2 transition using a Laguerre-Gaussian (LG) beam with higher orders. We observed narrow line shapes of the Doppler and hyperfine absorption profiles due to the introduction of the LG beam in comparison to the fundamental Gaussian beam. Narrowing of the line shape is dependent on the azimuthal mode index of the LG field. It is observed that the spatially dependent Rabi frequency plays a significant role behind these narrowing phenomenon.

  7. Effect of convection on the dendrite growth kinetics in undercooled melts of D2 tool steels

    NASA Astrophysics Data System (ADS)

    Valloton, J.; Herlach, D. M.; Henein, H.

    2016-03-01

    Rapid solidification of D2 tool steel is investigated experimentally using the electromagnetic levitation technique under terrestrial and reduced gravity conditions. The microstructures of samples covering a broad range of undercoolings (40 K ≤ ΔT ≤ 280 K) are analysed. At low undercooling coarse grained dendritic microstructure is observed, while at higher undercoolings this dendritic feature disappears in favour of a grain refined equiaxed structure. In the latter case, the eutectic carbides are more evenly dispersed throughout the microstructure. The sample solidified in microgravity during parabolic flight experiment exhibits only a few very large grains with twinning relationship. This highlights the effect of convection on grain refinement in this system.

  8. Tourette syndrome: prediction of phenotypic variation in monozygotic twins by caudate nucleus D2 receptor binding.

    PubMed

    Wolf, S S; Jones, D W; Knable, M B; Gorey, J G; Lee, K S; Hyde, T M; Coppola, R; Weinberger, D R

    1996-08-30

    Tourette syndrome, a chronic tic disorder with autosomal dominant inheritance, exhibits considerable phenotypic variability even within monozygotic twin pairs. The origins of this variability remain unclear. Recent findings have implicated the caudate nucleus as a locus of pathology, and pharmacological evidence supports dopaminergic involvement. Within monozygotic twins discordant for Tourette syndrome severity, differences in D2 dopamine receptor binding in the head of the caudate nucleus predicted differences in phenotypic severity (r = 0.99); this relation was not observed in putamen. These data may link Tourette syndrome with a spectrum of neuropsychiatric disorders that involve associative striatal circuitry.

  9. Type 1 metabotropic glutamate receptors (mGlu1) trigger the gating of GluD2 delta glutamate receptors

    PubMed Central

    Ady, Visou; Perroy, Julie; Tricoire, Ludovic; Piochon, Claire; Dadak, Selma; Chen, Xiaoru; Dusart, Isabelle; Fagni, Laurent; Lambolez, Bertrand; Levenes, Carole

    2014-01-01

    The orphan GluD2 receptor belongs to the ionotropic glutamate receptor family but does not bind glutamate. Ligand-gated GluD2 currents have never been evidenced, and whether GluD2 operates as an ion channel has been a long-standing question. Here, we show that GluD2 gating is triggered by type 1 metabotropic glutamate receptors, both in a heterologous expression system and in Purkinje cells. Thus, GluD2 is not only an adhesion molecule at synapses but also works as a channel. This gating mechanism reveals new properties of glutamate receptors that emerge from their interaction and opens unexpected perspectives regarding synaptic transmission and plasticity. PMID:24357660

  10. Behavioral synergism between D(1) and D(2) dopamine receptors in mice does not depend on gap junctions.

    PubMed

    Nolan, Eileen B; Harrison, Laura M; Lahoste, Gerald J; Ruskin, David N

    2007-05-01

    Activation of the D(1) and D(2) classes of dopamine receptor in the striatum synergistically promotes motor stereotypy. The mechanism of D(1)/D(2) receptor interaction remains unclear. To investigate the involvement of electrical synaptic transmission in this phenomenon, genetic inactivation of the neuronal gap junction (GJ) protein connexin 36 and pharmacological blockade of GJs were utilized. Stereotyped motor behavior was quantified after selective activation of D(1) receptors, D(2) receptors, or both receptors. These patterns of activation were produced by injection of the agonist apomorphine (3.0 mg/kg) 30 min after either the D(2) antagonist eticlopride (0.3 mg/kg), the D(1) antagonist SCH 23390 (0.1 mg/kg) or vehicle, respectively. Mixed background C57/BL6-129SvEv mice homozygous or heterozygous for the connexin 36 "knockout" allele displayed potent synergistic interaction between D(1) and D(2) receptor activation, and did not differ significantly from wild-type mice on any measure. All genotypes demonstrated long-lasting stereotypic sniffing, chewing, and/or licking after simultaneous activation of D(1) and D(2) receptors, effects that were absent following selective D(1) or D(2) activation. Swiss-Webster mice treated with the GJ blockers carbenoxolone (35 mg/kg), octanol (350 mg/kg) or mefloquine (50 mg/kg) also demonstrated the normal synergistic interaction between D(1) and D(2) receptors, although these drugs did block the grooming stimulated by selective D(1) receptor activation, independently of D(2) receptors. While D(1) receptor-stimulated grooming depends on GJs composed of connexins or possibly pannexins, the synergistic interaction of D(1) and D(2) receptors in control of stereotypy does not involve GJs.

  11. 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.

  12. 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.

  13. 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.

  14. Dynamics of the Rydberg electron in H*+D2-->D*+HD reactive collisions.

    PubMed

    Hayes, Michael Y; Skodje, Rex T

    2007-03-14

    Experimental crossed-beam studies carried out previously have indicated that the dynamics of the Rydberg-atom-molecule reaction H*+D2-->D*+HD are very similar to those of the corresponding ion-molecule reaction H++D2-->D++HD. The equivalence of the cross sections for these related systems would open up a new approach to the experimental study of ion-molecule reactions. However, a recent experimental and theoretical study has brought to light some important qualitative differences between the Rydberg-atom reaction and the ion-molecule reaction; in particular, the experimental cross section for the Rydberg-atom reaction exhibits a higher degree of forward-backward scattering asymmetry than predicted by a quasiclassical trajectory study of the ion-molecule reaction. In this paper, the authors consider the dynamics of the Rydberg-electron over the course of a reactive collision and the implications of these dynamics for the Rydberg-atom-molecule crossed-beam experiment. Using an approach based on perturbation theory, they estimate the attenuation of the experimental signal due to the Rydberg-electron dynamics as a function of the scattering angle. They show that at least part of the experimental asymmetry can be ascribed to this angle dependent attenuation. Their results offer general insight into the practical aspects of the experimental study of ion-molecule reactions by means of their Rydberg-atom counterparts. PMID:17362067

  15. 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

  16. 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}.

  17. Discussion of isomeric ratios in (p, n) and (d, 2 n) reaction

    NASA Astrophysics Data System (ADS)

    Bakhshiyan, T. M.

    2016-01-01

    Isomeric ratios (IR) in the (p, n) and (d, 2 n) reactions are considered. The dependence of IR values on the projectile type and energy, the target- and product-nucleus spin, the spin difference between the isomeric and ground states of products, and the product mass number is discussed. The isomeric ratios for 46 product nuclei (from 44m,gSc to 127m,gXe) obtained in reactions where target and product nuclei have identical mass numbers were calculated at energies from the reaction threshold to 50 MeV (with a step of Δ E = 1 MeV). The calculations in question were performed with the aid of the TALYS 1.4 code package. The calculated IR values were compared with their experimental counterparts available from the literature (EXFOR database). In the majority of cases, the calculated IR values agree well with the experimental data in question. It is noteworthy that the IR values obtained in (d, 2 n) reactions are substantially greater than those in (p, n) reactions.

  18. Microstructural Evolution during DPRM Process of Semisolid Ledeburitic D2 Tool Steel

    PubMed Central

    Mohammed, M. N.; Omar, M. Z.; Syarif, J.; Sajuri, Z.; Salleh, M. S.; Alhawari, K. S.

    2013-01-01

    Semisolid metal processing is a relatively new technology that offers several advantages over liquid processing and solid processing because of the unique behaviour and characteristic microstructure of metals in this state. With the aim of finding a minimum process chain for the manufacture of high-quality production at minimal cost for forming, the microstructural evolution of the ledeburitic AISI D2 tool steel in the semisolid state was studied experimentally. The potential of the direct partial remelting (DPRM) process for the production of AISI D2 with a uniform globular microstructure was revealed. The liquid fraction was determined using differential scanning calorimetry. The microstructures of the samples were investigated using an optical microscope and a scanning electron microscope equipped with an energy dispersive spectroscopy analyser, while X-ray phase analysis was performed to identify the phase evolution and the type of carbides. Mechanical characterisation was completed by hardness measurements. The typical microstructure after DPRM consists of metastable austenite which was located particularly in the globular grains (average grain size about 50 μm), while the remaining interspaces were filled by precipitated eutectic carbides on the grain boundaries and lamellar network. PMID:24223510

  19. Alcohol dependence, family history, and D2 dopamine receptor function as neuroendocrinologically assessed with apomorphine.

    PubMed

    Wiesbeck, G A; Mauerer, C; Thome, J; Jakob, F; Boening, J

    1995-11-01

    Fifteen alcohol dependent men with an alcohol dependent first degree relative (i.e. family history positive or FHP), 15 well matched alcohol dependent men without a family history for alcohol dependence (i.e. family history negative or FHN), and 15 healthy controls (CONTR) participated in this study. The three groups were compared according to their postsynaptic D2 dopamine receptor function as assessed by growth hormone release after stimulation with the dopamine receptor agonist apomorphine. Statistical evaluation was done by planned comparisons within a one-way ANOVA. Alcohol dependent subjects significantly differed from CONTRs as long as family history was not taken into account (t(42) = 2.38; P = 0.022*). When differentiating according to family history, both FHPs and FHNs maintained a blunted growth hormone response. However, the difference between FHNs and CONTRs, though present, dropped out of statistical significance (t(42) = 1.65; P = 0.105); at the same time, the difference between FHPs and CONTRs became slightly stronger (t(42) = 2.47; p = 0.017*). In conclusion, our data give neuroendocrinological support to the assumption that a reduced D2 dopamine receptor function in alcohol dependent men is not only a state marker of residual heavy drinking but also a genetically determined trait marker.

  20. 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.

  1. The protein arginine methyltransferase PRMT5 promotes D2-like dopamine receptor signaling.

    PubMed

    Likhite, Neah; Jackson, Christopher A; Liang, Mao-Shih; Krzyzanowski, Michelle C; Lei, Pedro; Wood, Jordan F; Birkaya, Barbara; Michaels, Kerry L; Andreadis, Stelios T; Clark, Stewart D; Yu, Michael C; Ferkey, Denise M

    2015-11-10

    Protein arginine methylation regulates diverse functions of eukaryotic cells, including gene expression, the DNA damage response, and circadian rhythms. We showed that arginine residues within the third intracellular loop of the human D2 dopamine receptor, which are conserved in the DOP-3 receptor in the nematode Caenorhabditis elegans, were methylated by protein arginine methyltransferase 5 (PRMT5). By mutating these arginine residues, we further showed that their methylation enhanced the D2 receptor-mediated inhibition of cyclic adenosine monophosphate (cAMP) signaling in cultured human embryonic kidney (HEK) 293T cells. Analysis of prmt-5-deficient worms indicated that methylation promoted the dopamine-mediated modulation of chemosensory and locomotory behaviors in C. elegans through the DOP-3 receptor. In addition to delineating a previously uncharacterized means of regulating GPCR (heterotrimeric guanine nucleotide-binding protein-coupled receptor) signaling, these findings may lead to the development of a new class of pharmacological therapies that modulate GPCR signaling by changing the methylation status of these key proteins. PMID:26554819

  2. CCK2 receptor-deficient mice have increased sensitivity of dopamine D2 receptors.

    PubMed

    Kõks, S; Abramov, U; Veraksits, A; Bourin, M; Matsui, T; Vasar, E

    2003-02-01

    The present study supports a role of CCK(2) receptors in the regulation of dopamine neurones. In pharmacological studies conducted on male CCK(2) receptor-deficient mice the changes in the activity of dopamine system were established. A low dose of dopamine agonist apomorphine (0.1 mg/kg), stimulating the pre-synaptic dopamine receptors, induced significantly stronger suppression of locomotor activity in mutant mice (-/-) compared to their wild-type littermates (+/+). The administration of amphetamine (3-6 mg/kg), a drug increasing dopamine release, caused a dose-dependent stimulation of locomotor activity in wild-type mice. In mice lacking CCK(2) receptors, a lower dose of amphetamine (3 mg/kg) tended to suppress the motor activity, whereas the higher dose (6 mg/kg) induced the significantly stronger motor stimulation in mutant mice. Moreover, in the CCK(2) receptor-deficient mice the affinity of dopamine D(2) receptors, but not 5-HT(2) receptors, was increased. Altogether, the targeted genetic suppression of CCK(2) receptors increased the sensitivity of pre- and post-synaptic dopamine D(2) receptors.

  3. Active control of divertor asymmetry on EAST by localized D2 and Ar puffing

    NASA Astrophysics Data System (ADS)

    Wang, Dongsheng; Guo, Houyang; Wang, Huiqian; Luo, Guangnan; Wu, Zhenwei; Wu, Jinhua; Gao, Wei; Wang, Liang; Li, Qiang; East Team

    2011-03-01

    The divertor asymmetry in particle and power fluxes has been investigated on the EAST superconducting tokamak [S. Wu and EAST Team, Fusion Eng. Des. 82, 463 (2007)] for both single null (SN) and double null (DN) divertor configurations. D2 and Ar puffing at various divertor locations has also been explored as an active means to reduce peak target heat load and control divertor asymmetry. For SN, peak heat load on the outer divertor target is 2-3 times that on the inner divertor target under typical ohmic plasma conditions. DN operation leads to a stronger in-out asymmetry favoring the outer divertor. D2 and Ar puffing promotes partial detachment near the strike points, greatly reducing peak target heat load (over 50%), while the far-SOL divertor plasma remains attached. What is remarkable is that the particle flux is even increased away from the strike points when the B×∇B drift is directed toward the divertor target, thus facilitating particle removal.

  4. In Hamsters Dopamine D2 Receptors affect Ventilation during and following Intermittent Hypoxia

    PubMed Central

    Schlenker, Evelyn H.

    2007-01-01

    We tested the hypothesis that in golden Syrian hamsters (Mesocricetus auratus) carotid body dopaminergic D2 receptors modulate ventilation in air, during exposure to intermittent hypoxia (IH) and reoxygenation. Ventilation was evaluated using the barometric method and CO2 production was determined using the flow through method. Hamsters (n=8) received either subcutaneous injections of vehicle, haloperidol (0.5 mg/kg) or domperidone (0.5 mg/kg). Ventilatory and metabolic variables were determined 30 minutes following injections, after each of 5 bouts of 5 minutes of 10% oxygen interspersed by normoxia (IH), and 15, 30, 45 and 60 minutes following IH when hamsters were exposed to air. Haloperidol, but not domperidone decreased body temperature in hamsters. Neither treatment affected CO2 production. Vehicle-treated hamsters exhibited ventilatory long term facilitation (VLTF) following IH. Haloperidol or domperidone decreased ventilation in air, during IH and eliminated VLTF due to changes in tidal volume and not frequency of breathing. Thus, in hamsters D2 receptors are involved in control of body temperature and ventilation during and following IH PMID:17884646

  5. High affinity dopamine D2 receptor radioligands. 1. Regional rat brain distribution of iodinated benzamides

    SciTech Connect

    Kessler, R.M.; Ansari, M.S.; de Paulis, T.; Schmidt, D.E.; Clanton, J.A.; Smith, H.E.; Manning, R.G.; Gillespie, D.; Ebert, M.H. )

    1991-08-01

    Five 125I-labeled substituted benzamides, which are close structural analogues of (S)-sulpiride, eticlopride, and isoremoxipride, were evaluated for their selective in vivo uptake into dopamine D2 receptor rich tissue of the rat brain. Iodopride (KD 0.88 nM), an iodine substituted benzamide structurally related to sulpiride, displayed a maximal striatum: cerebellar uptake ratio of 7.6. Demonstration of saturation of the receptor with (125I)iodopride in striatum required uptake in frontal cortex to be used, rather than cerebellar uptake, to define nonspecific binding. Two other ligands structurally related to eticlopride, iclopride (KD 0.23 nM) and itopride (KD 0.16 nM), displayed maximal striatal: cerebellar uptake ratios of 9.8 and 3.3, respectively. The most potent ligands, epidepride (KD 0.057 nM) and ioxipride (KD 0.070 nM) showed striatal:cerebellar uptake ratios of 234 and 65, respectively. The observed uptake ratios correlated poorly with the affinity constants for the dopamine D2 receptor alone, but were highly correlated (r = 0.92) with the product of the receptor dissociation constant (KD) and the apparent lipophilicity (kw), as determined by reverse-phase HPLC at pH 7.5. Total striatal uptake also appeared dependent on lipophilicity, with maximal uptake occurring for ligands having log kw 2.4-2.8.

  6. 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. PMID:25759299

  7. Overtone spectroscopy of H2D+ and D2H+ using laser induced reactions

    NASA Astrophysics Data System (ADS)

    Asvany, Oskar; Hugo, Edouard; Müller, Frank; Kühnemann, Frank; Schiller, Stephan; Tennyson, Jonathan; Schlemmer, Stephan

    2007-10-01

    The method of laser induced reaction is used to obtain high-resolution IR spectra of H2D+ and D2H+ in collision with n-H2 at a nominal temperature of 17K. For this purpose three cw-laser systems have been coupled to a 22-pole ion trap apparatus, two commercial diode laser systems in the ranges of 6100-6600cm-1 and 6760-7300cm-1, respectively, and a high-power optical parametric oscillator tunable in the range of 2600-3200cm-1. In total, 27 new overtone and combination transitions have been detected for H2D + and D2H+, as well as a weak line in the ν1 vibrational band of H2D+ (220←101) at 3164.118cm-1. The line positions are compared to high accuracy ab initio calculations, showing small but mode-dependent differences, being largest for three vibrational quanta in the ν2 symmetric bending of H2D+. Within the experimental accuracy, the relative values of the ab initio predicted Einstein B coefficients are confirmed.

  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. Rotational Tunneling of CH2D2 Monolayers on MgO(100)

    NASA Astrophysics Data System (ADS)

    Hicks, Andrew; Larese, John

    2013-03-01

    Understanding the detailed nature of the interactions governing physisorption is a central topic in surface science, with wide ranging energy applications in heterogeneous catalysis, gas separation, and hydrogen storage. For systems with a strong interaction potential relative to the rotational constant of the adsorbate, adsorbed molecules are constrained to minima in the rotational potential. Adsorbed molecules may then tunnel through the rotational barrier between potential minima. Rotational tunneling spectra (RTS) are extremely sensitive to changes in the symmetry and strength of the rotational potential and are unmatched in their ability to probe the electrostatic potentials associated with adsorption sites. Furthermore, RTS can be clearly observed using inelastic neutron scattering. Building upon previous work of CH4 on MgO (see J.Z. Larese, Physica B, 1998), RTS of CH3D and CH2D2 are interpreted using the pocket state (PS) formalism developed by Hüller et al. The ground librational state of the adsorbate is split into twelve ``pockets'', each localized around one of twelve minima in the rotational potential. We report recent RTS of single monolayers of CH3D and CH2D2 adsorbed on the MgO(100) surface using BASIS at the SNS at ORNL. These pioneering measurements represent the highest resolution investigation available for this (or any other) RTS. The discussion will include challenges in reconciling the transitions predicted by PS theory and the features observed in the experimental data.

  10. 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.

  11. Risk-taking behavior: dopamine D2/D3 receptors, feedback, and frontolimbic activity.

    PubMed

    Kohno, Milky; Ghahremani, Dara G; Morales, Angelica M; Robertson, Chelsea L; Ishibashi, Kenji; Morgan, Andrew T; Mandelkern, Mark A; London, Edythe D

    2015-01-01

    Decision-making involves frontolimbic and dopaminergic brain regions, but how prior choice outcomes, dopamine neurotransmission, and frontostriatal activity are integrated to affect choices is unclear. We tested 60 healthy volunteers using the Balloon Analogue Risk Task (BART) during functional magnetic resonance imaging. In the BART, participants can pump virtual balloons to increase potential monetary reward or cash out to receive accumulated reward; each pump presents greater risk and potential reward (represented by the pump number). In a separate session, we measured striatal D2/D3 dopamine receptor binding potential (BPND) with positron emission tomography in 13 of the participants. Losses were followed by fewer risky choices than wins; and during risk-taking after loss, amygdala and hippocampal activation exhibited greater modulation by pump number than after a cash-out event. Striatal D2/D3 BPND was positively related to the modulation of ventral striatal activation when participants decided to cash out and negatively to the number of pumps in the subsequent trial; but negatively related to the modulation of prefrontal cortical activation by pump number when participants took risk, and to overall earnings. These findings provide in vivo evidence for a potential mechanism by which dopaminergic neurotransmission may modulate risk-taking behavior through an interactive system of frontal and striatal activity. PMID:23966584

  12. The infrared spectrum of the He-C2D2 complex.

    PubMed

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

    2015-02-28

    Spectra of the helium-acetylene complex are elusive because this weakly bound system lies close to the free rotor limit. Previously, limited assignments of He-C2D2 transitions in the R(0) region of the ν3 fundamental band (≈2440 cm(-1)) were published. Here, new He-C2D2 infrared spectra of this band are obtained using a tunable optical parametric oscillator laser source to probe a pulsed supersonic slit jet expansion from a cooled nozzle, and the analysis is extended to the weaker and more difficult P(1) and R(1) regions. A term value approach is used to obtain a consistent set of "experimental" energy levels. These are compared directly with calculations using two recently reported ab initio intermolecular potential energy surfaces, which exhibit small but significant differences. Rovibrational energies for the He-C2H2 complex are also calculated using both surfaces. A Coriolis model, useful for predicting spectral intensities, is used to interpret the energy level patterns, and a comparison with the isoelectronic complex He-CO is made.

  13. Study on the morphology and properties of carburized and austempered microstructures in 430 D2 steel

    SciTech Connect

    Xinggui, W.; Suidong, Z.; Xin, C.; Chuenmei, L.; Liming, X.

    1995-12-31

    By means of carburizing and quenching, a high hard case can be produced in the surface of tool steel, but the brittleness of the case has limited its application in practice. In this paper, structure, composition and properties of the case and core carburized followed by austempering in 430D2 steel was studied. As the result of austempering, the optimum combination of strength and ductility of the carburized case has been achieved. There was no M3C phase in carburized case, indicating that the composition point of the carburized case lies in the M7C3 + Austenite quarter-phase field. In the isothermal period above Ms, lower bainite formed in the core structure, while a needle-like structure without carbides emerged in the outside case after a longer isothermal time. This dark needle-like structure seemed to be the isothermal martensite, which appeared to be dark since it was tempered in the following isothermal process. This tempered isotherm martensite probably improved the toughness and ductility of the carburized case; on the other hand, a large quantity of fine carbide formed in carburizing increased the wear resistance of the die steel and remedied the defect of heterogeneity of carbides in 430 D2 steel.

  14. 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. PMID:24983674

  15. 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

  16. Differential effects of oxycodone, hydrocodone, and morphine on the responses of D2/D3 dopamine receptors.

    PubMed

    Emery, Michael A; Bates, M L Shawn; Wellman, Paul J; Eitan, Shoshana

    2015-05-01

    Oxycodone and hydrocodone are opioids which are widely used for pain management and are also commonly misused and abused. The exposure to opioid analgesics has been associated with altered responses of D2-like dopamine receptors (D2DRs). Our recent results suggest that various opioids will differentially modulate the responses of D2DRs. The D2DRs are known to be involved in the pathology of addiction and other mental illnesses, indicating the need to improve our understanding of the effects of opioid analgesics on the responses of the D2DRs. Thus, in this study, we first established equianalgesic oral doses of oxycodone, hydrocodone, and morphine using the tail withdrawal assay. Then, mice were orally administered (gavage) with the various opioids or saline once daily for 6 days. Twenty-four hours later, the mice were tested for their locomotor response to quinpirole, a D2/D3 dopamine receptor agonist. Mice pretreated with oxycodone showed significantly greater locomotor supersensitivity to quinpirole than did morphine-pretreated mice, while hydrocodone-pretreated mice showed sensitivity in between that of mice treated with morphine and oxycodone. This finding suggests that various opioids differentially modulate the responses of D2DRs. It provides further evidence supporting of the notion that various opioids carry differential risks to the dopamine reward system. PMID:25617530

  17. Rice CYP90D2 and CYP90D3 catalyze C-23 hydroxylation of brassinosteroids in vitro.

    PubMed

    Sakamoto, Tomoaki; Ohnishi, Toshiyuki; Fujioka, Shozo; Watanabe, Bunta; Mizutani, Masaharu

    2012-09-01

    Brassinosteroids are biosynthesized from campesterol via several cytochrome P450 (P450)-catalyzed oxidative reactions. We report the biochemical characterization of two brassinosteroid-biosynthetic P450s from rice: CYP90D2 and CYP90D3. A rice dwarf mutant, ebisu dwarf (d2), which contains a defective copy of CYP90D2, is known to be a brassinosteroid-deficient mutant, and CYP90D2 has been considered to act as a C-3 dehydrogenase. However, in vitro biochemical assays using baculovirus/insect cell-produced proteins revealed that both CYP90D2 and CYP90D3 catalyze C-23 hydroxylation of various 22-hydroxylated brassinosteroids, but with markedly different catalytic efficiencies. Both enzymes preferentially convert (22S,24R)-22-hydroxyergost-4-en-3-one, (22S,24R)-22-hydroxy-5α-ergostan-3-one, and 3-epi-6-deoxocathasterone to the corresponding 23-hydroxylated products, but are less active in the conversion of (22S)-22-hydroxycampesterol and 6-deoxocathasterone, in vitro. Consistently, the levels of 23-hydroxylated products of these intermediates, namely, 6-deoxoteasterone, 3-dehydro-6-deoxoteasterone, and 6-deoxotyphasterol were decreased in d2 mutants. These results indicate that CYP90D2 and CYP90D3 can act as brassinosteroid C-23 hydroxylases in rice.

  18. 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.

  19. 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

  20. Socioeconomic status is associated with striatal dopamine D2/D3 receptors in healthy volunteers but not in cocaine abusers.

    PubMed

    Wiers, Corinde E; Shokri-Kojori, Ehsan; Cabrera, Elizabeth; Cunningham, Samantha; Wong, Christopher; Tomasi, Dardo; Wang, Gene-Jack; Volkow, Nora D

    2016-03-23

    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 [(11)C]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≤0.001). Despite matching groups for education, SES scores were lower in cocaine abusers than controls (p<0.001). In the control group only, SES scores significantly correlated with D2/D3R in caudate (r=0.35, p=0.024) and putamen (r=0.39, p=0.011) but not in ventral striatum (p=0.61); 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

  1. D2 antagonist during development decreases anxiety and infanticidal behavior in adult female prairie voles (Microtus ochrogaster).

    PubMed

    Hostetler, Caroline M; Harkey, Shanna L; Bales, Karen L

    2010-06-26

    On postnatal day 8, prairie vole pups were randomly assigned a treatment of 1mg/kg SKF38393 (D1 agonist), quinpirole (D2 agonist), SCH23390 (D1 antagonist), eticlopride (D2 antagonist), or saline vehicle. As adults, females treated with eticlopride exhibited reduced anxiety-like behavior in an elevated plus maze and a reduction in infanticidal behavior. These behavioral effects were not seen in males. These data demonstrate that a single exposure to a D2 antagonist during development can have persistent, sex-specific effects on behavior into adulthood. PMID:20152865

  2. Salmonella Disrupts Host Endocytic Trafficking by SopD2-Mediated Inhibition of Rab7.

    PubMed

    D'Costa, Vanessa M; Braun, Virginie; Landekic, Marija; Shi, Rong; Proteau, Ariane; McDonald, Laura; Cygler, Miroslaw; Grinstein, Sergio; Brumell, John H

    2015-09-01

    Intracellular bacterial pathogens of a diverse nature share the ability to evade host immunity by impairing trafficking of endocytic cargo to lysosomes for degradation, a process that is poorly understood. Here, we show that the Salmonella enterica type 3 secreted effector SopD2 mediates this process by binding the host regulatory GTPase Rab7 and inhibiting its nucleotide exchange. Consequently, this limits Rab7 interaction with its dynein- and kinesin-binding effectors RILP and FYCO1 and thereby disrupts host-driven regulation of microtubule motors. Our study identifies a bacterial effector capable of directly binding and thereby modulating Rab7 activity and a mechanism of endocytic trafficking disruption that may provide insight into the pathogenesis of other bacteria. Additionally, we provide a powerful tool for the study of Rab7 function, and a potential therapeutic target. PMID:26299973

  3. 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).

  4. 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.

  5. 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).

  6. 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.

  7. 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.

  8. Dopamine D2 Receptor-Mediated Regulation of Pancreatic β Cell Mass.

    PubMed

    Sakano, Daisuke; Choi, Sungik; Kataoka, Masateru; Shiraki, Nobuaki; Uesugi, Motonari; Kume, Kazuhiko; Kume, Shoen

    2016-07-12

    Understanding the molecular mechanisms that regulate β cell mass and proliferation is important for the treatment of diabetes. Here, we identified domperidone (DPD), a dopamine D2 receptor (DRD2) antagonist that enhances β cell mass. Over time, islet β cell loss occurs in dissociation cultures, and this was inhibited by DPD. DPD increased proliferation and decreased apoptosis of β cells through increasing intracellular cAMP. DPD prevented β cell dedifferentiation, which together highly contributed to the increased β cell mass. DRD2 knockdown phenocopied the effects of domperidone and increased the number of β cells. Drd2 overexpression sensitized the dopamine responsiveness of β cells and increased apoptosis. Further analysis revealed that the adenosine agonist 5'-N-ethylcarboxamidoadenosine, a previously identified promoter of β cell proliferation, acted with DPD to increase the number of β cells. In humans, dopamine also modulates β cell mass through DRD2 and exerts an inhibitory effect on adenosine signaling. PMID:27373926

  9. On thin evaporating drops: when is the d2-law valid?

    NASA Astrophysics Data System (ADS)

    Saxton, Matthew; Whiteley, Jonathan; Vella, Dominic; Oliver, James

    2015-11-01

    We study the evolution of a thin, axisymmetric, partially wetting drop as it evaporates. The stress singularity at the contact line is regularized using slip and we perform a matched-asymptotic analysis in the limit of small slip. A generalization of Tanner's law to account for the effect of mass transfer is derived and the behaviour of the drop close to extinction is analysed. We find a criterion for when the contact-set radius close to extinction evolves as the square-root of the time remaining until extinction--the famous d2-law. However, for a sufficiently large rate of evaporation, our analysis predicts that a `d 13 / 7-law' should be more appropriate. Our asymptotic results are validated by comparison with numerical simulations.

  10. 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.

  11. A velocity-dependent anomalous radial transport model for (2-D, 2-V) kinetic transport codes

    NASA Astrophysics Data System (ADS)

    Bodi, Kowsik; Krasheninnikov, Sergei; Cohen, Ron; Rognlien, Tom

    2008-11-01

    Plasma turbulence constitutes a significant part of radial plasma transport in magnetically confined plasmas. This turbulent transport is modeled in the form of anomalous convection and diffusion coefficients in fluid transport codes. There is a need to model the same in continuum kinetic edge codes [such as the (2-D, 2-V) transport version of TEMPEST, NEO, and the code being developed by the Edge Simulation Laboratory] with non-Maxwellian distributions. We present an anomalous transport model with velocity-dependent convection and diffusion coefficients leading to a diagonal transport matrix similar to that used in contemporary fluid transport models (e.g., UEDGE). Also presented are results of simulations corresponding to radial transport due to long-wavelength ExB turbulence using a velocity-independent diffusion coefficient. A BGK collision model is used to enable comparison with fluid transport codes.

  12. 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.-

  13. 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.

  14. High resolution infrared spectra of H2-Kr and D2-Kr van der Waals complexes.

    PubMed

    McKellar, A R W

    2005-02-22

    Infrared spectra of weakly bound hydrogen-krypton complexes have been studied at high spectral resolution (0.04 cm(-1)) using a long-path (154 m) low temperature (100 K) absorption cell and a Fourier transform spectrometer. In addition to spectra from the regions of the H(2) and D(2) fundamental vibrational bands in the midinfrared, the results also include the region of the pure rotational S(0)(0) transition of H(2) in the far infrared. A total of 219 measured line positions from these spectra have been fully assigned to specific quantum transitions and form the basis for determining a greatly improved semiempirical three-dimensional intermolecular potential energy surface for hydrogen-krypton in an accompanying paper.

  15. The photoinduced birefringence and mass transport in azo compound K-D-2

    NASA Astrophysics Data System (ADS)

    Klismeta, K.; Teteris, J.

    2015-06-01

    Azobenzene containing compounds are among light polarization sensitive materials - the moieties may align relative to the electric field vector of light, leading to anisotropy and birefringence in the sample. Another phenomenon which can be observed in azo compounds under influence of light is macroscopic movement of the material. In this work photoinduced processes in low molecular weight organic glass - bis-azobenzene containing compound K-D-2 were experimentally studied. Birefringence was induced with linearly polarized laser light (473, 532 and 635 nm) and measured at 633 nm wavelength. Polarization holography with recording beam configuration +45°/-45° was used to induce mass motion. Dependence of the surface relief depth on the recording laser wavelength in the visible spectrum (375 - 671 nm) was obtained. Formation of the SRG was observed with all used wavelengths and high birefringence values were obtained. Certain correlation between the absorption of the wavelength and photoinduced mass transport and birefringence is yet to be confirmed.

  16. Endothermic reactions of Ni + with H 2, HD and D 2

    NASA Astrophysics Data System (ADS)

    Armentrout, P. B.; Beauchamp, J. L.

    1980-08-01

    An ion-beam apparatus is employed to study the reaction of Ni + with H 2, HD, and D 2 as a function of kinetic energy. These reactions lead to the endothermic formation of NiH +, NiH + and NiD +, and NiD +, respectively. Interpretation of the threshold for these processes yields the average bond energies, D0(Ni +H) = 1.86 ± 0.09 eV and D0(Ni +D) = 1.90 ± 0.14 eV. The total reaction cross sections for all three systems are similar; however, a striking isotope effect is observed for Ni + reacting with HD. The dependence of the cross sections on relative kinetic energy is discussed in terms of simple models for reaction.

  17. Controlling the formation of excited neutral D* fragments of D2 using intense ultrashort laser pulses

    NASA Astrophysics Data System (ADS)

    Feizollah, Peyman; Berry, Ben; Severt, T.; Jochim, Bethany; Zohrabi, M.; Kanaka Raju, P.; Rajput, Jyoti; Carnes, K. D.; Esry, B. D.; Ben-Itzhak, I.

    2016-05-01

    Excited neutral D* fragments (n >> 1) are produced by the interaction of strong-field laser pulses with D2 molecules. In this work, we focus on the formation of low kinetic energy release (KER) D* fragments, which are relatively unstudied, using NIR (800-nm) and UV (400-nm) laser pulses. The KER spectrum is found to be very sensitive to the laser parameters, including laser chirp. By changing the chirp of the UV laser pulses, two separate low-KER peaks are generated instead of a single peak. Moreover, the ratio between these peaks can be controlled with the chirp. Similarly, by chirping the NIR pulses, the low-KER peak is attenuated and shifted to lower energy. This work was supported by the Chemical Sciences, Geosciences, and Biosciences Division, Office of Basic Energy Sciences, Office of Science, U. S. Department of Energy. BJ was also supported in part by DOE-SCGF (DE-AC05-06OR23100).

  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. On the neutron scattering length density of proteins in H2O/D2O

    NASA Astrophysics Data System (ADS)

    Efimova, Y. M.; van Well, A. A.; Hanefeld, U.; Wierczinski, B.; Bouwman, W. G.

    2004-07-01

    The structure of the protein layers adsorbed at different interfaces can be determined by using neutron-reflection and small-angle neutron scattering. For highlighting the adsorbed protein layer at the interface, the technique of contrast-variation by changing the H2O/D2O ratio, is often used. For determining the scattering length density, both the protein volume in solution and the total scattering length of the protein is needed. The volume is calculated from the amino-acid sequence. For calculating the scattering length, the H/D exchange of the labile protons of the protein should be taken into account. For monitoring the H/D exchange, Positive Electrospray Ionization Mass Spectroscopy was applied. We compare experimental results for the exchange in lysozyme and β-casein with theoretical calculations. The importance of using the correct protein scattering-length density is elucidated by simultaneous model fitting to neutron reflection data at different water contrasts.

  20. Tomo3D 2.0--exploitation of advanced vector extensions (AVX) for 3D reconstruction.

    PubMed

    Agulleiro, Jose-Ignacio; Fernandez, Jose-Jesus

    2015-02-01

    Tomo3D is a program for fast tomographic reconstruction on multicore computers. Its high speed stems from code optimization, vectorization with Streaming SIMD Extensions (SSE), multithreading and optimization of disk access. Recently, Advanced Vector eXtensions (AVX) have been introduced in the x86 processor architecture. Compared to SSE, AVX double the number of simultaneous operations, thus pointing to a potential twofold gain in speed. However, in practice, achieving this potential is extremely difficult. Here, we provide a technical description and an assessment of the optimizations included in Tomo3D to take advantage of AVX instructions. Tomo3D 2.0 allows huge reconstructions to be calculated in standard computers in a matter of minutes. Thus, it will be a valuable tool for electron tomography studies with increasing resolution needs. PMID:25528570

  1. Vibrational Anylasis on I(H{_2}O){^-} and I(D{_2}O){^-} Spectra

    NASA Astrophysics Data System (ADS)

    Huang, Meng; McCoy, Anne B.

    2013-06-01

    Hydrated halide clusters provide good systems for investigating the effect of the intramolecular hydrogen-bond on the spectrum of ions and molecules. In this work, the vibrational spectra of I(H{_2}O){^-} and I(D{_2}O){^-} were studied. We focused on the couplings between the two O-H stretch modes and the in-plane bending mode, which is the frustrated rotation of the water molecule in the plane of the complex. A reduced-dimensional analysis with these three modes was developed to investigate the effect of the couplings on the spectra. The model potential in the analysis was obtained from ab initio calculation with MP2/aug-cc-pVTZ-PP level of method and basis set. The doublet structure of the O-H stretch mode in the spectrum was attributed to the tunneling splitting from the in-plane bending mode double-well potential energy surface.

  2. Salmonella Disrupts Host Endocytic Trafficking by SopD2-Mediated Inhibition of Rab7.

    PubMed

    D'Costa, Vanessa M; Braun, Virginie; Landekic, Marija; Shi, Rong; Proteau, Ariane; McDonald, Laura; Cygler, Miroslaw; Grinstein, Sergio; Brumell, John H

    2015-09-01

    Intracellular bacterial pathogens of a diverse nature share the ability to evade host immunity by impairing trafficking of endocytic cargo to lysosomes for degradation, a process that is poorly understood. Here, we show that the Salmonella enterica type 3 secreted effector SopD2 mediates this process by binding the host regulatory GTPase Rab7 and inhibiting its nucleotide exchange. Consequently, this limits Rab7 interaction with its dynein- and kinesin-binding effectors RILP and FYCO1 and thereby disrupts host-driven regulation of microtubule motors. Our study identifies a bacterial effector capable of directly binding and thereby modulating Rab7 activity and a mechanism of endocytic trafficking disruption that may provide insight into the pathogenesis of other bacteria. Additionally, we provide a powerful tool for the study of Rab7 function, and a potential therapeutic target.

  3. Quantum interference between H + D2 quasiclassical reaction mechanisms

    NASA Astrophysics Data System (ADS)

    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.

  4. 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.

  5. Search on a hypercubic lattice using a quantum random walk. I. d>2

    SciTech Connect

    Patel, Apoorva; Rahaman, Md. Aminoor

    2010-09-15

    Random walks describe diffusion processes, where movement at every time step is restricted to only the neighboring locations. We construct a quantum random walk algorithm, based on discretization of the Dirac evolution operator inspired by staggered lattice fermions. We use it to investigate the spatial search problem, that is, to find a marked vertex on a d-dimensional hypercubic lattice. The restriction on movement hardly matters for d>2, and scaling behavior close to Grover's optimal algorithm (which has no restriction on movement) can be achieved. Using numerical simulations, we optimize the proportionality constants of the scaling behavior, and demonstrate the approach to that for Grover's algorithm (equivalent to the mean-field theory or the d{yields}{infinity} limit). In particular, the scaling behavior for d=3 is only about 25% higher than the optimal d{yields}{infinity} value.

  6. Highly efficient D2 generation by dehydrogenation of formic acid in D2O through H+/D+ exchange on an iridium catalyst: application to the synthesis of deuterated compounds by transfer deuterogenation.

    PubMed

    Wang, Wan-Hui; Hull, Jonathan F; Muckerman, James T; Fujita, Etsuko; Hirose, Takuji; Himeda, Yuichiro

    2012-07-23

    Deuterated compounds have received increasing attention in both academia and industrial fields. However, preparations of these compounds are limited for both economic and practical reasons. Herein, convenient generation of deuterium gas (D(2)) and the preparation of deuterated compounds on a laboratory scale are demonstrated by using a half-sandwich iridium complex with 4,4'-dihydroxy-2,2'-bipyridine. The "umpolung" (i.e., reversal of polarity) of a hydrogen atom of water was achieved in consecutive reactions, that is, a cationic H(+)/D(+) exchange reaction and anionic hydride or deuteride transfer, under mild conditions. Selective D(2) evolution (purity up to 89 %) was achieved by using HCO(2)H as an electron source and D(2)O as a deuterium source; a rhodium analogue provided HD gas (98 %) under similar conditions. Furthermore, pressurized D(2) (98 %) without CO gas was generated by using DCO(2)D in D(2)O in a glass autoclave. Transfer deuterogenation of ketones gave α-deuterated alcohols with almost quantitative yields and high deuterium content by using HCO(2)H in D(2)O. Mechanistic studies show that the H(+)/D(+) exchange reaction in the iridium hydride complex was much faster than β-elimination and hydride (deuteride) transfer. PMID:22718518

  7. 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.

  8. 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

  9. Working memory span capacity improved by a D2 but not D1 receptor family agonist.

    PubMed

    Tarantino, Isadore S; Sharp, Richard F; Geyer, Mark A; Meves, Jessica M; Young, Jared W

    2011-06-01

    Patients with schizophrenia exhibit poor working memory (WM). Although several subcomponents of WM can be measured, evidence suggests the primary subcomponent affected in schizophrenia is span capacity (WMC). Indeed, the NIMH-funded MATRICS initiative recommended assaying the WMC when assessing the efficacy of a putative therapeutic for FDA approval. Although dopamine D1 receptor agonists improve delay-dependent memory in animals, evidence for improvements in WMC due to dopamine D1 receptor activation is limited. In contrast, the dopamine D2-family agonist bromocriptine improves WMC in humans. The radial arm maze (RAM) can be used to assess WMC, although complications due to ceiling effects or strategy confounds have limited its use. We describe a 12-arm RAM protocol designed to assess whether the dopamine D1-family agonist SKF 38393 (0, 1, 3, and 10 mg/kg) or bromocriptine (0, 1, 3, and 10 mg/kg) could improve WMC in C57BL/6N mice (n=12) in cross-over designs. WMC increased and strategy usage decreased with training. The dopamine D1 agonist SKF 38393 had no effect on WMC or long-term memory. Bromocriptine decreased WMC errors, without affecting long-term memory, consistent with human studies. These data confirm that WMC can be measured in mice and reveal drug effects that are consistent with reported effects in humans. Future research is warranted to identify the subtype of the D2-family of receptors responsible for the observed improvement in WMC. Finally, this RAM procedure may prove useful in developing animal models of deficient WMC to further assess putative treatments for the cognitive deficits in schizophrenia. PMID:21232557

  10. 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

  11. 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

  12. STS-55 German payload specialists and backups pose in front of SL-D2 at KSC

    NASA Technical Reports Server (NTRS)

    1992-01-01

    STS-55 Columbia, Orbiter Vehicle (OV) 102, German payload specialists and backup (alternate) payload specialists pose in front of the Spacelab Deutsche 2 (SL-D2) science module at a Kennedy Space Center (KSC) processing facility. These four Germans have been assigned to support the STS-55/SL-D2 mission. Left to right are Payload Specialist 2 Hans Schlegel, backup Payload Specialist Dr. P. Gerhard Thiele (kneeling), Payload Specialist 1 Ulrich Walter, and backup Payload Specialist Renate Brummer. Walter and Schlegel are scheduled to fly aboard OV-102 for the mission while Brummer and Thiele will serve as alternates and fill supportive roles on the ground. Clearly visible on the SL-D2 module are the European Space Agency (ESA) insignia, the feedthrough plate, and the D2 insignia.

  13. Standardization of D2 lymphadenectomy and surgical quality control (KLASS-02-QC): a prospective, observational, multicenter study [NCT01283893

    PubMed Central

    2014-01-01

    Background Extended systemic lymphadenectomy (D2) is standard procedure for surgical treatment of advanced gastric cancer (AGC) although less extensive lymphadenectomy (D1) can be applied to early gastric cancer. Complete D2 lymphadenectomy is the mandatory procedure for studies that evaluate surgical treatment results of AGC. However, the actual extent of D2 lymphadenectomy varies among surgeons because of a lacking consensus on the anatomical definition of each lymph node station. This study is aimed to develop a consensus for D2 lymphadenectomy and also to qualify surgeons that can perform both laparoscopic and open D2 gastrectomy. Methods/Design This (KLASS-02-QC) is a prospective, observational, multicenter study to qualify the surgeons that will participate in the KLASS-02-RCT, which is a prospective, randomized, clinical trial comparing laparoscopic and open gastrectomy for AGC. Surgeons and reviewers participating in the study will be required to complete a questionnaire detailing their professional experience and specific gastrectomy surgical background/training, and the gastrectomy metrics of their primary hospitals. All surgeons must submit three laparoscopic and three open D2 gastrectomy videos, respectively. Each video will be allocated to five peer reviewers; thus each surgeon’s operations will be assessed by a total of 30 reviews. Based on blinded assessment of unedited videos by experts’ review, a separate review evaluation committee will decide whether or not the evaluated surgeon will participate in the KLASS-02-RCT. The primary outcome measure is each surgeon’s proficiency, as assessed by the reviewers based on evaluation criteria for completeness of D2 lymphadenectomy. Discussion We believe that our study for standardization of D2 lymphadenectomy and surgical quality control (KLASS-02-QC) will guarantee successful implementation of the subsequent KLASS-02-RCT study. After making consensus on D2 lymphadenectomy, we developed evaluation

  14. PET imaging of dopamine D2 receptor and transporter availability during acquisition of cocaine self-administration in rhesus monkeys.

    PubMed

    Czoty, Paul W; Gage, H Donald; Nader, Susan H; Reboussin, Beth A; Bounds, Michael; Nader, Michael A

    2007-03-01

    Previous studies have demonstrated that cocaine use alters availability of brain dopamine D2 receptors (D2R) and transporters (DAT). The present study examined the effects of low doses of cocaine on this neuroadaptation. Using positron emission tomography (PET), D2R and DAT availability in the caudate nucleus (Cd), putamen (Pt), anterior cingulate cortex (ACC), and amygdala (AMY) were assessed before and after monkeys acquired cocaine self-administration. Twelve rhesus monkeys were trained to self-administer intravenous cocaine (0.03 mg/kg per injection) under conditions that resulted in low drug intakes. PET scans using radiotracers targeting D2R ([F]fluoroclebopride, FCP) or DAT ([F]-(+)-N-(4-fluorobenzyl)-2β-propanoyl-3β-(4-chlorophenyl)tropane, FCT) were performed when monkeys were cocaine naive and after 9 weeks of self-administration. Before self-administration, D2R availability was significantly higher only in left vs. right Cd, whereas DAT availability was higher in left vs. right Cd, Pt, and ACC. Nonetheless, after cocaine exposure, left-right differences in D2R were apparent in 3 of 4 regions, but only in the ACC for DAT availability. Self-administration of this dose of cocaine did not significantly affect DAT availability in any region and only decreased D2R availability in the ACC. These results demonstrate lateralization of D2R and DAT availability in brain areas that mediate cocaine self-administration, even under conditions in which cocaine does not affect overall receptor availability. PMID:21768930

  15. 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.

  16. Striatal D1- and D2-type dopamine receptors are linked to motor response inhibition in human subjects.

    PubMed

    Robertson, Chelsea L; Ishibashi, Kenji; Mandelkern, Mark A; Brown, Amira K; Ghahremani, Dara G; Sabb, Fred; Bilder, Robert; Cannon, Tyrone; Borg, Jacqueline; London, Edythe D

    2015-04-15

    Motor response inhibition is mediated by neural circuits involving dopaminergic transmission; however, the relative contributions of dopaminergic signaling via D1- and D2-type receptors are unclear. Although evidence supports dissociable contributions of D1- and D2-type receptors to response inhibition in rats and associations of D2-type receptors to response inhibition in humans, the relationship between D1-type receptors and response inhibition has not been evaluated in humans. Here, we tested whether individual differences in striatal D1- and D2-type receptors are related to response inhibition in human subjects, possibly in opposing ways. Thirty-one volunteers participated. Response inhibition was indexed by stop-signal reaction time on the stop-signal task and commission errors on the continuous performance task, and tested for association with striatal D1- and D2-type receptor availability [binding potential referred to nondisplaceable uptake (BPND)], measured using positron emission tomography with [(11)C]NNC-112 and [(18)F]fallypride, respectively. Stop-signal reaction time was negatively correlated with D1- and D2-type BPND in whole striatum, with significant relationships involving the dorsal striatum, but not the ventral striatum, and no significant correlations involving the continuous performance task. The results indicate that dopamine D1- and D2-type receptors are associated with response inhibition, and identify the dorsal striatum as an important locus of dopaminergic control in stopping. Moreover, the similar contribution of both receptor subtypes suggests the importance of a relative balance between phasic and tonic dopaminergic activity subserved by D1- and D2-type receptors, respectively, in support of response inhibition. The results also suggest that the stop-signal task and the continuous performance task use different neurochemical mechanisms subserving motor response inhibition. PMID:25878272

  17. Properties of the B+-H2 and B+-D2 complexes: A theoretical and spectroscopic study

    NASA Astrophysics Data System (ADS)

    Poad, B. L. J.; Dryza, V.; Buchachenko, A. A.; Kłos, J.; Bieske, E. J.

    2012-09-01

    The rotationally resolved infrared spectrum of the B+-D2 ion-neutral complex is recorded in the D-D stretch vibration region (2805-2875 cm-1) by detecting B+ photofragments. Analysis of the spectrum confirms a T-shaped equilibrium geometry for the B+-D2 complex with a vibrationally averaged intermolecular bond length of 2.247 Å, around 0.02 Å shorter than for the previously characterised B+-H2 complex [V. Dryza, B. L. J. Poad, and E. J. Bieske, J. Am. Chem. Soc. 130, 12986 (2008), 10.1021/ja8018302]. The D-D stretch band centre occurs at 2839.76 ± 0.10 cm-1, representing a -153.8 cm-1 shift from the Q1(0) transition of the free D2 molecule. A new three dimensional ab initio potential energy surface for the B++H2 interaction is calculated using the coupled cluster RCCSD(T) method and is used in variational calculations for the rovibrational energies of B+-H2 and B+-D2. The calculations predict dissociation energies of 1254 cm-1 for B+-H2 with respect to the B++H2 (j = 0) limit, and 1313 cm-1 for B+-D2 with respect to the B++D2 (j = 0) limit. The theoretical approach reproduces the rotational and centrifugal constants of the B+-H2 and B+-D2 complexes to within 3%, and the magnitude of the contraction of the intermolecular bond accompanying excitation of the H2 or D2 sub-unit, but underestimates the H-H and D-D vibrational band shifts by 7%-8%. Combining the theoretical and experimental results allows a new, more accurate estimation for the B+-H2 band origin (3939.64 ± 0.10 cm-1).

  18. Coding the direct/indirect pathways by D1 and D2 receptors is not valid for accumbens projections.

    PubMed

    Kupchik, Yonatan M; Brown, Robyn M; Heinsbroek, Jasper A; Lobo, Mary Kay; Schwartz, Danielle J; Kalivas, Peter W

    2015-09-01

    It is widely accepted that D1 dopamine receptor-expressing striatal neurons convey their information directly to the output nuclei of the basal ganglia, whereas D2-expressing neurons do so indirectly via pallidal neurons. Combining optogenetics and electrophysiology, we found that this architecture does not apply to mouse nucleus accumbens projections to the ventral pallidum. Thus, current thinking attributing D1 and D2 selectivity to accumbens projections akin to dorsal striatal pathways needs to be reconsidered.

  19. Suramin blocks interaction between human FGF1 and FGFR2 D2 domain and reduces downstream signaling activity.

    PubMed

    Wu, Zong-Sian; Liu, Che Fu; Fu, Brian; Chou, Ruey-Hwang; Yu, Chin

    2016-09-01

    The extracellular portion of the human fibroblast growth factor receptor2 D2 domain (FGFR2 D2) interacts with human fibroblast growth factor 1 (hFGF1) to activate a downstream signaling cascade that ultimately affects mitosis and differentiation. Suramin is an antiparasiticdrug and a potent inhibitor of FGF-induced angiogenesis. Suramin has been shown to bind to hFGF1, and might block the interaction between hFGF1 and FGFR2 D2. Here, we titrated hFGF1 with FGFR2 D2 and suramin to elucidate their interactions using the detection of NMR. The docking results of both hFGF1-FGFR2 D2 domain and hFGF1-suramin complex were superimposed. The results indicate that suramin blocks the interaction between hFGF1 and FGFR2 D2. We used the PyMOL software to show the hydrophobic interaction of hFGF1-suramin. In addition, we used a Water-soluble Tetrazolium salts assay (WST1) to assess hFGF1 bioactivity. The results will be useful for the development of new antimitogenic activity drugs.

  20. Low level lead exposure increases sensitivity to the stimulus properties of dopamine D1 and D2 agonists.

    PubMed

    Cory-Slechta, D A; Widzowski, D V

    1991-07-01

    To examine the impact of Pb exposure on dopaminergic (DA) function, weanling rats were chronically exposed to 0, 50 or 250 ppm Pb acetate in drinking water. At 3 months of age, the rats were trained to discriminate the stimulus properties of either the D1 agonist SKF38393 (3.0 mg/kg i.p.; D1/sal) or the D2 agonist quinpirole (0.05 mg/kg i.p., D2/sal) from saline using a standard two-lever operant food-reinforced drug discrimination paradigm. Lead-exposed rats learned the discriminations faster than respective controls. Moreover, they exhibited greater levels of drug lever responding to lower doses of the training drugs (D1/sal and D2/sal), and to selected doses of other direct and indirect DA agonists (D2/sal only), including apomorphine, cocaine and (+)-amphetamine, and less blockade of drug lever responding by haloperidol (D2/sal). Taken together, these findings are consistent with a generalized DA supersensitivity. There were no differential Pb effects when non-DA compounds including morphine, pentobarbital and MK-801 were substituted for the training drugs, indicating the selectivity of the DA effects in the context of these experiments, and the improbability of a non-specific behavioral causation. Pb-exposed rats in the D2/sal group also showed a pronounced enhancement of drug lever responding when NMDA was substituted for quinpirole, suggesting the possibility of a Pb-induced NMDA supersensitivity as well. PMID:1681979

  1. Preliminary Neutronics Design and Analysis of D2O Cooled High Conversion PWRs

    SciTech Connect

    Hikaru Hiruta; Gilles Youinou

    2012-09-01

    This report presents a neutronics analysis of tight-pitch D2O-cooled PWRs loaded with MOX fuel and focuses essentially on the Pu breeding potential of such reactors as well as on an important safety parameter, the void coefficient, which has to be negative. It is well known that fast reactors have a better neutron economy and are better suited than thermal reactors to breed fissile material from neutron capture in fertile material. Such fast reactors (e.g. sodium-cooled reactors) usually rely on technologies that are very different from those of existing water-cooled reactors and are probably more expensive. This report investigates another possibility to obtain a fast neutron reactor while still relying mostly on a PWR technology by: (1) Tightening the lattice pitch to reduce the water-to-fuel volume ratio compared to that of a standard PWR. Water-to-fuel volume ratios of between 0.45 and 1 have been considered in this study while a value of about 2 is typical of standard PWRs, (2) Using D2O instead of H2O as a coolant. Indeed, because of its different neutron physics properties, the use of D2O hardens the neutron spectrum to an extent impossible with H2O when used in a tight-pitch lattice. The neutron spectra thus obtained are not as fast as those in sodium-cooled reactor but they can still be characterized as fast compared to that of standard PWR neutron spectra. In the phase space investigated in this study we did not find any configurations that would have, at the same time, a positive Pu mass balance (more Pu at the end than at the beginning of the irradiation) and a negative void coefficient. At this stage, the use of radial blankets has only been briefly addressed whereas the impact of axial blankets has been well defined. For example, with a D2O-to-fuel volume ratio of 0.45 and a core driver height of about 60 cm, the fissile Pu mass balance between the fresh fuel and the irradiated fuel (50 GWd/t) would be about -7.5% (i.e. there are 7.5% fewer fissile Pu

  2. PREFACE: International Symposium on Dynamic Deformation and Fracture of Advanced Materials (D2FAM 2013)

    NASA Astrophysics Data System (ADS)

    Silberschmidt, Vadim V.

    2013-07-01

    Intensification of manufacturing processes and expansion of usability envelopes of modern components and structures in many cases result in dynamic loading regimes that cannot be resented adequately employing quasi-static formulations of respective problems of solid mechanics. Specific features of dynamic deformation, damage and fracture processes are linked to various factors, most important among them being: a transient character of load application; complex scenarios of propagation, attenuation and reflection of stress waves in real materials, components and structures; strain-rate sensitivity of materials properties; various thermo-mechanical regimes. All these factors make both experimental characterisation and theoretical (analytical and numerical) analysis of dynamic deformation and fracture rather challenging; for instance, besides dealing with a spatial realisation of these processes, their evolution with time should be also accounted for. To meet these challenges, an International Symposium on Dynamic Deformation and Fracture of Advanced Materials D2FAM 2013 was held on 9-11 September 2013 in Loughborough, UK. Its aim was to bring together specialists in mechanics of materials, applied mathematics, physics, continuum mechanics, materials science as well as various areas of engineering to discuss advances in experimental and theoretical analysis, and numerical simulations of dynamic mechanical phenomena. Some 50 papers presented at the Symposium by researchers from 12 countries covered various topics including: high-strain-rate loading and deformation; dynamic fracture; impact and blast loading; high-speed penetration; impact fatigue; damping properties of advanced materials; thermomechanics of dynamic loading; stress waves in micro-structured materials; simulation of failure mechanisms and damage accumulation; processes in materials under dynamic loading; a response of components and structures to harsh environment. The materials discussed at D2FAM 2013

  3. Opposing relationships of BMI with BOLD and dopamine D2/3 receptor binding potential in the dorsal striatum.

    PubMed

    Cosgrove, Kelly P; Veldhuizen, Maria G; Sandiego, Christine M; Morris, Evan D; Small, Dana M

    2015-04-01

    Findings from clinical and preclinical studies converge to suggest that increased adiposity and/or exposure to a high fat diet are associated with alterations in dorsal striatal (DS) circuitry. In humans there is a reliable inverse relationship between body mass index (BMI) and response to palatable food consumption in the dorsal striatum (DS). Positron emission tomography (PET) studies also suggest altered DS dopamine type 2/3 receptor (D2R/D3R) availability in obesity; however, the direction of the association is unclear. It is also not clear whether dopamine receptor levels contribute to the lower blood oxygen level dependent (BOLD) response because PET studies have targeted the morbidly obese and, functional magnetic resonance imaging (fMRI) studies rarely include individuals with BMIs in this range. Therefore we examined whether the fMRI BOLD response in the DS to milkshake is associated with D2R/D3R availability measured with [(11) C]PHNO and PET in individuals with BMI ranging from healthy weight to moderately obese. Twenty-nine subjects participated in the fMRI study, 12 in the [(11) C]PHNO PET study, 8 of whom also completed the fMRI study. As predicted there was a significant negative association between DS BOLD response to milkshake and BMI. In contrast, BMI was positively associated with D2R/D3R availability. Dorsal striatal BOLD response was unrelated to D2R/D3R availability. Considered in the context of the larger literature our results suggest the existence of a non-linear relationship between D2R/D3R availability and BMI. Additionally, the altered BOLD responses to palatable food consumption observed in obesity are not clearly related to D2R/D3R receptor availability. Using [(11) C]PHNO and PET brain imaging techniques we show that body mass index was positively associated with D2R/D3R availability in the dorsal striatum, but that functional MR BOLD response was unrelated to D2R/D3R availability. These results suggest the existence of a nonlinear

  4. Identification and characterization of two nuclear factor-kappaB sites in the regulatory region of the dopamine D2 receptor.

    PubMed

    Bontempi, Sandra; Fiorentini, Chiara; Busi, Chiara; Guerra, Nicoletta; Spano, PierFranco; Missale, Cristina

    2007-05-01

    Regulation of D2 receptor (D2R) expression is crucial in the function of dopaminergic systems. Because alterations of D2R expression may contribute to the development of different disorders, it is important to elucidate the mechanisms regulating D2R gene transcription. We report the characterization of two putative nuclear factor-kappaB (NF-kappaB) motifs, referred to as D2-kappaB sites, in the human D2R promoter, and demonstrate that they bind NF-kappaB subunits and stimulate D2R promoter activity. D2-kappaB sites show different degrees of conservation and specificity, when compared with canonical kB sites. The D2-kappaB1 site (from -407 to -398) is highly conserved and binds p50/p65 and p50/c-Rel complexes, whereas D2-kappaB2 (from -513 to -504) is more degenerated and only binds p50/p65 heterodimers. Activation of D2-kappaB sites in COS-7 cells expressing a luciferase reporter vector containing the D2R promoter resulted in increased transcriptional activity. Site-directed mutagenesis of each D2-kappaB site differentially modified D2R promoter activity. In particular, mutation of the D2-kappaB1 motif did not affect D2R promoter response to p50/c-Rel complexes, whereas inactivation of the D2-kappaB2 site decreased it. Mutations of either D2-kappaB1 or D2-kappaB2 sites attenuated the D2R promoter transcriptional efficiency induced by p50/p65 complexes. Thus, D2R transcription mediated by p50/c-Rel is supported mainly by the D2-kappaB2 site, whereas both sites are necessary to support the full transcriptional activity mediated by p50/p65 complexes. A correlation was found between NF-kappaB activity and D2R expression in the pituitary and pituitary-derived cells but not in the striatum, suggesting that NF-kappaB regulation of D2R expression could be a pituitary-specific mechanism.

  5. Microwave Spectrum of the AsD2(&Xtilde;2B1) Radical: Harmonic Force Field and Molecular Structure.

    PubMed

    Fujiwara; Saito

    1998-12-01

    The pure rotational spectrum of AsD2 in the 2B1 ground electronic state was measured in the frequency region of 268-398 GHz by microwave spectroscopy. The AsD2 radical was generated in a free-space cell by dc-glow discharge of a gaseous mixture of D2 and He over arsenic powder. Fifty fine and hyperfine components of nine rotational transitions were measured and analyzed by least-squares methods determining the detailed molecular constants of AsD2: the rotational constants, the centrifugal distortion constants, the spin-rotation coupling constant with the centrifugal distortion terms, and the hyperfine coupling constants associated with the arsenic and deuterium nuclei. The harmonic force field of AsH2 was determined from the centrifugal distortion constants, the equilibrium vibrational frequency of nu2 mode of AsH2, and the inertial defects of AsH2 and AsD2. The harmonic force field was used to calculate vibrational corrections to the rotational constants of both species and thus the zero-point average structures for both species were derived; AsH2: rz(AsH) = 1.53436(15) Å, thetaz(HAsH) = 90.695(20) degrees, and AsD2: rz(AsD) = 1.52902(13) Å, thetaz(DAsD) = 90.722(17) degrees, where the errors in parentheses are due to residual inertial defects of the corrected moments of inertia. From the difference between the rz structures for AsH2 and AsD2 the re structure of AsH2 is estimated to be re(AsH) = 1.5158(6) Å, thetae(HAsH) = 90.79(8) degrees. Copyright 1998 Academic Press.

  6. Metabolite proofreading in carnosine and homocarnosine synthesis: molecular identification of PM20D2 as β-alanyl-lysine dipeptidase.

    PubMed

    Veiga-da-Cunha, Maria; Chevalier, Nathalie; Stroobant, Vincent; Vertommen, Didier; Van Schaftingen, Emile

    2014-07-11

    Carnosine synthase is the ATP-dependent ligase responsible for carnosine (β-alanyl-histidine) and homocarnosine (γ-aminobutyryl-histidine) synthesis in skeletal muscle and brain, respectively. This enzyme uses, also at substantial rates, lysine, ornithine, and arginine instead of histidine, yet the resulting dipeptides are virtually absent from muscle or brain, suggesting that they are removed by a "metabolite repair" enzyme. Using a radiolabeled substrate, we found that rat skeletal muscle, heart, and brain contained a cytosolic β-alanyl-lysine dipeptidase activity. This enzyme, which has the characteristics of a metalloenzyme, was purified ≈ 200-fold from rat skeletal muscle. Mass spectrometry analysis of the fractions obtained at different purification stages indicated parallel enrichment of PM20D2, a peptidase of unknown function belonging to the metallopeptidase 20 family. Western blotting showed coelution of PM20D2 with β-alanyl-lysine dipeptidase activity. Recombinant mouse PM20D2 hydrolyzed β-alanyl-lysine, β-alanyl-ornithine, γ-aminobutyryl-lysine, and γ-aminobutyryl-ornithine as its best substrates. It also acted at lower rates on β-alanyl-arginine and γ-aminobutyryl-arginine but virtually not on carnosine or homocarnosine. Although acting preferentially on basic dipeptides derived from β-alanine or γ-aminobutyrate, PM20D2 also acted at lower rates on some "classic dipeptides" like α-alanyl-lysine and α-lysyl-lysine. The same activity profile was observed with human PM20D2, yet this enzyme was ∼ 100-200-fold less active on all substrates tested than the mouse enzyme. Cotransfection in HEK293T cells of mouse or human PM20D2 together with carnosine synthase prevented the accumulation of abnormal dipeptides (β-alanyl-lysine, β-alanyl-ornithine, γ-aminobutyryl-lysine), thus favoring the synthesis of carnosine and homocarnosine and confirming the metabolite repair role of PM20D2.

  7. Striatal Dopamine D2/D3 Receptor Availability Is Associated with Executive Function in Healthy Controls but Not Methamphetamine Users

    PubMed Central

    Ballard, Michael E.; Dean, Andy C.; Mandelkern, Mark A.; London, Edythe D.

    2015-01-01

    Background Dopamine D2/D3 receptor availability in the striatum has been linked with executive function in healthy individuals, and is below control levels among drug addicts, possibly contributing to diminished executive function in the latter group. This study tested for an association of striatal D2/D3 receptor availability with a measure of executive function among research participants who met DSM-IV criteria for methamphetamine dependence. Methods Methamphetamine users and non-user controls (n = 18 per group) completed the Wisconsin Card Sorting Test and positron emission tomography with [18F]fallypride. Results The methamphetamine users displayed significantly lower striatal D2/D3 receptor availability on average than controls after controlling for age and education (p = 0.008), but they did not register greater proportions of either perseverative or non-perseverative errors when controlling for education (both ps ≥ 0.622). The proportion of non-perseverative, but not perseverative, errors was negatively correlated with striatal D2/D3 receptor availability among controls (r = -0.588, p = 0.010), but not methamphetamine users (r = 0.281, p = 0.258), and the group-wise interaction was significant (p = 0.030). Conclusions These results suggest that cognitive flexibility, as measured by perseverative errors on the Wisconsin Card Sorting Test, is not determined by signaling through striatal D2/D3 receptors in healthy controls, and that in stimulant abusers, who have lower D2/D3 receptor availability, compensation can effectively maintain other executive functions, which are associated with D2/D3 receptor signaling in controls. PMID:26657223

  8. Modulation of inhibitory and excitatory fast neurotransmission in the rat CNS by heavy water (D2O).

    PubMed

    Wakita, Masahito; Kotani, Naoki; Shoudai, Kiyomitsu; Yamaga, Toshitaka; Akaike, Norio

    2015-08-01

    The effects of heavy water (deuterium oxide, D2O) on GABAergic and glutamatergic spontaneous and evoked synaptic transmission were investigated in acute brain slice and isolated "synaptic bouton" preparations of rat hippocampal CA3 neurons. The substitution of D2O for H2O reduced the frequency and amplitude of GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) in a concentration-dependent manner but had no effect on glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs). In contrast, for evoked synaptic responses in isolated neurons, the amplitude of both inhibitory and excitatory postsynaptic currents (eIPSCs and eEPSCs) was decreased in a concentration-dependent manner. This was associated with increases of synaptic failure rate (Rf) and paired-pulse ratio (PPR). The effect was larger for eIPSCs compared with eEPSCs. These results clearly indicate that D2O acts differently on inhibitory and excitatory neurotransmitter release machinery. Furthermore, D2O significantly suppressed GABAA receptor-mediated whole cell current (IGABA) but did not affect glutamate receptor-mediated whole cell current (IGlu). The combined effects of D2O at both the pre- and postsynaptic sites may explain the greater inhibition of eIPSCs compared with eEPSCs. Finally, D2O did not enhance or otherwise affect the actions of the general anesthetics nitrous oxide and propofol on spontaneous or evoked GABAergic and glutamatergic neurotransmissions, or on IGABA and IGlu. Our results suggest that previously reported effects of D2O to mimic and/or modulate anesthesia potency result from mechanisms other than modulation of GABAergic and glutamatergic neurotransmission. PMID:26019316

  9. Effect of the aspartic acid D2 on the affinity of Polybia-MP1 to anionic lipid vesicles.

    PubMed

    Leite, Natália Bueno; Dos Santos Alvares, Dayane; de Souza, Bibiana Monson; Palma, Mário Sérgio; Ruggiero Neto, João

    2014-05-01

    Polybia-MP1 (IDWKKLLDAAKQIL-NH2), a helical peptide extracted from the venom of a Brazilian wasp, has broad-spectrum antimicrobial activities without being hemolytic or cytotoxic. This peptide has also displayed anticancer activity against cancer cell cultures. Despite its high selectivity, MP1 has an unusual low net charge (Q = +2). The aspartic residue (D2) in the N-terminal region plays an important role in its affinity and selectivity; its substitution by asparagine (D2N mutant) led to a less selective peptide. Aiming to explore the importance of this residue for the peptides' affinity, we compared the zwitterionic and anionic vesicle adsorption activity of Polybia-MP1 versus its D2N mutant and also mastoparan X (MPX). The adsorption, electrostatic, and conformational free energies were assessed by circular dichroism (CD) and fluorescence titrations using large unilamellar vesicles (LUVs) at the same conditions in association with measurement of the zeta potential of LUVs in the presence of the peptides. The adsorption free energies of the peptides, determined from the partition coefficients, indicated higher affinity of MP1 to anionic vesicles compared with the D2N mutant and MPX. The electrostatic and conformational free energies of MP1 in anionic vesicles are less favorable than those found for the D2N mutant and MPX. Therefore, the highest affinity of MP1 to anionic vesicles is likely due to other energetic contributions. The presence of D2 in MP1 makes these energetic components 1.2 and 1.5 kcal/mol more favorable compared with the D2N mutant and MPX, respectively.

  10. Aquaporin-3 in keratinocytes and skin: its role and interaction with phospholipase D2.

    PubMed

    Qin, Haixia; Zheng, Xiangjian; Zhong, Xiaofeng; Shetty, Anita K; Elias, Peter M; Bollag, Wendy B

    2011-04-15

    Aquaporin 3 (AQP3) is an aquaglyceroporin that transports water and glycerol and is expressed in the epidermis, among other epithelial tissues. We have recently shown that there is an association between this glycerol channel and phospholipase D2 (PLD2) in caveolin-rich membrane microdomains. While PLD2 is able to hydrolyze membrane phospholipids to generate phosphatidic acid, this enzyme also catalyzes, in the presence of primary alcohols, a transphosphatidylation reaction to produce a phosphatidylalcohol. We have proposed that AQP3 associated with PLD2 provides the physiological primary alcohol glycerol to PLD2 for use in the transphosphatidylation reaction to generate phosphatidylglycerol (PG). Further, we have proposed that PG functions as a signaling molecule to mediate early epidermal keratinocyte differentiation, and manipulation of this signaling module inhibits keratinocyte proliferation and enhances differentiation. In contrast, other investigators have suggested a proliferative role for AQP3 in keratinocytes. In addition, AQP3 knockout mice exhibit an epidermal phenotype, characterized by dry skin, decreased elasticity and delayed barrier repair and wound healing, which can be corrected by glycerol but not other humectants. AQP3 levels have also been found to be altered in human skin diseases. In this article the evidence supporting a role for AQP3 in the epidermis will be discussed.

  11. High precision study of muon catalyzed fusion in D2 and HD gas

    NASA Astrophysics Data System (ADS)

    Balin, D. V.; Ganzha, V. A.; Kozlov, S. M.; Maev, E. M.; Petrov, G. E.; Soroka, M. A.; Schapkin, G. N.; Semenchuk, G. G.; Trofimov, V. A.; Vasiliev, A. A.; Vorobyov, A. A.; Voropaev, N. I.; Petitjean, C.; Gartner, B.; Lauss, B.; Marton, J.; Zmeskal, J.; Case, T.; Crowe, K. M.; Kammel, P.; Hartmann, F. J.; Faifman, M. P.

    2011-03-01

    Muon catalyzed dd fusion in D2 and HD gases in the temperature range from 28 to 350 K was investigated in a series of experiments based on a time-projection ionization chamber operating with pure hydrogen. All main observables in this reaction chain were measured with high absolute precision including the resonant and non-resonant ddμ formation rates, the rate for hyperfine transitions in dμ atoms, the branching ratio of the two charge symmetric fusion channels 3He + n and t + p and the muon sticking probability. The report presents the final analysis of the data together with a comprehensive comparison with calculations based on recent μCF theories. The energy of the loosely bound ddμ state with quantum numbers J = 1, ν = 1, which is central to the mechanism of resonant molecule formation, is extracted with precision ɛ11(fit) = -1.9651(7) eV. in impressive agreement with the latest theoretical results ɛ11(theory) = -1.9646 eV.

  12. Production of Excited Atomic Hydrogen and Deuterium from H2 and D2 Photodissociation

    NASA Astrophysics Data System (ADS)

    Gay, T. J.; Bozek, J. D.; Furst, J. E.; Gould, H.; Kilcoyne, A. L. D.; Machacek, J. R.; Martin, F.; McLaughlin, K. W.; Sanz-Vicario, J. L.

    2007-06-01

    We have measured the production of both Lyα and Hα fluorescence from atomic H and D for the photodissociation of H2 and D2 by linearly-polarized photons with energies between 24 and 60 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. Our data are compared with ab initio calculations of the dissociation process, in which both doubly-excited state production and prompt ionization through non-resonant channels are considered. Agreement between our experimental data and that of earlier work [1], and with our theoretical calculations, is qualitative at best. [1] E.Melero Garc'ia, J.'Alvarez Ruiz, S.Menmuir, E.Rachlew, P.Erman, A.Kivim"aki, M.Glass-Maujean, R.Richter, and M.Coreno, J.Phys.B 39, 205 (2006). Support provided by the NSF (Grant PHY-0354946), DOE (LBNL/ALS) and ANSTO (Access to Major Research Facilities Programme).

  13. 3D-2D Deformable Image Registration Using Feature-Based Nonuniform Meshes.

    PubMed

    Zhong, Zichun; Guo, Xiaohu; Cai, Yiqi; Yang, Yin; Wang, Jing; Jia, Xun; Mao, Weihua

    2016-01-01

    By using prior information of planning CT images and feature-based nonuniform meshes, this paper demonstrates that volumetric images can be efficiently registered with a very small portion of 2D projection images of a Cone-Beam Computed Tomography (CBCT) scan. After a density field is computed based on the extracted feature edges from planning CT images, nonuniform tetrahedral meshes will be automatically generated to better characterize the image features according to the density field; that is, finer meshes are generated for features. The displacement vector fields (DVFs) are specified at the mesh vertices to drive the deformation of original CT images. Digitally reconstructed radiographs (DRRs) of the deformed anatomy are generated and compared with corresponding 2D projections. DVFs are optimized to minimize the objective function including differences between DRRs and projections and the regularity. To further accelerate the above 3D-2D registration, a procedure to obtain good initial deformations by deforming the volume surface to match 2D body boundary on projections has been developed. This complete method is evaluated quantitatively by using several digital phantoms and data from head and neck cancer patients. The feature-based nonuniform meshing method leads to better results than either uniform orthogonal grid or uniform tetrahedral meshes. PMID:27019849

  14. Photodetachment of O^- Yielding O(1D_2, {}^3P) Atoms, Viewed with Velocity Map Imaging

    NASA Astrophysics Data System (ADS)

    Gibson, Stephen T.; Laws, Benjamin A.; Lewis, Brenton R.; Duong, Ly

    2016-06-01

    lectron photodetachment of O^-(2P3/2,1/2) is measured using velocity-map imaging at wavelengths near 350 nm, where detachment yields both O(^1D_2) and O(^3P2,1,0) atoms, simultaneously, producing slow (˜ 0.1 eV) and fast electrons (˜ 2 eV). The photoelectron spectrum resolves the fine-structure transitions, which together with the well known atomic fine-structure splittings, and intensity ratios, provide an excellent test of the spectral quality of the velocity-map imaging technique. Although the photoelectron angular distribution for the two atomic limits have the same negative anisotropy sign, the energy dependence differs. The variation is qualitatively in accordance with R-matrix cross section calculations, that indicate a more gradual d-wave onset for the ^1D limit. However, more exact evaluation is only possible with information about the matrix element phases. Research supported by the Australian Research Council Discovery Project GrantDP160102585. physics.nist.gov/cgi-bin/ASD/energy1.pl O. Scharf and M. R. Godefried, arXiv:0808.3529v1 O. Zatsarinny and K. Bartschat, Phys. Rev. A, 73, 022714 (2006). doi:10.1103/PhysRevA.73.022714

  15. A Planar Quantum Transistor Based on 2D-2D Tunneling in Double Quantum Well Heterostructures

    SciTech Connect

    Baca, W.E.; Blount, M.A.; Hafich, M.J.; Lyo, S.K.; Moon, J.S.; Reno, J.L.; Simmons, J.A.; Wendt, J.R.

    1998-12-14

    We report on our work on the double electron layer tunneling transistor (DELTT), based on the gate-control of two-dimensional -- two-dimensional (2D-2D) tunneling in a double quantum well heterostructure. While previous quantum transistors have typically required tiny laterally-defined features, by contrast the DELTT is entirely planar and can be reliably fabricated in large numbers. We use a novel epoxy-bond-and-stop-etch (EBASE) flip-chip process, whereby submicron gating on opposite sides of semiconductor epitaxial layers as thin as 0.24 microns can be achieved. Because both electron layers in the DELTT are 2D, the resonant tunneling features are unusually sharp, and can be easily modulated with one or more surface gates. We demonstrate DELTTs with peak-to-valley ratios in the source-drain I-V curve of order 20:1 below 1 K. Both the height and position of the resonant current peak can be controlled by gate voltage over a wide range. DELTTs with larger subband energy offsets ({approximately} 21 meV) exhibit characteristics that are nearly as good at 77 K, in good agreement with our theoretical calculations. Using these devices, we also demonstrate bistable memories operating at 77 K. Finally, we briefly discuss the prospects for room temperature operation, increases in gain, and high-speed.

  16. Protein Kinase D2 Protects against Acute Colitis Induced by Dextran Sulfate Sodium in Mice

    PubMed Central

    Xiong, Jing; Zhou, Ming-feng; Wang, Ya-dong; Chen, Li-ping; Xu, Wan-fu; Wang, Yao-dong; Deng, Fan; Liu, Si-de

    2016-01-01

    Inflammatory bowel disease is characterized by dysregulation of the mucosal immune system resulting from impaired intestinal epithelial barrier function. Protein kinase D2 has been implicated in the regulation of immune responses. The present study was to define PKD2 might affect murine colitis. Colitis was induced in wild-type mice (PKD2WT/WT) and PKD2 catalytic activity deficient mice (PKD2SSAA/SSAA) with dextran sulfate sodium. PKD2SSAA-knockin mice displayed catalytic activity deficiency and increased susceptibility to DSS-induced colitis with enhanced weight loss, colonic inflammation compared with PKD2WT/WT mice. Furthermore, crucial inflammatory cytokines mRNA levels in PKD2SSAA-knockin mice were higher than controls accompanied with down-regulation of ZO-1, MUC2 and intestinal barrier dysfunction. However, there were no differences in the proliferation or apoptosis of intestinal epithelial cells in PKD2SSAA-knockin mice compared with wild-type controls. In addition, PKD2 expression was repressed in patients with IBD compared with healthy controls. These studies suggested that activation of PKD2 in the colonic epithelium microenvironment may contribute to protect against DSS-induced colitis through regulation of intestinal mucosal immunity and barrier function. PMID:27659202

  17. Communication: The rotational excitation of D2 by H: On the importance of the reactive channels

    NASA Astrophysics Data System (ADS)

    Lique, François; Faure, Alexandre

    2012-01-01

    We report fully-quantum time-independent calculations of cross sections and rate coefficients for the collisional excitation and dissociation of D2 by H, two astrophysically relevant processes. Our calculations are based on the recent H3 global potential energy surface of Mielke et al. [J. Chem. Phys. 116, 4142 (2002), 10.1063/1.1432319]. Results of exact three-dimensional calculations, i.e., including the reactive channels, are compared to pure inelastic two-dimensional calculations based on the rigid rotor approximation. A reasonable agreement is found between the two sets of inelastic cross sections over the whole energy range 10-9000 cm-1. At the highest collisional energies, where the reactive channels are significant, the rigid rotor approach slightly overestimates the cross sections, as expected. At moderate collisional energies, however, the opposite behaviour is observed. The rigid rotor approach is found to be reliable at temperatures below ˜500 K, with a significant but moderate contribution from reactive channels

  18. Ion Flux Characterization of H2 and D2 Plasmas Produced by an ECR Plasma Source

    NASA Astrophysics Data System (ADS)

    Kaiser, Eric; Capece, Angela; Roszell, John; Skinner, Charles; Koel, Bruce

    2013-10-01

    The use of lithium-conditioned plasma facing components in tokamaks has been shown to improve plasma confinement through a reduction in hydrogen recycling. Surface science techniques are being applied to probe the interactions between lithiated PFC's and H/D plasmas. A TectraTM Gen 2 plasma source has been commissioned that utilizes electron cyclotron resonance to produce a plasma discharge inside a vacuum test chamber and can produce ion fluxes similar to those typically seen in tokamaks. This source will be utilized to study H/D uptake by lithium films on Mo substrates as a precursor to NSTX-U experiments. In this work we report on the characterization of this source as a first step in its use in surface analysis studies. The source is operated in H2 and D2 gases and the subsequent ion flux of the plasma is measured by a Faraday Cup. Ion flux measurements are presented in a range of gas pressures and grid voltages up to 2 kV. Science Undergraduate Laboratory Internship funded by Department of Energy.

  19. A new inversion method for (T2, D) 2D NMR logging and fluid typing

    NASA Astrophysics Data System (ADS)

    Tan, Maojin; Zou, Youlong; Zhou, Cancan

    2013-02-01

    One-dimensional nuclear magnetic resonance (1D NMR) logging technology has some significant limitations in fluid typing. However, not only can two-dimensional nuclear magnetic resonance (2D NMR) provide some accurate porosity parameters, but it can also identify fluids more accurately than 1D NMR. In this paper, based on the relaxation mechanism of (T2, D) 2D NMR in a gradient magnetic field, a hybrid inversion method that combines least-squares-based QR decomposition (LSQR) and truncated singular value decomposition (TSVD) is examined in the 2D NMR inversion of various fluid models. The forward modeling and inversion tests are performed in detail with different acquisition parameters, such as magnetic field gradients (G) and echo spacing (TE) groups. The simulated results are discussed and described in detail, the influence of the above-mentioned observation parameters on the inversion accuracy is investigated and analyzed, and the observation parameters in multi-TE activation are optimized. Furthermore, the hybrid inversion can be applied to quantitatively determine the fluid saturation. To study the effects of noise level on the hybrid method and inversion results, the numerical simulation experiments are performed using different signal-to-noise-ratios (SNRs), and the effect of different SNRs on fluid typing using three fluid models are discussed and analyzed in detail.

  20. No association of dopamine D2 receptor molecular variant Cys311 and schizophrenia in Chinese patients

    SciTech Connect

    Chia-Hsiang Chen; Shih-Hsiang Chien; Hai-Gwo Hwu

    1996-07-26

    A serine-to-cysteine mutation of dopamine D2 receptor at codon 311 (Cys311) was found to have higher frequency in schizophrenic patients than in normal controls in Japanese by Arinami et al. The Cys311 allele was found to be associated with patients with younger age-of-onset, positive family history, and more positive symptoms. To investigate the possible involvement of Cys311 in schizophrenia in the Chinese population, 114 unrelated Taiwanese Chinese schizophrenic patients with positive family history and 88 normal controls were genotyped for Cys311. Four patients and 5 normal controls were heterozygotes of Ser311/Cys311; no homozygotes of Cys311 were identified in either group. The allele frequencies of Cys311 in Chinese schizophrenic patients and normal controls were 2% and 3%, respectively. No significant difference was detected between the two groups. Our results do not support the argument that the Cys311 allele of DRD2 poses a genetic risk for certain types of schizophrenia in Chinese populations. 18 refs.

  1. 3D Building Modeling in LoD2 Using the CityGML Standard

    NASA Astrophysics Data System (ADS)

    Preka, D.; Doulamis, A.

    2016-10-01

    Over the last decade, scientific research has been increasingly focused on the third dimension in all fields and especially in sciences related to geographic information, the visualization of natural phenomena and the visualization of the complex urban reality. The field of 3D visualization has achieved rapid development and dynamic progress, especially in urban applications, while the technical restrictions on the use of 3D information tend to subside due to advancements in technology. A variety of 3D modeling techniques and standards has already been developed, as they gain more traction in a wide range of applications. Such a modern standard is the CityGML, which is open and allows for sharing and exchanging of 3D city models. Within the scope of this study, key issues for the 3D modeling of spatial objects and cities are considered and specifically the key elements and abilities of CityGML standard, which is used in order to produce a 3D model of 14 buildings that constitute a block at the municipality of Kaisariani, Athens, in Level of Detail 2 (LoD2), as well as the corresponding relational database. The proposed tool is based upon the 3DCityDB package in tandem with a geospatial database (PostgreSQL w/ PostGIS 2.0 extension). The latter allows for execution of complex queries regarding the spatial distribution of data. The system is implemented in order to facilitate a real-life scenario in a suburb of Athens.

  2. NASA's Next Solar Sail: Lessons Learned from NanoSail - D2

    NASA Technical Reports Server (NTRS)

    Katan, Chelsea

    2012-01-01

    NanoSail-D2 unfurled January 17th, 2011 and commenced a nine month Low Earth Orbit path to reentry to evaluate a sail's capacity to deploy in space and deorbit satellites. The orbit was strongly affected by variables including but not limited to: initial attitude, orbit lighting, solar radiation pressure, aerodynamic drag, gravity, and Center of Pressure offsets. The effects of these variables were evaluated through a 3-DOF rigid body simulation. The sail experienced stability in orbits which were continuously lit, i.e. did not orbit behind Earth. Probable drag area experienced by the sail for the mission is also estimated from orbital data and compared to the attitude simulation results. Analysis focuses on sail behavior in full lighting conditions to establish the limits of the sails stability in full lighting. Solar radiation pressure, aerodynamic drag, and gravity torque effects are described. Lastly, a reasonable upper bound on the variation of the Center of Pressure from the geometric center of the sail plane is established. Each of these results contributes to the design requirements for future solar sails.

  3. Duality of parity doublets of helicity {+-}2 in D=2+1 dimensions

    SciTech Connect

    Dalmazi, D.; Mendonca, Elias L.

    2010-11-15

    In D=2+1 dimensions there are two dual descriptions of parity singlets of helicity {+-}1, namely, the self-dual model of first order (in derivatives) and the Maxwell-Chern-Simons theory of second order. Correspondingly, for helicity {+-}2 there are four models S{sub SD{+-}}{sup (r)} describing parity singlets of helicities {+-}2. They are of first, second, third, and fourth order (r=1, 2, 3, 4), respectively. Here we show that the generalized soldering of the opposite helicity models S{sub SD+}{sup (4)} and S{sub SD-}{sup (4)} leads to the linearized form of the new massive gravity suggested by Bergshoeff, Hohm, and Townsend (BHT) similarly to the soldering of S{sub SD+}{sup (3)} and S{sub SD-}{sup (3)}. We argue why in both cases we have the same result. We also find out a triple master action which interpolates between the three dual models: linearized BHT theory, S{sub SD+}{sup (3)}+S{sub SD-}{sup (3)}, and S{sub SD+}{sup (4)}+S{sub SD-}{sup (4)}. By comparing gauge invariant correlation functions we deduce dual maps between those models. In particular, we learn how to decompose the field of the linearized BHT theory in helicity eigenstates of the dual models up to gauge transformations.

  4. Study the Formation of H2, HD and D2 under Various Interstellar Conditions

    NASA Astrophysics Data System (ADS)

    Sahu, Dipen; Chakrabarti, Sandip Kumar; Das, Ankan

    2016-07-01

    Hydrogen is the most abundant molecule in the Interstellar medium (ISM). Formation of gas phase hydrogen molecule is inefficient; perhaps grain surface acts as a necessary ingredients for the formation of H_2 molecule. H atoms accrete on the grain surface, recombine there and desorb in the gas phase. Similarly, deuterium accretion on grain surfaces can produce simple dueterated molecules (HD and D_2) on the ISM. Unlike gas phase reactions, rate equations can not yield accurate result for grain surface reactions due to inherent randomness of surface species. We use Monte-Carlo method to follow this surface chemistry which effectively take care of this randomness. We use square grids and impose periodic boundary condition on them to mimic the spherical nature of grains. Various types of rough surfaces are considered to study the impact on effective production rates. We found that these simple but most important molecules are produced in low temperature (physisorption sites) as well as in high temperature (chemisorption sites) regions.

  5. Search on a hypercubic lattice using a quantum random walk. II. d=2

    NASA Astrophysics Data System (ADS)

    Patel, Apoorva; Raghunathan, K. S.; Rahaman, Md. Aminoor

    2010-09-01

    We investigate the spatial search problem on the two-dimensional square lattice, using the Dirac evolution operator discretized according to the staggered lattice fermion formalism. d=2 is the critical dimension for the spatial search problem, where infrared divergence of the evolution operator leads to logarithmic factors in the scaling behavior. As a result, the construction used in our accompanying article [A. Patel and M. A. Rahaman, Phys. Rev. APLRAAN1050-294710.1103/PhysRevA.82.032330 82, 032330 (2010)] provides an O(NlnN) algorithm, which is not optimal. The scaling behavior can be improved to O(NlnN) by cleverly controlling the massless Dirac evolution operator by an ancilla qubit, as proposed by Tulsi [Phys. Rev. APLRAAN1050-294710.1103/PhysRevA.78.012310 78, 012310 (2008)]. We reinterpret the ancilla control as introduction of an effective mass at the marked vertex, and optimize the proportionality constants of the scaling behavior of the algorithm by numerically tuning the parameters.

  6. 3D-2D registration for surgical guidance: effect of projection view angles on registration accuracy

    NASA Astrophysics Data System (ADS)

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

    2014-01-01

    An algorithm for intensity-based 3D-2D registration of CT and x-ray projections is evaluated, specifically using single- or dual-projection views to provide 3D localization. The registration framework employs the gradient information similarity metric and covariance matrix adaptation evolution strategy to solve for the patient pose in six degrees of freedom. Registration performance was evaluated in an anthropomorphic phantom and cadaver, using C-arm projection views acquired at angular separation, Δθ, ranging from ˜0°-180° at variable C-arm magnification. Registration accuracy was assessed in terms of 2D projection distance error and 3D target registration error (TRE) and compared to that of an electromagnetic (EM) tracker. The results indicate that angular separation as small as Δθ ˜10°-20° achieved TRE <2 mm with 95% confidence, comparable or superior to that of the EM tracker. The method allows direct registration of preoperative CT and planning data to intraoperative fluoroscopy, providing 3D localization free from conventional limitations associated with external fiducial markers, stereotactic frames, trackers and manual registration.

  7. Ligand-stimulated downregulation of the alpha interferon receptor: role of protein kinase D2.

    PubMed

    Zheng, Hui; Qian, Juan; Varghese, Bentley; Baker, Darren P; Fuchs, Serge

    2011-02-01

    Alpha interferon (IFN-α) controls homeostasis of hematopoietic stem cells, regulates antiviral resistance, inhibits angiogenesis, and suppresses tumor growth. This cytokine is often used to treat cancers and chronic viral infections. The extent of cellular responses to IFN-α is limited by the IFN-induced ubiquitination and degradation of the IFN-α/β receptor chain 1 (IFNAR1) chain of the cognate receptor. IFNAR1 ubiquitination is facilitated by the βTrcp E3 ubiquitin ligase that is recruited to IFNAR1 upon its degron phosphorylation, which is induced by the ligand. Here we report identification of protein kinase D2 (PKD2) as a kinase that mediates the ligand-inducible phosphorylation of IFNAR1 degron and enables binding of βTrcp to the receptor. Treatment of cells with IFN-α induces catalytic activity of PKD2 and stimulates its interaction with IFNAR1. Expression and kinase activity of PKD2 are required for the ligand-inducible stimulation of IFNAR1 ubiquitination and endocytosis and for accelerated proteolytic turnover of IFNAR1. Furthermore, inhibition or knockdown of PKD2 robustly augments intracellular signaling induced by IFN-α and increases the efficacy of its antiviral effects. The mechanisms of the ligand-inducible elimination of IFNAR1 are discussed, along with the potential medical significance of this regulation. PMID:21173164

  8. Pharmacological and signalling properties of a D2-like dopamine receptor (Dop3) in Tribolium castaneum.

    PubMed

    Verlinden, Heleen; Vleugels, Rut; Verdonck, Rik; Urlacher, Elodie; Vanden Broeck, Jozef; Mercer, Alison

    2015-01-01

    Dopamine is an important neurotransmitter in the central nervous system of vertebrates and invertebrates. Despite their evolutionary distance, striking parallels exist between deuterostomian and protostomian dopaminergic systems. In both, signalling is achieved via a complement of functionally distinct dopamine receptors. In this study, we investigated the sequence, pharmacology and tissue distribution of a D2-like dopamine receptor from the red flour beetle Tribolium castaneum (TricaDop3) and compared it with related G protein-coupled receptors in other invertebrate species. The TricaDop3 receptor-encoding cDNA shows considerable sequence similarity with members of the Dop3 receptor class. Real time qRT-PCR showed high expression in both the central brain and the optic lobes, consistent with the role of dopamine as neurotransmitter. Activation of TricaDop3 expressed in mammalian cells increased intracellular Ca(2+) signalling and decreased NKH-477 (a forskolin analogue)-stimulated cyclic AMP levels in a dose-dependent manner. We studied the pharmacological profile of the TricaDop3 receptor and demonstrated that the synthetic vertebrate dopamine receptor agonists, 2 - amino- 6,7 - dihydroxy - 1,2,3,4 - tetrahydronaphthalene hydrobromide (6,7-ADTN) and bromocriptine acted as agonists. Methysergide was the most potent of the antagonists tested and showed competitive inhibition in the presence of dopamine. This study offers important information on the Dop3 receptor from Tribolium castaneum that will facilitate functional analyses of dopamine receptors in insects and other invertebrates.

  9. FT-IR Spectra of Antifreeze Glycoproteins in Heavy Water and D2O Ice.

    NASA Astrophysics Data System (ADS)

    Tsvetkova, N. M.; Crowe, J. H.; Feeney, R. H.; Fink, W. H.; Yeh, Yin

    2000-03-01

    This work presents FT-IR studies on the antifreeze glycoprotein (AFGP)/heavy water (D2O) mixtures during freezing and melting. AFGP in the blood serum of polar fish are known to prevent ice crystal growth by a non-colligative mechanism. There are 8 known fractions of AFGP (1 8) that range in molecular mass from 33.7 to 2.6 kD respectively, each composed of alanine-alanine-threonine repeats, with a disaccharide attached to the threonine residue. The smallest peptide (AFGP-8) is structurally different from fractions 1-5 in that it contains proline substituting for alanine in certain positions. Substantial linewidth change of the D20 bending mode (ca. 1210 cm-1) was measured with solutions containing fractions 2-5 during both freezing and thawing cycles, suggesting significant coupling between protein and water molecules. At the same time, the Amide I band between 1620 and 1675 cm-1 shows that 310 helix and random coils are the main conformations of fractions 2-5 and fraction 8 in the presence of ice. In liquid state, b-sheet dominates the secondary structure of AFGP 8, whereas b-sheet and random coil are the main conformations of AFGP 2-5. These results are discussed in terms of the ability of AFGP 2-5 to affect the surface states of ice.

  10. 28Silicon Irradiation Impairs Contextual Fear Memory in B6D2F1 Mice.

    PubMed

    Raber, Jacob; Marzulla, Tessa; Stewart, Blair; Kronenberg, Amy; Turker, Mitchell S

    2015-06-01

    The space radiation environment consists of multiple species of charged particles, including (28)Si, (48)Ti and protons that may impact cognition, but their damaging effects have been poorly defined. In mouse studies, C57Bl6/J homozygous wild-type mice and genetic mutant mice on a C57Bl6/J background have typically been used for assessing effects of space radiation on cognition. In contrast, little is known about the radiation response of mice on a heterozygous background. Therefore, in the current study we tested the effects of (28)Si, (48)Ti and proton radiation on hippocampus-dependent contextual fear memory and hippocampus-independent cued fear memory in C57Bl6/J × DBA2/J F1 (B6D2F1) mice three months after irradiation. Contextual fear memory was impaired at a 1.6 Gy dose of (28)Si radiation, but not cued fear memory. (48)Ti or proton irradiation did not affect either type of memory. Based on earlier space radiation cognitive data in C57Bl6/J mice, these data highlight the importance of including different genetic backgrounds in studies aimed at assessing cognitive changes after exposure to space radiation.

  11. CRTH2, a prostaglandin D2 receptor, mediates depression-related behavior in mice.

    PubMed

    Onaka, Yusuke; Shintani, Norihito; Nakazawa, Takanobu; Haba, Ryota; Ago, Yukio; Wang, Hyper; Kanoh, Takuya; Hayata-Takano, Atsuko; Hirai, Hiroyuki; Nagata, Kin-Ya; Nakamura, Masataka; Hashimoto, Ryota; Matsuda, Toshio; Waschek, James A; Kasai, Atsushi; Nagayasu, Kazuki; Baba, Akemichi; Hashimoto, Hitoshi

    2015-05-01

    Depression is a complex neuropsychiatric disorder with an unclear molecular etiology. Inflammatory cytokines and molecular intermediates (including prostaglandins) are suggested to be involved in depression; however, the roles of prostaglandins and their respective receptors are largely unknown in depression. Using genetic and pharmacological approaches, we show here that chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2), a second receptor for prostaglandin D2 (PGD2), mediates depression-related behavior in mice. CRTH2-deficient (CRTH2(-/-)) mice showed antidepressant-like activity in a chronic corticosterone treatment-induced depression. Consistent with this observation, the pharmacological inhibition of CRTH2 via the clinically available drug ramatroban also rescued abnormal social interaction and depression-related behavior in well-established models, including chronic corticosterone-, lipopolysaccharide-, and tumor-induced pathologically relevant depression models. Importantly, chronic stress via corticosterone treatment increased mRNA levels in PGD2-producing enzymes, such as cyclooxygenase-2 and lipocalin-type PGD2 synthase, in the brain. Furthermore, the activity of the hippocampal noradrenergic system but not the dopaminergic or serotonergic systems was increased in CRTH2(-/-) mice. Together with the observation that untreated CRTH2(-/-) mice showed antidepressant-like activity in the forced swim test, these results provide evidence that central CRTH2-mediated signaling is critically involved in depression-related behavior. PMID:25698598

  12. CACNA2D2 promotes tumorigenesis by stimulating cell proliferation and angiogenesis.

    PubMed

    Warnier, M; Roudbaraki, M; Derouiche, S; Delcourt, P; Bokhobza, A; Prevarskaya, N; Mariot, P

    2015-10-16

    In the present study, we have assessed whether a putative calcium channel α2δ2 auxiliary subunit (CACNA2D2 gene) could be involved in prostate cancer (PCA) progression. We therefore carried out experiments to determine whether this protein is expressed in PCA LNCaP cells and in PCA tissues, and whether its expression may be altered during cancer development. In addition, we evaluated the influence on cell proliferation of overexpressing or downregulating this subunit. In vitro experiments show that α2δ2 subunit overexpression is associated with increased cell proliferation, alterations of calcium homeostasis and the recruitment of a nuclear factor of activated T-cells pathway. Furthermore, we carried out in vivo experiments on immuno-deficient nude mice in order to evaluate the tumorigenic potency of the α2δ2 subunit. We show that α2δ2-overexpressing PCA LNCaP cells are more tumorigenic than control LNCaP cells when injected into nude mice. In addition, gabapentin, a ligand of α2δ2, reduces tumor development in LNCaP xenografts. Finally, we show that the action of α2δ2 on tumor development occurs not only through a stimulation of proliferation, but also through a stimulation of angiogenesis, via an increased secretion of vascular endothelial growth factor in cells overexpressing α2δ2. PMID:25619833

  13. Communication target object recognition for D2D connection with feature size limit

    NASA Astrophysics Data System (ADS)

    Ok, Jiheon; Kim, Soochang; Kim, Young-hoon; Lee, Chulhee

    2015-03-01

    Recently, a new concept of device-to-device (D2D) communication, which is called "point-and-link communication" has attracted great attentions due to its intuitive and simple operation. This approach enables user to communicate with target devices without any pre-identification information such as SSIDs, MAC addresses by selecting the target image displayed on the user's own device. In this paper, we present an efficient object matching algorithm that can be applied to look(point)-and-link communications for mobile services. Due to the limited channel bandwidth and low computational power of mobile terminals, the matching algorithm should satisfy low-complexity, low-memory and realtime requirements. To meet these requirements, we propose fast and robust feature extraction by considering the descriptor size and processing time. The proposed algorithm utilizes a HSV color histogram, SIFT (Scale Invariant Feature Transform) features and object aspect ratios. To reduce the descriptor size under 300 bytes, a limited number of SIFT key points were chosen as feature points and histograms were binarized while maintaining required performance. Experimental results show the robustness and the efficiency of the proposed algorithm.

  14. Prostaglandin D2 synthase/GPR44: a signaling axis in PNS myelination.

    PubMed

    Trimarco, Amelia; Forese, Maria Grazia; Alfieri, Valentina; Lucente, Alessandra; Brambilla, Paola; Dina, Giorgia; Pieragostino, Damiana; Sacchetta, Paolo; Urade, Yoshihiro; Boizet-Bonhoure, Brigitte; Martinelli Boneschi, Filippo; Quattrini, Angelo; Taveggia, Carla

    2014-12-01

    Neuregulin 1 type III is processed following regulated intramembrane proteolysis, which allows communication from the plasma membrane to the nucleus. We found that the intracellular domain of neuregulin 1 type III upregulated the prostaglandin D2 synthase (L-pgds, also known as Ptgds) gene, which, together with the G protein-coupled receptor Gpr44, forms a previously unknown pathway in PNS myelination. Neuronal L-PGDS is secreted and produces the PGD2 prostanoid, a ligand of Gpr44. We found that mice lacking L-PGDS were hypomyelinated. Consistent with this, specific inhibition of L-PGDS activity impaired in vitro myelination and caused myelin damage. Furthermore, in vivo ablation and in vitro knockdown of glial Gpr44 impaired myelination. Finally, we identified Nfatc4, a key transcription factor for myelination, as one of the downstream effectors of PGD2 activity in Schwann cells. Thus, L-PGDS and Gpr44 are previously unknown components of an axo-glial interaction that controls PNS myelination and possibly myelin maintenance.

  15. Regulation of phospholipase D2 by H(2)O(2) in PC12 cells.

    PubMed

    Oh, S O; Hong, J H; Kim, Y R; Yoo, H S; Lee, S H; Lim, K; Hwang, B D; Exton, J H; Park, S K

    2000-12-01

    Phospholipase D2 (PLD2) is expressed in brain and inhibited by synuclein, which is involved in Parkinson's and Alzheimer's diseases. However, the activation mechanism of PLD2 in neuronal cells has not been defined clearly. Hydrogen peroxide (H(2)O(2)) plays roles in the neurodegenerative diseases and also acts as a second messenger of various molecules such as nerve growth factor. To study regulation mechanisms of PLD2 by H(2)O(2) in neuronal cells, we have made stable PC12 cell lines expressing PLD2 (PLD2-PC12 cells). H(2)O(2) treatment stimulated PLD activity in PLD2-PC12 cells in a dose- and time-dependent manner. This activation was inhibited by the treatment with protein kinase C (PKC) inhibitors or by depletion of PKCalpha, -delta, and -epsilon. Phorbol ester markedly activated PLD2. Co-treatment with phorbol ester and H(2)O(2) did not show an additive effect. Chelation of extracellular calcium substantially blocked the H(2)O(2)-induced activation of PLD2. A calcium ionophore induced PLD2 activation in a PKC-dependent manner. Protein-tyrosine kinase inhibitors inhibited H(2)O(2)-induced PLD activation slightly. These data indicate that H(2)O(2) can activate PLD2 in PC12 cells and that this activation is largely dependent on PKC and Ca(2+) ions and minimally dependent on tyrosine phosphorylation.

  16. First results from experiments performed with the ESA Anthrorack during the D-2 spacelab mission

    NASA Astrophysics Data System (ADS)

    Kuipers, A.

    1996-06-01

    In 1993 four astronauts performed physiological experiments on the payload "Anthrorack" during the second German Spacelab mission D-2. The Anthrorack set-up is a Spacelab double rack developed under the management of the European Space Agency. It consists of an ECHO machine, a respiratory monitoring system (gas analyzer with flow meter), a blood centrifuge, an ergometer, a finger blood pressure device, ECG, body impedance measurement device and a respiratory inductance plethysmograph. Experiment-specific equipment was used as well. Nineteen investigators performed experiments in the cardiovascular, pulmonary, fluid-renal and nutritional physiology area. Results on central venous pressure, ocular pressure, vascular resistance, cardiac output, tissue thickness and orthostatic intolerance are presented in the cardiovascular area. In the pulmonary area first results are mentioned on O 2 transport perfusion and ventilation distribution and breathing pattern. From the fluid-renal experiments, data from diuresis, sodium excretion and hormonal determinations are given. Finally results from glucose metabolism and nitrogen turnover experiments are presented.

  17. Phospholipase D2-dependent inhibition of the nuclear hormone receptor PPARgamma by cyclic phosphatidic acid.

    PubMed

    Tsukahara, Tamotsu; Tsukahara, Ryoko; Fujiwara, Yuko; Yue, Junming; Cheng, Yunhui; Guo, Huazhang; Bolen, Alyssa; Zhang, Chunxiang; Balazs, Louisa; Re, Fabio; Du, Guangwei; Frohman, Michael A; Baker, Daniel L; Parrill, Abby L; Uchiyama, Ayako; Kobayashi, Tetsuyuki; Murakami-Murofushi, Kimiko; Tigyi, Gabor

    2010-08-13

    Cyclic phosphatidic acid (1-acyl-2,3-cyclic-glycerophosphate, CPA), one of nature's simplest phospholipids, is found in cells from slime mold to humans and has a largely unknown function. We find here that CPA is generated in mammalian cells in a stimulus-coupled manner by phospholipase D2 (PLD2) and binds to and inhibits the nuclear hormone receptor PPARgamma with nanomolar affinity and high specificity through stabilizing its interaction with the corepressor SMRT. CPA production inhibits the PPARgamma target-gene transcription that normally drives adipocytic differentiation of 3T3-L1 cells, lipid accumulation in RAW264.7 cells and primary mouse macrophages, and arterial wall remodeling in a rat model in vivo. Inhibition of PLD2 by shRNA, a dominant-negative mutant, or a small molecule inhibitor blocks CPA production and relieves PPARgamma inhibition. We conclude that CPA is a second messenger and a physiological inhibitor of PPARgamma, revealing that PPARgamma is regulated by endogenous agonists as well as by antagonists. PMID:20705243

  18. Multiple roles of the prostaglandin D2 signaling pathway in reproduction.

    PubMed

    Rossitto, Moïra; Ujjan, Safdar; Poulat, Francis; Boizet-Bonhoure, Brigitte

    2015-01-01

    Prostaglandins signaling molecules are involved in numerous physiological processes. They are produced by several enzyme-limited reactions upon fatty acids, which are catalyzed by two cyclooxygenases and prostaglandin synthases. In particular, the prostaglandins E2 (PGE2), D2 (PGD2), and F2 (PGF2 α) have been shown to be involved in female reproductive mechanisms. Furthermore, widespread expression of lipocalin- and hematopoietic-PGD2 synthases in the male reproductive tract supports the purported roles of PGD2 in the development of both embryonic and adult testes, sperm maturation, and spermatogenesis. In this review, we summarize the putative roles of PGD2 signaling and the roles of both PGD2 synthases in testicular formation and function. We review the data reporting the involvement of PGD2 signaling in the differentiation of Sertoli and germ cells of the embryonic testis. Furthermore, we discuss the roles of lipocalin-PGD2 synthase in steroidogenesis and spermatogenesis, in terms of lipid molecule transport and PGD2 production. Finally, we discuss the hypothesis that PGD2 signaling may be affected in certain reproductive diseases, such as infertility, cryptorchidism, and testicular cancer.

  19. Human dopamine receptor D2/D3 availability predicts amygdala reactivity to unpleasant stimuli.

    PubMed

    Kobiella, Andrea; Vollstädt-Klein, Sabine; Bühler, Mira; Graf, Caroline; Buchholz, Hans-Georg; Bernow, Nina; Yakushev, Igor Y; Landvogt, Christian; Schreckenberger, Mathias; Gründer, Gerhard; Bartenstein, Peter; Fehr, Christoph; Smolka, Michael N

    2010-05-01

    Dopamine (DA) modulates the response of the amygdala. However, the relation between dopaminergic neurotransmission in striatal and extrastriatal brain regions and amygdala reactivity to affective stimuli has not yet been established. To address this issue, we measured DA D2/D3 receptor (DRD2/3) availability in twenty-eight healthy men (nicotine-dependent smokers and never-smokers) using positron emission tomography with [18F]fallypride. In the same group of participants, amygdala response to unpleasant visual stimuli was determined using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. The effects of DRD2/3 availability in emotion-related brain regions and nicotine dependence on amygdala response to unpleasant stimuli were examined by multiple regression analysis. We observed enhanced prefrontal DRD2/3 availability in those individuals with higher amygdala response to unpleasant stimuli. As compared to never-smokers, smokers showed an attenuated amygdala BOLD response to unpleasant stimuli. Thus, individuals with high prefrontal DRD2/3 availability may be more responsive toward aversive and stressful information. Through this mechanism, dopaminergic neurotransmission might influence vulnerability for affective and anxiety disorders. Neuronal reactivity to unpleasant stimuli seems to be reduced by smoking. This observation could explain increased smoking rates in individuals with mental disorders. PMID:19904802

  20. 3D-2D Deformable Image Registration Using Feature-Based Nonuniform Meshes

    PubMed Central

    Guo, Xiaohu; Cai, Yiqi; Yang, Yin; Wang, Jing; Jia, Xun

    2016-01-01

    By using prior information of planning CT images and feature-based nonuniform meshes, this paper demonstrates that volumetric images can be efficiently registered with a very small portion of 2D projection images of a Cone-Beam Computed Tomography (CBCT) scan. After a density field is computed based on the extracted feature edges from planning CT images, nonuniform tetrahedral meshes will be automatically generated to better characterize the image features according to the density field; that is, finer meshes are generated for features. The displacement vector fields (DVFs) are specified at the mesh vertices to drive the deformation of original CT images. Digitally reconstructed radiographs (DRRs) of the deformed anatomy are generated and compared with corresponding 2D projections. DVFs are optimized to minimize the objective function including differences between DRRs and projections and the regularity. To further accelerate the above 3D-2D registration, a procedure to obtain good initial deformations by deforming the volume surface to match 2D body boundary on projections has been developed. This complete method is evaluated quantitatively by using several digital phantoms and data from head and neck cancer patients. The feature-based nonuniform meshing method leads to better results than either uniform orthogonal grid or uniform tetrahedral meshes. PMID:27019849

  1. [Bacteriological evaluation of a procedure for disinfecting the Olympus GIF-D2 panendoscope].

    PubMed

    Ramírez Ramos, A; Domínguez, N; Makino, R; Barrera, C

    1980-01-01

    We have performed a total of 107 cultures from three critical areas of an Olympus Panendoscope Model GIF-D2 in order to evaluate bacteriologically cur system of desinfection of this endoscope. Samples were taken from the distal end, external surface and biopsy canal before and after an endoscopic examination was performed. The procedure of desinfection employed was as follows: washing of the distal end, external surface and biopsy canal with Hexaclorophel (Phisohex) diluted 50% with water and a second washing with tap water. In the middle of the study, we added a second washing of the biopsy canal with ten ml. of ether alcohol to allow for better drying. As a result of the present study we observed that in the distal end in 50% of the samples we encountered bacteria. Cultures of the external surface were positive in 20% of samples. The biopsy canal should be washed with ether alcohol to allow for complete drying, because when we did not use this method, Pseudomonas Aeruginosa was isolated. After this modification we did not isolate bacteria. The most frequent types of isolated bacteria were from the normal oropharyngeal flora. From the present study we can conclude that desinfection of the Panendespe with Hexaclorophen gives satisfactory results on the external surface of the endoscope. Biopsy canal requires additional washing with ether alcohol. However, both procedures do not assure a satisfactory desinfection of the distal end.

  2. Inheritance of steroid-independent male sexual behavior in male offspring of B6D2F1 mice.

    PubMed

    McInnis, Christine M; Bonthuis, Paul J; Rissman, Emilie F; Park, Jin Ho

    2016-04-01

    The importance of gonadal steroids in modulating male sexual behavior is well established. Individual differences in male sexual behavior, independent of gonadal steroids, are prevalent across a wide range of species, including man. However, the genetic mechanisms underlying steroid-independent male sexual behavior are poorly understood. A high proportion of B6D2F1 hybrid male mice demonstrates steroid-independent male sexual behavior (identified as "maters"), providing a mouse model that opens up avenues of investigation into the mechanisms regulating male sexual behavior in the absence of gonadal hormones. Recent studies have revealed several proteins that play a significant factor in regulating steroid-independent male sexual behavior in B6D2F1 male mice, including amyloid precursor protein (APP), tau, and synaptophysin. The specific goals of our study were to determine whether steroid-independent male sexual behavior was a heritable trait by determining if it was dependent upon the behavioral phenotype of the B6D2F1 sire, and whether the differential expression of APP, tau, and synaptophysin in the medial preoptic area found in the B6D2F1 sires that did and did not mate after gonadectomy was similar to those found in their male offspring. After adult B6D2F1 male mice were bred with C57BL/6J female mice, they and their male offspring (BXB1) were orchidectomized and identified as either maters or "non-maters". A significant proportion of the BXB1 maters was sired only from B6D2F1 maters, indicating that the steroid-independent male sexual behavior behavioral phenotype of the B6D2F1 hybrid males, when crossed with C57BL/6J female mice, is inherited by their male offspring. Additionally, APP, tau, and synaptophysin were elevated in in the medial preoptic area in both the B6D2F1 and BXB1 maters relative to the B6D2F1 and BXB1 non-maters, respectively, suggesting a potential genetic mechanism for the inheritance of steroid-independent male sexual behavior.

  3. Loss of D2 dopamine receptor function modulates cocaine-induced glutamatergic synaptic potentiation in the ventral tegmental area.

    PubMed

    Madhavan, Anuradha; Argilli, Emanuela; Bonci, Antonello; Whistler, Jennifer L

    2013-07-24

    Potentiation of glutamate responses is a critical synaptic response to cocaine exposure in ventral tegmental area (VTA) neurons. However, the mechanism by which cocaine exposure promotes potentiation of NMDA receptors (NMDARs) and subsequently AMPA receptors (AMPARs) is not fully understood. In this study we demonstrate that repeated cocaine treatment causes loss of D2 dopamine receptor functional responses via interaction with lysosome-targeting G-protein-associated sorting protein1 (GASP1). We also show that the absence of D2 downregulation in GASP1-KO mice prevents cocaine-induced potentiation of NMDAR currents, elevation of the AMPA/NMDA ratio, and redistribution of NMDAR and AMPAR subunits to the membrane. As a pharmacological parallel, coadministration of the high-affinity D2 agonist, aripiprazole, reduces not only functional downregulation of D2s in response to cocaine but also potentiation of NMDAR and AMPAR responses in wild-type mice. Together these data suggest that functional loss of D2 receptors is a critical mechanism mediating cocaine-induced glutamate plasticity in VTA neurons.

  4. Loss of D2 Dopamine Receptor Function Modulates Cocaine-Induced Glutamatergic Synaptic Potentiation in the Ventral Tegmental Area

    PubMed Central

    Madhavan, Anuradha; Argilli, Emanuela; Bonci, Antonello

    2013-01-01

    Potentiation of glutamate responses is a critical synaptic response to cocaine exposure in ventral tegmental area (VTA) neurons. However, the mechanism by which cocaine exposure promotes potentiation of NMDA receptors (NMDARs) and subsequently AMPA receptors (AMPARs) is not fully understood. In this study we demonstrate that repeated cocaine treatment causes loss of D2 dopamine receptor functional responses via interaction with lysosome-targeting G-protein-associated sorting protein1 (GASP1). We also show that the absence of D2 downregulation in GASP1-KO mice prevents cocaine-induced potentiation of NMDAR currents, elevation of the AMPA/NMDA ratio, and redistribution of NMDAR and AMPAR subunits to the membrane. As a pharmacological parallel, coadministration of the high-affinity D2 agonist, aripiprazole, reduces not only functional downregulation of D2s in response to cocaine but also potentiation of NMDAR and AMPAR responses in wild-type mice. Together these data suggest that functional loss of D2 receptors is a critical mechanism mediating cocaine-induced glutamate plasticity in VTA neurons. PMID:23884939

  5. Photon Return On-Sky Test of Pulsed Sodium Laser Guide Star with D2b Repumping

    NASA Astrophysics Data System (ADS)

    Jin, Kai; Wei, Kai; Feng, Lu; Bo, Yong; Zuo, JunWei; Li, Min; Fu, HanChu; Dai, XiaoLin; Bian, Qi; Yao, Ji; Xu, Chang; Wang, ZhiChao; Peng, QingJun; Xue, XiangHui; Cheng, XueWu; Rao, ChangHui; Xu, ZuYan; Zhang, YuDong

    2015-08-01

    Sodium laser guide star (LGS) system has become one of the critical components in modern astronomical adaptive optics system (AOS), especially for the next-generation extremely large telescopes, such as the Thirty Meter Telescope and the European Extremely Large Telescope. Since the wavefront detection performance of AOS is directly related to the brightness of LGS, it is important for AOS to maximize its photon generation efficiency by all means. Sodium D2b line repumping is such a technique that can greatly increase the returned photons for either sodium continuous wave (CW) laser or pulsed laser. This technique has been studied theoretically and field tested with a 20 W CW laser by European Southern Observatory team. However, field test results of a 20 W class pulsed laser with D2b repumping have not been reported yet. In this paper, our latest field test results with theoretical comparison of D2b repumping with a 20 W quasi-continuous wave (QCW) pulsed laser will be presented. With a linearly polarized beam, approximate 40% photon return enhancement was achieved when 10% of laser power was detuned to D2b line, which agreed well with results from a rate equation-based Monte Carlo photon return simulation program. Both experiment and simulation results indicate that with a higher laser intensity projected at the sodium layer, the D2b repumping will be more effective.

  6. Loss of D2 dopamine receptor function modulates cocaine-induced glutamatergic synaptic potentiation in the ventral tegmental area.

    PubMed

    Madhavan, Anuradha; Argilli, Emanuela; Bonci, Antonello; Whistler, Jennifer L

    2013-07-24

    Potentiation of glutamate responses is a critical synaptic response to cocaine exposure in ventral tegmental area (VTA) neurons. However, the mechanism by which cocaine exposure promotes potentiation of NMDA receptors (NMDARs) and subsequently AMPA receptors (AMPARs) is not fully understood. In this study we demonstrate that repeated cocaine treatment causes loss of D2 dopamine receptor functional responses via interaction with lysosome-targeting G-p