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Sample records for bicaudal d2 dynein

  1. A role for Bicaudal-D2 in radial cerebellar granule cell migration

    NARCIS (Netherlands)

    Jaarsma, Dick; van den Berg, Robert; Wulf, Phebe S; van Erp, Susan; Keijzer, Nanda; Schlager, Max A; de Graaff, Esther; De Zeeuw, Chris I; Pasterkamp, R Jeroen; Akhmanova, Anna; Hoogenraad, Casper C

    2014-01-01

    Bicaudal-D (BICD) belongs to an evolutionary conserved family of dynein adaptor proteins. It was first described in Drosophila as an essential factor in fly oogenesis and embryogenesis. Missense mutations in a human BICD homologue, BICD2, have been linked to a dominant mild early onset form of spina

  2. Bicaudal-D uses a parallel, homodimeric coiled coil with heterotypic registry to coordinate recruitment of cargos to dynein.

    Science.gov (United States)

    Liu, Yang; Salter, Hannah K; Holding, Andrew N; Johnson, Christopher M; Stephens, Elaine; Lukavsky, Peter J; Walshaw, John; Bullock, Simon L

    2013-06-01

    Cytoplasmic dynein is the major minus end-directed microtubule motor in eukaryotes. However, there is little structural insight into how different cargos are recognized and linked to the motor complex. Here we describe the 2.2 Å resolution crystal structure of a cargo-binding region of the dynein adaptor Bicaudal-D (BicD), which reveals a parallel coiled-coil homodimer. We identify a shared binding site for two cargo-associated proteins-Rab6 and the RNA-binding protein Egalitarian (Egl)-within a region of the BicD structure with classical, homotypic core packing. Structure-based mutagenesis in Drosophila provides evidence that occupancy of this site drives association of BicD with dynein, thereby coupling motor recruitment to cargo availability. The structure also contains a region in which, remarkably, the same residues in the polypeptide sequence have different heptad registry in each chain. In vitro and in vivo analysis of a classical Drosophila dominant mutation reveals that this heterotypic region regulates the recruitment of dynein to BicD. Our results support a model in which the heterotypic segment is part of a molecular switch that promotes release of BicD autoinhibition following cargo binding to the neighboring, homotypic coiled-coil region. Overall, our data reveal a pivotal role of a highly asymmetric coiled-coil domain in coordinating the assembly of cargo-motor complexes. PMID:23723415

  3. Bicaudal-D uses a parallel, homodimeric coiled coil with heterotypic registry to coordinate recruitment of cargos to dynein

    OpenAIRE

    Yang LIU; Salter, Hannah K.; Holding, Andrew N.; Johnson, Christopher M.; Stephens, Elaine; Lukavsky, Peter J.; Walshaw, John; Bullock, Simon L.

    2013-01-01

    Cargo transport by the microtubule motor dynein is critical to diverse cellular processes. However, little is known about how different cargos are recognized and linked to this motor complex. Here, Liu et al. investigate the cargo-binding region of the dynein adaptor BicD in Drosophila. They provide a crystal structure of BicD and identify a shared binding site for two cargo-associated proteins: Rab6 and the RNA-binding protein Egl. This study provides structural insight into the molecular in...

  4. Crystallographic characterization of the C-terminal coiled-coil region of mouse Bicaudal-D1 (BICD1).

    Science.gov (United States)

    Terawaki, Shin-ichi; Ootsuka, Hiroki; Higuchi, Yoshiki; Wakamatsu, Kaori

    2014-08-01

    Bicaudal-D1 (BICD1) is an α-helical coiled-coil protein which is evolutionarily conserved from Drosophila to mammals and facilitates the attachment of specific cargo factors to the dynein motor complex. The C-terminal coiled-coil region (CC3) of BICD1 plays an important role in sorting cargo, linking proteins such as the small GTPase Rab6 and the nuclear pore complex component Ran-binding protein 2 (RanBP2) to the dynein motor complex. This report describes the crystallization and X-ray data collection of the BICD1 CC3 region, as well as the preparation of the complex of BICD1 CC3 with a constitutively active mutant of Rab6. The crystals of the BICD1 CC3 region belonged to space group C2, with unit-cell parameters a = 59.0, b = 36.8, c = 104.3 Å, α = γ = 90, β = 99.8°. The X-ray diffraction data set was collected to 1.50 Å resolution. PMID:25084392

  5. Bicaudate diameter - the most specific and simple CT parameter in the diagnosis of Huntington's disease

    International Nuclear Information System (INIS)

    In addition to the neurological findings, the functional capacity of 12 patients with Huntington's disease was evaluated quantitatively according to the Shoulson and Fahn scale. This parameter was related to the following computed tomographic measurements: the greatest distance between the frontal horns (FH), the shortest distance between the heads of the caudate nuclei (bicaudate diameter, CC) and the quotient FH/CC. The ratio of the bicaudate diameter and the external diameter of the skull across the narrowest point of the heads of the caudate nuclei (CC/QTsub(cc)) was also need, as well as the bicaudate diameter and the maximum internal diameter of the skull (CC/ITsub(max)). The best correlation was found between the bicaudate diameter and functional capacity (r=-0.64, P<0.05). All the quotients containing the bicaudate diameter likewise showed a correlation with functional capacity, though to a less marked degree. Thus the bicaudate diameter appears to be the most specific and simple computed tomographic parameter for the differentiation of Huntington's disease from normal states or choreatic syndromes of different origin. (orig.)

  6. Structural basis for cargo binding and autoinhibition of Bicaudal-D1 by a parallel coiled-coil with homotypic registry

    International Nuclear Information System (INIS)

    Bicaudal-D1 (BICD1) is an α-helical coiled-coil protein mediating the attachment of specific cargo to cytoplasmic dynein. It plays an essential role in minus end-directed intracellular transport along microtubules. The third C-terminal coiled-coil region of BICD1 (BICD1 CC3) has an important role in cargo sorting, including intracellular vesicles associating with the small GTPase Rab6 and the nuclear pore complex Ran binding protein 2 (RanBP2), and inhibiting the association with cytoplasmic dynein by binding to the first N-terminal coiled-coil region (CC1). The crystal structure of BICD1 CC3 revealed a parallel homodimeric coiled-coil with asymmetry and complementary knobs-into-holes interactions, differing from Drosophila BicD CC3. Furthermore, our binding study indicated that BICD1 CC3 possesses a binding surface for two distinct cargos, Rab6 and RanBP2, and that the CC1-binding site overlaps with the Rab6-binding site. These findings suggest a molecular basis for cargo recognition and autoinhibition of BICD proteins during dynein-dependent intracellular retrograde transport. - Highlights: • BICD1 CC3 is a parallel homodimeric coiled-coil with axial asymmetry. • The coiled-coil packing of BICD1 CC3 is adapted to the equivalent heptad position. • BICD1 CC3 has distinct binding sites for two classes of cargo, Rab6 and RanBP2. • The CC1-binding site of BICD1 CC3 overlaps with the Rab6-binding site

  7. Structural basis for cargo binding and autoinhibition of Bicaudal-D1 by a parallel coiled-coil with homotypic registry

    Energy Technology Data Exchange (ETDEWEB)

    Terawaki, Shin-ichi, E-mail: terawaki@gunma-u.ac.jp [Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan); SPring-8 Center, RIKEN, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan); Yoshikane, Asuka [Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan); SPring-8 Center, RIKEN, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan); Higuchi, Yoshiki [Department of Life Science, Graduate School of Life Science, University of Hyogo, 3-2-1 Koto, Kamigori-cho, Ako-gun, Hyogo 678-1297 (Japan); Department of Picobiology, Graduate School of Life Science, University of Hyogo, 3-2-1 Koto, Kamigori-cho, Ako-gun, Hyogo 678-1297 (Japan); SPring-8 Center, RIKEN, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan); Wakamatsu, Kaori [Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515 (Japan); SPring-8 Center, RIKEN, 1-1-1 Koto, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan)

    2015-05-01

    Bicaudal-D1 (BICD1) is an α-helical coiled-coil protein mediating the attachment of specific cargo to cytoplasmic dynein. It plays an essential role in minus end-directed intracellular transport along microtubules. The third C-terminal coiled-coil region of BICD1 (BICD1 CC3) has an important role in cargo sorting, including intracellular vesicles associating with the small GTPase Rab6 and the nuclear pore complex Ran binding protein 2 (RanBP2), and inhibiting the association with cytoplasmic dynein by binding to the first N-terminal coiled-coil region (CC1). The crystal structure of BICD1 CC3 revealed a parallel homodimeric coiled-coil with asymmetry and complementary knobs-into-holes interactions, differing from Drosophila BicD CC3. Furthermore, our binding study indicated that BICD1 CC3 possesses a binding surface for two distinct cargos, Rab6 and RanBP2, and that the CC1-binding site overlaps with the Rab6-binding site. These findings suggest a molecular basis for cargo recognition and autoinhibition of BICD proteins during dynein-dependent intracellular retrograde transport. - Highlights: • BICD1 CC3 is a parallel homodimeric coiled-coil with axial asymmetry. • The coiled-coil packing of BICD1 CC3 is adapted to the equivalent heptad position. • BICD1 CC3 has distinct binding sites for two classes of cargo, Rab6 and RanBP2. • The CC1-binding site of BICD1 CC3 overlaps with the Rab6-binding site.

  8. Lipid Rafts Assemble Dynein Ensembles.

    Science.gov (United States)

    Nirschl, Jeffrey J; Ghiretti, Amy E; Holzbaur, Erika L F

    2016-05-01

    New work by Rai et al. identifies a novel mechanism regulating phagosome transport in cells: the clustering of dynein motors into lipid microdomains, leading to enhanced unidirectional motility. Clustering may be especially important for dynein, a motor that works most efficiently in teams. PMID:27061495

  9. Bicaudal is a conserved substrate for Drosophila and mammalian caspases and is essential for cell survival.

    Directory of Open Access Journals (Sweden)

    Emma M Creagh

    Full Text Available Members of the caspase family of cysteine proteases coordinate cell death through restricted proteolysis of diverse protein substrates and play a conserved role in apoptosis from nematodes to man. However, while numerous substrates for the mammalian cell death-associated caspases have now been described, few caspase substrates have been identified in other organisms. Here, we have utilized a proteomics-based approach to identify proteins that are cleaved by caspases during apoptosis in Drosophila D-Mel2 cells, a subline of the Schneider S2 cell line. This approach identified multiple novel substrates for the fly caspases and revealed that bicaudal/betaNAC is a conserved substrate for Drosophila and mammalian caspases. RNAi-mediated silencing of bicaudal expression in Drosophila D-Mel2 cells resulted in a block to proliferation, followed by spontaneous apoptosis. Similarly, silencing of expression of the mammalian bicaudal homologue, betaNAC, in HeLa, HEK293T, MCF-7 and MRC5 cells also resulted in spontaneous apoptosis. These data suggest that bicaudal/betaNAC is essential for cell survival and is a conserved target of caspases from flies to man.

  10. Bicaudal is a conserved substrate for Drosophila and mammalian caspases and is essential for cell survival.

    LENUS (Irish Health Repository)

    Creagh, Emma M

    2009-01-01

    Members of the caspase family of cysteine proteases coordinate cell death through restricted proteolysis of diverse protein substrates and play a conserved role in apoptosis from nematodes to man. However, while numerous substrates for the mammalian cell death-associated caspases have now been described, few caspase substrates have been identified in other organisms. Here, we have utilized a proteomics-based approach to identify proteins that are cleaved by caspases during apoptosis in Drosophila D-Mel2 cells, a subline of the Schneider S2 cell line. This approach identified multiple novel substrates for the fly caspases and revealed that bicaudal\\/betaNAC is a conserved substrate for Drosophila and mammalian caspases. RNAi-mediated silencing of bicaudal expression in Drosophila D-Mel2 cells resulted in a block to proliferation, followed by spontaneous apoptosis. Similarly, silencing of expression of the mammalian bicaudal homologue, betaNAC, in HeLa, HEK293T, MCF-7 and MRC5 cells also resulted in spontaneous apoptosis. These data suggest that bicaudal\\/betaNAC is essential for cell survival and is a conserved target of caspases from flies to man.

  11. Structure of human cytoplasmic dynein-2 primed for its powerstroke

    OpenAIRE

    Schmidt, Helgo; Zalyte, Ruta; Urnavicius, Linas; Carter, Andrew P.

    2014-01-01

    Members of the dynein family, consisting of cytoplasmic and axonemal isoforms, are motors that move towards the minus ends of microtubules. Cytoplasmic dynein-1 (dynein-1) plays roles in mitosis and cellular cargo transport 1 , and is implicated in viral infections 2 and neurodegenerative diseases 3 . Cytoplasmic dynein-2 (dynein-2) carries out intraflagellar transport 4 and is associated with human skeletal ciliopathies 5 . Dyneins share a conserved motor domain that couples cycles of ATP hy...

  12. Cytoplasmic Dynein Promotes HIV-1 Uncoating

    OpenAIRE

    Paulina Pawlica; Lionel Berthoux

    2014-01-01

    Retroviral capsid (CA) cores undergo uncoating during their retrograde transport (toward the nucleus), and/or after reaching the nuclear membrane. However, whether HIV-1 CA core uncoating is dependent upon its transport is not understood. There is some evidence that HIV-1 cores retrograde transport involves cytoplasmic dynein complexes translocating on microtubules. Here we investigate the role of dynein-dependent transport in HIV-1 uncoating. To interfere with dynein function, we depleted d...

  13. Structural biology of cytoplasmic and axonemal dyneins.

    Science.gov (United States)

    Ishikawa, Takashi

    2012-08-01

    Dyneins are microtubule-based, ATP-driven motor proteins with six tandemly linked AAA+ domains, a long N-terminal tail and a coiled-coil stalk. Cytoplasmic dyneins function as individual homodimers and are responsible for minus-end-oriented transport along microtubules. Axonemal dyneins of flagella/cilia are anchored in arrays to peripheral microtubule doublets by their N-terminal tails, and generate sliding motions of adjacent microtubule doublets toward the plus end. The coiled-coil stalk is responsible for communication between the AAA+ domains and the microtubule binding domain. A number of isoforms of axonemal dyneins are integrated to generate bending motion. In this article I will review recent structural studies and address the question as to how dyneins generate force and cause bending in flagella/cilia. PMID:22664481

  14. Model for bidirectional movement of cytoplasmic dynein

    CERN Document Server

    Sumathy, S

    2014-01-01

    Cytoplasmic dynein exhibits a directional processive movement on microtubule filaments and is known to move in steps of varying length based on the number of ATP molecules bound to it and the load that it carries. It is experimentally observed that dynein takes occasional backward steps and the frequency of such backward steps increases as the load approaches the stall force. Using a stochastic process model, we investigate the bidirectional movement of single head of a dynein motor. The probability for backward step is implemented based on Crook's fluctuation theorem of non-equilibrium statistical mechanics. We find that the movement of dynein motor is characterized with negative velocity implying backward motion beyond stall force. We observe that the motor moves backward for super stall forces by hydrolyzing the ATP exactly the same way as it does while moving forward for sub stall forces.

  15. Crystal Structure of the Dynein Motor Domain

    OpenAIRE

    Carter, Andrew P.; Cho, Carol; Jin, Lan; Vale, Ronald D.

    2011-01-01

    Dyneins are microtubule-based motor proteins that power ciliary beating, transport intracellular cargos, and help to construct the mitotic spindle. Evolved from ring-shaped hexameric AAA-family adenosine triphosphatases (ATPases), dynein’s large size and complexity have posed challenges for understanding its structure and mechanism. Here, we present a 6 angstrom crystal structure of a functional dimer of two ~300-kilodalton motor domains of yeast cytoplasmic dynein. The structure reveals an u...

  16. Neuronal migration defects in the Loa dynein mutant mouse

    OpenAIRE

    Ori-McKenney Kassandra M; Vallee Richard B

    2011-01-01

    Abstract Background Cytoplasmic dynein and its regulatory proteins have been implicated in neuronal and non-neuronal cell migration. A genetic model for analyzing the role of cytoplasmic dynein specifically in these processes has, however, been lacking. The Loa (Legs at odd angles) mouse with a mutation in the dynein heavy chain has been the focus of an increasing number of studies for its role in neuron degeneration. Despite the location of this mutation in the tail domain of the dynein heav...

  17. Cytoplasmic dynein promotes HIV-1 uncoating.

    Science.gov (United States)

    Pawlica, Paulina; Berthoux, Lionel

    2014-11-01

    Retroviral capsid (CA) cores undergo uncoating during their retrograde transport (toward the nucleus), and/or after reaching the nuclear membrane. However, whether HIV-1 CA core uncoating is dependent upon its transport is not understood. There is some evidence that HIV-1 cores retrograde transport involves cytoplasmic dynein complexes translocating on microtubules. Here we investigate the role of dynein-dependent transport in HIV-1 uncoating. To interfere with dynein function, we depleted dynein heavy chain (DHC) using RNA interference, and we over-expressed p50/dynamitin. In immunofluorescence microscopy experiments, DHC depletion caused an accumulation of CA foci in HIV-1 infected cells. Using a biochemical assay to monitor HIV-1 CA core disassembly in infected cells, we observed an increase in amounts of intact (pelletable) CA cores upon DHC depletion or p50 over-expression. Results from these two complementary assays suggest that inhibiting dynein-mediated transport interferes with HIV-1 uncoating in infected cells, indicating the existence of a functional link between HIV-1 transport and uncoating. PMID:25375884

  18. Cytoplasmic Dynein Promotes HIV-1 Uncoating

    Directory of Open Access Journals (Sweden)

    Paulina Pawlica

    2014-11-01

    Full Text Available Retroviral capsid (CA cores undergo uncoating during their retrograde transport (toward the nucleus, and/or after reaching the nuclear membrane. However, whether HIV-1 CA core uncoating is dependent upon its transport is not understood. There is some evidence that HIV-1 cores retrograde transport involves cytoplasmic dynein complexes translocating on microtubules. Here we investigate the role of dynein-dependent transport in HIV-1 uncoating. To interfere with dynein function, we depleted dynein heavy chain (DHC using RNA interference, and we over-expressed p50/dynamitin. In immunofluorescence microscopy experiments, DHC depletion caused an accumulation of CA foci in HIV-1 infected cells. Using a biochemical assay to monitor HIV-1 CA core disassembly in infected cells, we observed an increase in amounts of intact (pelletable CA cores upon DHC depletion or p50 over-expression. Results from these two complementary assays suggest that inhibiting dynein-mediated transport interferes with HIV-1 uncoating in infected cells, indicating the existence of a functional link between HIV-1 transport and uncoating.

  19. The dynein cortical anchor Num1 activates dynein motility by relieving Pac1/LIS1-mediated inhibition.

    Science.gov (United States)

    Lammers, Lindsay G; Markus, Steven M

    2015-10-26

    Cortically anchored dynein orients the spindle through interactions with astral microtubules. In budding yeast, dynein is offloaded to Num1 receptors from microtubule plus ends. Rather than walking toward minus ends, dynein remains associated with plus ends due in part to its association with Pac1/LIS1, an inhibitor of dynein motility. The mechanism by which dynein is switched from "off" at the plus ends to "on" at the cell cortex remains unknown. Here, we show that overexpression of the coiled-coil domain of Num1 specifically depletes dynein-dynactin-Pac1/LIS1 complexes from microtubule plus ends and reduces dynein-Pac1/LIS1 colocalization. Depletion of dynein from plus ends requires its microtubule-binding domain, suggesting that motility is required. An enhanced Pac1/LIS1 affinity mutant of dynein or overexpression of Pac1/LIS1 rescues dynein plus end depletion. Live-cell imaging reveals minus end-directed dynein-dynactin motility along microtubules upon overexpression of the coiled-coil domain of Num1, an event that is not observed in wild-type cells. Our findings indicate that dynein activity is directly switched "on" by Num1, which induces Pac1/LIS1 removal. PMID:26483554

  20. Neuronal migration defects in the Loa dynein mutant mouse

    Directory of Open Access Journals (Sweden)

    Ori-McKenney Kassandra M

    2011-05-01

    Full Text Available Abstract Background Cytoplasmic dynein and its regulatory proteins have been implicated in neuronal and non-neuronal cell migration. A genetic model for analyzing the role of cytoplasmic dynein specifically in these processes has, however, been lacking. The Loa (Legs at odd angles mouse with a mutation in the dynein heavy chain has been the focus of an increasing number of studies for its role in neuron degeneration. Despite the location of this mutation in the tail domain of the dynein heavy chain, we previously found a striking effect on coordination between the two dynein motor domains, resulting in a defect in dynein run length in vitro and in vivo. Results We have now tested for effects of the Loa mutation on neuronal migration in the developing neocortex. Loa homozygotes showed clear defects in neocortical lamination and neuronal migration resulting from a reduction in the rate of radial migration of bipolar neurons. Conclusions These results present a new genetic model for understanding the dynein pathway and its functions during neuronal migration. They also provide the first evidence for a link between dynein processivity and somal movement, which is essential for proper development of the brain.

  1. Autoregulatory Mechanism for Dynactin Control of Processive and Diffusive Dynein Transport

    OpenAIRE

    Tripathy, Suvranta K.; Weil, Sarah J.; Chen, Chen; Anand, Preetha; Vallee, Richard B.; Gross, Steven P.

    2014-01-01

    Dynactin is the longest known cytoplasmic dynein regulator, with roles in dynein recruitment to subcellular cargo and in stimulating processive dynein movement. The latter function was thought to involve the N-terminal microtubule binding region of the major dynactin polypeptide p150 Glued , though recent results disputed this. To understand how dynactin regulates dynein we generated recombinant fragments of the N-terminal half of p150 Glued . We find that the dynein-binding coiled-coil α-hel...

  2. Crystal clear insights into how the dynein motor moves.

    Science.gov (United States)

    Carter, Andrew P

    2013-02-01

    Dyneins are motor proteins that move along microtubules. They have many roles in the cell. They drive the beating of cilia and flagella, move cargos in the cytoplasm and function in the mitotic spindle. Dyneins are large and complex protein machines. Until recently, the way they move was poorly understood. In 2012, two high-resolution crystal structures of the >2500-amino-acid dynein motor domain were published. This Commentary will compare these structures and integrate the findings with other recent studies in order to suggest how dynein works. The dynein motor produces movement in a manner that is distinct from myosin and kinesin, the other cytoskeletal motors. Its powerstroke is produced by ATP-induced remodelling of a protein domain known as the linker. It binds to microtubules through a small domain at the tip of a long stalk. Dynein communicates with the microtubule-binding domain by an unconventional sliding movement of the helices in the stalk coiled-coil. Even the way the two motor domains in a dynein dimer walk processively along the microtubule is unusual. PMID:23525020

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

    OpenAIRE

    Kayserili Karabey, Hülya; Schmidts, Miriam; Hou, Yuqing; Cortes, 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; 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. W...

  4. Catch bond mechanism in Dynein motor driven collective transport

    CERN Document Server

    Nair, Anil; Mitra, Mithun K; Muhuri, Sudipto; Chaudhuri, Abhishek

    2016-01-01

    Recent experiments have demonstrated that dynein motor exhibits catch bonding behaviour, in which the unbinding rate of a single dynein decreases with increasing force, for a certain range of force. Motivated by these experiments, we propose a model for catch bonding in dynein using a threshold force bond deformation (TFBD) model wherein catch bonding sets in beyond a critical applied load force. We study the effect of catch bonding on unidirectional transport properties of cellular cargo carried by multiple dynein motors within the framework of this model. We find catch bonding can result in dramatic changes in the transport properties, which are in sharp contrast to kinesin driven unidirectional transport, where catch bonding is absent. We predict that, under certain conditions, the average velocity of the cellular cargo can actually increase as applied load is increased. We characterize the transport properties in terms of a velocity profile phase plot in the parameter space of the catch bond strength and ...

  5. A structural model reveals energy transduction in dynein

    OpenAIRE

    Serohijos, Adrian W. R.; Chen, Yiwen; Ding, Feng; Elston, Timothy C.; Dokholyan, Nikolay V.

    2006-01-01

    Intracellular active transport is driven by ATP-hydrolyzing motor proteins that move along cytoskeletal filaments. In particular, the microtubule-associated dynein motor is involved in the transport of organelles and vesicles, the maintenance of the Golgi, and mitosis. However, unlike kinesin and myosin, the mechanism by which dynein converts chemical energy into mechanical force remains largely a mystery, due primarily to the lack of a high-resolution molecular structure. Using homology mode...

  6. Dlic1 deficiency impairs ciliogenesis of photoreceptors by destabilizing dynein

    Institute of Scientific and Technical Information of China (English)

    Shanshan Kong; Xinrong Du; Chao Peng; Yiming Wu; Huirong Li; Xi Jin; Ling Hou

    2013-01-01

    Cytoplasmic dynein 1 is fundamentally important for transporting a variety of essential cargoes along microtubules within eukaryotic cells.However,in mammals,few mutants are available for studying the effects of defects in dynein-controlled processes in the context of the whole organism.Here,we deleted mouse Dlic1 gene encoding DLIC1,a subunit of the dynein complex.Dlic1-/-mice are viable,but display severe photoreceptor degeneration.Ablation of Dlic1 results in ectopic accumulation of outer segment (OS) proteins,and impairs OS growth and ciliogenesis of photoreceptors by interfering with Rabll-vesicle trafficking and blocking efficient OS protein transport from Golgi to the basal body.Our studies show that Dlic1 deficiency partially blocks vesicle export from endoplasmic reticulum (ER),but seems not to affect vesicle transport from the ER to Golgi.Further mechanistic study reveals that lack of Dlic1 destabilizes dynein subunits and alters the normal subcellular distribution of dynein in photoreceptors,probably due to the impaired transport function of dynein.Our results demonstrate that Dlic1 plays important roles in ciliogenesis and protein transport to the OS,and is required for photoreceptor development and survival.The Dlic1-/-mice also provide a new mouse model to study human retinal degeneration.

  7. A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein

    OpenAIRE

    Gleave, Emma S.; Schmidt, Helgo; Carter, Andrew P.

    2014-01-01

    Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor do...

  8. Model for Unidirectional Movement of Axonemal and Cytoplasmic Dynein Molecules

    Institute of Scientific and Technical Information of China (English)

    Ping XIE; Shuo-Xing DOU; Peng-Ye WANG

    2006-01-01

    A model for the unidirectional movement of dynein is presented based on the structural observations and biochemical experimental results available. In this model, the binding affinity of dynein for microtubule (MT) is independent of its nucleotide state and the change between strong and weak MT-binding is determined naturally by the variation of relative orientation between the stalk and MT, as the stalk rotates following nucleotide-state transition. Thus the enigmatic communication from the adenosine triphosphate (ATP)-binding site in the globular domain to the far MT-binding site in the tip of the stalk, which is a prerequisite in conventional models, is not required. Using the present model, the previous experimental results such as the effect of ATP and adenosine diphosphate (ADP) bindings on dissociation of dynein from MT, the movement of single-headed axonemal dyneins at saturating ATP concentration, the load dependence of step-size for the movement of two-headed cytoplasmic dyneins and the dependence of stall force on ATP concentration can be well explained.

  9. CMF70 is a subunit of the dynein regulatory complex.

    Science.gov (United States)

    Kabututu, Zakayi P; Thayer, Michelle; Melehani, Jason H; Hill, Kent L

    2010-10-15

    Flagellar motility drives propulsion of several important pathogens and is essential for human development and physiology. Motility of the eukaryotic flagellum requires coordinate regulation of thousands of dynein motors arrayed along the axoneme, but the proteins underlying dynein regulation are largely unknown. The dynein regulatory complex, DRC, is recognized as a focal point of axonemal dynein regulation, but only a single DRC subunit, trypanin/PF2, is currently known. The component of motile flagella 70 protein, CMF70, is broadly and uniquely conserved among organisms with motile flagella, suggesting a role in axonemal motility. Here we demonstrate that CMF70 is part of the DRC from Trypanosoma brucei. CMF70 is located along the flagellum, co-sediments with trypanin in sucrose gradients and co-immunoprecipitates with trypanin. RNAi knockdown of CMF70 causes motility defects in a wild-type background and suppresses flagellar paralysis in cells with central pair defects, thus meeting the functional definition of a DRC subunit. Trypanin and CMF70 are mutually conserved in at least five of six extant eukaryotic clades, indicating that the DRC was probably present in the last common eukaryotic ancestor. We have identified only the second known subunit of this ubiquitous dynein regulatory system, highlighting the utility of combined genomic and functional analyses for identifying novel subunits of axonemal sub-complexes. PMID:20876659

  10. Schwann cell myelination requires Dynein function

    Directory of Open Access Journals (Sweden)

    Langworthy Melissa M

    2012-11-01

    Full Text Available Abstract Background Interaction of Schwann cells with axons triggers signal transduction that drives expression of Pou3f1 and Egr2 transcription factors, which in turn promote myelination. Signal transduction appears to be mediated, at least in part, by cyclic adenosine monophosphate (cAMP because elevation of cAMP levels can stimulate myelination in the absence of axon contact. The mechanisms by which the myelinating signal is conveyed remain unclear. Results By analyzing mutations that disrupt myelination in zebrafish, we learned that Dynein cytoplasmic 1 heavy chain 1 (Dync1h1, which functions as a motor for intracellular molecular trafficking, is required for peripheral myelination. In dync1h1 mutants, Schwann cell progenitors migrated to peripheral nerves but then failed to express Pou3f1 and Egr2 or make myelin membrane. Genetic mosaic experiments revealed that robust Myelin Basic Protein expression required Dync1h1 function within both Schwann cells and axons. Finally, treatment of dync1h1 mutants with a drug to elevate cAMP levels stimulated myelin gene expression. Conclusion Dync1h1 is required for retrograde transport in axons and mutations of Dync1h1 have been implicated in axon disease. Our data now provide evidence that Dync1h1 is also required for efficient myelination of peripheral axons by Schwann cells, perhaps by facilitating signal transduction necessary for myelination.

  11. The primary structure of rat brain (cytoplasmic) dynein heavy chain, a cytoplasmic motor enzyme.

    OpenAIRE

    Zhang, Z.; Tanaka, Y.; Nonaka, S; Aizawa, H.; Kawasaki, H; Nakata, T; Hirokawa, N

    1993-01-01

    Overlapping cDNA clones encoding the heavy chain of rat brain cytoplasmic dynein have been isolated. The isolated cDNA clones contain an open reading frame of 13,932 bp encoding 4644 aa (M(r), 532,213). The deduced protein sequence of the heavy chain of rat brain dynein shows significant similarity to sea urchin flagellar beta-dynein (27.0% identical) and to Dictyostelium cytoplasmic dynein (53.5% identical) throughout the entire sequence. The heavy chain of rat brain (cytoplasmic) dynein con...

  12. The Third P-loop Domain in Cytoplasmic Dynein Heavy Chain Is Essential for Dynein Motor Function and ATP-sensitive Microtubule Binding

    OpenAIRE

    Silvanovich, Andre; Li, Min-gang; Serr, Madeline; Mische, Sarah; Hays, Thomas S.

    2003-01-01

    Sequence comparisons and structural analyses show that the dynein heavy chain motor subunit is related to the AAA family of chaperone-like ATPases. The core structure of the dynein motor unit derives from the assembly of six AAA domains into a hexameric ring. In dynein, the first four AAA domains contain consensus nucleotide triphosphate-binding motifs, or P-loops. The recent structural models of dynein heavy chain have fostered the hypothesis that the energy derived from hydrolysis at P-loop...

  13. Review: Structure and mechanism of the dynein motor ATPase.

    Science.gov (United States)

    Schmidt, Helgo; Carter, Andrew P

    2016-08-01

    Dyneins are multiprotein complexes that move cargo along microtubules in the minus end direction. The largest individual component of the dynein complex is the heavy chain. Its C-terminal 3500 amino-acid residues form the motor domain, which hydrolyses ATP in its ring of AAA+ (ATPases associated with diverse cellular activities) domains to generate the force for movement. The production of force is synchronized with cycles of microtubule binding and release, another important prerequisite for efficient motility along the microtubule. Although the large scale conformational changes that lead to force production and microtubule affinity regulation are well established, it has been largely enigmatic how ATP-hydrolysis in the AAA+ ring causes these rearrangements. The past five years have seen a surge of high resolution information on the dynein motor domain that finally allowed unprecedented insights into this important open question. This review, part of the "ATP and GTP hydrolysis in Biology" special issue, will summarize our current understanding of the dynein motor mechanism with a special emphasis on the recently obtained crystal and EM structures. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 557-567, 2016. PMID:27062277

  14. Nuclear migration: rock and roll facilitated by dynein and kinesin.

    Science.gov (United States)

    Zhang, Xiaochang; Han, Min

    2010-12-01

    The nucleus encounters other organelles as well as high cytoplasmic pressures during its migration within the cell. A new study describes how the action of kinesin and dynein motors is coordinated at the nuclear envelope to rock and roll the nucleus in Caenorhabditis elegans. PMID:21145020

  15. D2-tree

    DEFF Research Database (Denmark)

    Brodal, Gerth Stølting; Sioutas, Spyros; Pantazos, Kostas;

    2015-01-01

    We present a new overlay, called the Deterministic Decentralized tree (D2-tree). The D2-tree compares favorably to other overlays for the following reasons: (a) it provides matching and better complexities, which are deterministic for the supported operations; (b) the management of nodes (peers...

  16. Cell cycle-dependent microtubule-based dynamic transport of cytoplasmic dynein in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Takuya Kobayashi

    Full Text Available BACKGROUND: Cytoplasmic dynein complex is a large multi-subunit microtubule (MT-associated molecular motor involved in various cellular functions including organelle positioning, vesicle transport and cell division. However, regulatory mechanism of the cell-cycle dependent distribution of dynein has not fully been understood. METHODOLOGY/PRINCIPAL FINDINGS: Here we report live-cell imaging of cytoplasmic dynein in HeLa cells, by expressing multifunctional green fluorescent protein (mfGFP-tagged 74-kDa intermediate chain (IC74. IC74-mfGFP was successfully incorporated into functional dynein complex. In interphase, dynein moved bi-directionally along with MTs, which might carry cargos such as transport vesicles. A substantial fraction of dynein moved toward cell periphery together with EB1, a member of MT plus end-tracking proteins (+TIPs, suggesting +TIPs-mediated transport of dynein. In late-interphase and prophase, dynein was localized at the centrosomes and the radial MT array. In prometaphase and metaphase, dynein was localized at spindle MTs where it frequently moved from spindle poles toward chromosomes or cell cortex. +TIPs may be involved in the transport of spindle dyneins. Possible kinetochore and cortical dyneins were also observed. CONCLUSIONS AND SIGNIFICANCE: These findings suggest that cytoplasmic dynein is transported to the site of action in preparation for the following cellular events, primarily by the MT-based transport. The MT-based transport may have greater advantage than simple diffusion of soluble dynein in rapid and efficient transport of the limited concentration of the protein.

  17. Direction of force generated by the inner row of dynein arms on flagellar microtubules

    OpenAIRE

    1987-01-01

    Our goal was to determine the direction of force generation of the inner dynein arms in flagellar axonemes. We developed an efficient means of extracting the outer row of dynein arms in demembranated sperm tail axonemes, leaving the inner row of dynein arms structurally and functionally intact. Sperm tail axonemes depleted of outer arms beat at half the beat frequency of sperm tails with intact arms over a wide range of ATP concentrations. The isolated, outer arm-depleted axonemes were induce...

  18. A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein.

    Science.gov (United States)

    Gleave, Emma S; Schmidt, Helgo; Carter, Andrew P

    2014-06-01

    Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. PMID:24680784

  19. Diverse Roles of Axonemal Dyneins in Drosophila Auditory Neuron Function and Mechanical Amplification in Hearing

    Science.gov (United States)

    Karak, Somdatta; Jacobs, Julie S.; Kittelmann, Maike; Spalthoff, Christian; Katana, Radoslaw; Sivan-Loukianova, Elena; Schon, Michael A.; Kernan, Maurice J.; Eberl, Daniel F.; Göpfert, Martin C.

    2015-01-01

    Much like vertebrate hair cells, the chordotonal sensory neurons that mediate hearing in Drosophila are motile and amplify the mechanical input of the ear. Because the neurons bear mechanosensory primary cilia whose microtubule axonemes display dynein arms, we hypothesized that their motility is powered by dyneins. Here, we describe two axonemal dynein proteins that are required for Drosophila auditory neuron function, localize to their primary cilia, and differently contribute to mechanical amplification in hearing. Promoter fusions revealed that the two axonemal dynein genes Dmdnah3 (=CG17150) and Dmdnai2 (=CG6053) are expressed in chordotonal neurons, including the auditory ones in the fly’s ear. Null alleles of both dyneins equally abolished electrical auditory neuron responses, yet whereas mutations in Dmdnah3 facilitated mechanical amplification, amplification was abolished by mutations in Dmdnai2. Epistasis analysis revealed that Dmdnah3 acts downstream of Nan-Iav channels in controlling the amplificatory gain. Dmdnai2, in addition to being required for amplification, was essential for outer dynein arms in auditory neuron cilia. This establishes diverse roles of axonemal dyneins in Drosophila auditory neuron function and links auditory neuron motility to primary cilia and axonemal dyneins. Mutant defects in sperm competition suggest that both dyneins also function in sperm motility. PMID:26608786

  20. Dynactin functions as both a dynamic tether and brake during dynein-driven motility

    Science.gov (United States)

    Ayloo, Swathi; Lazarus, Jacob E.; Dodda, Aditya; Tokito, Mariko; Ostap, E. Michael; Holzbaur, Erika L. F.

    2014-09-01

    Dynactin is an essential cofactor for most cellular functions of the microtubule motor cytoplasmic dynein, but the mechanism by which dynactin activates dynein remains unclear. Here we use single molecule approaches to investigate dynein regulation by the dynactin subunit p150Glued. We investigate the formation and motility of a dynein-p150Glued co-complex using dual-colour total internal reflection fluorescence microscopy. p150Glued recruits and tethers dynein to the microtubule in a concentration-dependent manner. Single molecule imaging of motility in cell extracts demonstrates that the CAP-Gly domain of p150Glued decreases the detachment rate of the dynein-dynactin complex from the microtubule and also acts as a brake to slow the dynein motor. Consistent with this important role, two neurodegenerative disease-causing mutations in the CAP-Gly domain abrogate these functions in our assays. Together, these observations support a model in which dynactin enhances the initial recruitment of dynein onto microtubules and promotes the sustained engagement of dynein with its cytoskeletal track.

  1. CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs

    DEFF Research Database (Denmark)

    Merveille, Anne-Christine; Davis, Erica E; Becker-Heck, Anita;

    2011-01-01

    -assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with...... axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex....

  2. Tissue Specific Roles of Dynein Light Chain 1 in Regulating Germ Cell Apoptosis in Ceanorhabditis elegans

    DEFF Research Database (Denmark)

    Morthorst, Tine Hørning

    2015-01-01

    physiological apoptosis inside the dying germ cells through a dynein-dependent pathway. DLC-1 and dynein heavy chain (DHC-1) localizes to the nuclear membrane of apoptotic germ cells, and depletion of either one inhibits the induction of physiological apoptosis, but not damage induced apoptosis. Their pro...

  3. The D2 Susy Zoo

    CERN Document Server

    Bak, D; Townsend, P K; Bak, Dongsu; Ohta, Nobuyoshi; Townsend, Paul K.

    2007-01-01

    We present new supersymmetric solutions of the Dirac-Born-Infeld equations for time-independent D2-branes, including a 1/2 supersymmetric `dyonic' D2-brane and various 1/4 supersymmetric configurations that include `twisted' supertubes, superfunnels with arbitrary planar cross-section, asymptotically planar D2-branes, and non-singular intersections of `magnetic' D2-branes. Our analysis is exhaustive for D2-branes in three space dimensions.

  4. The D2 Susy Zoo

    OpenAIRE

    Bak, Dongsu; Ohta, Nobuyoshi; Townsend, Paul K

    2006-01-01

    We present new supersymmetric solutions of the Dirac-Born-Infeld equations for time-independent D2-branes, including a 1/2 supersymmetric `dyonic' D2-brane and various 1/4 supersymmetric configurations that include `twisted' supertubes, superfunnels with arbitrary planar cross-section, asymptotically planar D2-branes, and non-singular intersections of `magnetic' D2-branes. Our analysis is exhaustive for D2-branes in three space dimensions.

  5. Supersymmetric D2 anti-D2 Strings

    OpenAIRE

    Bak, Dongsu; Ohta, Nobuyoshi

    2001-01-01

    We consider the flat supersymmetric D2 and anti-D2 system, which follows from ordinary noncommutative D2 anti-D2 branes by turning on an appropriate worldvolume electric field describing dissolved fundamental strings. We study the strings stretched between D2 and anti-D2 branes and show explicitly that the would-be tachyonic states become massless. We compute the string spectrum and clarify the induced noncommutativity on the worldvolume. The results are compared with the matrix theory descri...

  6. Structure of human cytoplasmic dynein-2 primed for its power stroke.

    Science.gov (United States)

    Schmidt, Helgo; Zalyte, Ruta; Urnavicius, Linas; Carter, Andrew P

    2015-02-19

    Members of the dynein family, consisting of cytoplasmic and axonemal isoforms, are motors that move towards the minus ends of microtubules. Cytoplasmic dynein-1 (dynein-1) plays roles in mitosis and cellular cargo transport, and is implicated in viral infections and neurodegenerative diseases. Cytoplasmic dynein-2 (dynein-2) performs intraflagellar transport and is associated with human skeletal ciliopathies. Dyneins share a conserved motor domain that couples cycles of ATP hydrolysis with conformational changes to produce movement. Here we present the crystal structure of the human cytoplasmic dynein-2 motor bound to the ATP-hydrolysis transition state analogue ADP.vanadate. The structure reveals a closure of the motor's ring of six AAA+ domains (ATPases associated with various cellular activites: AAA1-AAA6). This induces a steric clash with the linker, the key element for the generation of movement, driving it into a conformation that is primed to produce force. Ring closure also changes the interface between the stalk and buttress coiled-coil extensions of the motor domain. This drives helix sliding in the stalk which causes the microtubule binding domain at its tip to release from the microtubule. Our structure answers the key questions of how ATP hydrolysis leads to linker remodelling and microtubule affinity regulation. PMID:25470043

  7. Alteration of Dynein Function Affects α-Synuclein Degradation via the Autophagosome-Lysosome Pathway

    OpenAIRE

    Da Li; Ji-Jun Shi; Cheng-Jie Mao; Sha Liu; Jian-Da Wang; Jing Chen; Fen Wang; Ya-Ping Yang; Wei-Dong Hu; Li-Fang Hu; Chun-Feng Liu

    2013-01-01

    Growing evidence suggests that dynein dysfunction may be implicated in the pathogenesis of neurodegeneration. It plays a central role in aggresome formation, the delivery of autophagosome to lysosome for fusion and degradation, which is a pro-survival mechanism essential for the bulk degradation of misfolded proteins and damaged organells. Previous studies reported that dynein dysfuntion was associated with aberrant aggregation of α-synuclein, which is a major component of inclusion bodies in...

  8. Fluorescent ATP analog mant-ATP reports dynein activity in the isolated Chlamydomonas axoneme

    Science.gov (United States)

    Feofilova, Maria; Howard, Jonathon

    Eukaryotic flagella are long rod-like extensions of cells, which play a fundamental role in single cell movement, as well as in fluid transport. Flagella contain a highly evolutionary conserved mechanical structure called the axoneme. The motion of the flagellum is generated by dynein motor proteins located all along the length of the axoneme. How the force production of motors is controlled spatially and temporally is still an open question. Therefore, monitoring dynein activity in the axonemal structure is expected to provide novel insights in regulation of the beat. We use high sensitivity fluorescence microscopy to monitor the binding and hydrolysis kinetics of the fluorescently labeled ATP analogue mant-ATP (2'(3')-O-(N-methylanthraniloyl) adenosine 5'-triphosphate), which is known to support dynein activity. By studying the kinetics of mant-ATP fluorescence, we identified distinct mant-ATP binding sites in the axoneme. The application of this method to axonemes with reduced amounts of dynein, showed evidence that one of the sites is associated with binding to dynein. In the future, we would like to use this method to find the spatial distribution of dynein activity in the axoneme.

  9. Adenovirus Recruits Dynein by an Evolutionary Novel Mechanism Involving Direct Binding to pH-Primed Hexon

    Directory of Open Access Journals (Sweden)

    Julian Scherer

    2011-08-01

    Full Text Available Following receptor-mediated uptake into endocytic vesicles and escape from the endosome, adenovirus is transported by cytoplasmic dynein along microtubules to the perinuclear region of the cell. How motor proteins are recruited to viruses for their own use has begun to be investigated only recently. We review here the evidence for a role for dynein and other motor proteins in adenovirus infectivity. We also discuss the implications of recent studies on the mechanism of dynein recruitment to adenovirus for understanding the relationship between pathogenic and physiological cargo recruitment and for the evolutionary origins of dynein-mediated adenovirus transport.

  10. Trypanin, a component of the flagellar Dynein regulatory complex, is essential in bloodstream form African trypanosomes.

    Directory of Open Access Journals (Sweden)

    Katherine S Ralston

    2006-09-01

    Full Text Available The Trypanosoma brucei flagellum is a multifunctional organelle with critical roles in motility, cellular morphogenesis, and cell division. Although motility is thought to be important throughout the trypanosome lifecycle, most studies of flagellum structure and function have been restricted to the procyclic lifecycle stage, and our knowledge of the bloodstream form flagellum is limited. We have previously shown that trypanin functions as part of a flagellar dynein regulatory system that transmits regulatory signals from the central pair apparatus and radial spokes to axonemal dyneins. Here we investigate the requirement for this dynein regulatory system in bloodstream form trypanosomes. We demonstrate that trypanin is localized to the flagellum of bloodstream form trypanosomes, in a pattern identical to that seen in procyclic cells. Surprisingly, trypanin RNA interference is lethal in the bloodstream form. These knockdown mutants fail to initiate cytokinesis, but undergo multiple rounds of organelle replication, accumulating multiple flagella, nuclei, kinetoplasts, mitochondria, and flagellum attachment zone structures. These findings suggest that normal flagellar beat is essential in bloodstream form trypanosomes and underscore the emerging concept that there is a dichotomy between trypanosome lifecycle stages with respect to factors that contribute to cell division and cell morphogenesis. This is the first time that a defined dynein regulatory complex has been shown to be essential in any organism and implicates the dynein regulatory complex and other enzymatic regulators of flagellar motility as candidate drug targets for the treatment of African sleeping sickness.

  11. Misfolded Gβ is recruited to cytoplasmic dynein by Nudel for efficient clearance

    Institute of Scientific and Technical Information of China (English)

    Yihan Wan; Zhenye Yang; Jing Guo; Qiangge Zhang; Liyong Zeng; Wei Song; Yue Xiao; Xueliang Zhu

    2012-01-01

    The Gβγ heterodimer is an important signal transducer.Gβ,however,is prone to misfolding due to its requirement for Gγ and chaperones for proper folding.How cells dispose of misfolded Gβ (mfGβ) is not clear.Here,we showed that mfGβ was able to be polyubiquitinated and subsequently degraded by the proteasome.It was sequestered in aggresomes after the inhibition of the proteasome activity with MG132.Sustained activation of Gβγ signaling further elevated cellular levels of the ubiquitinated Gβ.Moreover,Nudel,a regulator of cytoplasmic dynein,the microtubule minus end-directed motor,directly interacted with both the unubiquitinated and ubiquitinated mfGβ.Increasing the levels of both mfGβ and Nudel promoted the association of Gβ with both Nudel and dynein,resulting in robust aggresome formation in a dynein-dependent manner.Depletion of Nudel by RNAi reduced the dynein-associated mfGβ,impaired the MG132-induced aggresome formation,and markedly prolonged the half-life of nascent Gβ.Therefore,cytosolic mfGβ is recruited to dynein by Nudel and transported to the centrosome for rapid sequestration and degradation.Such a process not only eliminates mfGβ efficiently for the control of protein quality,but may also help to terminate the Gβγ signaling.

  12. A splice variant of RILP induces lysosomal clustering independent of dynein recruitment

    International Nuclear Information System (INIS)

    The small GTPase Rab7 controls fusion and transport of late endocytic compartments. A critical mediator is the Rab7 effector RILP that recruits the minus-end dynein-dynactin motor complex to these compartments. We identified a natural occurring splice variant of RILP (RILPsv) lacking only 27 amino acids encoded by exon VII. Both variants bind Rab7, prolong its GTP-bound state, and induce clustering of late endocytic compartments. However, RILPsv does not recruit the dynein-dynactin complex, implicating exon VII in motor recruitment. Clustering might still occur via dimerization, since both RILP and RILPsv are able to form hetero- and homo-dimers. Moreover, both effectors compete for Rab7 binding but with different outcome for dynein-dynactin recruitment and transport. Hence, RILPsv provides an extra dimension to the control of vesicle fusion and transport by the small GTPase Rab7

  13. Force generation and step-size fluctuations in a dynein motor

    International Nuclear Information System (INIS)

    Molecular motors such as dynein are known to move by taking steps of different sizes, depending on the load. Here, we develop a simple, discrete, minimal ratchet model for a motor that can take steps of sizes δ∘ and 2δ∘ in order to provide a bare-bones description of dynein. We obtain the force–velocity curves and diffusivity for this motor for different concentrations of ATP. We also study the mechano-chemical energy transduction and thermodynamic efficiency of the motor. Further, by investigating the statistics of step sizes for the motor, we show that the average step size and fluctuation in step sizes have a non-monotonic force dependence. We develop closed-form analytical expressions for all our results, which despite the simplicity of the model give a reasonable match with the known experiments and simulations on dynein. (paper)

  14. Structure of the entire stalk region of the Dynein motor domain.

    Science.gov (United States)

    Nishikawa, Yosuke; Oyama, Takuji; Kamiya, Narutoshi; Kon, Takahide; Toyoshima, Yoko Y; Nakamura, Haruki; Kurisu, Genji

    2014-09-23

    Dyneins are large microtubule-based motor complexes that power a range of cellular processes including the transport of organelles, as well as the beating of cilia and flagella. The motor domain is located within the dynein heavy chain and comprises an N-terminal mechanical linker element, a central ring of six AAA+ modules of which four bind or hydrolyze ATP, and a long stalk extending from the AAA+ring with a microtubule-binding domain (MTBD) at its tip. A crucial mechanism underlying the motile activity of cytoskeletal motor proteins is precise coupling between the ATPase and track-binding activities. In dynein, a stalk region consisting of a long (~15nm) antiparallel coiled coil separates these two activities, which must facilitate communication between them. This communication is mediated by a small degree of helix sliding in the coiled coil. However, no high-resolution structure is available of the entire stalk region including the MTBD. Here, we have reported the structure of the entire stalk region of mouse cytoplasmic dynein in a weak microtubule-binding state, which was determined using X-ray crystallography, and have compared it with the dynein motor domain from Dictyostelium discoideum in a strong microtubule-binding state and with a mouse MTBD with its distal portion of the coiled coil fused to seryl-tRNA synthetase from Thermus thermophilus. Our results strongly support the helix-sliding model based on the complete structure of the dynein stalk with a different form of coiled-coil packing. We also propose a plausible mechanism of helix sliding together with further analysis using molecular dynamics simulations. Our results present the importance of conserved proline residues for an elastic motion of stalk coiled coil and imply the manner of change between high-affinity state and low-affinity state of MTBD. PMID:25058684

  15. The evolution of sperm axoneme structure and the dynein heavy chain complement in cecidomid insects.

    Science.gov (United States)

    Ciolfi, S; Mencarelli, C; Dallai, R

    2016-04-01

    The 9 + 2 axoneme of cilia and flagella is specialized machinery aimed at the production of efficient, finely tuned motility, and it has been evolutionarily conserved from protists to mammals. However, the sperm cells of several insects express unconventional axonemes, which represent unique models for studying the structural-functional relationships underlying axonemal function and evolution. Cecidomids comprise a group of dipterans characterized by an overall tendency to deviate from the standard axonemal pattern. In particular, the subfamily Cecidomyiinae shows a series of progressive modifications of the sperm axoneme. We previously analyzed the unusual sperm axonemes of Asphondylia ruebsaameni (Asphondyliidi) and Monarthropalpus buxi (Cecidomyiidi), which are characterized by the absence of any structure related to the control of motility (that is, the central pair complex, radial spokes and inner dynein arms); however, these sperm are motile, and motility is driven by the outer dynein arms only. This simplification of the motility machinery is accompanied by a parallel reduction in the dynein isoform complement. Here, we complete our survey of the axonemal organization and the parallel evolution of sperm dynein complement in cecidomids with the characterization of both the sperm ultrastructure and the dynein genes in Dryomyia lichtensteini, a representative of Lasiopteridi, the cecidomid taxon with aberrant and immotile sperm cells. On the basis of the whole set of our data, we discuss the potential molecular mechanism(s) underlying the progressive modification of axoneme in cecidomids, leading first to a reduction of dynein genes and eventually to the complete loss of motility. © 2016 Wiley Periodicals, Inc. PMID:26940973

  16. Lineal Trails of D2-D2bar Superstrings

    OpenAIRE

    Cho, Jin-Ho; Oh, Phillial; Park, Cheonsoo; Shin, Jonghyeon

    2003-01-01

    We study the superstrings suspended between a D2- and an anti-D2-brane. We quantize the string in the presence of some general configuration of gauge fields over the (anti-)D-brane world volumes. The interstring can move only in a specific direction that is normal to the difference of the electric fields of each (anti-)D-branes. Especially when the electric fields are the same, the interstring cannot move. We obtain the condition for the tachyons to disappear from the spectrum.

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

    Directory of Open Access Journals (Sweden)

    Vanessa M. D’Costa

    2015-09-01

    Full Text Available 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.

  18. Structural Change in the Dynein Stalk Region Associated with Two Different Affinities for the Microtubule.

    Science.gov (United States)

    Nishikawa, Yosuke; Inatomi, Momoko; Iwasaki, Haruka; Kurisu, Genji

    2016-05-01

    Dynein is a large microtubule-based motor complex that requires tight coupling of intra-molecular ATP hydrolysis with the generation of mechanical force and track-binding activity. However, the microtubule-binding domain is structurally separated by about 15nm from the nucleotide-binding sites by a coiled-coil stalk. Thus, long-range two-way communication is necessary for coordination between the catalytic cycle of ATP hydrolysis and dynein's track-binding affinities. To investigate the structural changes that occur in the dynein stalk region to produce two different microtubule affinities, here we improve the resolution limit of the previously reported structure of the entire stalk region and we investigate structural changes in the dynein stalk and strut/buttress regions by comparing currently available X-ray structures. In the light of recent crystal structures, the basis of the transition from the low-affinity to the high-affinity coiled-coil registry is discussed. A concerted movement model previously reported by Carter and Vale is modified more specifically, and we proposed it as the open zipper model. PMID:26585405

  19. WD60/FAP163 is a dynein intermediate chain required for retrograde intraflagellar transport in cilia.

    Science.gov (United States)

    Patel-King, Ramila S; Gilberti, Renée M; Hom, Erik F Y; King, Stephen M

    2013-09-01

    Retrograde intraflagellar transport (IFT) is required for assembly of cilia. We identify a Chlamydomonas flagellar protein (flagellar-associated protein 163 [FAP163]) as being closely related to the D1bIC(FAP133) intermediate chain (IC) of the dynein that powers this movement. Biochemical analysis revealed that FAP163 is present in the flagellar matrix and is actively trafficked by IFT. Furthermore, FAP163 copurified with D1bIC(FAP133) and the LC8 dynein light chain, indicating that it is an integral component of the retrograde IFT dynein. To assess the functional role of FAP163, we generated an RNA interference knockdown of the orthologous protein (WD60) in planaria. The Smed-wd60(RNAi) animals had a severe ciliary assembly defect that dramatically compromised whole-organism motility. Most cilia were present as short stubs that had accumulated large quantities of IFT particle-like material between the doublet microtubules and the membrane. The few remaining approximately full-length cilia had a chaotic beat with a frequency reduced from 24 to ∼10 Hz. Thus WD60/FAP163 is a dynein IC that is absolutely required for retrograde IFT and ciliary assembly. PMID:23864713

  20. Overexpression of cytoplasmic dynein's globular head causes a collapse of the interphase microtubule network in Dictyostelium.

    Science.gov (United States)

    Koonce, M P; Samsó, M

    1996-06-01

    Cytoplasmic dynein is a minus-end directed microtubule-based motor. Using a molecular genetic approach, we have begun to dissect structure-function relationships of dynein in the cellular slime mold Dictyostelium. Expression of a carboxy-terminal 380-kDa fragment of the heavy chain produces a protein that approximates the size and shape of the globular, mechanochemical head of dynein. This polypeptide cosediments with microtubules in an ATP-sensitive fashion and undergoes a UV-vanadate cleavage reaction. The deleted amino-terminal region appears to participate in dimerization of the native protein and in binding the intermediate and light chains. Overexpression of the 380-kDa carboxy-terminal construct in Dictyostelium produces a distinct phenotype in which the interphase radial microtubule array appears collapsed. In many cells, the microtubules form loose bundles that are whorled around the nucleus. Similar expression of a central 107-kDa fragment of the heavy chain does not produce this result. The data presented here suggest that dynein may participate in maintaining the spatial pattern of the interphase microtubule network. PMID:8816999

  1. The role of the dynein light intermediate chain in retrograde IFT and flagellar function in Chlamydomonas.

    Science.gov (United States)

    Reck, Jaimee; Schauer, Alexandria M; VanderWaal Mills, Kristyn; Bower, Raqual; Tritschler, Douglas; Perrone, Catherine A; Porter, Mary E

    2016-08-01

    The assembly of cilia and flagella depends on the activity of two microtubule motor complexes, kinesin-2 and dynein-2/1b, but the specific functions of the different subunits are poorly defined. Here we analyze Chlamydomonas strains expressing different amounts of the dynein 1b light intermediate chain (D1bLIC). Disruption of D1bLIC alters the stability of the dynein 1b complex and reduces both the frequency and velocity of retrograde intraflagellar transport (IFT), but it does not eliminate retrograde IFT. Flagellar assembly, motility, gliding, and mating are altered in a dose-dependent manner. iTRAQ-based proteomics identifies a small subset of proteins that are significantly reduced or elevated in d1blic flagella. Transformation with D1bLIC-GFP rescues the mutant phenotypes, and D1bLIC-GFP assembles into the dynein 1b complex at wild-type levels. D1bLIC-GFP is transported with anterograde IFT particles to the flagellar tip, dissociates into smaller particles, and begins processive retrograde IFT in <2 s. These studies demonstrate the role of D1bLIC in facilitating the recycling of IFT subunits and other proteins, identify new components potentially involved in the regulation of IFT, flagellar assembly, and flagellar signaling, and provide insight into the role of D1bLIC and retrograde IFT in other organisms. PMID:27251063

  2. Cytoplasmic dynein and its regulatory proteins in Golgi pathology in nervous system disorders

    NARCIS (Netherlands)

    Jaarsma, Dick; Hoogenraad, Casper C

    2015-01-01

    The Golgi apparatus is a dynamic organelle involved in processing and sorting of lipids and proteins. In neurons, the Golgi apparatus is important for the development of axons and dendrites and maintenance of their highly complex polarized morphology. The motor protein complex cytoplasmic dynein has

  3. LRRC6 mutation causes primary ciliary dyskinesia with dynein arm defects.

    Directory of Open Access Journals (Sweden)

    Amjad Horani

    Full Text Available Despite recent progress in defining the ciliome, the genetic basis for many cases of primary ciliary dyskinesia (PCD remains elusive. We evaluated five children from two unrelated, consanguineous Palestinian families who had PCD with typical clinical features, reduced nasal nitric oxide concentrations, and absent dynein arms. Linkage analyses revealed a single common homozygous region on chromosome 8 and one candidate was conserved in organisms with motile cilia. Sequencing revealed a single novel mutation in LRRC6 (Leucine-rich repeat containing protein 6 that fit the model of autosomal recessive genetic transmission, leading to a change of a highly conserved amino acid from aspartic acid to histidine (Asp146His. LRRC6 was localized to the cytoplasm and was up-regulated during ciliogenesis in human airway epithelial cells in a Foxj1-dependent fashion. Nasal epithelial cells isolated from affected individuals and shRNA-mediated silencing in human airway epithelial cells, showed reduced LRRC6 expression, absent dynein arms, and slowed cilia beat frequency. Dynein arm proteins were either absent or mislocalized to the cytoplasm in airway epithelial cells from a primary ciliary dyskinesia subject. These findings suggest that LRRC6 plays a role in dynein arm assembly or trafficking and when mutated leads to primary ciliary dyskinesia with laterality defects.

  4. Dynein Separately Partners with NDE1 and Dynactin To Orchestrate T Cell Focused Secretion.

    Science.gov (United States)

    Nath, Shubhankar; Christian, Laura; Tan, Sarah Youngsun; Ki, Sanghee; Ehrlich, Lauren I R; Poenie, Martin

    2016-09-15

    Helper and cytotoxic T cells accomplish focused secretion through the movement of vesicles toward the microtubule organizing center (MTOC) and translocation of the MTOC to the target contact site. In this study, using Jurkat cells and OT-I TCR transgenic primary murine CTLs, we show that the dynein-binding proteins nuclear distribution E homolog 1 (NDE1) and dynactin (as represented by p150(Glued)) form mutually exclusive complexes with dynein, exhibit nonoverlapping distributions in target-stimulated cells, and mediate different transport events. When Jurkat cells expressing a dominant negative form of NDE1 (NDE1-enhanced GFP fusion) were activated by Staphylococcus enterotoxin E-coated Raji cells, NDE1 and dynein failed to accumulate at the immunological synapse (IS) and MTOC translocation was inhibited. Knockdown of NDE1 in Jurkat cells or primary mouse CTLs also inhibited MTOC translocation and CTL-mediated killing. In contrast to NDE1, knockdown of p150(Glued), which depleted the alternative dynein/dynactin complex, resulted in impaired accumulation of CTLA4 and granzyme B-containing intracellular vesicles at the IS, whereas MTOC translocation was not affected. Depletion of p150(Glued) in CTLs also inhibited CTL-mediated lysis. We conclude that the NDE1/Lissencephaly 1 and dynactin complexes separately mediate two key components of T cell-focused secretion, namely translocation of the MTOC and lytic granules to the IS, respectively. PMID:27534551

  5. Alcohol-induced defects in hepatic transcytosis may be explained by impaired dynein function.

    Science.gov (United States)

    Groebner, Jennifer L; Fernandez, David J; Tuma, Dean J; Tuma, Pamela L

    2014-12-01

    Alcoholic liver disease has been clinically well described, but the molecular mechanisms leading to hepatotoxicity have not been fully elucidated. Previously, we determined that microtubules are hyperacetylated and more stable in ethanol-treated WIF-B cells, VL-17A cells, liver slices, and in livers from ethanol-fed rats. From our recent studies, we believe that these modifications can explain alcohol-induced defects in microtubule motor-dependent protein trafficking including nuclear translocation of a subset of transcription factors. Since cytoplasmic dynein/dynactin is known to mediate both microtubule-dependent translocation and basolateral to apical/canalicular transcytosis, we predicted that transcytosis is impaired in ethanol-treated hepatic cells. We monitored transcytosis of three classes of newly synthesized canalicular proteins in polarized, hepatic WIF-B cells, an emerging model system for the study of liver disease. As predicted, canalicular delivery of all proteins tested was impaired in ethanol-treated cells. Unlike in control cells, transcytosing proteins were observed in discrete sub-canalicular puncta en route to the canalicular surface that aligned along acetylated microtubules. We further determined that the stalled transcytosing proteins colocalized with dynein/dynactin in treated cells. No changes in vesicle association were observed for either dynein or dynactin in ethanol-treated cells, but significantly enhanced dynein binding to microtubules was observed. From these results, we propose that enhanced dynein binding to microtubules in ethanol-treated cells leads to decreased motor processivity resulting in vesicle stalling and in impaired canalicular delivery. Our studies also importantly indicate that modulating cellular acetylation levels with clinically tolerated deacetylase agonists may be a novel therapeutic strategy for treating alcoholic liver disease. PMID:25148871

  6. Finding the Cell Center by a Balance of Dynein and Myosin Pulling and Microtubule Pushing: A Computational Study

    OpenAIRE

    Zhu, Jie; Burakov, Anton; Rodionov, Vladimir; Mogilner, Alex

    2010-01-01

    The centrosome position in many types of interphase cells is actively maintained in the cell center. Our previous work indicated that the centrosome is kept at the center by pulling force generated by dynein and actin flow produced by myosin contraction and that an unidentified factor that depends on microtubule dynamics destabilizes position of the centrosome. Here, we use modeling to simulate the centrosome positioning based on the idea that the balance of three forces—dyneins pulling along...

  7. Dynein Light Intermediate Chain 2 Facilitates the Metaphase to Anaphase Transition by Inactivating the Spindle Assembly Checkpoint.

    Directory of Open Access Journals (Sweden)

    Sagar P Mahale

    Full Text Available The multi-functional molecular motor cytoplasmic dynein performs diverse essential roles during mitosis. The mechanistic importance of the dynein Light Intermediate Chain homologs, LIC1 and LIC2 is unappreciated, especially in the context of mitosis. LIC1 and LIC2 are believed to exist in distinct cytoplasmic dynein complexes as obligate subunits. LIC1 had earlier been reported to be required for metaphase to anaphase progression by inactivating the kinetochore-microtubule attachment-sensing arm of the spindle assembly checkpoint (SAC. However, the functional importance of LIC2 during mitosis remains elusive. Here we report prominent novel roles for the LIC2 subunit of cytoplasmic dynein in regulating the spindle assembly checkpoint. LIC2 depletion in mammalian cells led to prolonged metaphase arrest in the presence of an active SAC and also to stretched kinetochores, thus implicating it in SAC inactivation. Quantitative fluorescence microscopy of SAC components revealed accumulation of both attachment- and tension-sensing checkpoint proteins at metaphase kinetochores upon LIC2 depletion. These observations support a stronger and more diverse role in checkpoint inactivation for LIC2 in comparison to its close homolog LIC1. Our study uncovers a novel functional hierarchy during mitotic checkpoint inactivation between the closely related but homologous LIC subunits of cytoplasmic dynein. These subtle functional distinctions between dynein subpopulations could be exploited to study specific aspects of the spindle assembly checkpoint, which is a key mediator of fidelity in eukaryotic cell division.

  8. Dynein Light Intermediate Chain 2 Facilitates the Metaphase to Anaphase Transition by Inactivating the Spindle Assembly Checkpoint

    Science.gov (United States)

    Mahale, Sagar P.; Sharma, Amit; Mylavarapu, Sivaram V. S.

    2016-01-01

    The multi-functional molecular motor cytoplasmic dynein performs diverse essential roles during mitosis. The mechanistic importance of the dynein Light Intermediate Chain homologs, LIC1 and LIC2 is unappreciated, especially in the context of mitosis. LIC1 and LIC2 are believed to exist in distinct cytoplasmic dynein complexes as obligate subunits. LIC1 had earlier been reported to be required for metaphase to anaphase progression by inactivating the kinetochore-microtubule attachment-sensing arm of the spindle assembly checkpoint (SAC). However, the functional importance of LIC2 during mitosis remains elusive. Here we report prominent novel roles for the LIC2 subunit of cytoplasmic dynein in regulating the spindle assembly checkpoint. LIC2 depletion in mammalian cells led to prolonged metaphase arrest in the presence of an active SAC and also to stretched kinetochores, thus implicating it in SAC inactivation. Quantitative fluorescence microscopy of SAC components revealed accumulation of both attachment- and tension-sensing checkpoint proteins at metaphase kinetochores upon LIC2 depletion. These observations support a stronger and more diverse role in checkpoint inactivation for LIC2 in comparison to its close homolog LIC1. Our study uncovers a novel functional hierarchy during mitotic checkpoint inactivation between the closely related but homologous LIC subunits of cytoplasmic dynein. These subtle functional distinctions between dynein subpopulations could be exploited to study specific aspects of the spindle assembly checkpoint, which is a key mediator of fidelity in eukaryotic cell division. PMID:27441562

  9. Two new D2 QSOs

    International Nuclear Information System (INIS)

    It is stated that extragalactic radio sources fall into one of two categories. In one the emission is extended, with two main peaks tens or hundreds of kiloparsecs apart straddling the associated optical object, while in the other the source is compact (typically less than a kiloparsec in size), with optical and radio positions that coincide to within the errors of measurement. More rarely, double sources may belong to a third category, which has been classified as D2, and of which the type example is 3C273. Sources of this class consist of a small variable nuclear component coincident with the optical object, and a second larger component with a much steeper spectrum. High resolution observations made with radio-link interferometers based on Jodrell Bank are here reported, which show that the QSOs 3C345 and 3C454.3 have extended radio structure similar to that of 3C273. Hence these sources, previously believed to be compact, should also be classified as D2. Details of the observations are given. (author)

  10. Normalizing Dopamine D2 Receptor-Mediated Responses in D2 Null Mutant Mice by Virus-Mediated Receptor Restoration: Comparing D2L and D2S

    OpenAIRE

    Neve, Kim A.; Ford, Christopher P.; Buck, David C; Grandy, David K; Neve, Rachael L.; Phillips, Tamara J.

    2013-01-01

    D2 receptor null mutant (Drd2−/−) mice have altered responses to the rewarding and locomotor effects of psychostimulant drugs, which is evidence of a necessary role for D2 receptors in these behaviors. Furthermore, work with mice that constitutively express only the D2 receptor short form (D2S), as a result of genetic deletion of the long form (D2L), provides the basis for a current model in which D2L is thought to be the postsynaptic D2 receptor on medium spiny neurons in the basal forebrain...

  11. Cytoplasmic Dynein Is Required for the Spatial Organization of Protein Aggregates in Filamentous Fungi

    Directory of Open Access Journals (Sweden)

    Martin J. Egan

    2015-04-01

    Full Text Available Eukaryotes have evolved multiple strategies for maintaining cellular protein homeostasis. One such mechanism involves neutralization of deleterious protein aggregates via their defined spatial segregation. Here, using the molecular disaggregase Hsp104 as a marker for protein aggregation, we describe the spatial and temporal dynamics of protein aggregates in the filamentous fungus Aspergillus nidulans. Filamentous fungi, such as A. nidulans, are a diverse group of species of major health and economic importance and also serve as model systems for studying highly polarized eukaryotic cells. We find that microtubules promote the formation of Hsp104-positive aggregates, which coalesce into discrete subcellular structures in a process dependent on the microtubule-based motor cytoplasmic dynein. Finally, we find that impaired clearance of these inclusions negatively impacts retrograde trafficking of endosomes, a conventional dynein cargo, indicating that microtubule-based transport can be overwhelmed by chronic cellular stress.

  12. Dynamic Behavior of Microtubules during Dynein-dependent Nuclear Migrations of Meiotic Prophase in Fission Yeast

    OpenAIRE

    Yamamoto, Ayumu; Tsutsumi, Chihiro; Kojima, Hiroaki; Oiwa, Kazuhiro; Hiraoka, Yasushi

    2001-01-01

    During meiotic prophase in fission yeast, the nucleus migrates back and forth between the two ends of the cell, led by the spindle pole body (SPB). This nuclear oscillation is dependent on astral microtubules radiating from the SPB and a microtubule motor, cytoplasmic dynein. Here we have examined the dynamic behavior of astral microtubules labeled with the green fluorescent protein during meiotic prophase with the use of optical sectioning microscopy. During nuclear migrations, the SPB mostl...

  13. Whacked and Rab35 polarize dynein motor complex-dependent seamless tube growth

    OpenAIRE

    Schottenfeld-Roames, Jodi; Ghabrial, Amin S.

    2012-01-01

    Seamless tubes form intracellularly without cell-cell or autocellular junctions. Such tubes have been described across phyla, but remain mysterious despite their simple architecture. In Drosophila, seamless tubes are found within tracheal terminal cells, which have dozens of branched protrusions extending hundreds of microns. We find that mutations in multiple components of the dynein motor complex block seamless tube growth, raising the possibility that the lumenal membrane forms through min...

  14. A Low Affinity Ground State Conformation for the Dynein Microtubule Binding Domain*

    OpenAIRE

    McNaughton, Lynn; Tikhonenko, Irina; Banavali, Nilesh K.; LeMaster, David M.; Koonce, Michael P.

    2010-01-01

    Dynein interacts with microtubules through a dedicated binding domain that is dynamically controlled to achieve high or low affinity, depending on the state of nucleotide bound in a distant catalytic pocket. The active sites for microtubule binding and ATP hydrolysis communicate via conformational changes transduced through a ∼10-nm length antiparallel coiled-coil stalk, which connects the binding domain to the roughly 300-kDa motor core. Recently, an x-ray structure of the murine cytoplasmic...

  15. Role of fungal dynein in hyphal growth, microtubule organization, spindle pole body motility and nuclear migration.

    Science.gov (United States)

    Inoue, S; Turgeon, B G; Yoder, O C; Aist, J R

    1998-06-01

    Cytoplasmic dynein is a microtubule-associated motor protein with several putative subcellular functions. Sequencing of the gene (DHC1) for cytoplasmic dynein heavy chain of the filamentous ascomycete, Nectria haematococca, revealed a 4,349-codon open reading frame (interrupted by two introns) with four highly conserved P-loop motifs, typical of cytoplasmic dynein heavy chains. The predicted amino acid sequence is 78.0% identical to the cytoplasmic dynein heavy chain of Neurospora crassa, 70.2% identical to that of Aspergillus nidulans and 24.8% identical to that of Saccharomyces cerevisiae. The genomic copy of DHC1 in N. haematococca wild-type strain T213 was disrupted by inserting a selectable marker into the central motor domain. Mutants grew at 33% of the wild-type rate, forming dense compact colonies composed of spiral and highly branched hyphae. Major cytological phenotypes included (1) absence of aster-like arrays of cytoplasmic microtubules focused at the spindle pole bodies of post-mitotic and interphase nuclei, (2) limited post-mitotic nuclear migration, (3) lack of spindle pole body motility at interphase, (4) failure of spindle pole bodies to anchor interphase nuclei, (5) nonuniform distribution of interphase nuclei and (6) small or ephemeral Spitzenkörper at the apices of hyphal tip cells. Microtubule distribution in the apical region of tip cells of the mutant was essentially normal. The nonuniform distribution of nuclei in hyphae resulted primarily from a lack of both post-mitotic nuclear migration and anchoring of interphase nuclei by the spindle pole bodies. The results support the hypothesis that DHC1 is required for the motility and functions of spindle pole bodies, normal secretory vesicle transport to the hyphal apex and normal hyphal tip cell morphogenesis. PMID:9580563

  16. Drosophila Dynein intermediate chain gene, Dic61B, is required for spermatogenesis.

    Directory of Open Access Journals (Sweden)

    Roshan Fatima

    Full Text Available This study reports the identification and characterization of a novel gene, Dic61B, required for male fertility in Drosophila. Complementation mapping of a novel male sterile mutation, ms21, isolated in our lab revealed it to be allelic to CG7051 at 61B1 cytogenetic region, since two piggyBac insertion alleles, CG7051(c05439 and CG7051(f07138 failed to complement. CG7051 putatively encodes a Dynein intermediate chain. All three mutants, ms21, CG7051(c05439 and CG7051(f07138, exhibited absolute recessive male sterility with abnormally coiled sperm axonemes causing faulty sperm individualization as revealed by Phalloidin staining in Don Juan-GFP background. Sequencing of PCR amplicons uncovered two point mutations in ms21 allele and confirmed the piggyBac insertions in CG7051(c05439 and CG7051(f07138 alleles to be in 5'UTR and 4(th exon of CG7051 respectively, excision of which reverted the male sterility. In situ hybridization to polytene chromosomes demonstrated CG7051 to be a single copy gene. RT-PCR of testis RNA revealed defective splicing of the CG7051 transcripts in mutants. Interestingly, expression of cytoplasmic dynein intermediate chain, α, β, γ tubulins and α-spectrin was normal in mutants while ultra structural studies revealed defects in the assembly of sperm axonemes. Bioinformatics further highlighted the homology of CG7051 to axonemal dynein intermediate chain of various organisms, including DNAI1 of humans, mutations in which lead to male sterility due to immotile sperms. Based on these observations we conclude that CG7051 encodes a novel axonemal dynein intermediate chain essential for male fertility in Drosophila and rename it as Dic61B. This is the first axonemal Dic gene of Drosophila to be characterized at molecular level and shown to be required for spermatogenesis.

  17. Coarse-grained modeling of the structural states and transition underlying the powerstroke of dynein motor domain.

    Science.gov (United States)

    Zheng, Wenjun

    2012-04-21

    This study aims to model a minimal dynein motor domain capable of motor function, which consists of the linker domain, six AAA+ modules (AAA1-AAA6), coiled coil stalk, and C-terminus domain. To this end, we have used the newly solved X-ray structures of dynein motor domain to perform a coarse-grained modeling of dynein's post- and pre-powerstroke conformation and the conformational transition between them. First, we have used normal mode analysis to identify a single normal mode that captures the coupled motions of AAA1-AAA2 closing and linker domain rotation, which enables the ATP-driven recovery stroke of dynein. Second, based on the post-powerstroke conformation solved crystallographically, we have modeled dynein's pre-powerstroke conformation by computationally inducing AAA1-AAA2 closing and sliding of coiled coil stalk, and the resulting model features a linker domain near the pre-powerstroke position and a slightly tilted stalk. Third, we have modeled the conformational transition from pre- to post-powerstroke conformation, which predicts a clear sequence of structural events that couple microtubule binding, powerstroke and product release, and supports a signaling path from stalk to AAA1 via AAA3 and AAA4. Finally, we have found that a closed AAA3-AAA4 interface (compatible with nucleotide binding) is essential to the mechano-chemical coupling in dynein. Our modeling not only offers unprecedented structural insights to the motor function of dynein as described by past single-molecule, fluorescence resonance energy transfer, and electron microscopy studies, but also provides new predictions for future experiments to test. PMID:22519354

  18. 7 CFR 15d.2 - Discrimination prohibited.

    Science.gov (United States)

    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...

  19. Torus-like Dielectric D2-brane

    OpenAIRE

    Hyakutake, Yoshifumi

    2001-01-01

    We find new solutions corresponding to torus-like generalization of dielectric D2-brane from the viewpoint of D2-brane action and N D0-branes one. These are meta-stable and would decay to the spherical dielectric D2-brane.

  20. Mutations in ZMYND10, a gene essential for proper axonemal assembly of inner and outer dynein arms in humans and flies, cause primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Moore, Daniel J; Onoufriadis, Alexandros; Shoemark, Amelia;

    2013-01-01

    Primary ciliary dyskinesia (PCD) is a ciliopathy characterized by airway disease, infertility, and laterality defects, often caused by dual loss of the inner dynein arms (IDAs) and outer dynein arms (ODAs), which power cilia and flagella beating. Using whole-exome and candidate-gene Sanger resequ...

  1. UNITS IN $F_2D_{2p}$

    OpenAIRE

    Kaur, Kuldeep; Khan, Manju

    2012-01-01

    Let $p$ be an odd prime, $D_{2p}$ be the dihedral group of order 2p, and $F_{2}$ be the finite field with two elements. If * denotes the canonical involution of the group algebra $F_2D_{2p}$, then bicyclic units are unitary units. In this note, we investigate the structure of the group $\\mathcal{B}(F_2D_{2p})$, generated by the bicyclic units of the group algebra $F_2D_{2p}$. Further, we obtain the structure of the unit group $\\mathcal{U}(F_2D_{2p})$ and the unitary subgroup $\\mathcal{U}_*(F_...

  2. Communication between the AAA+ ring and microtubule-binding domain of dynein1

    OpenAIRE

    Carter, Andrew P.; Vale, Ronald D.

    2010-01-01

    Dyneins are microtubule motors, the core of which consists of a ring of AAA+ domains. ATP-driven conformational changes of the AAA+ ring are used to drive the movement of a mechanical element (termed the linker domain) that provides the motor’s powerstroke and to change the affinity of the motor for microtubules (strong binding during the power stroke and weak binding to allow stepping and recocking of the linker domain). Dynein’s microtubule-binding domain (MTBD) is located at the end of a 1...

  3. Monte Carlo Simulation on Coordinated Movement of Kinesin and Dynein Motors

    Institute of Scientific and Technical Information of China (English)

    WANG Hong; DOU Shuo-Xing; WANG Peng-Ye

    2008-01-01

    Kinesin and dynein are two important classes of molecular motors which are responsible for active organelle trafficking and cell division.They call work together to carry a cargo,moving along the microtubule in a coordinated way.We use Monte Carlo method to simulate the dynamics of this coordinated movement.Based on four essential assumptions,our simulations reproduce some features of the recent in vivo experiments.The fast moving speed of the cargo js simulated and the speed distribution is presented.

  4. The regulation of RhoGEF Lfc by dynein light chain Tctex-1

    Science.gov (United States)

    Balan, Marc

    Lfc is a guanine nucleotide exchange factor (GEF) that activates the small GTPase RhoA, and its GEF activity is tightly regulated through protein-protein interactions, phosphorylation, and cellular localization. Lfc is anchored to microtubules through its interaction with the dynein light chain Tctex-1, which results in inhibition of Lfc's GEF activity. Here we present a crystallographic structure of Tctex-1 in complex with Lfc with residues 143-155 of Lfc bound at the Tctex-1 dimer interface. Structural alignment of our structure with Tctex-1 in complex with the dynein intermediate chain (DIC) shows the binding site of the DIC peptide and Lfc substantially overlap. Biochemical evidence, NMR perturbations assays and intrinsic fluorescence provide structural validation and support an extension of the Lfc binding site to the andalpha;-helices that may accommodate additional contact points with Tctex-1. We postulate a potential mechanism for Lfcandrsquo;s recruitment to the microtubules through a tripartite complex with Tctex-1 and DIC.

  5. Engineered Tug-of-War Between Kinesin and Dynein Controls Direction of Microtubule Based Transport In Vivo.

    Science.gov (United States)

    Rezaul, Karim; Gupta, Dipika; Semenova, Irina; Ikeda, Kazuho; Kraikivski, Pavel; Yu, Ji; Cowan, Ann; Zaliapin, Ilya; Rodionov, Vladimir

    2016-05-01

    Bidirectional transport of membrane organelles along microtubules (MTs) is driven by plus-end directed kinesins and minus-end directed dynein bound to the same cargo. Activities of opposing MT motors produce bidirectional movement of membrane organelles and cytoplasmic particles along MT transport tracks. Directionality of MT-based transport might be controlled by a protein complex that determines which motor type is active at any given moment of time, or determined by the outcome of a tug-of-war between MT motors dragging cargo organelles in opposite directions. However, evidence in support of each mechanisms of regulation is based mostly on the results of theoretical analyses or indirect experimental data. Here, we test whether the direction of movement of membrane organelles in vivo can be controlled by the tug-of-war between opposing MT motors alone, by attaching a large number of kinesin-1 motors to organelles transported by dynein to minus-ends of MTs. We find that recruitment of kinesin significantly reduces the length and velocity of minus-end-directed dynein-dependent MT runs, leading to a reversal of the overall direction of dynein-driven organelles in vivo. Therefore, in the absence of external regulators tug-of-war between opposing MT motors alone is sufficient to determine the directionality of MT transport in vivo. PMID:26843027

  6. Cell-nonautonomous inhibition of radiation-induced apoptosis by dynein light chain 1 in Caenorhabditis elegans.

    Science.gov (United States)

    Morthorst, T H; Olsen, A

    2013-01-01

    The evolutionarily conserved process of programmed cell death, apoptosis, is essential for development of multicellular organisms and is also a protective mechanism against cellular damage. We have identified dynein light chain 1 (DLC-1) as a new regulator of germ cell apoptosis in Caenorhabditis elegans. The DLC-1 protein is highly conserved across species and is a part of the dynein motor complex. There is, however, increasing evidence for dynein-independent functions of DLC-1, and our data describe a novel dynein-independent role. In mammalian cells, DLC-1 is important for cellular transport, cell division and regulation of protein activity, and it has been implicated in cancer. In C. elegans, we find that knockdown of dlc-1 by RNA interference (RNAi) induces excessive apoptosis in the germline but not in somatic cells during development. We show that DLC-1 mediates apoptosis through the genes lin-35, egl-1 and ced-13, which are all involved in the response to ionising radiation (IR)-induced apoptosis. In accordance with this, we show that IR cannot further induce apoptosis in dlc-1(RNAi) animals. Furthermore, we find that DLC-1 is functioning cell nonautonomously through the same pathway as kri-1 in response to IR-induced apoptosis and that DLC-1 regulates the levels of KRI-1. Our results strengthen the notion of a highly dynamic communication between somatic cells and germ cells in regulating the apoptotic process. PMID:24030151

  7. Human Immunodeficiency Virus Type 1 Employs the Cellular Dynein Light Chain 1 Protein for Reverse Transcription through Interaction with Its Integrase Protein

    OpenAIRE

    Jayappa, Kallesh Danappa; Ao, Zhujun; Wang, Xiaoxia; Mouland, Andrew J.; Shekhar, Sudhanshu; Yang, Xi; Yao, Xiaojian

    2015-01-01

    In this study, we examined the requirement for host dynein adapter proteins such as dynein light chain 1 (DYNLL1), dynein light chain Tctex-type 1 (DYNLT1), and p150Glued in early steps of human immunodeficiency virus type 1 (HIV-1) replication. We found that the knockdown (KD) of DYNLL1, but not DYNLT1 or p150Glued, resulted in significantly lower levels of HIV-1 reverse transcription in cells. Following an attempt to determine how DYNLL1 could impact HIV-1 reverse transcription, we detected...

  8. Hypothyroidism Affects D2 Receptor-mediated Breathing without altering D2 Receptor Expression

    OpenAIRE

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

    2014-01-01

    Bromocriptine depressed ventilation in air and D2 receptor expression in the nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated that in age- matched hypothyroid female hamsters, the pattern of D2 receptor modulation of breathing and D2 receptor expression would differ from those reported in hypothyroid males. In females hypothyroidism did not affect D2 receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine, but not carmoxirole (a periphera...

  9. Whacked and Rab35 polarize dynein-motor-complex-dependent seamless tube growth.

    Science.gov (United States)

    Schottenfeld-Roames, Jodi; Ghabrial, Amin S

    2012-04-01

    Seamless tubes form intracellularly without cell-cell or autocellular junctions. Such tubes have been described across phyla, but remain mysterious despite their simple architecture. In Drosophila, seamless tubes are found within tracheal terminal cells, which have dozens of branched protrusions extending hundreds of micrometres. We find that mutations in multiple components of the dynein motor complex block seamless tube growth, raising the possibility that the lumenal membrane forms through minus-end-directed transport of apical membrane components along microtubules. Growth of seamless tubes is polarized along the proximodistal axis by Rab35 and its apical membrane-localized GAP, Whacked. Strikingly, loss of whacked (or constitutive activation of Rab35) leads to tube overgrowth at terminal cell branch tips, whereas overexpression of Whacked (or dominant-negative Rab35) causes formation of ectopic tubes surrounding the terminal cell nucleus. Thus, vesicle trafficking has key roles in making and shaping seamless tubes. PMID:22407366

  10. Nudel Contributes to Microtubule Anchoring at the Mother Centriole and Is Involved in Both Dynein-dependent and -independent Centrosomal Protein Assembly

    OpenAIRE

    Guo, Jing; Yang, Zhenye; Song, Wei; Chen, Qi; Wang, Fubin; Zhang, Qiangge; Zhu, Xueliang

    2006-01-01

    The centrosome is the major microtubule-organizing center in animal cells. Although the cytoplasmic dynein regulator Nudel interacts with centrosomes, its role herein remains unclear. Here, we show that in Cos7 cells Nudel is a mother centriole protein with rapid turnover independent of dynein activity. During centriole duplication, Nudel targets to the new mother centriole later than ninein but earlier than dynactin. Its centrosome localization requires a C-terminal region that is essential ...

  11. Integrated pathway analysis of nasopharyngeal carcinoma implicates the axonemal dynein complex in the Malaysian cohort.

    Science.gov (United States)

    Chin, Yoon-Ming; Tan, Lu Ping; Abdul Aziz, Norazlin; Mushiroda, Taisei; Kubo, Michiaki; Mohd Kornain, Noor Kaslina; Tan, Geok Wee; Khoo, Alan Soo-Beng; Krishnan, Gopala; Pua, Kin-Choo; Yap, Yoke-Yeow; Teo, Soo-Hwang; Lim, Paul Vey-Hong; Nakamura, Yusuke; Lum, Chee Lun; Ng, Ching-Ching

    2016-10-15

    Nasopharyngeal carcinoma (NPC) is an epithelial squamous cell carcinoma on the mucosal lining of the nasopharynx. The etiology of NPC remains elusive despite many reported studies. Most studies employ a single platform approach, neglecting the cumulative influence of both the genome and transcriptome toward NPC development. We aim to employ an integrated pathway approach to identify dysregulated pathways linked to NPC. Our approach combines imputation NPC GWAS data from a Malaysian cohort as well as published expression data GSE12452 from both NPC and non-NPC nasopharynx tissues. Pathway association for GWAS data was performed using MAGENTA while for expression data, GSA-SNP was used with gene p values derived from differential expression values from GEO2R. Our study identified NPC association in the gene ontology (GO) axonemal dynein complex pathway (pGWAS-GSEA  = 1.98 × 10(-2) ; pExpr-GSEA  = 1.27 × 10(-24) ; pBonf-Combined  = 4.15 × 10(-21) ). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues (pAmpliSeq-GSEA  = 6.56 × 10(-4) ). Loss of function in the axonemal dynein complex causes impaired cilia function, leading to poor mucociliary clearance and subsequently upper or lower respiratory tract infection, the former of which includes the nasopharynx. Our approach illustrates the potential use of integrated pathway analysis in detecting gene sets involved in the development of NPC in the Malaysian cohort. PMID:27236004

  12. Dynein Light Chain 1 (DYNLT1 Interacts with Normal and Oncogenic Nucleoporins.

    Directory of Open Access Journals (Sweden)

    Nayan J Sarma

    Full Text Available The chimeric oncoprotein NUP98-HOXA9 results from the t(7;11(p15;p15 chromosomal translocation and is associated with acute myeloid leukemia. It causes aberrant gene regulation and leukemic transformation through mechanisms that are not fully understood. NUP98-HOXA9 consists of an N-terminal portion of the nucleoporin NUP98 that contains many FG repeats fused to the DNA-binding homeodomain of HOXA9. We used a Cytotrap yeast two-hybrid assay to identify proteins that interact with NUP98-HOXA9. We identified Dynein Light Chain 1 (DYNLT1, an integral 14 KDa protein subunit of the large microtubule-based cytoplasmic dynein complex, as an interaction partner of NUP98-HOXA9. Binding was confirmed by in vitro pull down and co-immunoprecipitation assays and the FG repeat region of NUP98-HOXA9 was shown to be essential for the interaction. RNAi-mediated knockdown of DYNLT1 resulted in reduction of the ability of NUP98-HOXA9 to activate transcription and also inhibited the ability of NUP98-HOXA9 to induce proliferation of primary human hematopoietic CD34+ cells. DYNLT1 also showed a strong interaction with wild-type NUP98 and other nucleoporins containing FG repeats. Immunofluorescence analysis showed that DYNLT1 localizes primarily to the nuclear periphery, where it co-localizes with the nuclear pore complex, and to the cytoplasm. Deletion studies showed that the interactions of the nucleoporins with DYNLT1 are dependent predominantly on the C-terminal half of the DYNLT1. These data show for the first time that DYNLT1 interacts with nucleoporins and plays a role in the dysregulation of gene expression and induction of hematopoietic cell proliferation by the leukemogenic nucleoporin fusion, NUP98-HOXA9.

  13. Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria

    DEFF Research Database (Denmark)

    Kranendijk, Martijn; Struys, Eduard A; Gibson, K Michael; Wickenhagen, Wjera V; Abdenur, Jose E; Buechner, Jochen; Christensen, Ernst; de Kremer, Raquel Dodelson; Errami, Abdellatif; Gissen, Paul; Gradowska, Wanda; Hobson, Emma; Islam, Lily; Korman, Stanley H; Kurczynski, Thaddeus; Maranda, Bruno; Meli, Concetta; Rizzo, Cristiano; Sansaricq, Claude; Trefz, Friedrich K; Webster, Rachel; Jakobs, Cornelis; Salomons, Gajja S

    2010-01-01

    We performed molecular, enzyme, and metabolic studies in 50 patients with D-2-hydroxyglutaric aciduria (D-2-HGA) who accumulated D-2-hydroxyglutarate (D-2-HG) in physiological fluids. Presumed pathogenic mutations were detected in 24 of 50 patients in the D-2-hydroxyglutarate dehydrogenase (D2HGD...

  14. Dynein disruption perturbs post-synaptic components and contributes to impaired MuSK clustering at the NMJ: implication in ALS.

    Science.gov (United States)

    Vilmont, Valérie; Cadot, Bruno; Vezin, Elsa; Le Grand, Fabien; Gomes, Edgar R

    2016-01-01

    The neuromuscular junction (NMJ) allows the transformation of a neuronal message into a mechanical force by muscle contraction and is the target of several neuromuscular disorders. While the neuronal side is under extensive research, the muscle appeared recently to have a growing role in the formation and integrity of the neuromuscular junction. We used an in vitro model of mature myofibers to study the role of dynein on major postsynaptic proteins. We found that dynein affects the expression and the clustering of acetylcholine receptors (AChRs), muscle specific tyrosine kinase (MuSK) and Rapsyn. We also show that myofibers with dynein impairment or from an amyotrophic lateral sclerosis (ALS) model (SOD1(G93A)) show similar defects in myofiber formation and agrin-induced AChR clustering suggesting a role for dynein impairment in ALS progression. Finally, we found that dynein can affect MuSK traffic through the endosomal pathway. Collectively, our studies show that defects in dynein can lead to impairment of muscle NMJ components' expression and clustering. We propose that NMJ defects could happen via defective MuSK traffic and that this could be one of the pathological features involved in neurodegeneration such as ALS. PMID:27283349

  15. Evidence for genetic heterogeneity in D-2-hydroxyglutaric aciduria

    DEFF Research Database (Denmark)

    Kranendijk, Martijn; Struys, Eduard A; Gibson, K Michael;

    2010-01-01

    We performed molecular, enzyme, and metabolic studies in 50 patients with D-2-hydroxyglutaric aciduria (D-2-HGA) who accumulated D-2-hydroxyglutarate (D-2-HG) in physiological fluids. Presumed pathogenic mutations were detected in 24 of 50 patients in the D-2-hydroxyglutarate dehydrogenase (D2HGDH......) gene, which encodes D-2-hydroxyglutarate dehydrogenase (D-2-HGDH). Enzyme assay of D-2-HGDH confirmed that all patients with mutations had impaired enzyme activity, whereas patients with D-2-HGA whose enzyme activity was normal did not have mutations. Significantly lower D-2-HG concentrations in body...... fluids were observed in mutation-positive D-2-HGA patients than in mutation-negative patients. These results imply that multiple genetic loci may be associated with hyperexcretion of D-2-HG. Accordingly, we suggest a new classification: D-2-HGA Type I associates with D-2-HGDH deficiency, whereas...

  16. Structure–function–folding relationships and native energy landscape of dynein light chain protein: nuclear magnetic resonance insights

    Indian Academy of Sciences (India)

    P M Krishna Mohan; Ramakrishna V Hosur

    2009-09-01

    The detailed characterization of the structure, dynamics and folding process of a protein is crucial for understanding the biological functions it performs. Modern biophysical and nuclear magnetic resonance (NMR) techniques have provided a way to obtain accurate structural and thermodynamic information on various species populated on the energy landscape of a given protein. In this context, we review here the structure–function–folding relationship of an important protein, namely, dynein light chain protein (DLC8). DLC8, the smallest subunit of the dynein motor complex, acts as a cargo adaptor. The protein exists as a dimer under physiological conditions and dissociates into a pure monomer below pH 4. Cargo binding occurs at the dimer interface. Dimer stability and relay of perturbations through the dimer interface are anticipated to be playing crucial roles in the variety of functions the protein performs. NMR investigations have provided great insights into these aspects of DLC8 in recent years.

  17. The Involvement of the Intermediate Chain of Cytoplasmic Dynein in Binding the Motor Complex to Membranous Organelles of Xenopus Oocytes

    OpenAIRE

    Steffen, Walter; Karki, Sher; Vaughan, Kevin T.; Vallee, Richard B.; Holzbaur, Erika L F; Weiss, Dieter G.; Kuznetsov, Sergei A.

    1997-01-01

    Cytoplasmic dynein is one of the major motor proteins involved in intracellular transport. It is a protein complex consisting of four subunit classes: heavy chains, intermediate chains (ICs), light intermediate chains, and light chains. In a previous study, we had generated new monoclonal antibodies to the ICs and mapped the ICs to the base of the motor. Because the ICs have been implicated in targeting the motor to cargo, we tested whether these new antibodies to the intermediate chain could...

  18. Characterization of a subunit of the outer dynein arm docking complex necessary for correct flagellar assembly in Leishmania donovani.

    Directory of Open Access Journals (Sweden)

    Simone Harder

    Full Text Available BACKGROUND: In order to proceed through their life cycle, Leishmania parasites switch between sandflies and mammals. The flagellated promastigote cells transmitted by the insect vector are phagocytized by macrophages within the mammalian host and convert into the amastigote stage, which possesses a rudimentary flagellum only. During an earlier proteomic study of the stage differentiation of the parasite we identified a component of the outer dynein arm docking complex, a structure of the flagellar axoneme. The 70 kDa subunit of the outer dynein arm docking complex consists of three subunits altogether and is essential for the assembly of the outer dynein arm onto the doublet microtubule of the flagella. According to the nomenclature of the well-studied Chlamydomonas reinhardtii complex we named the Leishmania protein LdDC2. METHODOLOGY/PRINCIPAL FINDINGS: This study features a characterization of the protein over the life cycle of the parasite. It is synthesized exclusively in the promastigote stage and localizes to the flagellum. Gene replacement mutants of lddc2 show reduced growth rates and diminished flagellar length. Additionally, the normally spindle-shaped promastigote parasites reveal a more spherical cell shape giving them an amastigote-like appearance. The mutants lose their motility and wiggle in place. Ultrastructural analyses reveal that the outer dynein arm is missing. Furthermore, expression of the amastigote-specific A2 gene family was detected in the deletion mutants in the absence of a stage conversion stimulus. In vitro infectivity is slightly increased in the mutant cell line compared to wild-type Leishmania donovani parasites. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the correct assembly of the flagellum has a great influence on the investigated characteristics of Leishmania parasites. The lack of a single flagellar protein causes an aberrant morphology, impaired growth and altered infectiousness of the parasite.

  19. Dynein Heavy Chain, Encoded by Two Genes in Agaricomycetes, Is Required for Nuclear Migration in Schizophyllum commune.

    Directory of Open Access Journals (Sweden)

    Melanie Brunsch

    Full Text Available The white-rot fungus Schizophyllum commune (Agaricomycetes was used to study the cell biology of microtubular trafficking during mating interactions, when the two partners exchange nuclei, which are transported along microtubule tracks. For this transport activity, the motor protein dynein is required. In S. commune, the dynein heavy chain is encoded in two parts by two separate genes, dhc1 and dhc2. The N-terminal protein Dhc1 supplies the dimerization domain, while Dhc2 encodes the motor machinery and the microtubule binding domain. This split motor protein is unique to Basidiomycota, where three different sequence patterns suggest independent split events during evolution. To investigate the function of the dynein heavy chain, the gene dhc1 and the motor domain in dhc2 were deleted. Both resulting mutants were viable, but revealed phenotypes in hyphal growth morphology and mating behavior as well as in sexual development. Viability of strain Δdhc2 is due to the higher expression of kinesin-2 and kinesin-14, which was proven via RNA sequencing.

  20. 24,26-dihydroxyvitamin D2: a unique physiological metabolite of vitamin D2

    International Nuclear Information System (INIS)

    A new vitamin D2 metabolite, 24,26-dihydroxyvitamin D2, has been detected in the plasma of rats fed physiologic amounts of vitamin D2. The identity of the new metabolite (isolated from cow plasma) was established by ultraviolet absorbance, mass spectroscopy, chemical reactivity, and NMR spectroscopy. Among these, the mass spectrum was unique for the presence of a peak at M - 48 that was attributed to an intramolecular rearrangement involving both the C-24 and C-26 hydroxyl groups. A 300-MHz 1H NMR spectrum of 40 μg of metabolite indicated a downfield shift of the C-28 methyl group signal to δ 1.30 and a multiplet at δ 3.66 corresponding to the hydroxylated C-26 methyl group. They determined that the formation of 24,26-dihydroxyvitamin D2 represented a major pathway for further metabolism of 24-hydroxyvitamin D2 in rats, exceeding the formation of 24,25-dihydroxyvitamin D2. Standard bioassays revealed that 24,26-dihydroxyvitamin D2 possessed very little biological activity and most likely represents a deactivation pathway for 24-hydroxyvitamin D2

  1. Seasonal Variation of Provitamin D2 and Vitamin D2 in Perennial Ryegrass (Lolium perenne L.)

    DEFF Research Database (Denmark)

    Jäpelt, Rie Bak; Didion, Thomas; Smedsgaard, Jørn;

    2011-01-01

    Ergosterol (provitamin D(2)) is converted to vitamin D(2) in grass by exposure to UV light. Six varieties of perennial ryegrass (Lolium perenne L.) were harvested four times during the season, and the contents of vitamin D(2) and ergosterol were analyzed by a sensitive and selective liquid...... chromatography tandem mass spectrometry method. Weather factors were recorded, and a principal component analysis was performed to study which factors were important for the formation of vitamin D(2). The results suggest that a combination of weather factors is involved and that the contents of ergosterol and...... vitamin D(2) change more than a factor of 10 during the season. These results demonstrate that grass potentially can be a significant source of vitamin D for grazing animals and animals fed on silage and hay....

  2. Cocaine inhibits dopamine D2 receptor signaling via sigma-1-D2 receptor heteromers.

    Directory of Open Access Journals (Sweden)

    Gemma Navarro

    Full Text Available Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain.

  3. Attosecond Control in Photoionization of D2

    International Nuclear Information System (INIS)

    We study the dissociative photoionization of D2 by an attosecond pulse train (APT) in the presence of a near-infrared (IR) field. Strong oscillations in the D+ kinetic energy release spectrum with a half period of the optical cycle of the infrared field are observed and attributed to interferences between ionization pathways involving different harmonic orders of the APT due to the IR-induced coupling between the 1sσg and 2pσu ionization channels.

  4. [High molecular weight protein detected in higher plant cells by antibodies against dynein is associated with vesicular organelles including Golgi apparatus].

    Science.gov (United States)

    Shanina, N A; Lazareva, E M; Chentsov, Iu S; Smirnova, E A

    2008-01-01

    The cytoplasmic dynein is a multisubunit complex driving organelles along microtubules to their minus-end. We used antibodies against two functional domains (motor and microtubule-binding) of one of principal components of the complex--dynein heavy chain of slime mould Dictyostelium discoideum--to test root meristem cells of wheat Triticum aestivum. The antibodies reacted with a high molecular weight protein (> 500 kDa) in the total cell extract and the band recognized by the antibodies in plant extracts had a lower electrophoretic mobility than the high molecular weight band of mammalian dynein. Antibodies coupled to protein A-Sepharose precipitated the high molecular weight protein from the purified cell extracts. Immunocytochemical analysis demonstrated that the antigen recognized by antibodies against dynein heavy chains is associated with the vesicles whose localization depends on the cell cycle stage. The antigen-positive vesicles were localized to the perinuclear region in interphase and early prophase, to the spindle periphery and to spindle pole region during mitosis, and to the interzonal region in the period of fragmoplast and cell plate formation. Some antigen-positive vesicles also reacted with antibodies against Golgi protein markers. The obtained data indicate that higher plant cells contain a high molecular weight protein interacting with antibodies against the motor and microtubules-binding domains of Dictyostelium dynein heavy chain. The revealed antigen was associated with the vesicular structures in the cytoplasm including the Golgi apparatus. PMID:18409378

  5. Docking-complex-independent alignment of Chlamydomonas outer dynein arms with 24-nm periodicity in vitro.

    Science.gov (United States)

    Oda, Toshiyuki; Abe, Tatsuki; Yanagisawa, Haruaki; Kikkawa, Masahide

    2016-04-15

    The docking complex is a molecular complex necessary for assembly of outer dynein arms (ODAs) on the axonemal doublet microtubules (DMTs) in cilia and flagella. The docking complex is hypothesized to be a 24-nm molecular ruler because ODAs align along the DMTs with 24-nm periodicity. In this study, we rigorously tested this hypothesis using structural and genetic methods. We found that the ODAs can bind to DMTs and porcine microtubules with 24-nm periodicities even in the absence of the docking complexin vitro Using cryo-electron tomography and structural labeling, we observed that the docking complex took an unexpectedly flexible conformation and did not lie along the length of DMTs. In the absence of docking complex, ODAs were released from the DMT at relatively low ionic strength conditions, suggesting that the docking complex strengthens the electrostatic interactions between the ODA and DMT. Based on these results, we conclude that the docking complex serves as a flexible stabilizer of the ODA rather than as a molecular ruler. PMID:26933181

  6. D2 Lymphadenectomy in Gastric Cancer Surgery

    Institute of Scientific and Technical Information of China (English)

    Jingyu Deng; Han Liang

    2009-01-01

    Gastric cancer is one of the most common causes of cancer death worldwide. Surgery is the most widely utilized treatment for resectable gastric cancer. Evidence indicates that lymph node involvement and depth of invasion of the primary tumor are the most important prognostic factors for gastric cancer patients. Therefore, lymph node clearance is deemed a key procedure in gastric cancer surgery for the prognostic value to patients. Although the appropriate lymphadenectomy during gastrectomy for cancer still remains controversial, extended lymph node dissection (D2 lymphadenectomy) should be recommended in high volume hospitals.

  7. Generating Generalized $G_{D-2}$ solutions

    CERN Document Server

    Bretón, N; López, L A

    2008-01-01

    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 4 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.

  8. Photosensitized cleavage of dynein heavy chains. Cleavage at the V1 site by irradiation at 365 nm in the presence of ATP and vanadate

    Energy Technology Data Exchange (ETDEWEB)

    Gibbons, I.R.; Lee-Eiford, A.; Mocz, G.; Phillipson, C.A.; Tang, W.J.; Gibbons, B.H.

    1987-02-25

    Irradiation of soluble dynein 1 from sea urchin sperm flagella at 365 nm in the presence of MgATP and 0.05-50 microM vanadate (Vi) cleaves the alpha and beta heavy chains (Mr 428,000) at their V1 sites to give peptides of Mr 228,000 and 200,000, without the nonspecific side effects produced by irradiation at 254 nm as described earlier. The decrease in intact heavy chain material is biphasic; in 10 microM Vi, approximately 80% occurs with a half-time of 7 min and the remainder with a half-time of about 90 min, and the yield of cleavage peptides is better than 90%. Loss of dynein ATPase activity appears to be a direct result of the cleavage process and is not significantly affected by the presence of up to 0.1 M cysteamine (CA, 60-23-1) or 2-aminoethyl carbamimidothioic acid dihydrobromide (CA, 56-10-0) as free radical trapping agents. The concentration of Vi required for 50% maximal initial cleavage rate is 4.5 microM, while that for 50% ATPase inhibition is 0.8 microM, both in a 0.6 M NaCl medium. In the presence of 20 microM Vi, CTP and UTP support cleavage at about half the rate of ATP, whereas GTP and ITP support cleavage only if the Vi concentration is raised to about 200 microM. Substitution of any of the transition metal cations Cr2+, Mn2+, Fe2+, or Co2+ for the usual Mg2+ suppresses the photocleavage, presumably by quenching the excited chromophore prior to scission of the heavy chain. The photocleaved dynein 1 binds to dynein-depleted flagella similarly to intact dynein 1, but upon reactivation of the flagella with 1 mM ATP their motility is partially inhibited, rather than being augmented as with intact dynein.

  9. Vanadate-sensitized cleavage of dynein heavy chains by 365-nm irradiation of demembranated sperm flagella and its effect on the flagellar motility

    Energy Technology Data Exchange (ETDEWEB)

    Gibbons, B.H.; Gibbons, I.R.

    1987-06-15

    Irradiation of demembranated flagella of sea urchin sperm at 365 nm in the presence of 0.05-1 mM MgATP and 5-10 microM vanadate (Vi) cleaves the alpha and beta heavy chains of the outer arm dynein at the same site and at about the same rate as reported previously for the solubilized dynein. The decrease in intact alpha and beta heavy chain material is biphasic, with about 80% being lost with a half-time of 8-10 min, and the remainder more slowly. Five other axonemal polypeptides of Mr greater than 350,000 are lost similarly, concomitant with the appearance of at least 9 new peptides of Mr 150,000-250,000. The motility of irradiated sperm flagella upon subsequent dilution into reactivation medium containing 1 mM ATP and 2.5 mM catechol shows a progressive decrease in flagellar beat frequency for irradiation times that produce up to about 50% cleavage of the dynein heavy chains; more prolonged irradiation causes irreversible loss of motility. Competition between photocleaved and intact outer arm dynein for rebinding to dynein-depleted sperm flagella shows that cleavage has little effect upon the ability for rebinding, although the cleaved dynein partially inhibits subsequent motility. Substitution of MnATP for the MgATP in the irradiation medium prevents the loss of all of the axonemal polypeptides during irradiation for up to 60 min and also protects the potential for subsequent flagellar motility.

  10. The Affinity of the Dynein Microtubule-Binding Domain is Modulated by the Conformation of its Coiled-Coil Stalk*

    OpenAIRE

    Gibbons, I. R.; Garbarino, Joan E.; Tan, Carol E.; Reck-Peterson, Samara L; Vale, Ronald D.; Carter, Andrew P.

    2005-01-01

    The microtubule binding domain (MTBD) of dynein is separated from the AAA core of the motor by an ~15 nm stalk that is predicted to consist of an anti-parallel coiled coil. However, the structure of this coiled-coil and the mechanism it uses to mediate communication between the MTBD and ATP-binding core are unknown. Here, we sought to identify the optimal alignment between the hydrophobic heptad repeats in the two strands of the stalk coiled-coil. To do this, we fused the MTBD of mouse cytopl...

  11. Dopamine D2 receptor SPECT imaging

    International Nuclear Information System (INIS)

    The purposes of this study were to evaluate the utility of kit formulation, the basic in vivo charactristics, and clinical usefulness of dopamine D2 receptor imaging with 123I-(S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrodinyl)methyl]-benzamide (123I-IBZM). We studied 22 normal controls, 3 early symptomatic Huntington's disease patients, and 1 patient with visual hallucination on and off neuroleptics. 123I-IBZM could be conveniently prepared with a high degree of purity from a kit, but with relatively low radiochemical yield. We demonstrated 123I-IBZM receptor binding equilibrium by performing serial SPECT scanning in a normal volunteer. The basal ganglia/frontal cortex (BG/FC) ratios plateaued after the specific binding reached equilibrium approximately 60 minutes after injection. The BG/FC ratio declined significantly with age. The ratios for the Huntington's disease patients were significantly lower than those for normal controls. The images of the patient off neuroleptic therapy showed dramatically increased BG activity compared with those obtained while on therapy. The BG/FC ratio provides an estimate of Bmax/Kd and hence the receptor density. It appears important to perform SPECT early in the equilibrium phase and at a fixed time after injection to obtain significantly high signal to noise ratios. 123I-IBZM is an ideal tracer for SPECT including a rotating gamma camera type which can provide estimates of the receptor density objectively by calculating the BG/FC ratio, and is a promising agent for the investigation of dopamine D2 receptors in clinical conditions. (author)

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

    Science.gov (United States)

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

    2016-02-17

    We have recently reported G-protein coupled receptor (GPCR) model structures for the active and inactive states of the human dopamine D2 receptor (D2R) using adrenergic crystal structures as templates. Since the therapeutic concentrations of dopamine agonists that suppress the release of prolactin are the same as those that act at the high-affinity state of the D2 receptor (D2High), D2High in the anterior pituitary gland is considered to be the functional state of the receptor. In addition, the therapeutic concentrations of anti-Parkinson drugs are also related to the dissociation constants in the D2High form of the receptor. The discrimination between the high- and low-affinity (D2Low) components of the D2R is not obvious and requires advanced computer-assisted structural biology investigations. Therefore, in this work, the derived D2High and D2Low receptor models (GPCR monomer and dimer three-dimensional structures) are used as drug-binding targets to investigate binding interactions of dopamine and apomorphine. The study reveals a match between the experimental dissociation constants of dopamine and apomorphine at their high- and low-affinity sites of the D2 receptor in monomer and dimer and their calculated dissociation constants. The allosteric receptor-receptor interaction for dopamine D2R dimer is associated with the accessibility of adjacent residues of transmembrane region 4. The measured negative cooperativity between agonist ligand at dopamine D2 receptor is also correctly predicted using the D2R homodimerization model. PMID:26645629

  13. Hyperelliptic plane curves of type (d,d-2)

    OpenAIRE

    Sakai, Fumio; Saleem, Mohammad; Tono, Keita

    2008-01-01

    In a previous paper, we classified and constructed all rational plane curves of type (d,d-2). In this paper, we generalize these results to irreducible plane curves of type (d,d-2) with positive genus.

  14. Neutron Streaming in D2O Pipes

    International Nuclear Information System (INIS)

    An investigation has been carried out concerning the attenuation of neutrons inside D2O-filled pipes penetrating a concrete shield. As the purpose has been to simulate the conditions around a heavy water power reactor, pipes surrounded by an annular air gap have also been considered. Thermal, epithermal and fast neutron fluxes have been measured in three separate pipes (15, 22 and 28 cm in diameter and 100 cm long) with annulii ranging from 0 to 9.7 cm in width. The thermal flux distribution has been predicted theoretically by assuming it to be composed of three components originating from a fast exponential volume source and two surface sources at the origin; a 1/E-distributed source and a thermal source, of which the latter proved to be negligible. The fast flux distribution has been approximated by a single exponential expression for the configuration with no annulus and with the sum of two exponentials when an annulus is present. The agreement between measured and calculated values for the thermal flux is better than a factor 1.5 after about 10 cm. For deep penetration (>40 cm) the agreement is within 20 % and only the fast volume source contributes appreciably to the thermal flux. This holds for all cases both with and without annulus. The agreement in the case of the fast flux is within a factor 1.3 (>40 cm) for no annulus geometry and about 2-3 with annulus. Curves are presented for obtaining necessary parameters ('removal' cross section and extrapolated radius) for other geometries than those covered in this report

  15. 21 CFR 582.5950 - Vitamin D2.

    Science.gov (United States)

    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...

  16. Effectiveness of a dynein team in a tug of war helped by reduced load sensitivity of detachment: evidence from the study of bidirectional endosome transport in D. discoideum

    International Nuclear Information System (INIS)

    Bidirectional cargo transport by molecular motors in cells is a complex phenomenon in which the cargo (usually a vesicle) alternately moves in retrograde and anterograde directions. In this case, teams of oppositely pulling motors (e.g., kinesin and dynein) bind to the cargo, simultaneously, and ‘coordinate’ their activity such that the motion consists of spells of positively and negatively directed segments, separated by pauses of varying duration. A set of recent experiments have analyzed the bidirectional motion of endosomes in the amoeba D. discoideum in detail. It was found that in between directional switches, a team of five to six dyneins stall a cargo against a stronger kinesin in a tug of war, which lasts for almost a second. As the mean detachment time of a kinesin under its stall load was also observed to be ∼1 s, we infer that the collective detachment time of the dynein assembly must also be similar. Here, we analyze this inference from a modeling perspective, using experimentally measured single-molecule parameters as inputs. We find that the commonly assumed exponential load-dependent detachment rate is inconsistent with observations, as it predicts that a five-dynein assembly will detach under its combined stall load in less than a hundredth of a second. A modified model where the load-dependent unbinding rate is assumed to saturate at stall-force level for super-stall loads gives results which are in agreement with experimental data. Our analysis suggests that the load-dependent detachment of a dynein in a team is qualitatively different at sub-stall and super-stall loads, a conclusion which is likely to have implications in other situations involving collective effects of many motors. (paper)

  17. Analysis list: Nr1d2 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Nr1d2 Liver + mm9 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Nr1d2.1.tsv... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Nr1d2.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Nr1d2....10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Nr1d2.Liver.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Liver.gml ...

  18. Underground design Laxemar, Layout D2

    Energy Technology Data Exchange (ETDEWEB)

    2009-11-15

    Laxemar candidate area is located in the province of Smaaland, some 320 km south of Stockholm. The area is located close to the shoreline of the Baltic Sea and is within the municipality of Oskarshamn, and immediately west of the Oskarshamn nuclear power plant and the Central interim storage facility for spent fuel (Clab). The easternmost part (Simpevarp subarea) includes the Simpevarp peninsula, which hosts the power plants and the Clab facility. The island of Aespoe, containing the Aespoe Hard Rock Laboratory is located some three kilometres northeast of the central parts of Laxemar. The Laxemar subarea covers some 12.5 km2, compared with the Simepvarp subarea, which is approximately 6.6 km2. The Laxemar candidate area has been investigated in stages, referred to as the initial site investigations (ISI) and the complete site investigations (CSI). These investigations commenced in 2002 and were completed in 2008. During the site investigations, several studies and design steps (D0, D1 and D2) were carried out to ensure that sufficient space was available for the 6,000-canister layout within the target volume at a depth of approximately 500 m. The findings from design Step D2 for the underground facilities including the access ramp, shafts, rock caverns in a Central Area, transport tunnels, and deposition tunnels and deposition holes are contained in this report. The layout for these underground excavations at the deposition horizon requires an area of 5.7 km2, and the total rock volume to be excavated is 3,008 x 103 m3 using a total tunnel length of approximately 115 km. The behaviour of the underground openings associated with this layout is expected to be similar to the behaviour of other underground openings in the Scandinavian shield at similar depths. The dominant mode of instability is expected to be structurally controlled wedge failure. Stability of the openings will be achieved with traditional underground rock support and by orienting the openings

  19. Underground design Laxemar, Layout D2

    International Nuclear Information System (INIS)

    Laxemar candidate area is located in the province of Smaaland, some 320 km south of Stockholm. The area is located close to the shoreline of the Baltic Sea and is within the municipality of Oskarshamn, and immediately west of the Oskarshamn nuclear power plant and the Central interim storage facility for spent fuel (Clab). The easternmost part (Simpevarp subarea) includes the Simpevarp peninsula, which hosts the power plants and the Clab facility. The island of Aespoe, containing the Aespoe Hard Rock Laboratory is located some three kilometres northeast of the central parts of Laxemar. The Laxemar subarea covers some 12.5 km2, compared with the Simepvarp subarea, which is approximately 6.6 km2. The Laxemar candidate area has been investigated in stages, referred to as the initial site investigations (ISI) and the complete site investigations (CSI). These investigations commenced in 2002 and were completed in 2008. During the site investigations, several studies and design steps (D0, D1 and D2) were carried out to ensure that sufficient space was available for the 6,000-canister layout within the target volume at a depth of approximately 500 m. The findings from design Step D2 for the underground facilities including the access ramp, shafts, rock caverns in a Central Area, transport tunnels, and deposition tunnels and deposition holes are contained in this report. The layout for these underground excavations at the deposition horizon requires an area of 5.7 km2, and the total rock volume to be excavated is 3,008 x 103 m3 using a total tunnel length of approximately 115 km. The behaviour of the underground openings associated with this layout is expected to be similar to the behaviour of other underground openings in the Scandinavian shield at similar depths. The dominant mode of instability is expected to be structurally controlled wedge failure. Stability of the openings will be achieved with traditional underground rock support and by orienting the openings

  20. Elliptic supertube and a Bogomol'nyi-Prasad-Sommerfield D2-brane--anti-D2-brane Pair

    OpenAIRE

    Cho, Jin-Ho; Oh, Phillial

    2001-01-01

    An exact solution, in which a D2-brane and an anti-D2-brane are connected by an elliptically tubular D2-brane, is obtained without any junction condition. The solution is shown to preserve one quarter of the supersymmetries of the type-IIA Minkowski vacuum. We show that the configuration cannot be obtained by "blowing-up" from some inhomogeneously D0-charged superstrings. The BPS bound tells us that it is rather composed of D0-charged D2-brane-anti-D2-brane pair and a strip of superstrings co...

  1. Drosophila gurken (TGFalpha) mRNA localizes as particles that move within the oocyte in two dynein-dependent steps.

    Science.gov (United States)

    MacDougall, Nina; Clark, Alejandra; MacDougall, Eilidh; Davis, Ilan

    2003-03-01

    In Drosophila oocytes, gurken mRNA localization orientates the TGF-alpha signal to establish the anteroposterior and dorsoventral axes. We have elucidated the path and mechanism of gurken mRNA localization by time-lapse cinematography of injected fluorescent transcripts in living oocytes. gurken RNA assembles into particles that move in two distinct steps, both requiring microtubules and cytoplasmic Dynein. gurken particles first move toward the anterior and then turn and move dorsally toward the oocyte nucleus. We present evidence suggesting that the two steps of gurken RNA transport occur on distinct arrays of microtubules. Such distinct microtubule networks could provide a general mechanism for one motor to transport different cargos to distinct subcellular destinations. PMID:12636913

  2. The Mechanism of Dynein Light Chain LC8-mediated Oligomerization of the Ana2 Centriole Duplication Factor*

    Science.gov (United States)

    Slevin, Lauren K.; Romes, Erin M.; Dandulakis, Mary G.; Slep, Kevin C.

    2014-01-01

    Centrioles play a key role in nucleating polarized microtubule networks. In actively dividing cells, centrioles establish the bipolar mitotic spindle and are essential for genomic stability. Drosophila anastral spindle-2 (Ana2) is a conserved centriole duplication factor. Although recent work has demonstrated that an Ana2-dynein light chain (LC8) centriolar complex is critical for proper spindle positioning in neuroblasts, how Ana2 and LC8 interact is yet to be established. Here we examine the Ana2-LC8 interaction and map two LC8-binding sites within the central region of Ana2, Ana2M (residues 156–251). Ana2 LC8-binding site 1 contains a signature TQT motif and robustly binds LC8 (KD of 1.1 μm), whereas site 2 contains a TQC motif and binds LC8 with lower affinity (KD of 13 μm). Both LC8-binding sites flank a predicted ∼34-residue α-helix. We present two independent atomic structures of LC8 dimers in complex with Ana2 LC8-binding site 1 and site 2 peptides. The Ana2 peptides form β-strands that extend a central composite LC8 β-sandwich. LC8 recognizes the signature TQT motif in the first LC8 binding site of Ana2, forming extensive van der Waals contacts and hydrogen bonding with the peptide, whereas the Ana2 site 2 TQC motif forms a uniquely extended β-strand, not observed in other dynein light chain-target complexes. Size exclusion chromatography coupled with multiangle static light scattering demonstrates that LC8 dimers bind Ana2M sites and induce Ana2 tetramerization, yielding an Ana2M4-LC88 complex. LC8-mediated Ana2 oligomerization probably enhances Ana2 avidity for centriole-binding factors and may bridge multiple factors as required during spindle positioning and centriole biogenesis. PMID:24920673

  3. The mechanism of dynein light chain LC8-mediated oligomerization of the Ana2 centriole duplication factor.

    Science.gov (United States)

    Slevin, Lauren K; Romes, Erin M; Dandulakis, Mary G; Slep, Kevin C

    2014-07-25

    Centrioles play a key role in nucleating polarized microtubule networks. In actively dividing cells, centrioles establish the bipolar mitotic spindle and are essential for genomic stability. Drosophila anastral spindle-2 (Ana2) is a conserved centriole duplication factor. Although recent work has demonstrated that an Ana2-dynein light chain (LC8) centriolar complex is critical for proper spindle positioning in neuroblasts, how Ana2 and LC8 interact is yet to be established. Here we examine the Ana2-LC8 interaction and map two LC8-binding sites within the central region of Ana2, Ana2M (residues 156-251). Ana2 LC8-binding site 1 contains a signature TQT motif and robustly binds LC8 (KD of 1.1 μm), whereas site 2 contains a TQC motif and binds LC8 with lower affinity (KD of 13 μm). Both LC8-binding sites flank a predicted ~34-residue α-helix. We present two independent atomic structures of LC8 dimers in complex with Ana2 LC8-binding site 1 and site 2 peptides. The Ana2 peptides form β-strands that extend a central composite LC8 β-sandwich. LC8 recognizes the signature TQT motif in the first LC8 binding site of Ana2, forming extensive van der Waals contacts and hydrogen bonding with the peptide, whereas the Ana2 site 2 TQC motif forms a uniquely extended β-strand, not observed in other dynein light chain-target complexes. Size exclusion chromatography coupled with multiangle static light scattering demonstrates that LC8 dimers bind Ana2M sites and induce Ana2 tetramerization, yielding an Ana2M4-LC88 complex. LC8-mediated Ana2 oligomerization probably enhances Ana2 avidity for centriole-binding factors and may bridge multiple factors as required during spindle positioning and centriole biogenesis. PMID:24920673

  4. 26 CFR 1.1503(d)-2 - Domestic use.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Domestic use. 1.1503(d)-2 Section 1.1503(d)-2...) INCOME TAXES Administrative Provisions and Other Rules § 1.1503(d)-2 Domestic use. A domestic use of a... be subject to tax in the United States. A domestic use shall be deemed to occur in the year the...

  5. 21 CFR 172.379 - Vitamin D2.

    Science.gov (United States)

    2010-04-01

    ... Federal Register approves this incorporation by reference in accordance with 5 U.S.C 552(a) and 1 CFR part... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Vitamin D2. 172.379 Section 172.379 Food and Drugs... Dietary and Nutritional Additives § 172.379 Vitamin D2. Vitamin D2 may be used safely in foods as...

  6. Time-Dependent Measure of a Nano-Scale Force-Pulse Driven by the Axonemal Dynein Motors in Individual Live Sperm Cells

    Energy Technology Data Exchange (ETDEWEB)

    Allen, M J; Rudd, R E; McElfresh, M W; Balhorn, R

    2009-04-23

    Nano-scale mechanical forces generated by motor proteins are crucial to normal cellular and organismal functioning. The ability to measure and exploit such forces would be important to developing motile biomimetic nanodevices powered by biological motors for Nanomedicine. Axonemal dynein motors positioned inside the sperm flagellum drive microtubule sliding giving rise to rhythmic beating of the flagellum. This force-generating action makes it possible for the sperm cell to move through viscous media. Here we report new nano-scale information on how the propulsive force is generated by the sperm flagellum and how this force varies over time. Single cell recordings reveal discrete {approx}50 ms pulses oscillating with amplitude 9.8 {+-} 2.6 nN independent of pulse frequency (3.5-19.5 Hz). The average work carried out by each cell is 4.6 x 10{sup -16} J per pulse, equivalent to the hydrolysis of {approx}5,500 ATP molecules. The mechanochemical coupling at each active dynein head is {approx}2.2 pN/ATP, and {approx}3.9 pN per dynein arm, in agreement with previously published values obtained using different methods.

  7. 生椎茸中のプレビタミンD_2およびビタミンD_2の同定

    OpenAIRE

    高村, 一知; 星野, 浩子; 叶多, 謙蔵; タカムラ, カズノリ; ホシノ, ヒロコ; カノウタ, ケンゾウ; Kazunori, Takamura; HIROKO, HOSHINO; KENZO, KANOHTA

    1993-01-01

    Pre-vitamin D_2(pre-D_2)and vitamin D_2(D_2)in raw shiitake mushroom were identified by liquid chromatography-mass spectrometry (LC-MS) with modified plasmaspray. 1. Pre-D_2 and D_2 in raw shiitake mushroom were separated by LC. 2. Pre-D_2 was confirmed parent ion(m/z 397 [M+H]^+)to scan number 259 of total ion chromatogram. 3. D_2 was cofirmed parent ion(m/z 397 [M+H]^+) to scan number 296 of total ion chromatogram. 4. We have succeeded in obtaining mass spectra of pre-D_2 and D_2 that does ...

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

    OpenAIRE

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

    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 ago...

  9. Neutron emission during Pd-D2O electrolysis

    International Nuclear Information System (INIS)

    A clear correlation has been found between neutron counting and the pulsation of an electrolysis current obtained with different Pd cathodes (rolled and wire) in D2O. Different spectra as a function of time synchronized with the electrolysis current of Pd-D2O and Pd-H2O are presented, all in identical conditions. Measurements in Pd-D2O lack the (statistically significant) synchronic increments in counting which are observed when the electrolite used is D2O. On the hypothesis that the observed neutrons are originated in Deuteron fusion with a branching ratio 0.5, the obtained countings correspond to a fusion rate of approximately 0.5 fusions/second. (Author)

  10. Nuclear methods for detecting a diversion of D2O

    International Nuclear Information System (INIS)

    The possibility of diverting D2O for use in clandestine reactors capable of weapons grade nuclear material production has created interest in safeguarding D2O. As part of a program to investigate the technological aspects of safeguarding D2O, several proposed nuclear based non-destructive measurement methods have been proposed which do not require the D2O containers to be opened. These nuclear techniques all proved workable and could lend themselves, in principle, to field application. They are neutron transmission measurements, neutron capture gamma detection, photoneutron production, and measurements of the lifetime of neutrons injected in the barrel. Since much of the instrumentation is common to several methods, more than one technique may be employed to give added assurance. 6 figures, 2 tables

  11. Quantitative imaging of D-2-hydroxyglutarate (D2HG in selected histological tissue areas by a novel bioluminescence technique

    Directory of Open Access Journals (Sweden)

    Nadine Fabienne Voelxen

    2016-03-01

    Full Text Available AbstractPatients with malignant gliomas have a poor prognosis with average survival of less than one 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, which was discovered first in this tumor entity. D2HG is generated in large amounts due to various gain-of–function mutations in the isocitrate dehydrogenases IDH-1 and IDH-2. 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 (LC/MS. 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.

  12. Amphetamine Self-Administration Attenuates Dopamine D2 Autoreceptor Function

    OpenAIRE

    Calipari, Erin S.; Sun, Haiguo; Eldeeb, Khalil; Luessen, Deborah J; Feng, Xin; Howlett, Allyn C.; JONES, SARA R.; Chen, Rong

    2014-01-01

    Dopamine D2 autoreceptors located on the midbrain dopaminergic neurons modulate dopamine (DA) neuron firing, DA release, and DA synthesis through a negative-feedback mechanism. Dysfunctional D2 autoreceptors following repeated drug exposure could lead to aberrant DA activity in the ventral tegmental area (VTA) and projection areas such as nucleus accumbens (NAcc), promoting drug-seeking and -taking behavior. Therefore, it is important to understand molecular mechanisms underlying drug-induced...

  13. Photoaffinity ligand for dopamine D2 receptors: azidoclebopride

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-02-01

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

  14. Studies on the metabolism of prostaglandin D2 in humans

    International Nuclear Information System (INIS)

    Fifty μCi of [3H]-prostaglandin D2 tracer (100 Ci/mMole) was infused intravenously into a normal human male volunteer. Seventy-five percent of the infused radioactivity was excreted into the urine within 5 hours. This urine was added to urine obtained from two mastocytosis patients with marked overproduction of prostaglandin D2. Twenty-five radiolabelled prostaglandin D2 urinary metabolites were chromatographically isolated and purified and subsequently identified by gas chromatography-mass spectrometry. Twenty-three of these metabolites, comprising 37% of the recovered radioactivity, had prostaglandin F-ring structures, and only 2 metabolites, comprising 2.7% of the recovered radioactivity retained the prostaglandin D-ring structure. The single most abundant metabolite identified was 9,11-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-energy-1,20-dioic acid which was isolated in a tricyclic form. Different isomeric forms of several prostaglandin F-ring metabolites were identified. To further investigate the metabolism of prostaglandin D2, in vitro studies examining the metabolic transformation of prostaglandin D2 by human liver were conducted. This study documents that prostaglandin D2 is metabolized to PGF-ring metabolites in vivo in humans, and is converted to a structurally new prostaglandin, 9/sub α/, 11/sub β/-PGF2 in vitro by a cytosolic NADPH-dependent 11-Ketoreductase in the human liver

  15. Fasciola hepatica calcium-binding protein FhCaBP2: structure of the dynein light chain-like domain.

    Science.gov (United States)

    Nguyen, Thanh H; Thomas, Charlotte M; Timson, David J; van Raaij, Mark J

    2016-07-01

    The common liver fluke Fasciola hepatica causes an increasing burden on human and animal health, partly because of the spread of drug-resistant isolates. As a consequence, there is considerable interest in developing new drugs to combat liver fluke infections. A group of potential targets is a family of calcium-binding proteins which combine an N-terminal domain with two EF-hand motifs and a C-terminal domain with predicted similarity to dynein light chains (DLC-like domain). The function of these proteins is unknown, although in several species, they have been localised to the tegument, an important structure at the host-parasite interface. Here, we report the X-ray crystal structure of the DLC-like domain of F. hepatica calcium-binding protein 2 (FhCaBP2), solved using single-wavelength anomalous diffraction and refined at 2.3 Å resolution in two different crystal forms. The FhCaBP2 DLC-like domain has a structure similar to other DLC domains, with an anti-parallel β-sheet packed against an α-helical hairpin. Like other DLC domains, it dimerises through its β2-strand, which extends in an arch and forms the fifth strand in an extended β-sheet of the other monomer. The structure provides molecular details of the dimerisation of FhCaBP2, the first example from this family of parasite proteins. PMID:27083189

  16. L(d1, d2,..., dt)-Number λ(Cn; d1, d2,...,dt) of Cycles

    Institute of Scientific and Technical Information of China (English)

    GAO Zhen Bin; ZHANG Xiao Dong

    2009-01-01

    An L(d1,d2,...,dt)-labeling of a graph G is a function f from its vertex set V(G) to the set {0, 1,..., k} for some positive integer k such that {f(x) - f(y)| ≥ di, if the distance between vertices x and y in G is equal to i for i = 1,2,...,t. The L(d1,d2,...,dt)-number λ(G;d1,d2,... ,dt) of G is the smallest integer number k such that G has an L(d1,d2,... ,dt)labeling with max{f(x)|x ∈ V(G)} = k. In this paper, we obtain the exact values for λ(Cn; 2, 2,1) and λ(Cn; 3, 2, 1), and present lower and upper bounds for λ(Cn; 2,..., 2,1,..., 1)

  17. Backbone and side-chain ¹H, ¹⁵N, and ¹³C resonance assignments of the microtubule-binding domain of yeast cytoplasmic dynein in the high and low-affinity states.

    Science.gov (United States)

    Takarada, Osamu; Nishida, Noritaka; Kikkawa, Masahide; Shimada, Ichio

    2014-10-01

    Cytoplasmic dynein is a motor protein that walks toward the minus end of microtubules (MTs) by utilizing the energy of ATP hydrolysis. The heavy chain of cytoplasmic dynein contains the microtubule-binding domain (MTBD). Switching of MTBD between high and low affinity states for MTs is crucial for processive movement of cytoplasmic dynein. Previous biochemical studies demonstrated that the affinity of MTBD is regulated by the AAA+ family ATPase domain, which is separated by 15 nm long coiled-coil helix. In order to elucidate the structural basis of the affinity switching mechanism of MTBD, we designed two MTBD constructs, termed MTBD-High and MTBD-Low, which are locked in high and low affinity state for MTs, respectively, by introducing a disulfide bond between the coiled-coil helix. Here, we established the backbone and side-chain assignments of MTBD-High and MTBD-Low for further structural analyses. PMID:23975349

  18. Antipsychotic efficacy: relationship to optimal D2-receptor occupancy.

    Science.gov (United States)

    Pani, Luca; Pira, Luigi; Marchese, Giorgio

    2007-07-01

    Clinically important differences exist between antipsychotic agents and formulations in terms of safety and tolerability. Features of the biochemical interaction between the antipsychotic and the D2-receptor may underlie these differences. This article reviews current information on the relationship between antipsychotic receptor occupancy and clinical response. A literature search was performed using the keywords 'antipsychotic or neuroleptic', 'receptor' and 'occupancy' and 'dopamine' and 'D2' supplemented by the authors' knowledge of the literature. Imaging and clinical data have generally supported the hypotheses that optimal D2-receptor occupancy in the striatum lies in a 'therapeutic window' between approximately 65 and approximately 80%, however, pharmacokinetic and pharmacodynamic properties of a drug should also be taken into account to fully evaluate its therapeutic effects. Additional research, perhaps in preclinical models, is needed to establish D2-receptor occupancy in various regions of the brain and the optimal duration of D2-receptor blockade in order to maximise efficacy and tolerability profiles of atypical antipsychotics and thereby improve treatment outcomes for patients with schizophrenia. PMID:17419008

  19. KOREAN MOBILE OPERATORS' VALUE MAP FOR LTE D2D

    Directory of Open Access Journals (Sweden)

    Taisiya Kim

    2015-04-01

    Full Text Available Managing the wireless data traffic is a main concern for mobile network operators in Information of Things (IoT environment. Long Term Evolution Device to Device (LTE D2D is regarding as a solution for the spectrum problem. It will bring an impact on providers and the whole mobile environment. The main purpose of this study is to analyze the role of key players, who share spectrum with mobile operators, and to present the value map of relationship among Korean mobile operators and other key players in LTE D2D discovery (commercial channel, as complicated relationships of key players are expected. Then, this study suggests scenario for ‘Targeted Advertising’ service of LTE D2D. LTE D2D is early discussion stage and scenario has limitation of specific business model. However, results of this study are significant for the present stage and provide implications for future researches on strategies for LTE D2D environment.

  20. Symmetries and String Field Theory in D=2

    CERN Document Server

    Kaku, M

    1993-01-01

    (This talk was presented at the Third International Wigner Symposium on Group Theory, Oxford, September, 1993.) Matrix models provides us with the most powerful framework in which to analyze D=2 string theory, yet some of its miraculous features, such as discrete states and $w(\\infty)$, remain rather obscure, because the string degrees of freedom have been removed. Liouville theory, on the other hand, has all its string degrees of freedom intact, yet is notoriously difficult to solve. In this paper, we present the second quantized formulation of Liouville theory in D=2, where discrete states and $w(\\infty)$ have a natural, field theoretic interpretation. We generalize the non-polynomial closed string field theory, first developed by the author and the Kyoto and MIT groups, to the D=2 case. We find that, in second quantized field theory language, the rather mysterious features of matrix models have an intuitively transparent interpretation, similar to standard gauge theory. Latex file.

  1. H2 and D2 diffusion in bisphenol A polycarbonate

    International Nuclear Information System (INIS)

    The permeabilities and diffusivities of H2 and D2 in bisphenol A polycarbonate have been measured over a broad temperature range (-125 to +75C). The H2/D2 diffusivity selectivity ranges from 1.15 at +75C down to 1.05 at -125C. A simple model of transport based on diffusive jumps of gas molecules between small cavities which are described by three dimensional harmonic oscillator potentials. Incorporation of quantum isotope mass effects into this model provides an explanation for the observed differences between H2 and D2 diffusion. Overall, these results suggest that polymer chain dynamics may play only a minor role in the transport of very small penetrant molecules in glassy polymers

  2. Evidence against dopamine D1/D2 receptor heteromers

    Science.gov (United States)

    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

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

    OpenAIRE

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

    2011-01-01

    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 expres...

  4. Emotional response in dopamine D2L receptor-deficient mice

    OpenAIRE

    Hranilovic, Dubravka; Bucan, Maja; Wang, Yanyan

    2008-01-01

    The dopamine D2 receptor (D2R) system has been implicated in emotional processing which is often impaired in neuropsychiatric disorders. The long (D2L) and the short (D2S) isoforms of D2R are generated by alternative splicing of the same gene. To study differential roles of the two D2R isoforms, D2L-deficient mice (D2L−/−) expressing functional D2S were previously generated. In this study the contribution of D2L isoform to emotional response was investigated by examining behaviors that reflec...

  5. Mastering of technology of D2 die steel hot rolling

    International Nuclear Information System (INIS)

    The technology of melting and hot rolling of the D2 die steel, analogous to the national Kh12MF-type steel, is described. The course of the D2 steel reduced hot plasticity is identified the content of highly large quantities of primary carbides and correspondingly presence of a rough net of the eutectic constituent. Decrease in the molybdenum, vanadium and carbon content within the limits of the brand composition made it possible to reduce the fractions pf the eutectic carbides. Introduction of the developed modes of electrical melting and hot rolling resulted in the increase of the yield up to 73.9%

  6. Sputtering of ErD2: experiment and theory

    International Nuclear Information System (INIS)

    Experimental measurements were made of the sputtering yield of ErD2 targets bombarded by D and A ions in the energy range 50-400 keV. A semiempirical sputtering theory is presented that relates sputtering to the energy deposited into atomic collisions beneath the target surface as well as at the surface. The theory accurately predicts the sputtering yields for both D and A bombardment. Additional calculated sputtering yields for ErD2 targets are presented which should allow extrapolation to any ion in the range of Z = 1 to Z = 36 with an accuracy better than 50 percent

  7. Dopamine D2-like receptor signaling suppresses human osteoclastogenesis.

    Science.gov (United States)

    Hanami, Kentaro; Nakano, Kazuhisa; Saito, Kazuyoshi; Okada, Yosuke; Yamaoka, Kunihiro; Kubo, Satoshi; Kondo, Masahiro; Tanaka, Yoshiya

    2013-09-01

    Dopamine, a major neurotransmitter, transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. Although the relevance of neuroendocrine system to bone metabolism has been emerging, the precise effects of dopaminergic signaling upon osteoclastogenesis remain unknown. Here, we demonstrate that human monocyte-derived osteoclast precursor cells express all dopamine-receptor subtypes. Dopamine and dopamine D2-like receptor agonists such as pramipexole and quinpirole reduced the formation of TRAP-positive multi-nucleated cells, cathepsin K mRNA expression, and pit formation area in vitro. These inhibitory effects were reversed by pre-treatment with a D2-like receptor antagonist haloperidol or a Gαi inhibitor pertussis toxin, but not with the D1-like receptor antagonist SCH-23390. Dopamine and dopamine D2-like receptor agonists, but not a D1-like receptor agonist, suppressed intracellular cAMP concentration as well as RANKL-meditated induction of c-Fos and NFATc1 mRNA expression in human osteoclast precursor cells. Finally, the dopamine D2-like receptor agonist suppressed LPS-induced osteoclast formation in murine bone marrow culture ex vivo. These findings indicate that dopaminergic signaling plays an important role in bone homeostasis via direct effects upon osteoclast differentiation and further suggest that the clinical use of neuroleptics is likely to affect bone mass. PMID:23631878

  8. Study on dopamine D2 binding capacity in vascular parkinsonism

    International Nuclear Information System (INIS)

    To investigate whether the striatal dopamine receptor function is involved in the development of vascular parkinsonism (VP), a positron emission tomography (PET) study was conducted on 9 patients with VP by using [11C] N-methylspiperone as the tracer. The rate of binding availability in the striatal dopamine D2 receptor (k3) was determined semiquantitatively, and the values were compared to the predicted normal values based on the results from 7 normal volunteers. Of 9 patients with VP, the normalized D2 receptor binding [%k3] was more than 90% in 5 patients, 89 to 87% in 3, and 75% in one. These values showed no evident correlation with the Hoehn and Yahr stage. The laterality of the striatal %k3 did not correspond to that of the parkinsonism. Thus, the striatal dopamine D2 receptor binding was not severely impaired and did not correlate with the neurological status in patients with VP. This may indicate that striatal dopamine D2 receptor function is not primarily associated with the development of the parkinsonism in VP. (author)

  9. Midbrain dopamine D2/3 receptor binding in schizophrenia.

    Science.gov (United States)

    Tuppurainen, Heli; Kuikka, Jyrki T; Laakso, Mikko P; Viinamäki, Heimo; Husso, Minna; Tiihonen, Jari

    2006-09-01

    Several studies suggest that dysregulation of dopaminergic transmission in the midbrain and thalamus may contribute to the symptomatology of schizophrenia. The objective of this study was to examine the putative alteration of dopamine D(2/3 )receptor densities in the thalamus and midbrain of drug-naïve schizophrenic patients. We used the high-affinity single-photon emission tomography ligand [(123)I]epidepride for imaging D(2/3 )receptor binding sites in six neuroleptic-naïve schizophrenic patients, and seven healthy controls. Schizophrenic symptoms were evaluated by the Positive and Negative Syndrome Scale. Significantly lower D(2/3 )values were observed in the midbrain of patients with schizophrenia compared to controls (P = 0.02). No statistically significant difference was observed in the thalamus between two groups. Negative correlations were found between thalamic D(2/3 )receptor binding and general psychopathological schizophrenic symptoms (r from -0.78 to -0.92). These observations implicate altered dopaminergic activity in the midbrain of schizophrenic patients. PMID:16783502

  10. Path integral approach to bosonization of D=2 field theories

    CERN Document Server

    Kiyanov-Charsky, S A

    1995-01-01

    We suggest a method of bosonizing any D=2 theory. We demonstrate how it works with the examples of the Thirring and the Schwinger models, known results are reproduced. This method, being applied to the Gross-Neveu model, yields nonlinear boson WZW-type theory with additional constraint in the field space. Relation to the nonlinear sigma - model is also discussed.

  11. Cellular modifications produced by D2O in yeast culture

    International Nuclear Information System (INIS)

    The cellular cycle of the Saccharomyces Cerevisiae, chosen as experimental object, is unmodified by the presence in the culture medium of D2O at different concentrations. An increased concentration of D2O in the culture medium leads to a decrease of the number of budded cells, to metabolic alterations, to DNA structure modification as well as to enzymatic changes produced by blocking. Other anomalies appear, as a function of the cell defence capacity and of the influence of the factors from the nutrient substrate or exterior medium. Due to D2O, the medium's pH changes and modifications at the enzyme level and of the cell microstructure and morphology occur. The enzymatic reactions take place in D2O slower than in H2O. Three-dimensional modifications appear in the organic components of the live cell which, in turn, produce profound modifications in the cell growth and division. Due to the kinetic and isotopic effects, modifications of the biochemical reactions affecting the cell integrity happen

  12. D-2 receptor binding in dopa-responsive dystonia

    NARCIS (Netherlands)

    Kunig, G; Leenders, KL; Antonini, A; Vontobel, P; Weindl, A; Meinck, HM

    1998-01-01

    We have studied dopamine D-2 receptor binding by [C-11]raclopride positron emission tomography in 14 patients with dopa-responsive dystonia (DRD). Data were compared with 16 levodopa-treated patients with Parkinson's disease (PD) and 26 healthy controls. The results revealed an elevated [C-11]raclop

  13. Musical Expression with the D2MMG Interface

    DEFF Research Database (Denmark)

    Jensen, Karl Kristoffer; Graugaard, Lars

    2006-01-01

    Distribution in Multiple Musical Gestures (D2MMG) uses a robust interface for detecting simple drawing gestures. The gestures affect low- and high-level aspects of sound and music through inherent modes organized as primary and secondary gestures. This enables expressive live performance and impr...

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

    OpenAIRE

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

    2006-01-01

    We report an alternative, hydroxylating pathway for the metabolism of vitamin D2 in a cytochrome P450 side chain cleavage (P450scc; CYP11A1) reconstituted system. NMR analyses identified solely 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 derivatives. 20-Hydroxyvitamin D2 was produced at a rate of 0.34 mol·min−1·mol−1 P450scc, and 17,20-dihydroxyvitamin D2 was produced at a rate of 0.13 mol·min−1·mol−1. In adrenal mitochondria, vitamin D2 was metabolized to six monohydroxy products. Nev...

  15. The separation of U and Y by D2EHPA

    International Nuclear Information System (INIS)

    The separation of uranium and yttrium in hydrochloric acid was extracted by D2EHPA in dodecane. This process used liquid-liquid extraction method. The variables studied were the concentration of hydrochloric acid, the concentration of extractant, time of extraction, and the temperature of extraction. The data evaluation of the research showed that the optimum condition was as follows: the concentration of HCI = 0.2 M, the concentration of extractant = 0.15 M D2EHPA, the time of extraction = 15 minutes, and the temperature of extraction = 20oC. It was found that the distribution coefficient of uranium was = 34.43, the distribution coefficient of yttrium was = 2.20, and the separation factor of U-Y= 15.65

  16. Dualities in the d=2 asymmetric chiral field sigma models

    International Nuclear Information System (INIS)

    Continuous dual symmetry of equations of asymmetric chiral field (ACF) in d=2 (equations of non-linear σ-models with ambiguous effect) and realization of duality transformations in explicit geometrical language of Cartran form is disclosed. Connection of this symmetry with ACF integrability is clarified. Both simple and supersymmetrical cases are considered. Notions of dual algebra and dual σ-model are introduced, their significance for understanding classical and quantum structure d=2 of ACF models is revealed. It is shown, in particular, that transition to points of infrared ACF stability can be described purely algebraically as constraction of dual algebra bringing about the fact that space-factor of the corresponding dual σ-model becomes plane. Equations of asymmetrical n vector-field model are analyzed from the similar view point. The Cartran form method permits to state that classical dynamics of this model is trivial

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

    CERN Document Server

    Guarino, Adolfo; Varela, Oscar

    2016-01-01

    The addition of supersymmetric Chern-Simons terms to ${\\cal N}=8$ super-Yang-Mills theory in three-dimensions is expected to make the latter flow into infrared superconformal 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 $D=4$ ${\\cal N}=8$ supergravity with a dyonic $\\textrm{ISO(7)}$ 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 $\\textrm{SU}(3)\\times \\textrm{U}(1)$-invariant flow into an ${\\cal N}=2$ conformal phase recently discovered.

  18. Symmetries and String Field Theory in D=2

    OpenAIRE

    Kaku, Michio

    1993-01-01

    (This talk was presented at the Third International Wigner Symposium on Group Theory, Oxford, September, 1993.) Matrix models provides us with the most powerful framework in which to analyze D=2 string theory, yet some of its miraculous features, such as discrete states and $w(\\infty)$, remain rather obscure, because the string degrees of freedom have been removed. Liouville theory, on the other hand, has all its string degrees of freedom intact, yet is notoriously difficult to solve. In this...

  19. Electrochemical boriding and characterization of AISI D2 tool steel

    International Nuclear Information System (INIS)

    D2 is an air-hardening tool steel and due to its high chromium content provides very good protection against wear and oxidation, especially at elevated temperatures. Boriding of D2 steel can further enhance its surface mechanical and tribological properties. Unfortunately, it has been very difficult to achieve a very dense and uniformly thick boride layers on D2 steel using traditional boriding processes. In an attempt to overcome such a deficiency, we explored the suitability and potential usefulness of electrochemical boriding for achieving thick and hard boride layers on this tool steel in a molten borax electrolyte at 850, 900, 950 and 1000 °C for durations ranging from 15 min to 1 h. The microstructural characterization and phase analysis of the resultant boride layers were performed using optical, scanning electron microscopy and X-ray diffraction methods. Our studies have confirmed that a single phase Fe2B layer or a composite layer consisting of FeB + Fe2B is feasible on the surface of D2 steel depending on the length of boriding time. The boride layers formed after shorter durations (i.e., 15 min) mainly consisted of Fe2B phase and was about 30 μm thick. The thickness of the layer formed in 60 min was about 60 μm and composed mainly of FeB and Fe2B. The cross sectional micro-hardness values of the boride layers varied between 14 and 22 GPa, depending on the phase composition.

  20. Electrochemical boriding and characterization of AISI D2 tool steel

    Energy Technology Data Exchange (ETDEWEB)

    Sista, V., E-mail: vsista@anl.gov [Argonne National Laboratory, Energy Systems Division, Argonne, IL (United States); Kahvecioglu, O. [Istanbul Technical University, Department of Metallurgy and Materials Engineering, Istanbul (Turkey); Eryilmaz, O.L.; Erdemir, A. [Argonne National Laboratory, Energy Systems Division, Argonne, IL (United States); Timur, S. [Istanbul Technical University, Department of Metallurgy and Materials Engineering, Istanbul (Turkey)

    2011-12-30

    D2 is an air-hardening tool steel and due to its high chromium content provides very good protection against wear and oxidation, especially at elevated temperatures. Boriding of D2 steel can further enhance its surface mechanical and tribological properties. Unfortunately, it has been very difficult to achieve a very dense and uniformly thick boride layers on D2 steel using traditional boriding processes. In an attempt to overcome such a deficiency, we explored the suitability and potential usefulness of electrochemical boriding for achieving thick and hard boride layers on this tool steel in a molten borax electrolyte at 850, 900, 950 and 1000 Degree-Sign C for durations ranging from 15 min to 1 h. The microstructural characterization and phase analysis of the resultant boride layers were performed using optical, scanning electron microscopy and X-ray diffraction methods. Our studies have confirmed that a single phase Fe{sub 2}B layer or a composite layer consisting of FeB + Fe{sub 2}B is feasible on the surface of D2 steel depending on the length of boriding time. The boride layers formed after shorter durations (i.e., 15 min) mainly consisted of Fe{sub 2}B phase and was about 30 {mu}m thick. The thickness of the layer formed in 60 min was about 60 {mu}m and composed mainly of FeB and Fe{sub 2}B. The cross sectional micro-hardness values of the boride layers varied between 14 and 22 GPa, depending on the phase composition.

  1. D2.4. Briefing paper for first workshop

    OpenAIRE

    Watson, Hayley; Wadhwa, Kush; van Os, Nico; Dekkers, Chris; Baruh, Lemi; Papadimitriou, Alex

    2015-01-01

    EXECUTIVE SUMMARY This briefing paper provides an overview of the key findings from the completion of three reports relating to the use of new media in crisis situations that have been completed as part of the COSMIC project. COSMIC, “Contribution of Social Media in Crisis management”, is a two-year project that is funded under the European Commission's Seventh Framework Programme FP7-SEC-2012 under grant agreement no. 312737. The first report, D2.1, identified existin...

  2. Molecular vibrational trapping revisited: a case study with D2+

    CERN Document Server

    Badankó, P; Vibók, Á

    2016-01-01

    This article presents a detailed study of the photodissociation probability of D_{2}^{+} for a wide range of photon energy. One dimensional numerical calculations have been performed to provide the best possible physical quantities that characterize the vibrational trapping or bond hardening effect during the photodissociation dynamics. These results undoubtedly show that the nodes of the nuclear vibrational wave packets play a decisive role in the vibrational trapping, in addition to the current understating of this phenomenon.

  3. Freezing of heavy water (D2O) nanodroplets.

    Science.gov (United States)

    Bhabhe, Ashutosh; Pathak, Harshad; Wyslouzil, Barbara E

    2013-07-01

    We follow the freezing of heavy water (D2O) nanodroplets formed in a supersonic nozzle apparatus using position resolved pressure trace measurements, Fourier transform infrared spectroscopy, and small-angle X-ray scattering. For these 3-9 nm radii droplets, freezing starts between 223 and 225 K, at volume based ice nucleation rates Jice,V on the order of 10(23) cm(-3) s(-1) or surface based ice nucleation rates Jice,S on the order of 10(16) cm(-2) s(-1). The temperatures corresponding to the onset of D2O ice nucleation are higher than those reported for H2O by Manka et al. [Manka, A.; Pathak, H.; Tanimura, S.; Wölk, J.; Strey, R.; Wyslouzil, B. E. Phys. Chem. Chem. Phys.2012, 14, 4505]. Although the values of Jice,S scale somewhat better with droplet size than values of Jice,V, the data are not accurate enough to state that nucleation is surface initiated. Finally, using current estimates of the thermophysical properties of D2O and the theoretical framework presented by Murray et al. [Murray, B. J.; Broadley, S. L.; Wilson, T. W.; Bull, S. J.; Wills, R. H.; Christenson, H. K.; Murray, E. J. Phys. Chem. Chem. Phys.2010, 12, 10380], we find that the theoretical ice nucleation rates are within 3 orders of magnitude of the measured rates over an ∼15 K temperature range. PMID:23763363

  4. Brain dopamine D-2 receptors in senile dementia

    International Nuclear Information System (INIS)

    Brain dopamine D-2 receptors were analysed in the caudate nucleus, putamen and nucleus accumbens in 49 patients with different types of neuropathologically verified dementia and in 39 controls by the binding of 3H-spiroperidol. The binding was significantly decreased in all brain areas in patients with Alzheimer's disease (AD), while the changes in patients with multi-infarct dementia (MID) or combined dementia (CD) were non-significant. According to a Scatchard analysis, this decrease in binding was due to the reduced number of receptors. On the other hand, the binding of 3H-spiroperidol was significantly increased in those patients who had received neuroleptic drugs. Significant correlations between 3H-spiroperidol binding and neuropathological changes were seen only in AD patients in the nucleus accumbens. The nucleus accumbens was also the only brain area in which there was a significant correlation between dopamine D-2 and the number of muscarinic receptors in AD patients. The findings of this study on dopamine D-2 receptors suggest the involvement of the nigrostriatal dopaminergic system in AD but not in the other two major types of dementia. (Author)

  5. Estimation of D2O content in D2O-H2O mixtures by measurement of density at 298.15 K

    International Nuclear Information System (INIS)

    The densities of pure D2O and aqueous solutions of D2O at 0.1 MPa were determined experimentally. Density equations for pure D2O and aqueous solutions of D2O were proposed. An excellent agreement between predicted and experimental values was observed. Based on these measurements, one simple method (based on density) is also proposed for estimating the D2O content in the D2O-H2O mixtures at 298.15 K. (author)

  6. Metabolism of Vitamin D2 to 17,20,24-Trihydroxyvitamin D2 by Cytochrome P450scc (CYP11A1)

    OpenAIRE

    Nguyen, Minh N.; Slominski, Andrzej; Li, Wei; Ng, Yun Rui; Tuckey, Robert C.

    2008-01-01

    As well as catalyzing the conversion of cholesterol to pregnenolone for steroid synthesis, cytochrome P450scc (P450scc) can also metabolize vitamins D2 (D2) and D3 (D3). Two products of D2 metabolism by P450scc, 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2, have been identified and shown to exert biological activity on cultured keratinocytes. The aim of this study was to fully characterize the metabolism of D2 by P450scc, including identifying additional products...

  7. Each Individual Isoform of the Dopamine D2 Receptor Protects from Lactotroph Hyperplasia

    OpenAIRE

    Radl, Daniela; De Mei, Claudia; Chen, Eric; Lee, Hyuna; Borrelli, Emiliana

    2013-01-01

    Dopamine acting through D2 receptors (D2Rs) controls lactotroph proliferation and prolactin (PRL) levels. Ablation of this receptor in mice results in lactotroph hyperplasia and prolactinomas in aged females. Alternative splicing of the Drd2 gene generates 2 independent isoforms, a long (D2L) and a short (D2S) isoform, which are present in all D2R-expressing cells. Here, we addressed the role of D2L and D2S on lactotroph physiology through the generation and analysis of D2S-null mice and thei...

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

    OpenAIRE

    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 ...

  9. Analysis of [3′,3′-d2]-nicotine and [3′,3′-d2]-cotinine by capillary liquid chromatography-electrospray tandem mass spectrometry

    OpenAIRE

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

    2007-01-01

    A selective and sensitive LC/MS/MS assay was developed for the quantification of d2-nicotine and d2-cotinine in plasma of current and past smokers administered d2-nicotine. After solid phase extraction and liquid liquid extraction, HPLC separation was achieved on a capillary hydrophilic interaction chromatography phase column. The analytes were monitored by tandem mass spectrometry with electrospray positive ionization. Linear calibration curves were generated for d2-nicotine (0.03 to 6.0 ng/...

  10. Improvements of AIMS D2DB matching for product patterns

    Science.gov (United States)

    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.

  11. Ultrasonic method for measurement of D2O concentration

    International Nuclear Information System (INIS)

    A correlation of the velocity of sound with mole percent of heavy water in D2O-H2O mixtures has been measured using a modified commercially available instrument. This is being developed as a practical method for the analysis of heavy water stored in 210 l drums. The drums need not be opened, and measurements can be made under field conditions. The application of this method would permit quick, in-field verification of drum contents in production or user facilities without having to violate drum seals

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

    OpenAIRE

    Naghdi, M.

    2014-01-01

    We introduce some (anti-) M/D-branes through turning on the corresponding field strengths of the 11- and 10-dimensional supergravity theories over AdS4×M7|6 spaces, where we use S7/Zk and CP3 for the internal spaces. Indeed, when we add M2/D2-branes on the same directions with the near horizon branes of the Aharony–Bergman–Jafferis–Maldacena model, all symmetries and supersymmetries are preserved trivially. In this case, we obtain a localized object just in the horizon. This normalizable bulk...

  13. Thermodynamics of the localized D2-D6 system

    OpenAIRE

    Gomez-Reino, Marta; Naculich, Stephen; Schnitzer, Howard

    2004-01-01

    An exact fully-localized extremal supergravity solution for N_2 D2 branes and N_6 D6 branes, which is dual to 3-dimensional supersymmetric SU(N_2) gauge theory with N_6 fundamentals, was found by Cherkis and Hashimoto. In order to consider the thermal properties of the gauge theory we present the non-extremal extension of this solution to first order in an expansion near the core of the D6 branes. We compute the Hawking temperature and the black brane horizon area/entropy. The leading order e...

  14. Anomeric and tautomeric equilibria in D-2-glucosamine Schiff bases

    Science.gov (United States)

    Kołodziej, B.; Grech, E.; Schilf, W.; Kamieński, B.; Makowski, M.; Rozwadowski, Z.; Dziembowska, T.

    2007-11-01

    The structure of some glucosamine Schiff bases has been studied by means of ab initio RHF and DFT calculation and CP/MAS 13C and 15N NMR measurements. The anomeric and tautomeric equilibria in a DMSO solution have been studied by 1H, 13C and 15N NMR spectroscopy. The anomeric composition of D-2-glucosamine Schiff bases in the solid state and in DMSO solution has been shown to depends on the tautomeric form of Schiff bases and electronic properties of substituents on the aromatic ring.

  15. Circular Dichrosim in Photoionization of H2 and D2

    International Nuclear Information System (INIS)

    In this work, circular dichroism in H2 (D2) photoionization is studied in detail. We have selected several photon energies for a case study: 19 eV for which only direct ionization to the 1sσg ionization channel is present, 27 eV where autoionization of Q11Σ+u doubly excited states takes place, and 32.5 eV for which autoionization from Q1 and doubly excited states and direct ionization to 1sσg and 2pσu channels strongly interfere. The latter case shows clear evidence of different behavior of the photoionization against radiation helicity.

  16. Characterising the D2 statistic: word matches in biological sequences

    OpenAIRE

    Foret, Sylvain; Wilson, Susan R; Burden, Conrad J.

    2009-01-01

    Word matches are often used in sequence comparison methods, either as a measure of sequence similarity or in the first search steps of algorithms such as BLAST or BLAT. The D2 statistic is the number of matches of words of k letters between two sequences. Recent advances have been made in the characterisation of this statistic and in the approximation of its distribution. Here, these results are extended to the case of approximate word matches. We compute the exact value of the variance of th...

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

    Science.gov (United States)

    Naghdi, M.

    2014-03-01

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

  18. Algebraization of Jaśkowski’s Paraconsistent Logic D2

    OpenAIRE

    Ciuciura Janusz

    2015-01-01

    The aim of this paper is to present an algebraic approach to Jaśkowski’s paraconsistent logic D2. We present: a D2-discursive algebra, Lindenbaum- Tarski algebra for D2 and D2-matrices. The analysis is mainly based on the results obtained by Jerzy Kotas in the 70s.

  19. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Water Heaters-Electric D2 Appendix D2 to... PRODUCTS REQUIRED UNDER THE ENERGY POLICY AND CONSERVATION ACT (âAPPLIANCE LABELING RULEâ) Pt. 305, App. D2 Appendix D2 to Part 305—Water Heaters—Electric Range Information CAPACITY FIRST HOUR RATING Range...

  20. Tame automorphisms of C^3 with multidegree of the form (3,d_2,d_3)

    OpenAIRE

    Karas, Marek

    2009-01-01

    In this note we prove that the sequence (3,d_2,d_3), where d_3>= d_2>= 3, is the multidegee of some tame automorphism of C^3, if and only if 3|d_2 or d_3 is a linaer combination of 3 and d_2 with coefficients in N.

  1. Distinct roles of dopamine D2L and D2S receptor isoforms in the regulation of protein phosphorylation at presynaptic and postsynaptic sites

    OpenAIRE

    Lindgren, Niklas; Usiello, Alessandro; Goiny, Michel; Haycock, John; Erbs, Eric; Greengard, Paul; Hökfelt, Tomas; Borrelli, Emiliana; Fisone, Gilberto

    2003-01-01

    Dopamine D2 receptors are highly expressed in the dorsal striatum where they participate in the regulation of (i) tyrosine hydroxylase (TH), in nigrostriatal nerve terminals, and (ii) the dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), in medium spiny neurons. Two isoforms of the D2 receptor are generated by differential splicing of the same gene and are referred to as short (D2S) and long (D2L) dopamine receptors. Here we have used wild-type mice, dopamine D2 receptor knock...

  2. M-theory Solutions Invariant under $D(2,1;\\gamma) \\oplus D(2,1;\\gamma)$

    CERN Document Server

    Bachas, Constantin; Estes, John; Krym, Darya

    2013-01-01

    We simplify and extend the construction of half-BPS solutions to 11-dimensional supergravity, with isometry superalgebra D(2,1;\\gamma) \\oplus D(2,1;\\gamma). Their space-time has the form AdS_3 x S^3 x S^3 warped over a Riemann surface \\Sigma. It describes near-horizon geometries of M2 branes ending on, or intersecting with, M5 branes along a common string. The general solution to the BPS equations is specified by a reduced set of data (\\gamma, h, G), where \\gamma is the real parameter of the isometry superalgebra, and h and G are functions on \\Sigma whose differential equations and regularity conditions depend only on the sign of \\gamma. The magnitude of \\gamma enters only through the map of h, G onto the supergravity fields, thereby promoting all solutions into families parametrized by |\\gamma|. By analyzing the regularity conditions for the supergravity fields, we prove two general theorems: (i) that the only solution with a 2-dimensional CFT dual is AdS_3 x S^3 x S^3 x R^2, modulo discrete identifications ...

  3. Effects of the d 2 dwarfing gene in pearl millet.

    Science.gov (United States)

    Bidinger, F R; Raju, D S

    1990-04-01

    Dwarf varieties have had virtually no impact on the production of pearl millet, in contrast to the case of wheat, rice, and sorghum. This research compared tall and dwarf near-isogenic F1 hybrids to attempt to determine if there were deleterious effects of the d 2 dwarfing gene that might account for the lack of release/cultivation of dwarf pearl millet cultivars. Dwarf isohybrids on average yielded less than the tails, because of a smaller average seed size combined with a similar grain number per unit area. There was, however, a larger contribution of background genetic variation (pollinator, male-sterile, and interaction effects) to hybrid variation for nearly all characters measured, including seed size, than there was of the dwarfing gene. Selection of dwarf parents capable of producing hybrids with equal seed size and yield to that of tall parents should not be difficult. PMID:24226457

  4. Thermodynamics of the localized D2-D6 system

    International Nuclear Information System (INIS)

    An exact fully-localized extremal supergravity solution for N2 D2-branes and N6 D6-branes, which is dual to 3-dimensional supersymmetric SU(N2) gauge theory with N6 fundamentals, was found by Cherkis and Hashimoto. In order to consider the thermal properties of the gauge theory we present the non-extremal extension of this solution to first order in an expansion near the core of the D6-branes. We compute the Hawking temperature and the black-brane horizon area/entropy. The leading-order entropy, which is proportional to N23/2N61/2TH2, is not corrected to first order in the expansion. This result is consistent with the analogous weak-coupling result at the correspondence point N2 similar to N6

  5. Multiplet calculus and compensating fields in D=2 conformal supergravity

    International Nuclear Information System (INIS)

    The construction of conformal (1,1) and (1,0) supergravity is discussed. The representations of the local supersymmetry algebra on scalar, spinor and vector multiplets are given, and a procedure for constructing invariant actions is established. Several previously known and unknown Lagrange densities for these multiplets are constructed. A compensating multiplet of fields with non-linear transformation law is found. It can be used to construct conformal actions for the (super)gravity fields, such as the dilaton term in string theories. It can also be used to pass to Poincare supergravity by classical gauge fixing. It has a dual multiplet compensating for local Lorentz transformations. From this multiplet one can construct a new kind of Poincare-like supergravity with local dilatation invariance, but broken d=2 Lorentz invariance. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Naghdi, M. [University of Ilam, Department of Physics, Faculty of Basic Sciences, Ilam (Iran, Islamic Republic of)

    2014-03-15

    We introduce some (anti-) M/D-branes through turning on the corresponding field strengths of the 11- and 10-dimensional supergravity theories over AdS{sub 4} x M{sup 7} {sup vertical} {sup stroke} {sup 6} spaces, where we use S{sup 7}/Z{sub k} and CP{sup 3} for the internal spaces. Indeed, when we add M2/D2-branes on the same directions with the near horizon branes of the Aharony-Bergman-Jafferis- Maldacena model, all symmetries and supersymmetries are preserved trivially. In this case, we obtain a localized object just in the horizon. This normalizable bulk massless scalar mode is a singlet of SO(8) and SU(4) x U(1), and it agrees with a marginal boundary operator of the conformal dimension of Δ{sub +} = 3. However, after performing a special conformal transformation, we see that the solution is localized in the Euclideanized AdS{sub 4} space and is attributable to the included anti-M2/D2-branes, which are also necessary to ensure that there is no back-reaction. The resultant theory now breaks all N = 8, 6 supersymmetries to N = 0, while the other symmetries are so preserved. The dual boundary operator is then set up from the skew-whiffing of the representations 8s and 8v for the supercharges and scalars, respectively, while the fermions remain fixed in 8c of the original theory. Besides, we also address another alternate bulk to boundary matching procedure through turning on one of the gauge fields of the full U(N){sub k} x U(N){sub -k} gauge group along the same lines with a similar situation to the one faced in the AdS{sub 5}/CFT{sub 4} correspondence. The latter approach covers the difficulty already faced with in the bulk-boundary matching procedure for k = 1, 2 as well. (orig.)

  7. Impact of Underlaid Multi-antenna D2D on Cellular Downlink in Massive MIMO Systems

    OpenAIRE

    Agarwal, Amit; Mukherjee, Sudarshan; Mohammed, Saif Khan

    2015-01-01

    In this paper, we consider a massive multiple-input multiple-output (MIMO) downlink system underlaid with a network of multi-antenna D2D user equipments (UEs). Each D2D transmitter (Tx) uses all its antennas to beamform information towards its desired D2D receiver, which uses only a single antenna for reception. While beamforming at the D2D Tx reduces D2D interference to the neighbouring cellular UEs (CUEs), the cellular-to-D2D interference is also negligible due to highly directional beamfor...

  8. Guard zone based D2D underlaid cellular networks with two-tier dependence

    OpenAIRE

    Chen, Zheng; Kountouris, Marios

    2015-01-01

    International audience Device-to-device (D2D) communication is under active investigation and may be a key feature in 5G networks for its great potential in improving network spectral and energy efficiency. Underlaying proximity-based D2D communication links in current cellular networks allows D2D users to opportunistically access the cellular spectrum, thus causing interference not only in the D2D tier but also between D2D and macrocell tiers. In this paper, we consider a D2D underlaid ce...

  9. Generation of UV laser light by stimulated Raman scattering in D2, D2/Ar and D2/He using a pulsed Nd:YAG laser at 355nm

    Institute of Scientific and Technical Information of China (English)

    徐贲; 岳古明; 张寅超; 胡欢陵; 周军; 胡顺星

    2003-01-01

    A pulsed Nd:YAG laser at 355nm is used to pump Raman cell filled with D2,D2/Ar and D2/He.With adequately adjusted parameters,the maximum photon conversion efficiency of the first-order Stokes light(S1,396.796nm)reaches 33.33% in D2/Ar and the stability of S1 in pure D2 is fairly high,the energy drift being less than 10% when the pump energy drifts in the range of 5%.The conversion efficiency and stability,which are functions of the composition and pressure of the Raman medium and the energy of pump laser,are investigated.The result has been used to optimize the laser transmitter system for a differential absorption lidar system to measure NO2 concentration profiles.

  10. The embedding of $\\mathcal{O}_{d_1d_2}$ into $\\mathcal{O}_{d_1}\\otimes\\mathcal{O}_{d_2}$

    OpenAIRE

    Chambers, Amy B.

    2014-01-01

    As a particular example of a general theorem presented in \\cite{me}, there is a conditional expectation from the tensor product of Cuntz algebras, $\\mathcal{O}_{d_1}\\otimes\\mathcal{O}_{d_2}$, onto the Cuntz algebra $\\mathcal{O}_{d_1d_2}$. Motivated by this example, we examine the embedding of $\\mathcal{O}_{d_1d_2}$ in $\\mathcal{O}_{d_1}\\otimes\\mathcal{O}_{d_2}$, first by examining the index of the conditional expectation mentioned, and then by expressing $\\mathcal{O}_{d_1}\\otimes\\mathcal{O...

  11. 国内维生素D2研究与产业化现状%Status in Research and Industrialization of Vitamin D2 in China

    Institute of Scientific and Technical Information of China (English)

    张照明; 袁利明; 孙延红

    2007-01-01

    简介维生素D2的调节钙磷代谢、抑制癌细胞增殖、调节血压和免疫系统等功能,广泛应用于医药、食品、饲料等领域.重点论述国内维生素D2研究与产业化开发现状,详细介绍了维生素D2的光化学法生产工艺,展望了维生素D2广阔的市场前景.

  12. Vagina vasorum dissection during D2 lymphadenectomy for gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jian-Jun Peng; Yu-Long He; Wen-Hua Zhan; Ping Xiao; Shi-Rong Cai; Chang-Hua Zhang; Hui Wu

    2007-01-01

    AIM:To explore the relationship between metastasis and vagina vasorum in the progress of gastric carcinoma and to find some facts and references for gastric surgeons.METHODS:One hundred and seven specimens of left or right gastric arteries (55 left and 52 right) were gathered from 59 patients undergoing radical gastrectomy for gastric carcinoma. All the frozen specimens were cut into 3 μm-thick sections and stained with hematoxylin-eosin (HE) and immunohistochemical method separately. Cytokeratin (CK) and mesothelial cells (MC) were stained with immunohistochemical method. Cancer cells inside vagina vasorum were detected and* the structure of artery wall was observed under microscope.RESULTS:Metastatic cancer cells or tubercles were found inside vagina vasorum in some stage Ⅲ or Ⅳ specimens,but not in stage Ⅰ or Ⅱ specimens. Tumor cells in vagina vasorum were CK positive in 26 specimens of 14 tumors. Among them,stage in was found in 4 specimens of 2 tumors,and stage Ⅳ in 22 specimens of 12 tumors. None of these specimens was positive for MC. The positive rate of CK increased with TNM staging. Compared with the lower part,tumors in the upper and middle parts of stomach were more,likely to metastasize into vagina vasorum.CONCLUSION:Vagina vasorum dissection should be performed during D2 lymphadenectomy for TNM stage Ⅲ or Ⅳ gastric carcinoma.

  13. Modeling of ligand binding to dopamine D2 receptor

    Directory of Open Access Journals (Sweden)

    Ostopovici-Halip Liliana

    2014-01-01

    Full Text Available The dopaminic receptors have been for long time the major targets for developing new small molecules with high affinity and selectivity to treat psychiatric disorders, neurodegeneration, drug abuse, and other therapeutic areas. In the absence of a 3D structure for the human D2 dopamine (HDD2 receptor, the efforts for discovery and design of new potential drugs rely on comparative models generation, docking and pharmacophore development studies. To get a better understanding of the HDD2 receptor binding site and the ligand-receptor interactions a homology model of HDD2 receptor based on the X-ray structure of β2-adrenergic receptor has been built and used to dock a set of partial agonists of HDD2 receptor. The main characteristics of the binding mode for the HDD2 partial agonists set are given by the ligand particular folding and a complex network of contacts represented by stacking interactions, salt bridge and hydrogen bond formation. The characterization of the partial agonist binding mode at HDD2 receptor provide the needed information to generate pharmacophore models which represent essential information in the future virtual screening studies in order to identify new potential HDD2 partial agonists.

  14. Thermodynamics of the localized D2-D6 system

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-Reino, Marta [Martin Fisher School of Physics, Brandeis University, Waltham, MA 02454 (United States)]. E-mail: marta@brandeis.edu; Naculich, Stephen G. [Department of Physics, Bowdoin College, Brunswick, ME 04011 (United States)]. E-mail: naculich@bowdoin.edu; Schnitzer, Howard J. [Martin Fisher School of Physics, Brandeis University, Waltham, MA 02454 (United States)]. E-mail: schnitzer@brandeis.edu

    2005-05-02

    An exact fully-localized extremal supergravity solution for N{sub 2} D2-branes and N{sub 6} D6-branes, which is dual to 3-dimensional supersymmetric SU(N{sub 2}) gauge theory with N{sub 6} fundamentals, was found by Cherkis and Hashimoto. In order to consider the thermal properties of the gauge theory we present the non-extremal extension of this solution to first order in an expansion near the core of the D6-branes. We compute the Hawking temperature and the black-brane horizon area/entropy. The leading-order entropy, which is proportional to N{sub 2}{sup 3/2}N{sub 6}{sup 1/2}T{sub H}{sup 2}, is not corrected to first order in the expansion. This result is consistent with the analogous weak-coupling result at the correspondence point N{sub 2} similar to N{sub 6}.

  15. Determination of the evaporation coefficient of D2O

    Directory of Open Access Journals (Sweden)

    R. C. Cohen

    2008-11-01

    Full Text Available The evaporation rate of D2O has been determined by Raman thermometry of a droplet train (12–15 μm diameter injected into vacuum (~10-5 torr. The cooling rate measured as a function of time in vacuum was fit to a model that accounts for temperature gradients between the surface and the core of the droplets, yielding an evaporation coefficient (γe of 0.57±0.06. This is nearly identical to that found for H2O (0.62±0.09 using the same experimental method and model, and indicates the existence of a kinetic barrier to evaporation. The application of a recently developed transition-state theory (TST model suggests that the kinetic barrier is due to librational and hindered translational motions at the liquid surface, and that the lack of an isotope effect is due to competing energetic and entropic factors. The implications of these results for cloud and aerosol particles in the atmosphere are discussed.

  16. Modulation of A2a receptor antagonist on D2 receptor internalization and ERK phosphorylation

    OpenAIRE

    Huang, Li; Wu, Dong-Dong; Zhang, Lei; Feng, Lin-yin

    2013-01-01

    Aim: To explore the effects of heterodimerization of D2 receptor/A2a receptor (D2R/A2aR) on D2R internalization and D2R downstream signaling in primary cultured striatal neurons and HEK293 cells co-expressing A2aR and D2R in vitro. Methods: Primary cultured rat striatal neurons and HEK293 cells co-expressing A2aR and D2R were treated with A2aR- or D2R-specific agonists. D2R internalization was detected using a biotinylation assay and confocal microscopy. ERK, Src kinase and β-arrestin were me...

  17. EVALUATION OF N-RATIO IN SELECTING PATIENTS FOR ADJUVANT CHEMORADIOTHERAPY AFTER D2-GASTRECTOMY

    OpenAIRE

    Wilson Luiz da COSTA JUNIOR; Felipe Jose Fernandez COIMBRA; Batista, Thales Paulo; RIBEIRO, Heber Salvador de Castro; DINIZ, Alessandro Landskron

    2013-01-01

    Context Whether adjuvant chemoradiotherapy may contribute to improve survival outcomes after D2-gastrectomy remains controvertial. Objective To explore the clinical utility of N-Ratio in selecting gastric cancer patients for adjuvant chemoradiotherapy after D2-gastrectomy. Methods A retrospective cohort study was carried out on gastric cancer patients who underwent D2-gastrectomy alone or D2-gastrectomy plus adjuvant chemoradiotherapy (INT-0116 protocol) at the Hospital A. C. Camargo from...

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

    Science.gov (United States)

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

    2014-10-01

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

  19. Implantation of energetic D+ ions into carbon dioxide ices and implications for our solar system: formation of D2O and D2CO3

    International Nuclear Information System (INIS)

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

  20. D2O and the sodium pump in squid nerve membrane

    International Nuclear Information System (INIS)

    In 10 K artificial seawater (ASW), D2O replacement reduced the Na efflux of squid axons by about one third. In 0 K ASW, D2O replacement had little effect. D2O reduced the K+ sensitivity of the efflux but increased the affinity for K+. A 4 degrees decrease in temperature mimicked the effects of D2O. When axons were injected with arginine, to decrease the ATP/ADP ratio, they lost K+ sensitivity in normal ASW, as expected. Their efflux into 0 K ASW became D2O sensitive. The results are discussed in terms of conformational changes in the Na pump molecular complex

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

    OpenAIRE

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

    2009-01-01

    The molecular determinants of β-cell mass expansion remain poorly understood. Cyclin D2 is the major D-type cyclin expressed in β-cells, essential for adult β-cell growth. We hypothesized that cyclin D2 could be actively regulated in β-cells, which could allow mitogenic stimuli to influence β-cell expansion. Cyclin D2 protein was sharply increased after partial pancreatectomy, but cyclin D2 mRNA was unchanged, suggesting posttranscriptional regulatory mechanisms influence cyclin D2 expression...

  2. Verification experiment of EPR paradox by (d, 2He) reaction

    International Nuclear Information System (INIS)

    FBR paradox which was brought forward by Einstein, Podolsky and Rosen is expressed by Bell's inequality of spin correlation theoretically. In principle it is possible to verify the inequality by measuring spin correlation between two particles having spin 1/2 from a decay of 1S0 experimentally. Most of the past experiments to verify the inequality, however, have been performed by using photons. On the other hand, only one experiment by using hadron system was carried out by Lamehi and Mitting, where the [1S0] state was produced by proton-proton scattering at first, and then the spin orientations after the scattering were measured. Unfortunately, there exit some sources of ambiguity to reach definite conclusion from their result because the experiment was done at rather high energy of 13.5 MeV. In the experiment planned by the present author it is designed to overcome the experimental difficulties, which Lamehi and Mitting encountered, by (1) generating high purity singlet [1S0] state of two protons by (d, 2He) type nuclear reaction at intermediate energy range, and by (2) developing high performance spin-correlation polarimeter which can analyze spins of two protons simultaneously to minimize the systematic errors. The excitation energy of 2He corresponding to the proton-proton relative energy can be experimentally controlled. An idea singlet is realized by choosing the state with sufficiently small relative energy. It is planned to measure the spin correlation function by using SMART (Swinger and Magnetic Analyzer with Rotator and Twister) at RIKEN Accelerator Research Facility. Einstein POLarimeter (EPOL) to be installed on the second focal plane of SMART is under development, with which high precision measurements of spin orientations of two high energy protons simultaneously coming into limited space from 2He decay are made selecting the subject events from very many background events. Monte Carlo simulation predicts the possibility to verify the breaking of

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

    Science.gov (United States)

    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

  4. On the clinical impact of cerebral dopamine D2 receptor scintigraphy

    International Nuclear Information System (INIS)

    The present review describes findings and clinical indications for the dopamine D2 receptor scintigraphy. Methods for the examination of D2 receptors are positron emission tomography (PET) using 11C- or 18F-labelled butyrophenones or benzamides or single photon emission tomography (SPECT) using 123I-iodobenzamide (IBZM) respectively. The most important indication in neurology is the differential diagnosis of Parkinsonism: Patients with early Parkinson's disease show an increased D2 receptor binding (D2-RB) compared to control subjects. However, patients suffering from Steele-Richardson-Olszewski-Syndrome or Multiple System Atrophy show a decreased D2-RB and are generally non-responsive to treatment. Postsynaptic blockade of D2 receptors results in a drug induced Parkinsonian syndrome, which can be diagnosed by D2 scintigraphy. Further possible indications occur in psychiatry: The assessment of receptor occupancy is useful in schizophrenic patients treated with neuroleptics. Additionally, D2 receptor scintigraphy might help to clarify the differential diagnosis between neuroleptic malignant syndrome and lethal catatonia. The method might be useful for supervising neurobiochemical changes in drug dependency and during withdrawal. Assessment of dopamine D2 receptor binding can simplify the choice of therapy in depressive disorder: Patients showing a low D2 binding are likely to improve following an antidepressive drug treatment whereas sleep deprivation is promising in patients with high D2 binding. (orig.)

  5. Sorption and desorption phenomena of D2O on the surface of piping materials

    International Nuclear Information System (INIS)

    D2O adsorption and desorption behavior on stainless steel, Cr2O3 and NiO have been studied with a Fourier transform infrared absorption spectrometer (FT-IR) and a quadrupole mass spectrometer (QMS). The O-D stretching vibration band was observed in the region of 2100-2700 cm-1, which was considered to be from the physically adsorbed D2O on the sample. Adsorption of D2O was found to be heterogeneous on the surface. Desorption of D2O with a higher O-D vibration frequency occurred more slowly. The light irradiation was found to enhance D2O desorption. The 250 nm light stimulated D2O desorption more strongly than the one of 400 or 600 nm. It seems that D2O with a higher O-D wave number is more effective for light stimulated desorption. (orig.)

  6. Mutations in GAS8, a Gene Encoding a Nexin-Dynein Regulatory Complex Subunit, Cause Primary Ciliary Dyskinesia with Axonemal Disorganization.

    Science.gov (United States)

    Jeanson, Ludovic; Thomas, Lucie; Copin, Bruno; Coste, André; Sermet-Gaudelus, Isabelle; Dastot-Le Moal, Florence; Duquesnoy, Philippe; Montantin, Guy; Collot, Nathalie; Tissier, Sylvie; Papon, Jean-François; Clement, Annick; Louis, Bruno; Escudier, Estelle; Amselem, Serge; Legendre, Marie

    2016-08-01

    Primary ciliary dyskinesia (PCD) is an autosomal recessive disease characterized by chronic respiratory infections of the upper and lower airways, hypofertility, and, in approximately half of the cases, situs inversus. This complex phenotype results from defects in motile cilia and sperm flagella. Among the numerous genes involved in PCD, very few-including CCDC39 and CCDC40-carry mutations that lead to a disorganization of ciliary axonemes with microtubule misalignment. Focusing on this particular phenotype, we identified bi-allelic loss-of-function mutations in GAS8, a gene that encodes a subunit of the nexin-dynein regulatory complex (N-DRC) orthologous to DRC4 of the flagellated alga Chlamydomonas reinhardtii. Unlike the majority of PCD patients, individuals with GAS8 mutations have motile cilia, which, as documented by high-speed videomicroscopy, display a subtle beating pattern defect characterized by slightly reduced bending amplitude. Immunofluorescence studies performed on patients' respiratory cilia revealed that GAS8 is not required for the proper expression of CCDC39 and CCDC40. Rather, mutations in GAS8 affect the subcellular localization of another N-DRC subunit called DRC3. Overall, this study, which identifies GAS8 as a PCD gene, unveils the key importance of the corresponding protein in N-DRC integrity and in the proper alignment of axonemal microtubules in humans. PMID:27120127

  7. D2声学测量系统的测试功能%Testing Function of The D2 Acoustic Measurement System

    Institute of Scientific and Technical Information of China (English)

    王延君

    2010-01-01

    @@ D2声学测量系统,是美国AcoustX公司专为影院的综合测试和测量而设计的一套声学测量工具,已经通过了卢卡斯的认证.其中包括如图1所示的4支话筒及支架、D2调制器、D2控制器、USBPre 数字音频接口及Win|RTA测试软件(在所附光盘上).

  8. 多巴胺D2受体的同源模建研究%Homology modeling of Dopamine D2 receptor

    Institute of Scientific and Technical Information of China (English)

    芮亚然; 刘维国; 李冬玲; 张严

    2012-01-01

    Dopamine (DA) is the most abundant catecholaminergic neurotransmitter in the brain.It controls a variety of physiological functions of the central nervous system by Dopamine receptor, and Dopamine D2 receptor has been associated with a variety of neuropathological diseases, such as drug addiction, schizophrenia. Parkinson's disease. But so Tar. the structure of Dopamine D2 receptor is not available, which limited the design and development of relevenl drugs in this paper, the homology model of Dopamine D2 receptor was developed by using the Dopamine D3 receptor (JPBL) as template, which has (he highest sequence identity to D2 receptor. After Optimization and molecular dynamics simulation, the refined model structure was obtained. The final refined model was assessed by Profile-3D and Ramachamlran plot programs, then verified by docking with stepholidine(SPD). The results show that the Dopamine D2 model which we built is reasonable and reliable.%多巴胺是大脑中含量最丰富的儿茶酚胺类神经递质,主要通过多巴胺受体调控中枢神经系统的多种生理功能,其中多巴胺D2受体与药物成瘾、精神分裂症、帕金森病等多种疾病的发生相关.然而多巴胺D2受体的晶体结构至今尚未解析出来,给相关疾病的药物设计与开发带来困难.本文采用同源模建的方法,用目前与多巴胺D2受体同源性最高的多巴胺D3受体(3PBL)作为模板,构建多巴胺D2受体的三维结构.经过优化和分子动力学模拟,用Profile-3D和Ramachandran plot对模型进行评估,然后用多巴胺D2受体拮抗剂千金藤啶碱(stepholidine,SPD)进行对接验证,证明构建的多巴胺D2受体模型合理、可靠.

  9. 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

    Science.gov (United States)

    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.

  10. 关于图的L(d1,d2)-标号问题%The L(d1, d2)-Labeling Problem on Graphs

    Institute of Scientific and Technical Information of China (English)

    邵振东; 刘家壮

    2006-01-01

    The L(2, 1)-labeling is formulated from the frequency assignment problem. We study the L(d1, d2)- labeling which is a generalization of the L(2, 1)-labeling. Vertex 2-coloring, 2-chromatic number and other related concepts are firstly defined, and the upper bound for 2-chromatic number is given; a very general relationship between λd1 ,d2 (G) and minimum degree δ(G) and maximum degree △(G) is then derived; finally, the upper bounds of L(d1, d2)-labelings of general and planar graphs are given.%图的L(2,1)-标号问题是由频率分配问题归结而来,本文研究作为L(2,1)-标号问题的推广的L(d1,d2)-标号问题.首先定义了顶点2-着色,2-色数及其它有关概念,给出了2-色数的上界.然后得出了λd1,d2(G)与δ(G)和△(G)的一般关系.最后得出了一般图与平面图的λd1,d2(G)的上界.

  11. HPLC法测定维生素D2果糖酸钙注射液中维生素D2含量测定

    Institute of Scientific and Technical Information of China (English)

    刘丹; 赵慎非

    2014-01-01

    目的:建立检查维生素D2果糖酸钙中维生素D2的含量测定的高效液相色谱法。方法采用Thermo硅胶(5μm,4.6×250mm)色谱柱,流动相为正己烷-正戊醇(997∶3),流速1.2mL· min -1,检测波长为254nm。结果维生素 D2在0.4736μg· mL -1~4.262μg· mL -1范围内浓度和维生素D2与内标峰面积比呈良好的线性关系。平均回收率为103.2%(RSD=2.4%,n=9)。结论本文方法较为准确、快速,适合于维生素D2果糖酸钙中维生素D2的含量测定的质量控制。

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

    Science.gov (United States)

    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

  13. Functional coupling between heterologously expressed dopamine D(2) receptors and KCNQ channels

    DEFF Research Database (Denmark)

    Ljungstrom, Trine; Grunnet, Morten; Jensen, Bo Skaaning;

    2003-01-01

    Activation of KCNQ potassium channels by stimulation of co-expressed dopamine D(2) receptors was studied electrophysiologically in Xenopus laevis oocytes and in mammalian cells. To address the specificity of the interaction between D(2)-like receptors and KCNQ channels, combinations of KCNQ1......-5 channels and D(2)-like receptors (D(2L), D(3), and D(4)) were investigated in Xenopus oocytes. Activation of either receptor with the selective D(2)-like receptor agonist quinpirole (100 nM) stimulated all the KCNQ currents, independently of the subunit combination, indicating a common pathway of receptor......-channel interaction. The KCNQ4 current was investigated in further detail and was increased by 19.9+/-1.6% ( n=20) by D(2L) receptor stimulation. The effect could be mimicked by injection of GTPgammaS and prevented by injection of Bordetella pertussis toxin, indicating that channel stimulation was mediated via a G...

  14. The Hugoniot equation of state of the fluid He+D2 mixtures

    Institute of Scientific and Technical Information of China (English)

    CUI Cai-xia

    2004-01-01

    The fluid variational theory and effective one-component model have been used to calculate the Hugoniot equation of state (EOS) of fluid He, D2, and He+D2 mixtures with different He:D2 compositions under high pressures and temperatures. An examination of the confidence of above computation is performed by comparing experiment and calculation, in which the similar calculation procedure used for He+D2 is adopted, of He and D2 each, since no experimental data are available to conduct this kind of comparison. Good agreement in both comparisons is found. This fact may be looked as if an indirect positive verification of calculation procedure used here at least in the pressure and temperature domain covered by the experimental data of He and D2 used for comparison, numerically nearly up to 35 GPa and 105K.

  15. On the ideal behaviour of the equimolar H2O-D2O mixture

    International Nuclear Information System (INIS)

    New high precision vapour pressure data on equimolar H2O-D2O mixtures are analysed. The results show that the H2O-HDO-D2O liquid mixture can be considered as an ideal solution within the limits of the presently available data. The present investigation supports the earlier conclusion that the law of the geometric mean for the vapour pressure isotope effect in the series H2O, HDO and D2O is not obeyed. (author)

  16. Evidence that Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    OpenAIRE

    Volkow, Nora D.; Tomasi, Dardo; Wang, Gene-Jack; Telang, Frank; Fowler, Joanna S.; Logan, Jean; Benveniste, Helene; Kim, Ron; Thanos, Panayotis K.; Ferré, Sergi

    2012-01-01

    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 [11C]raclopride in controls) in striatum, but could not determine if this reflected dopamine increases ([11C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases in...

  17. Structure and Properties of Burnished and Nitrided AISI D2 Tool Steel

    OpenAIRE

    Daniel TOBOŁA; Witold BROSTOW; Kazimierz CZECHOWSKI; Piotr RUSEK; Iwona WRONSKA

    2015-01-01

    D2 belongs to traditional steels, frequently used in metalworking industry. Shot peening and nitriding are known to improve the wear resistance of D2. In this work we focus on processes of slide burnishing and industrial low temperature gas nitriding. The D2 steel specimens were first subjected to heat treatments (HT) prescribed by the manufacturer, turning (T), then burnishing (B) and nitriding (N). The reason for turning was achieving appropriate surface roughness. Deformation induced in sl...

  18. Cocaine Self-Administration Produces a Persistent Increase in Dopamine D2High Receptors

    OpenAIRE

    Briand, Lisa A.; Flagel, Shelly B.; Seeman, Philip; ROBINSON, TERRY E.

    2008-01-01

    Cocaine addicts are reported to have decreased numbers of striatal dopamine D2 receptors. However, in rodents, repeated cocaine administration consistently produces hypersensitivity to the psychomotor activating effects of both indirect dopamine agonists, such as cocaine itself, and importantly, to direct-acting D2 receptor agonists. The current study reports a possible resolution to this long-standing paradox. The dopamine D2 receptor exists in both a low and a high affinity state, and dopam...

  19. The SH2D2A gene and susceptibility to multiple sclerosis

    DEFF Research Database (Denmark)

    Lorentzen, A.R.; Smestad, C.; Lie, B.A.;

    2008-01-01

    We previously reported an association between the SH2D2A gene encoding TSAd and multiple sclerosis (MS). Here a total of 2128 Nordic MS patients and 2004 controls were genotyped for the SH2D2A promoter GA repeat polymorphism and rs926103 encoding a serine to asparagine substitution at amino acid...... SH2D2A gene may contribute to susceptibility to MS Udgivelsesdato: 2008/7/15...

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

    OpenAIRE

    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.

    2005-01-01

    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 ...

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

    Science.gov (United States)

    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. Advective-diffusive transport of D2O in unsaturated media under evaporation condition

    International Nuclear Information System (INIS)

    Advective-diffusive transport of HTO in unsaturated media was investigated empirically using deuterated water (D2O) and columns filled with glass beads. The tortuosity factor was evaluated by numerical model calculations corresponding to first experiment for diffusion under no-evaporation condition. Temporal variations in depth profiles of D2O concentrations in the columns were observed by second experiment, which considers the transferring and spreading of D2O by pore-water flow caused by evaporation. Measurements and model calculations indicated that diffusion was about two times more efficient than dispersion for D2O spreading process under this evaporation condition. (author)

  3. Distribution of dopamine D2-like receptors in the human thalamus: autoradiographic and PET studies.

    Science.gov (United States)

    Rieck, Richard W; Ansari, M S; Whetsell, William O; Deutch, Ariel Y; Kessler, Robert M

    2004-02-01

    The distribution of dopamine (DA) D(2)-like receptors in the human thalamus was studied using in vitro autoradiographic techniques and in vivo positron emission tomography in normal control subjects. [(125)I]Epidepride, which binds with high affinity to DA D(2) and D(3) receptors, was used in autoradiographic studies to determine the distribution and density of D(2)-like receptors, and the epidepride analogue [(18)F]fallypride positron was used for positron emission tomography studies to delineate D(2)-like receptors in vivo. Both approaches revealed a heterogeneous distribution of thalamic D(2/3) receptors, with relatively high densities in the intralaminar and midline thalamic nuclei, including the paraventricular, parataenial, paracentral, centrolateral, and centromedian/parafascicular nuclei. Moderate densities of D(2/3) sites were seen in the mediodorsal and anterior nuclei, while other thalamic nuclei expressed lower levels of D(2)-like receptors. Most thalamic nuclei that express high densities of D(2)-like receptors project to forebrain DA terminal fields, suggesting that both the thalamic neurons expressing D(2)-like receptors and the projection targets of these neurons are regulated by DA. Because the midline/intralaminar nuclei receive prominent projections from both the ascending reticular activating core and the hypothalamus, these thalamic nuclei may integrate activity conveying both interoceptive and exteroceptive information to telencephalic DA systems involved in reward and cognition. PMID:14627996

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

    Science.gov (United States)

    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

  5. Promoter de-methylation of cyclin D2 by sulforaphane in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Hsu Anna

    2011-10-01

    Full Text Available Abstract Sulforaphane (SFN, an isothiocyanate derived from cruciferous vegetables, induces potent anti-proliferative effects in prostate cancer cells. One mechanism that may contribute to the anti-proliferative effects of SFN is the modulation of epigenetic marks, such as inhibition of histone deacetylase (HDAC enzymes. However, the effects of SFN on other common epigenetic marks such as DNA methylation are understudied. Promoter hyper-methylation of cyclin D2, a major regulator of cell cycle, is correlated with prostate cancer progression, and restoration of cyclin D2 expression exerts anti-proliferative effects on LnCap prostate cancer cells. Our study aimed to investigate the effects of SFN on DNA methylation status of cyclin D2 promoter, and how alteration in promoter methylation impacts cyclin D2 gene expression in LnCap cells. We found that SFN significantly decreased the expression of DNA methyltransferases (DNMTs, especially DNMT1 and DNMT3b. Furthermore, SFN significantly decreased methylation in cyclin D2 promoter regions containing c-Myc and multiple Sp1 binding sites. Reduced methlyation of cyclin D2 promoter corresponded to an increase in cyclin D2 transcript levels, suggesting that SFN may de-repress methylation-silenced cyclin D2 by impacting epigenetic pathways. Our results demonstrated the ability of SFN to epigenetically modulate cyclin D2 expression, and provide novel insights into the mechanisms by which SFN may regulate gene expression as a prostate cancer chemopreventive agent.

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

    Science.gov (United States)

    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

  7. Distributed SIR-Aware Opportunistic Access Control for D2D Underlaid Cellular Networks

    OpenAIRE

    Chen, Zheng; Kountouris, Marios

    2014-01-01

    In this paper, we propose a distributed interference and channel-aware opportunistic access control technique for D2D underlaid cellular networks, in which each potential D2D link is active whenever its estimated signal-to-interference ratio (SIR) is above a predetermined threshold so as to maximize the D2D area spectral efficiency. The objective of our SIR-aware opportunistic access scheme is to provide sufficient coverage probability and to increase the aggregate rate of D2D links by harnes...

  8. Zero-Outage Cellular Downlink with Fixed-Rate D2D Underlay

    DEFF Research Database (Denmark)

    Kiilerich Pratas, Nuno; Popovski, Petar

    2015-01-01

    Two of the emerging trends in wireless cellular systems are Device-to-Device (D2D) and Machine-to-Machine (M2M) communications. D2D enables efficient reuse of the licensed spectrum to support localized transmissions, while M2M connections are often characterized by fixed and low transmission rates....... D2D connections can be instrumental in localized aggregation of uplink M2M traffic to a more capable cellular device, before being finally delivered to the Base Station (BS). In this paper we show that a fixed M2M rate is an enabler of efficient Machine-Type D2D underlay operation taking place...

  9. Device-Relaying in Cellular D2D Networks: A Fairness Perspective

    OpenAIRE

    Chaaban, Anas; Sezgin, Aydin

    2015-01-01

    Device-to-Device (D2D) communication is envisioned to be an integral component of 5G networks, and a technique for meeting the demand for high data rates. In a cellular network, D2D allows not only direct communication between users, but also device relaying. In this paper, a simple instance of device-relaying is investigated, and the impact of D2D on fairness among users is studied. Namely, a cellular network consisting of two D2D-enabled users and a base-station (BS) is considered. Thus, th...

  10. Experimental studies on the formation of D2O and D2O2 by implantation of energetic D+ ions into oxygen ices

    International Nuclear Information System (INIS)

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

  11. Dopamine D2 receptors are organized in bands in normal human temporal cortex.

    Science.gov (United States)

    Goldsmith, S K; Joyce, J N

    1996-09-01

    Previous studies have documented a highly compartmentalized and laminar organization of dopamine D2 receptors in human hippocampus, entorhinal and perirhinal cortices. These areas receive input from regions of polysensory association cortices of the superior and inferior temporal sulci that evidence functional modules identified by other techniques. We examined the isocortical regions of temporal lobe for an equally well-differentiated pattern of D2 receptor expression as observed in their paleocortical temporal lobe targets. Using quantitative autoradiography we identified an organization of three-dimensional bands of high concentrations of dopamine D2 receptors throughout the rostral-caudal extent of the normal human temporal cortex. In the coronal plane, these D2 receptor-enriched bands had a columnar appearance with the concentration of D2 receptors almost two-fold higher within the bands than in the immediately adjacent cortex. These D2 receptor-enriched bands had a distinct laminar appearance with a paucity of [125I]epidepride binding to D2 receptors over the granule cell layer and higher concentrations of D2 receptors in laminae III and V than in the immediately adjacent cortex. They had a consistent width (mean width of 2.83 +/- 0.62 mm) in the coronal plane, but had their long axes in the rostrocaudal plane (some were at least 2500 microns in length). Hence, they exist as three-dimensional D2 receptor-enriched and receptor-poor modules with their long axes in the rostrocaudal plane. Tyrosine hydroxylase-immunoreactive fibers were observed to cross orthogonally to the long axes of the D2 receptor enriched bands. Other monoamine receptors (beta-adrenergic, 5-hydroxytryptamine2), and markers for myelin (anti-myelin basic protein immunohistochemistry), glia (5'-nucleotidase), and energy metabolism (cytochrome oxidase) showed a laminar organization but failed to demarcate the D2 receptor-enriched bands. The majority of these D2 receptor-enriched bands were

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

    Science.gov (United States)

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

    2016-08-01

    Dexamethasone treatment of newborn rats inhibited cardiomyocyte proliferation and stimulated premature terminal differentiation of cardiomyocytes in the developing heart. Yet mechanisms remain undetermined. The present study tested the hypothesis that the direct effect of glucocorticoid receptor-mediated epigenetic repression of cyclin D2 gene in the cardiomyocyte plays a key role in the dexamethasone-mediated effects in the developing heart. Cardiomyocytes were isolated from 2-day-old rats. Cells were stained with a cardiomyocyte marker α-actinin and a proliferation marker Ki67. Cyclin D2 expression was evaluated by Western blot and quantitative real-time polymerase chain reaction. Promoter methylation of CcnD2 was determined by methylated DNA immunoprecipitation (MeDIP). Overexpression of Cyclin D2 was conducted by transfection of FlexiCcnD2 (+CcnD2) construct. Treatment of cardiomyocytes isolated from newborn rats with dexamethasone for 48 hours significantly inhibited cardiomyocyte proliferation with increased binucleation and decreased cyclin D2 protein abundance. These effects were blocked with Ru486 (mifepristone). In addition, the dexamethasone treatment significantly increased cyclin D2 gene promoter methylation in newborn rat cardiomyocytes. 5-Aza-2'-deoxycytidine inhibited dexamethasone-mediated promoter methylation, recovered dexamethasone-induced cyclin D2 gene repression, and blocked the dexamethasone-elicited effects on cardiomyocyte proliferation and binucleation. In addition, the overexpression of cyclin D2 restored the dexamethasone-mediated inhibition of proliferation and increase in binucleation in newborn rat cardiomyocytes. The results demonstrate that dexamethasone acting on glucocorticoid receptors has a direct effect and inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via epigenetic repression of cyclin D2 gene. PMID:27302109

  13. Mutant glycyl-tRNA synthetase (Gars ameliorates SOD1(G93A motor neuron degeneration phenotype but has little affect on Loa dynein heavy chain mutant mice.

    Directory of Open Access Journals (Sweden)

    Gareth T Banks

    Full Text Available BACKGROUND: In humans, mutations in the enzyme glycyl-tRNA synthetase (GARS cause motor and sensory axon loss in the peripheral nervous system, and clinical phenotypes ranging from Charcot-Marie-Tooth neuropathy to a severe infantile form of spinal muscular atrophy. GARS is ubiquitously expressed and may have functions in addition to its canonical role in protein synthesis through catalyzing the addition of glycine to cognate tRNAs. METHODOLOGY/PRINCIPAL FINDINGS: We have recently described a new mouse model with a point mutation in the Gars gene resulting in a cysteine to arginine change at residue 201. Heterozygous Gars(C201R/+ mice have locomotor and sensory deficits. In an investigation of genetic mutations that lead to death of motor and sensory neurons, we have crossed the Gars(C201R/+ mice to two other mutants: the TgSOD1(G93A model of human amyotrophic lateral sclerosis and the Legs at odd angles mouse (Dync1h1(Loa which has a defect in the heavy chain of the dynein complex. We found the Dync1h1(Loa/+;Gars(C201R/+ double heterozygous mice are more impaired than either parent, and this is may be an additive effect of both mutations. Surprisingly, the Gars(C201R mutation significantly delayed disease onset in the SOD1(G93A;Gars(C201R/+ double heterozygous mutant mice and increased lifespan by 29% on the genetic background investigated. CONCLUSIONS/SIGNIFICANCE: These findings raise intriguing possibilities for the study of pathogenetic mechanisms in all three mouse mutant strains.

  14. Left-right symmetry breaking in mice by left-right dynein may occur via a biased chromatid segregation mechanism, without directly involving the Nodal gene

    Directory of Open Access Journals (Sweden)

    StephanSauer

    2012-11-01

    Full Text Available Ever since cloning the classic iv mutation identified the ‘left-right dynein’ (lrd gene in mice, most research on body laterality determination has focused on its function in motile cilia at the node embryonic organizer. This model is attractive, as it links chirality of cilia architecture to asymmetry development. However, lrd is also expressed in blastocysts and embryonic stem cells, where it was shown to bias the segregation of recombined sister chromatids away from each other in mitosis. These data suggested that lrd is part of a cellular mechanism that recognizes and selectively segregates sister chromatids based on their replication history: old ‘Watson’ vs. old ‘Crick’ strands. We previously proposed that the mouse left-right axis is established via an asymmetric cell division prior to/or during gastrulation. In this model, left-right dynein selectively segregates epigenetically differentiated sister chromatids harboring a hypothetical ‘left-right axis development 1’ (‘lra1’ gene during the left-right axis establishing cell division. Here, asymmetry development would be ultimately governed by the chirality of the cytoskeleton and the DNA molecule. Our model predicts that randomization of chromatid segregation in lrd mutants should produce embryos with 25% situs solitus, 25% situs inversus, and 50% embryonic death due to heterotaxia and isomerism. Here we confirmed this prediction by using two distinct lrd mutant alleles. Other than lrd, thus far Nodal gene is the most upstream function implicated in visceral organs laterality determination. We next tested whether the Nodal gene constitutes the lra1 gene hypothesized in the model by testing mutant’s effect on 50% embryonic lethality observed in lrd mutants. Since Nodal mutation did not suppress lethality, we conclude that Nodal is not equivalent to the lra1 gene. In summary, we describe the origin of 50% lethality in lrd mutant mice not yet explained by any other

  15. FhCaBP2: a Fasciola hepatica calcium-binding protein with EF-hand and dynein light chain domains.

    Science.gov (United States)

    Thomas, Charlotte M; Timson, David J

    2015-09-01

    FhCaBP2 is a Fasciola hepatica protein which belongs to a family of helminth calcium-binding proteins which combine an N-terminal domain containing two EF-hand motifs and a C-terminal dynein light chain-like (DLC-like) domain. Its predicted structure showed two globular domains joined by a flexible linker. Recombinant FhCaBP2 interacted reversibly with calcium and manganese ions, but not with magnesium, barium, strontium, copper (II), colbalt (II), iron (II), nickel, lead or potassium ions. Cadmium (II) ions appeared to bind non-site-specifically and destabilize the protein. Interaction with either calcium or magnesium ions results in a conformational change in which the protein's surface becomes more hydrophobic. The EF-hand domain alone was able to interact with calcium and manganese ions; the DLC-like domain was not. Alteration of a residue (Asp-58 to Ala) in the second EF-hand motif in this domain abolished ion-binding activity. This suggests that the second EF-hand is the one responsible for ion-binding. FhCaBP2 homodimerizes and the extent of dimerization was not affected by calcium ions or by the aspartate to alanine substitution in the second EF-hand. The isolated EF-hand and DLC-like domains are both capable of homodimerization. FhCaBP2 interacted with the calmodulin antagonists trifluoperazine, chlorpromazine, thiamylal and W7. Interestingly, while chlorpromazine and thiamylal interacted with the EF-hand domain (as expected), trifluoperazine and W7 bound to the DLC-like domain. Overall, FhCaBP2 has distinct biochemical properties compared with other members of this protein family from Fasciola hepatica, a fact which supports the hypothesis that these proteins have different physiological roles. PMID:26152524

  16. Comparative molecular docking analysis of cytoplasmic dynein light chain DYNLL1 with pilin to explore the molecular mechanism of pathogenesis caused by Pseudomonas aeruginosa PAO.

    Directory of Open Access Journals (Sweden)

    Samina Kausar

    Full Text Available Cytoplasmic dynein light chain 1 (DYNLL1 is a component of large protein complex, which is implicated in cargo transport processes, and is known to interact with many cellular and viral proteins through its short consensus motif (K/RXTQT. Still, it remains to be explored that bacterial proteins also exhibit similar recognition sequences to make them vulnerable to host defense mechanism. We employed multiple docking protocols including AUTODOCK, PatchDock, ZDOCK, DOCK/PIERR and CLUSPRO to explore the DYNLL1 and Pilin interaction followed by molecular dynamics simulation assays. Subsequent structural comparison of the predicted binding site for DYNLL1-Pilin complex against the experimentally verified DYNLL1 binding partners was performed to cross check the residual contributions and to determine the binding mode. On the basis of in silico analysis, here we describe a novel interaction of DYNLL1 and receptor binding domain of Pilin (the main protein constituent of bacterial type IV Pili of gram negative bacteria Pseudomonas aeruginosa (PAO, which is the third most common nosocomial pathogen associated with the life-threatening infections. Evidently, our results underscore that Pilin specific motif (KSTQD exhibits a close structural similarity to that of Vaccinia virus polymerase, P protein Rabies and P protein Mokola viruses. We speculate that binding of DYNLL1 to Pilin may trigger an uncontrolled inflammatory response of the host immune system during P. aeruginosa chronic infections thereby opening a new pioneering area to investigate the role of DYNLL1 in gram negative bacterial infections other than viral infections. Moreover, by manifesting a strict correspondence between sequence and function, our study anticipates a novel drug target site to control the complications caused by P. aeruginosa infections.

  17. D2.3.2 Evaluation results of the LinkedUp VIDI competition

    NARCIS (Netherlands)

    Drachsler, Hendrik; Stoyanov, Slavi; Herder, Eelco; Marieke, Guy; Maren, Scheffel

    2014-01-01

    This document D2.3.2 is the second report of Task 2.4 - Evaluation of challenge submissions. Task 2.4 is about the actual assessment of the participating projects within the LinkedUp Veni, Vidi and Vici competition on the basis of the LinkedUp Evaluation Framework (D2.2.1). The main objective of Tas

  18. D2.2.2 Final Version of the LinkedUp Evaluation Framework

    NARCIS (Netherlands)

    Drachsler, Hendrik; Stoyanov, Slavi; Guy, Marieke; Scheffel, Maren

    2014-01-01

    This document (D2.2.2) describes the LinkedUp consortium’s experience in developing and on- going improvement of the LinkedUp Evaluation Framework throughout three web open educational data competitions: Veni, Vidi, Vici. D2.2.2 is the final report regarding the Evaluation Framework (EF). It synthes

  19. D2.3.3 Evaluation results of the LinkedUp VICI competition

    NARCIS (Netherlands)

    Drachsler, Hendrik

    2014-01-01

    This document D2.3.3 is the final report of Task 2.4 – Evaluation of challenge submissions. Task 2.4 is about the actual assessment of the participating projects within the LinkedUp Veni, Vidi and Vici competition on the basis of the LinkedUp Evaluation Framework (D2.2.1). The main objective of Task

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

    NARCIS (Netherlands)

    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

  1. Multiphoton lonization Spectrum of Nitrogen Oxide by D~2∑←X2П

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The resonance-enhanced multiphoton ionization (REMPI) spectrum of NO has been obtained. The spectral lines can be attributed to NO D2∑←X2П transitions. NO molecules are ionized via the resonant intermediate D2∑ states and by (3+2) REMPI process.

  2. Self-alignment of neon 5d2- level in hollow cathode discharge

    OpenAIRE

    Zhechev, D. Z.

    1982-01-01

    A self-alignment of 5d2-level of neon (configuration 2p 5 5d) is detected in a hollow cathode discharge. After correction of the Hanle-signal width for the effect of trapping, the radiative life time of 5d2-level is found to be (37 ± 7) ns.

  3. Multiphoton Ionization Spectrum of Nitrogen Oxide by D2∑←X2∏

    Institute of Scientific and Technical Information of China (English)

    Lianshui Zhang; Guiyin Zhang; Xiaodong Yang; Bo Sun; Xiaohui Zhao

    2003-01-01

    The resonance-enhanced multiphoton ionization (REMPI) spectrum of NO has been obtained. The spectral lines can be attributed to NO D2∑←X2∏ transitions. NO molecules are ionized via the resonant intermediate D2∑ states and by (3+2) REMPI process.

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

    Science.gov (United States)

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

    2011-09-01

    UvrD is an SF1 family helicase involved in DNA repair that is widely conserved in bacteria. Mycobacterium tuberculosis has two annotated UvrD homologues; here we investigate the role of UvrD2. The uvrD2 gene at its native locus could be knocked out only in the presence of a second copy of the gene, demonstrating that uvrD2 is essential. Analysis of the putative protein domain structure of UvrD2 shows a distinctive domain architecture, with an extended C terminus containing an HRDC domain normally found in SF2 family helicases and a linking domain carrying a tetracysteine motif. Truncated constructs lacking the C-terminal domains of UvrD2 were able to compensate for the loss of the chromosomal copy, showing that these C-terminal domains are not essential. Although UvrD2 is a functional helicase, a mutant form of the protein lacking helicase activity was able to permit deletion of uvrD2 at its native locus. However, a mutant protein unable to hydrolyze ATP or translocate along DNA was not able to compensate for lack of the wild-type protein. Therefore, we concluded that the essential role played by UvrD2 is unlikely to involve its DNA unwinding activity and is more likely to involve DNA translocation and, possibly, protein displacement. PMID:21725019

  5. Striatal dopamine D2/3 receptor availability in treatment resistant depression.

    Directory of Open Access Journals (Sweden)

    Bart P de Kwaasteniet

    Full Text Available 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 D(2/3 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.

  6. Immunohistochemical detection of dopamine D2 receptors in human pituitary adenomas.

    Science.gov (United States)

    Pawlikowski, Marek

    2010-09-30

    Thirty one pituitary adenomas and 3 samples of peritumoral anterior pituitary tissue were immunostained with an antibody raised against dopamine D2 receptor protein. The positive reactions were found in cell cytoplasm, a subpopulation of cell nuclei and the intratumoral blood vessels walls. As expected, the positive immunostaining was shown in cytoplasm and/or cell nuclei of all examined prolactinomas (7/7). In acromegaly the positive D2 staining occurred in 5/7 samples, in gonadotropinomas in 6/8 and in plurihormonal adenomas 2/4. The lowest expression was observed in corticotropinomas (1/5). These findings corroborate with the well known efficacy of D2 agonists in the treatment of prolactinomas and somatotropinomas, and support the rationale of the therapeutic trials with these compounds in gonadotropinomas. Moreover, the presence of D2 receptors in intratumoral blood vessels walls constitutes the possibility of the anti-angiogenic action of D2 agonists in pituitary adenomas. PMID:21071344

  7. Immunohistochemical detection of dopamine D2 receptors in human pituitary adenomas.

    Directory of Open Access Journals (Sweden)

    Marek Pawlikowski

    2010-11-01

    Full Text Available Thirty one pituitary adenomas and 3 samples of peritumoral anterior pituitary tissue were immunostained with an antibody raised against dopamine D2 receptor protein. The positive reactions were found in cell cytoplasm, a subpopulation of cell nuclei and the intratumoral blood vessels walls. As expected, the positive immunostaining was shown in cytoplasm and/or cell nuclei of all examined prolactinomas (7/7. In acromegaly the positive D2 staining occurred in 5/7 samples, in gonadotropinomas in 6/8 and in plurihormonal adenomas 2/4. The lowest expression was observed in corticotropinomas (1/5. These findings corroborate with the well known efficacy of D2 agonists in the treatment of prolactinomas and somatotropinomas, and support the rationale of the therapeutic trials with these compounds in gonadotropinomas. Moreover, the presence of D2 receptors in intratumoral blood vessels walls constitutes the possibility of the anti-angiogenic action of D2 agonists in pituitary adenomas.

  8. Preparation and use of very pure o-D2. Technical report No. 1

    International Nuclear Information System (INIS)

    Optimum production and utilization of spin-polarized deuterium as a fusion fuel requires long nuclear spin-lattice relaxation times at temperatures near 4K. This can be achieved with very high purity ortho-D2. We report new experimental methods and results of total-adsorption catalysis of D2 para-ortho conversion in the 4 to 15K temperature region, using as catalysts activated alumina and partially-activated charcoal. Because of the strongly anisotropic adsorbate binding on alumina, the ortho-D2 equilibrium concentration near 10 to 12K (where the conversion time is acceptable) is not high enough, and near 4K (where the equilibium ortho-D2 concentration is satisfactory) the conversion time is almost prohibitively too long to permit achievement of the desired ortho-D2 purity. Although doping alumina with paramagnetic ions could improve this situation, it would be at the expense of excessive back-conversion upon desorption

  9. A Note on the Generalized Ramanujan-Nagell Equation D1x2 + D2=Pn%关于广义Ramanujan-Nagell方程D1 x2+D2=pn的一点注记

    Institute of Scientific and Technical Information of China (English)

    乐茂华; 陈锡庚

    2001-01-01

    设r,D1,D2是适合gcd(D1,D2)=1的正整数,又设p是适合p| D1D2的奇素数.本文证明了:如果D1+D2=4Pr且方程D1x2+D2=Pn有正整数解(x,n),则3pr-D2=±2,而且此时该方程仅有解(x,n)=(|pr-D2|/2,3r).

  10. Sigma1 and dopamine D2 receptor occupancy in the mouse brain after a single administration of haloperidol and two dopamine D2-like receptor ligands

    International Nuclear Information System (INIS)

    We investigated sigma1 and dopamine D2 receptor occupancy in mouse brain after a single injection of haloperidol, nemonapride, or spiperone using [11C]SA4503 and [11C]raclopride, respectively. Co-injection of the three compounds significantly blocked the uptake of each radioligand. Six hours later, only haloperidol blocked [11C]SA4503 uptake, while all three reduced [11C]raclopride uptake. Sigma1 receptor occupancy by haloperidol was reduced to 19% at day 2 when D2 receptor occupancy disappeared. [11C]SA4503 would be applicable to the investigation of sigma1 receptor occupancy of antispychotic drugs using PET

  11. Observations of long-lived H-2 and D-2 ions from non-thermal plasmas

    International Nuclear Information System (INIS)

    Strong mass signals of H-2 and D-2 ions have been observed from low-pressure dielectric barrier discharge hydrogen and deuterium plasmas via molecular beam mass spectrometry. The observed H-2/H- and D-2/D- ratios (∼0.35-0.4) are over five orders of magnitude higher than those observed by other techniques. The kinetic energy of H-2 and D-2 ions sampled from the plasmas was determined to be widely distributed, from a few eV to >100 eV, giving lifetimes greater than ∼40 μs for H-2 and ∼55 μs for D-2. The highest vib-rotational excitation of neutral H2 species in the plasma was determined to be about J = 0, v = 5 or J = 19, v = 0 via threshold ionization mass spectrometry. The possible pumping mechanisms for generating H-2 with further high J, required by the current high-rotation model, have been proposed. Similar to the lifetime of D-2 determined recently by another group, the H-2 lifetime observed in this work is about two orders of magnitude longer than that predicted by the current theoretical model. To explain these experimental observations regarding the meta-stability of long-lived H-2 and D-2 ions, the improved current high-rotation model or other new models, including the possible existence of some long-lived electronically excited states of H-2/D-2, need to be developed

  12. Structure-Based Virtual Screening for Dopamine D2 Receptor Ligands as Potential Antipsychotics.

    Science.gov (United States)

    Kaczor, Agnieszka A; Silva, Andrea G; Loza, María I; Kolb, Peter; Castro, Marián; Poso, Antti

    2016-04-01

    Structure-based virtual screening using a D2 receptor homology model was performed to identify dopamine D2 receptor ligands as potential antipsychotics. From screening a library of 6.5 million compounds, 21 were selected and were subjected to experimental validation. From these 21 compounds tested, ten D2 ligands were identified (47.6 % success rate, among them D2 receptor antagonists, as expected) that have additional affinity for other receptors tested, in particular 5-HT2A receptors. The affinity (Ki values) of the compounds ranged from 58 nm to about 24 μm. Similarity and fragment analysis indicated a significant degree of structural novelty among the identified compounds. We found one D2 receptor antagonist that did not have a protonatable nitrogen atom, which is a key structural element of the classical D2 pharmacophore model necessary for interaction with the conserved Asp(3.32) residue. This compound exhibited greater than 20-fold binding selectivity for the D2 receptor over the D3 receptor. We provide additional evidence that the amide hydrogen atom of this compound forms a hydrogen bond with Asp(3.32), as determined by tests of its derivatives that cannot maintain this interaction. PMID:26990027

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

    Science.gov (United States)

    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-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. PMID:26241351

  14. NeuroD2 regulates the development of hippocampal mossy fiber synapses

    Directory of Open Access Journals (Sweden)

    Wilke Scott A

    2012-02-01

    Full Text Available Abstract Background The assembly of neural circuits requires the concerted action of both genetically determined and activity-dependent mechanisms. Calcium-regulated transcription may link these processes, but the influence of specific transcription factors on the differentiation of synapse-specific properties is poorly understood. Here we characterize the influence of NeuroD2, a calcium-dependent transcription factor, in regulating the structural and functional maturation of the hippocampal mossy fiber (MF synapse. Results Using NeuroD2 null mice and in vivo lentivirus-mediated gene knockdown, we demonstrate a critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF inputs. We also use electrophysiological recordings from CA3 neurons while stimulating MF axons to show that NeuroD2 regulates the differentiation of functional properties at the MF synapse. Finally, we find that NeuroD2 regulates PSD95 expression in hippocampal neurons and that PSD95 loss of function in vivo reproduces CA3 neuron spine defects observed in NeuroD2 null mice. Conclusion These experiments identify NeuroD2 as a key transcription factor that regulates the structural and functional differentiation of MF synapses in vivo.

  15. Summary of breakout Sessions D1 and D2: D1 and D2, mechanical recovery: Containment recovery and standards; and storage, disposal and landfill options

    International Nuclear Information System (INIS)

    The discussions in breakout sessions D1 and D2 are summarized. The topics discussed include the need to improve existing equipment, the need to take advantage of the window of opportunity, the need to minimize research and development redundancy, and the need to keep communications going between researchers and users

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

    Science.gov (United States)

    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

  17. Impaired Timing Precision Produced by Striatal D2 Receptor Overexpression is Mediated by Cognitive and Motivational Deficits

    OpenAIRE

    Ward, Ryan D; Kellendonk, Christoph; Simpson, Eleanor H.; Lipatova, Olga; Drew, Michael R.; Fairhurst, Stephen; Kandel, Eric R.; Balsam, Peter D

    2009-01-01

    Increased striatal dopamine D2 receptor activity is thought to contribute to the pathophysiology of schizophrenia. To model this condition in mice, Kellendonk et al. (2006) generated transgenic mice which selectively overexpress the D2 receptor in striatum (D2OE). Drew et al. (2007) reported that D2OE mice display deficits in interval timing and motivation. The present study further explored the impaired timing in D2OE mice. Experiment 1 assessed the role of motivation in producing timing def...

  18. Progressive supranuclear palsy dopamine D2 receptor tomoscintigraphy to detect L-dopamine efficiency

    International Nuclear Information System (INIS)

    Progressive supranuclear palsy (PSP) may sometimes be misdiagnosed as Parkinson's disease in its early stages, hence an early positive diagnosis of PSP based on dopamine D2 receptor density could be extremely valuable. In the present case report, the absence of dopamine D2 receptors was clearly demonstrated in the striatum using 123I-iodobenzamide (IBZM) tomoscintigraphy. This illustrates the potential use of IBZM tomoscintigraphy to identify Parkinson-like's disease presenting with decreased dopamine D2 receptor density; and hence to predict L-Dopa effectiveness. Further studies are needed to evaluate the value of IBZM tomoscintigraphy in the different Parkinson's like diseases. (authors). 11 refs., 2 figs

  19. Permeation of a H2 + HD + D2 gas mixture through a polymer membrane

    International Nuclear Information System (INIS)

    The selective permeation of a H2 + HD + D2 gas mixture through a polyethylene terephthalate membrane was studied at T 20 0C. It was found that the permeation of the HD through the membrane leads to a smaller overall hydrogen-deuterium separation factor than that determined in the permeation experiments with pure H2 and D2. On the other hand, a process of isotopic exchange between deuterium atoms from the penetrant gas stream and hydrogen atoms from the polymer membrane is assumed and discussed in order to explain temporal variations of the H2, HD and D2 concentrations of the permanent gas stream. (author)

  20. Domain Requirements for DNA Unwinding by Mycobacterial UvrD2, an Essential DNA Helicase†

    OpenAIRE

    Sinha, Krishna Murari; Stephanou, Nicolas C.; Unciuleac, Mihaela-Carmen; Glickman, Michael S.; Shuman, Stewart

    2008-01-01

    Mycobacterial UvrD2 is a DNA-dependent ATPase with 3′ to 5′ helicase activity. UvrD2 is an atypical helicase, insofar as its N-terminal ATPase domain resembles the superfamily I helicases UvrD/PcrA, yet it has a C-terminal HRDC domain, which is a feature of RecQ-type superfamily II helicases. The ATPase and HRDC domains are connected by a CxxC-(14)-CxxC tetracysteine module that defines a new clade of UvrD2-like bacterial helicases found only in Actinomycetales. By characterizing truncated ve...

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

    OpenAIRE

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

    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 D1...

  2. Dopamine D1-D2 receptor heteromer signaling pathway in the brain: emerging physiological relevance

    Directory of Open Access Journals (Sweden)

    Hasbi Ahmed

    2011-06-01

    Full Text Available Abstract Dopamine is an important catecholamine neurotransmitter modulating many physiological functions, and is linked to psychopathology of many diseases such as schizophrenia and drug addiction. Dopamine D1 and D2 receptors are the most abundant dopaminergic receptors in the striatum, and although a clear segregation between the pathways expressing these two receptors has been reported in certain subregions, the presence of D1-D2 receptor heteromers within a unique subset of neurons, forming a novel signaling transducing functional entity has been shown. Recently, significant progress has been made in elucidating the signaling pathways activated by the D1-D2 receptor heteromer and their potential physiological relevance.

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

    Science.gov (United States)

    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

  4. The herpes simplex virus 1 U(L)34 protein interacts with a cytoplasmic dynein intermediate chain and targets nuclear membrane.

    Science.gov (United States)

    Ye, G J; Vaughan, K T; Vallee, R B; Roizman, B

    2000-02-01

    To express the function encoded in its genome, the herpes simplex virus 1 capsid-tegument structure released by deenvelopment during entry into cells must be transported retrograde to the nuclear pore where viral DNA is released into the nucleus. This path is essential in the case of virus entering axons of dorsal root ganglia. The objective of the study was to identify the viral proteins that may be involved in the transport. We report the following findings. (i) The neuronal isoform of the intermediate chain (IC-1a) of the dynein complex pulled down, from lysates of [(35)S]methionine-labeled infected cells, two viral proteins identified as the products of U(L)34 and U(L)31 open reading frames, respectively. U(L)34 protein is a virion protein associated with cellular membranes and phosphorylated by the viral kinase U(S)3. U(L)31 protein is a largely insoluble, evenly dispersed nuclear phosphoprotein required for optimal processing and packaging of viral DNA into preformed capsids. Reciprocal pulldown experiments verified the interaction of IC-1a and U(L)34 protein. In similar experiments, U(L)34 protein was found to interact with U(L)31 protein and the major capsid protein ICP5. (ii) To determine whether U(L)34 protein is transported to the nuclear membrane, a requirement if it is involved in transport, the U(L)34 protein was inserted into a baculovirus vector under the cytomegalovirus major early promoter. Cells infected with the recombinant baculovirus expressed U(L)34 protein in a dose-dependent manner, and the U(L)34 protein localized primarily in the nuclear membrane. An unexpected finding was that U(L)34-expressing cells showed a dissociation of the inner and outer nuclear membranes reminiscent of the morphologic changes seen in cells productively infected with herpes simplex virus 1. U(L)34, like many other viral proteins, may have multiple functions expressed both early and late in infection. PMID:10627546

  5. Estimated D2-DT-T2 phase diagram in the three-phase region

    International Nuclear Information System (INIS)

    A composite of experimental eH2-D2 phase-diagram data at the three-phase line is assembled from the literature. The phase diagram is a smooth cigar shape without a eutectic point, indicating complete miscibility of liquid and solid phases. Additional data are used to estimate the D2-T2, D2-DT, and DT-T2 binary phase diagrams. These are assembled into the ternary D2-DT-T2 phase diagram. A surface representing the chemical equilibrium of the three species is added to the phase diagram. At chemical equilibrium, it is estimated that 50-50 liquid D-T at 19.7 K is in equilibrium with 42 mole percent T vapor and 54 percent T solid. Infrared spectroscopy is suggested as a means of component analysis of liquid and solid mixtures

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

    International Nuclear Information System (INIS)

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

  7. D2 wins 2006 Best Concept Award from Food Management Magazine

    OpenAIRE

    DeLauder, Rachel

    2006-01-01

    Student Programs' Housing and Dining Services is pleased to announce that D2, Virginia Tech's international marketplace-style dining facility, has been awarded one of Food Management Magazine's 2006 Best Concept Awards for Best Renovation.

  8. Free-field realization of the exceptional current superalgebra D(2,1;α)k

    International Nuclear Information System (INIS)

    The free-field representations of the D(2, 1; α) current superalgebra and the corresponding energy–momentum tensor are constructed. The related screening currents of the first kind are also presented. (paper)

  9. Striatal Dopamine D-2/3 Receptor Availability in Treatment Resistant Depression

    NARCIS (Netherlands)

    de Kwaasteniet, Bart P.; Pinto, Chedwa; Ruhe, 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 D-2/3 recep

  10. Relationship of frontal D2/3 binding potentials to cognition

    DEFF Research Database (Denmark)

    Fagerlund, Birgitte; Pinborg, Lars H; Mortensen, Erik Lykke;

    2013-01-01

    Studies of in vivo dopamine receptors in schizophrenia have mostly focused on D2 receptors in striatal areas or on D1 receptors in cortex. No previous study has examined the correlation between cortical dopamine D2/3 receptor binding potentials and cognition in schizophrenia patients. The objective...... was to examine this relation in the frontal cortex in first-episode, drug-naive schizophrenia patients. Based on preclinical and pharmacological evidence, we specifically expected to find a relation between D2/3 receptor binding potentials and set shifting. This was a cross-sectional, case......-control study using single-photon emission computerized tomography with the D2/3-receptor ligand [123I]epidepride, co-registered with structural magnetic resonance imaging and correlated to cognitive measures. Participants were 24 antipsychotic-naive, first-episode schizophrenia patients and 20 healthy controls...

  11. Selective Alignment of D2 Induced by Two Ultrashort Laser Pulses

    Institute of Scientific and Technical Information of China (English)

    Zeng-qiang Yang; Zhi-rong Guo; Gui-xian Ge

    2009-01-01

    The dynamics of molecular rotational wave packets of D2 induced by ultrashort laser pulses was investigated numerically by solving the time-dependent Schrodinger equation. Results show that an ultrashort pulse can manipulate a coherent rotational wave packet of D2 se-lectively. In the calculation, a first laser pulse was used to create a coherent rotational wave packet from an initial thermal ensemble of D2 at the temperature of 300 K. The second laser pulse was used to manipulate the rotational wave packet selectively around the first quarter and the three quarters revival. The alignment parameter and its Fourier transform amplitude both illustrate that the relative populations of even and odd rotational states in the final rotational wave packet of D2 can be manipulated by precisely selecting the time delay between the first and the second ultrashort pulse.

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

    Science.gov (United States)

    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

  13. Global ATM security Management - D2.2 - Security objective report

    OpenAIRE

    Airbus DS CYB, .; Paz Goncalves Martins, Ana; Stelkens-Kobsch, Tim H.; Schaper, Meilin; Selex ES, .; Airbus Prosky, .; Thales Alenia Space, .; BRTE, .; ENAV, .; ULANC, .; RNCA, .; Thales RT, .; SEA, .; ISDEFE, .; ROMATSA, .

    2015-01-01

    This document is the deliverable D2.2 – Security objective report of GAMMA WP2 “ATM threat assessment model”, providing a list of security objectives for the ATM system. It is based on the risk assessment made in D2.1 with the context and scope, threat scenarios and risks identified on the ATM system, in order to provide a list of security objectives.

  14. Regulation of dopamine D2 receptors by sodium and pH

    International Nuclear Information System (INIS)

    The role of Na+ and H+ in the regulation of D2 receptor affinity for ligands was studied to determine the molecular mechanisms of this phenomenon. The potency of substituted benzamide derivatives and agonists at D2 receptors depended on the concentration of Na+ and H+, whereas the potency of other antagonists was relatively unaltered by changes in pH or Na+ concentration. The potency of agonists was generally decreased in the presence of NaCl or lowered pH. For example, in the absence of sodium the affinity of D2 receptors for dopamine was decreased 17-fold by lowering of the pH from 8.0 to pH 6.8. Addition of NaCl caused 2-4-fold decreases in affinity for most agonists. The affinity of the receptors for two substituted benzamide derivatives, on the other hand, was reduced 6-44-fold by elevated concentrations of H+ but was enhanced 7-24-fold in the presence of Na+. The regulation by H+ of the potency of dopamine was selective for D2 receptors, because binding of dopamine to neostriatal D1 receptors was unaffected by changes in pH. Decreasing of the pH from 8.0 or 7.3 to 6.8 facilitated the dissociation of the substituted benzamide ligand 125I epidepride from D2 receptors but inhibited dissociation of 3H spiperone. Furthermore, the presence of NaCl or lowered pH slowed inactivation of D2 receptors by N-ethylmaleimide. Together, these data suggest that the conformation of D2 receptors is regulated by both Na+ and H+. The affinity of D2 receptors for agonists and substituted benzamide antagonists varies according to the conformational state of the receptors, whereas other antagonists bind to both forms with approximately equal potency. Amiloride is a compound that interacts with many sodium-binding macromolecules

  15. Regulation of dopamine D2 receptors by sodium and pH

    Energy Technology Data Exchange (ETDEWEB)

    Neve, K.A. (VA Medical Center, Portland, OR (USA))

    1991-04-01

    The role of Na+ and H+ in the regulation of D2 receptor affinity for ligands was studied to determine the molecular mechanisms of this phenomenon. The potency of substituted benzamide derivatives and agonists at D2 receptors depended on the concentration of Na+ and H+, whereas the potency of other antagonists was relatively unaltered by changes in pH or Na+ concentration. The potency of agonists was generally decreased in the presence of NaCl or lowered pH. For example, in the absence of sodium the affinity of D2 receptors for dopamine was decreased 17-fold by lowering of the pH from 8.0 to pH 6.8. Addition of NaCl caused 2-4-fold decreases in affinity for most agonists. The affinity of the receptors for two substituted benzamide derivatives, on the other hand, was reduced 6-44-fold by elevated concentrations of H+ but was enhanced 7-24-fold in the presence of Na+. The regulation by H+ of the potency of dopamine was selective for D2 receptors, because binding of dopamine to neostriatal D1 receptors was unaffected by changes in pH. Decreasing of the pH from 8.0 or 7.3 to 6.8 facilitated the dissociation of the substituted benzamide ligand {sup 125}I epidepride from D2 receptors but inhibited dissociation of {sup 3}H spiperone. Furthermore, the presence of NaCl or lowered pH slowed inactivation of D2 receptors by N-ethylmaleimide. Together, these data suggest that the conformation of D2 receptors is regulated by both Na+ and H+. The affinity of D2 receptors for agonists and substituted benzamide antagonists varies according to the conformational state of the receptors, whereas other antagonists bind to both forms with approximately equal potency. Amiloride is a compound that interacts with many sodium-binding macromolecules.

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

    OpenAIRE

    Carney, Amanda E.; Rebecca D Sanders; 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′ pro...

  17. Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity

    OpenAIRE

    Trifilieff, Pierre; Martinez, Diana

    2013-01-01

    Dependence to drugs of abuse is closely associated with impulsivity, or the propensity to choose a lower, but immediate, reward over a delayed, but more valuable outcome. Here, we review clinical and preclinical studies showing that striatal dopamine signaling and D2 receptor levels – which have been shown to be decreased in addiction - directly impact impulsivity, which is itself predictive of drug self-administration. Based on these studies, we propose that the alterations in D2 receptor bi...

  18. Quantization of the N=2m simple supergravity in d=2+1

    International Nuclear Information System (INIS)

    In d=2+1 simple supergravity is a trivial theory and it has a Chern-Simons interpretation. Thus the overall sign of each one of the fermionic terms in the action for N>1 is arbitrary. By making use of these facts it is shown that for the N=2m simple supergravity in d=2+1 there exists a real polarization and an explicit construction of the physical Hilbert space is possible. (author). 11 refs

  19. Immunohistochemical detection of dopamine D2 receptors in human pituitary adenomas.

    OpenAIRE

    Marek Pawlikowski

    2010-01-01

    Thirty one pituitary adenomas and 3 samples of peritumoral anterior pituitary tissue were immunostained with an antibody raised against dopamine D2 receptor protein. The positive reactions were found in cell cytoplasm, a subpopulation of cell nuclei and the intratumoral blood vessels walls. As expected, the positive immunostaining was shown in cytoplasm and/or cell nuclei of all examined prolactinomas (7/7). In acromegaly the positive D2 staining occurred in 5/7 samples, in gonadotropinomas i...

  20. Neurotensin Induces Presynaptic Depression of D2 Dopamine Autoreceptor-Mediated Neurotransmission in Midbrain Dopaminergic Neurons

    OpenAIRE

    Piccart, Elisabeth; Courtney, Nicholas A.; Branch, Sarah Y.; Ford, Christopher P.; Beckstead, Michael J.

    2015-01-01

    Increased dopaminergic signaling is a hallmark of severe mesencephalic pathologies such as schizophrenia and psychostimulant abuse. Activity of midbrain dopaminergic neurons is under strict control of inhibitory D2 autoreceptors. Application of the modulatory peptide neurotensin (NT) to midbrain dopaminergic neurons transiently increases activity by decreasing D2 dopamine autoreceptor function, yet little is known about the mechanisms that underlie long-lasting effects. Here, we performed pat...

  1. Safety-Evaluation Report related to the D2/D3 steam-generator design modification

    International Nuclear Information System (INIS)

    This Safety Evaluation Report (SER) related to the D2/D3 steam generator design modification has been prepared by the Office of Nuclear Reactor Regulation of the US Nuclear Regulatory Commission. The purpose of this SER is to issue the staff's evaluation of the acceptability of the design modification for both installation and full-power operation in the D2/D3 steam generators based on the Design Review Panel Report of January 1983

  2. Genetic Contributions to Avoidance-Based Decisions: Striatal D2 receptor Polymorphisms

    OpenAIRE

    Frank, Michael J.; Hutchison, Kent

    2009-01-01

    Individuals differ in their tendencies to seek positive decision outcomes or to avoid negative ones. At the neurobiological level, our model suggests that phasic changes in dopamine support learning to reinforce good decisions via striatal D1 receptors, and to avoid maladaptive choices via striatal D2 receptors. Accordingly, in a previous study individual differences in positive and negative learning were strongly modulated by two genetic polymorphisms factors related to striatal D1 and D2 fu...

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

    Science.gov (United States)

    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

  4. Esoteric X-01 D2终极限量版SACD/CD播放机

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    高端品牌Esoteric最近推出了X系列SACD/CD播放机的最高端机种X-01 D2 SACD/CD播放机。与X系列Esoteric SACD/CD播放机一样,X-01 D2也采用了独特的读取精确的“VRDS-NEO”转盘系统。

  5. Dopamine D2 receptor radiotracers [11C](+)-PHNO and [3H]raclopride are indistinguishably inhibited by D2 agonists and antagonists ex vivo

    International Nuclear Information System (INIS)

    Introduction: In vitro, the dopamine D2 receptor exists in two states, with high and low affinity for agonists. The high-affinity state is the physiologically active state thought to be involved in dopaminergic illnesses such as schizophrenia. The positron emission tomography radiotracer [11C](+)-PHNO ([11C](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4] oxazin-9-o l), being a D2 agonist, should selectively label the high-affinity state at tracer dose and therefore be more susceptible to competition by agonist as compared to the antagonist [3H]raclopride, which binds to both affinity states. Methods: We tested this prediction using ex vivo dual-radiotracer experiments in conscious rats. D2 antagonists (haloperidol or clozapine), a partial agonist (aripiprazole), a full agonist [(-)-NPA] or the dopamine-releasing drug amphetamine (AMPH) were administered to rats prior to an intravenous coinjection of [11C](+)-PHNO and [3H]raclopride. Rats were sacrificed 60 min after radiotracer injection. Striatum, cerebellum and plasma samples were counted for 11C and 3H. The specific binding ratio {SBR, i.e., [%ID/g (striatum)-%ID/g (cerebellum)]/(%ID/g (cerebellum)} was used as the outcome measure. Results: In response to D2 antagonists, partial agonist or full agonist, [11C](+)-PHNO and [3H]raclopride SBRs responded indistinguishably in terms of both ED50 and Hill slope (e.g., (-)-NPA ED50 values are 0.027 and 0.023 mg/kg for [11C](+)-PHNO and [3H]raclopride, respectively). In response to AMPH challenge, [11C](+)-PHNO and [3H]raclopride SBRs were inhibited to the same degree. Conclusions: We have shown that the SBRs of [11C](+)-PHNO- and [3H]raclopride do not differ in their response to agonist challenge. These results do not support predictions of the in vivo binding behavior of a D2 agonist radiotracer and cast some doubt on the in vivo applicability of the D2 two-state model, as described by in vitro binding experiments

  6. Dopamine D2 receptor radiotracers [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride are indistinguishably inhibited by D2 agonists and antagonists ex vivo

    Energy Technology Data Exchange (ETDEWEB)

    McCormick, Patrick N. [Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada)], E-mail: patrick.mccormick@camhpet.ca; Kapur, Shitij [Department of Psychiatry, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); PET Center, Center for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada); Seeman, Philip [Department of Psychiatry, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); Department of Pharmacology, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); Wilson, Alan A. [Department of Psychiatry, University of Toronto, Toronto, Ontario, M5S 1A8 (Canada); PET Center, Center for Addiction and Mental Health, Toronto, Ontario, M5T 1R8 (Canada)

    2008-01-15

    Introduction: In vitro, the dopamine D2 receptor exists in two states, with high and low affinity for agonists. The high-affinity state is the physiologically active state thought to be involved in dopaminergic illnesses such as schizophrenia. The positron emission tomography radiotracer [{sup 11}C](+)-PHNO ([{sup 11}C](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4] oxazin-9-o l), being a D2 agonist, should selectively label the high-affinity state at tracer dose and therefore be more susceptible to competition by agonist as compared to the antagonist [{sup 3}H]raclopride, which binds to both affinity states. Methods: We tested this prediction using ex vivo dual-radiotracer experiments in conscious rats. D2 antagonists (haloperidol or clozapine), a partial agonist (aripiprazole), a full agonist [(-)-NPA] or the dopamine-releasing drug amphetamine (AMPH) were administered to rats prior to an intravenous coinjection of [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride. Rats were sacrificed 60 min after radiotracer injection. Striatum, cerebellum and plasma samples were counted for {sup 11}C and {sup 3}H. The specific binding ratio {l_brace}SBR, i.e., [%ID/g (striatum)-%ID/g (cerebellum)]/(%ID/g (cerebellum){r_brace} was used as the outcome measure. Results: In response to D2 antagonists, partial agonist or full agonist, [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride SBRs responded indistinguishably in terms of both ED{sub 50} and Hill slope (e.g., (-)-NPA ED{sub 50} values are 0.027 and 0.023 mg/kg for [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride, respectively). In response to AMPH challenge, [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride SBRs were inhibited to the same degree. Conclusions: We have shown that the SBRs of [{sup 11}C](+)-PHNO- and [{sup 3}H]raclopride do not differ in their response to agonist challenge. These results do not support predictions of the in vivo binding behavior of a D2 agonist radiotracer and cast some doubt on the in vivo

  7. Characterization of D2 tool steel friction surfaced coatings over low carbon steel

    International Nuclear Information System (INIS)

    Highlights: • Solid state coating by friction surfacing method. • D2 tool steel is coated over relatively softer low carbon steel. • Defect free interface between tool steel coating and low carbon steel substrate. • D2 coatings exhibited higher hardness and good wear resistance. • Highly refined martensitic microstructure in the coating. - Abstract: In this work D2 tool steel coating is produced over a low carbon steel substrate using friction surfacing process. The process parameters are optimized to get a defect free coating. Microstructural characterization is carried out using optical microscopy, scanning electron microscopy and X-ray diffraction. Infrared thermography is used to measure the thermal profile during friction surfacing of D2 steel. Wear performance of the coating is studied using Pin-on-Disk wear tests. A lower rotational speed of the consumable rod and higher translational speed of the substrate is found to result in thinner coatings. Friction surfaced D2 steel coating showed fine-grained martensitic microstructure compared to the as-received consumable rod which showed predominantly ferrite microstructure. Refinement of carbides in the coating is observed due to the stirring action of the process. The infrared thermography studies showed the peak temperature attained by the D2 coating to be about 1200 °C. The combined effect of martensitic microstructure and refined carbides resulted in higher hardness and wear resistance of the coating

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

    Science.gov (United States)

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

    2015-02-18

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

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

    Science.gov (United States)

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

    2016-08-01

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

  10. Regulation of human D1, D2(long), D2(short), D3 and D4 dopamine receptors by amiloride and amiloride analogues

    OpenAIRE

    Hoare, S R J; Coldwell, M C; Armstrong, D.; Strange, P G

    2000-01-01

    The modulatory effects of the allosteric effectors methylisobutylamiloride (MIA), benzamil and amiloride have been examined at human D1, D2, D3 and D4 dopamine receptors. The subtype selectivity and the mechanism of action of this allosteric regulation was examined.In radioligand dissociation experiments each modulator accelerated dissociation from all four receptor subtypes indicating allosteric regulation. MIA displayed selectivity for the D3 subtype for acceleration of radioligand dissocia...

  11. High affinity dopamine D2 receptor radioligands. 2. [125I]epidepride, a potent and specific radioligand for the characterization of striatal and extrastriatal dopamine D2 receptors

    International Nuclear Information System (INIS)

    Epidepride, (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2,3-dimethoxybenzamide, the iodine analogue of isoremoxipride (FLB 457), was found to be a very potent dopamine D2 receptor antagonist. Optimal in vitro binding required incubation at 25C for 4 h at pH 7.4 in a buffer containing 120 mM NaCl, 5 mM KCl, 2 mM CaCl2 and 1 nM MgCl2. Scatchard analysis of in vitro binding to striatal, medical frontal cortical, hippocampal and cerebellar membranes revealed a KD of 24 pM in all regions, with Bmax's of 36.7, 1.04, 0.85, and 0.37 pmol/g tissue, respectively. The Hill coefficients ranged from 0.91-1.00 in all four regions. The IC50's for inhibition of [125I]epidepride binding to striatal, medial frontal cortical, and hippocampal membranes for SCH 23390, SKF 83566, serotonin, ketanserin, mianserin, naloxone, QNB, prasozin, clonidine, alprenolol, and norepinephrine ranged from 1 μM to >10 μM. Partial displacement of [125I]epidepride by nanomolar concentrations of clonidine was noted in the frontal cortex and hippocampus, but not in the striatum. Scatchard analysis of epidepride binding to α2 noradrenergic receptors in the frontal cortex and hippocampus revealed an apparent KD of 9 nM. At an epidepride concentration equal to the KD for the D2 receptor, i.e., 25 pM, no striatal α2 binding was seen and only 7% of the specific epidepride binding in the cortex or hippocampus was due to binding at the α2 site. Correlation of inhibition of [3H]spiperone and [125I]epidepride binding to striatal membranes by a variety of D2 ligands revealed a correlation coefficient of 0.99, indicating that epidepride labels a D2 site

  12. Determination of Vitamin D2 Content in Vitamin D2 and Calcium Hydrogen Phosphate Tablets by RP-HPLC%反相高效液相色谱法测定维D2磷酸氢钙片中维生素D2含量

    Institute of Scientific and Technical Information of China (English)

    冯国

    2013-01-01

    Objective To establish a RP-HPLC method for the content determination of vitamin D2 in Vitamin D2 and Calcium Hydrogen Phosphate Tablets.Methods The chromatographic column of AlltimaTM C18 was adopted with the mobile phase of acetonitrilemethanol(1∶9).The detection wavelength was set at 265 nm,the flow velocity was 1.0 mL/min and column temperature was 30 ℃.Results The sample size of vitamin D2 within the range of 0.005-0.065 μg(r=1.000 0)showed the good linearity with the peak area.The mean recovery rate was 99.38%,RSD =0.68% (n =9).Conclusion This method has the advantages of rapidness,simpleness,accuracy and low test cost,and can be used for the quality control of vitamin D2 in Vitamin D2 and Calcium Hydrogen Phosphate Tablets.%目的 建立测定维D2磷酸氢钙片中维生素D2含量的反相高效液相色谱法.方法 采用Alhima C18色谱柱(250 mm×4.6mm,5 μm),流动相为乙腈-甲醇(1∶9),检测波长为265 nm,流速为1.0 mL/min,柱温30℃.结果 维生素D2进样量在0.005~0.065 μg范围内与峰面积具有良好的线性关系,r=1.0000,平均回收率为99.38%,RSD=0.68%(n=9).结论 该法具有快速、简便、准确、检验成本低的优点,可用于维D2磷酸氢钙片中维生素D2的质量控制.

  13. Localization of D1 and D2 dopamine receptors in brain with subtype-specific antibodies.

    Science.gov (United States)

    Levey, A I; Hersch, S M; Rye, D B; Sunahara, R K; Niznik, H B; Kitt, C A; Price, D L; Maggio, R; Brann, M R; Ciliax, B J

    1993-10-01

    Five or more dopamine receptor genes are expressed in brain. However, the pharmacological similarities of the encoded D1-D5 receptors have hindered studies of the localization and functions of the subtypes. To better understand the roles of the individual receptors, antibodies were raised against recombinant D1 and D2 proteins and were shown to bind to the receptor subtypes specifically in Western blot and immunoprecipitation studies. Each antibody reacted selectively with the respective receptor protein expressed both in cells transfected with the cDNAs and in brain. By immunocytochemistry, D1 and D2 had similar regional distributions in rat, monkey, and human brain, with the most intense staining in striatum, olfactory bulb, and substantia nigra. Within each region, however, the precise distributions of each subtype were distinct and often complementary. D1 and D2 were differentially enriched in striatal patch and matrix compartments, in selective layers of the olfactory bulb, and in either substantia nigra pars compacta or reticulata. Electron microscopy demonstrated that D1 and D2 also had highly selective subcellular distributions. In the rat neostriatum, the majority of D1 and D2 immunoreactivity was localized in postsynaptic sites in subsets of spiny dendrites and spine heads in rat neostriatum. Presynaptic D1 and D2 receptors were also observed, indicating both subtypes may regulate neurotransmitter release. D1 was also present in axon terminals in the substantia nigra. These results provide a morphological substrate for understanding the pre- and postsynaptic functions of the genetically defined D1 and D2 receptors in discrete neuronal circuits in mammalian brain. PMID:8415621

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

    Science.gov (United States)

    Jiang, Quan; Lian, Anji; He, Qi

    2016-07-01

    Dopamine (DA) is an important neurotransmitter in the central nervous system of vertebrates and possesses key hypophysiotropic functions. Early studies have shown that DA has a potent inhibitory effect on somatolactin (SL) release in fish. However, the mechanisms responsible for DA inhibition of SL gene expression are largely unknown. To this end, tilapia DA type-1 (D1) and type-2 (D2) receptor transcripts were examined in the neurointermediate lobe (NIL) of the tilapia pituitary by real-time PCR. In tilapia, DA not only was effective in inhibiting SL mRNA levels in vivo and in vitro, but also could abolish pituitary adenylate cyclase-activating polypeptide (PACAP)- and salmon gonadotropin-releasing hormone (sGnRH)-stimulated SL gene expression at the pituitary level. In parallel studies, the specific D2 receptor agonists quinpirole and bromocriptine could mimic the DA-inhibited SL gene expression. Furthermore, the D2 receptor antagonists domperidone and (-)-sulpiride could abolish the SL response to DA or the D2 agonist quinpirole, whereas D1 receptor antagonists SCH23390 and SKF83566 were not effective in this respect. In primary cultures of tilapia NIL cells, D2 agonist quinpirole-inhibited cAMP production could be blocked by co-treatment with the D2 antagonist domperidone and the ability of forskolin to increase cAMP production was also inhibited by quinpirole. Using a pharmacological approach, the AC/cAMP pathway was shown to be involved in quinpirole-inhibited SL mRNA expression. These results provide evidence that DA can directly inhibit SL gene expression at the tilapia pituitary level via D2 receptor through the AC/cAMP-dependent mechanism. PMID:26970582

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

    International Nuclear Information System (INIS)

    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 [11C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([11C]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 [11C]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.

  16. In vivo and in vitro detection of dopamine d2 receptors in uveal melanomas.

    Science.gov (United States)

    Bodei, Lisa; Hofland, Leo J; Ferone, Diego; Mooy, Cornelia M; Kros, Johan M; Paridaens, Dion A; Baarsma, Seerp G; Ferdeghini, Marco; Van Hagen, Martin P; Krenning, Eric P; Kwekkeboom, Dik J

    2003-12-01

    Scintigraphy with radiolabeled benzamides was used in melanoma patients. Studies with a newer benzamide called 123I-epidepride, a high-affinity D2 receptor (D2R) antagonist, showed high sensitivity in D2R-positive pituitary adenomas. We evaluated the presence of D2R in patients with uveal melanomas in vivo with 123I-epidepride, and in vitro in melanomas, using immunohistochemistry (IHC) and 125I-epidepride autoradiography. We studied the in vivo tumor-to-background (TB) ratios in six patients with posterior uveal melanoma (one previously enucleated). IHC was performed in 3 of 6 tumors after enucleation and in another 20 uveal melanomas, 7 metastatic lymph nodes from skin melanoma, and 2 normal specimens. 125I-epidepride autoradiography was performed in 10 uveal melanomas (3 of which were studied in vivo), 7 metastases, and 2 normal samples. Radioligand uptake was present in the affected eye of 5 patients with uveal melanoma (TB = 3.1-6.1) and absent in the operated one (TB = 1). Eight uveal tumors were positive at IHC (35%), 14 weakly positive (61%), and 1 negative (4%). Two metastases were positive (29%), 2 weakly positive (29%), and 3 negative (42%). Two uveal tumors were positive at autoradiography (20%), 7 had nonspecific binding (70%), and 1 was negative (10%). One metastasis was positive (14%), while 6 were negative (86%). 123I-epidepride scintigraphy in uveal melanomas seems promising for sensitivity and image quality. D2R was demonstrated in a significant proportion of the melanomas, although 123I-epidepride uptake might also be nonspecific and unrelated to D2R binding. Although further studies on larger series are needed, 123I-epidepride could represent a future tool to study the expression of D2R in other classes of neuroendocrine tumors. PMID:14969602

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Cell-free protein synthesis and purification of human dopamine D2 receptor long isoform.

    Science.gov (United States)

    Basu, Dipannita; Castellano, Jessica M; Thomas, Nancy; Mishra, Ram K

    2013-01-01

    The human dopamine D2 receptor long isoform (D2L) has significant implications in neurological and neuropsychiatric disorders such as Parkinson's disease and schizophrenia. Detailed structural knowledge of this receptor is limited owing to its highly hydrophobic nature, which leads to protein aggregation and host toxicity when expressed in cellular systems. The newly emerging field of cell-free protein expression presents numerous advantages to overcome these challenges. This system utilizes protein synthesis machinery and exogenous DNA to synthesize functional proteins outside of intact cells. This study utilizes two different cell-free systems for the synthesis of human dopamine D2L receptor. These include the Escherichia coli lysate-based system and the wheat-germ lysate-based system. The bacterial cell-free method used pET 100/D-TOPO vector to synthesize hexa-histidine-tagged D2L receptor using a dialysis bag system; the resulting protein was purified using nickel-nitrilotriacetic acid affinity resin. The wheat germ system used pEU-glutathione-S-transferase (GST) vector to synthesize GST-tagged D2L receptor using a bilayer translation method; the resulting protein was purified using a GST affinity resin. The presence and binding capacity of the synthesized D2L receptor was confirmed by immunoblotting and radioligand competition assays, respectively. Additionally, in-gel protein sequencing via Nano LC-MS/MS was used to confirm protein synthesis via the wheat germ system. The results showed both systems to synthesize microgram quantities of the receptor. Improved expression of this highly challenging protein can improve research and understanding of the human dopamine D2L receptor. PMID:23424095

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

    Energy Technology Data Exchange (ETDEWEB)

    Wang, G.J.; Volkow, N.D.; Logan, J. [Brookhaven National Lab., Upton, NY (United States)]|[SUNY, Stony Brook, NY (United States)]|[Psychiatry Services VAMC Northport, NY (United States)] [and others

    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.

  20. Positronium formation and hydrated positron reactions in H2O, D2O, 1.74 M PPS/H2O and 1.74 M PPS/D2O solutions of Cl−, Br− and I−

    DEFF Research Database (Denmark)

    Mogensen, O. E.; Pedersen, Niels Jørgen

    1986-01-01

    Angular correlation of annihilation photons were measured for H2O, D2O, 1.74 M PPS/H2O and 1.74 M PPS/D2O solutions of Cl−, Br− and I−. The three components of the angular correlation spectra for D2O and H2O were nearly identical in shape. The positronium (Ps) yields for the H2O and D2O solutions...

  1. 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.

    Science.gov (United States)

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

    2016-04-01

    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 (Pbread in increasing S-25(OH)D2 (Pbread 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

  2. D2 dissection in laparoscopic and open gastrectomy for gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ming Cui; Jia-Di Xing; Wei Yang; Yi-Yuan Ma; Zhen-Dan Yao; Nan Zhang; Xiang-Qian Su

    2012-01-01

    AIM:To evaluate the radicalness and safety of laparoscopic D2 dissection for gastric cancer.METHODS:Clinicopathological data from 209 patients with gastric cancer,who underwent radical gastrectomy with D2 dissection between January 2007 and February 2011,were analyzed retrospectively.Among these patients,131 patients underwent laparoscopyassisted gastrectomy (LAG) and 78 underwent open gastrectomy (OG).The parameters analyzed included operative time,blood loss,blood transfusion,morbidity,mortality,the number of harvested lymph nodes (HLNs),and pathological stage.RESULTS:There were no significant differences in sex,age,types of radical resection [radical proximal gastrectomy (PG + D2),radical distal gastrectomy (DG + D2) and radical total gastrectomy (TG + D2)],and stages between the LAG and OG groups (P > 0.05).Among the two groups,127 cases (96.9%) and 76 cases (97.4%) had 15 or more HLNs,respectively.The average number of HLNs was 26.1 ± 11.4 in the LAG group and 24.2 ± 9.3 in the OG group (P =0.233).In the same type of radical resection,there were no significant differences in the number of HLNs between the two groups (PG + D2:21.7 ± 7.5 vs 22.4 4-9.3;DG + D2:25.7 ± 11.0 vs 22.3 ± 7.9; TG + D2:30.9 ± 13.4 vs 29.3 ± 10.4; P > 0.05 for all comparisons).Tumor free margins were obtained in all cases.Compared with OG group,the LAG group had significantly less blood loss,but a longer operation time (P < 0.001).The morbidity of the LAG group was 9.9%,which was not significantly different from the OG group (7.7%) (P=0.587).The mortality was zero in both groups.CONCLUSION:Laparoscopic D2 dissection is equivalent to OG in the number of HLNs,regardless of tumor location.Thus,this procedure can achieve the same radicalness as OG.

  3. Extrastriatal dopamine D 2/3 receptor density and distribution in drug-naive schizophrenic patients.

    Science.gov (United States)

    Tuppurainen, H; Kuikka, J; Viinamäki, H; Husso-Saastamoinen, M; Bergström, K; Tiihonen, J

    2003-04-01

    Several lines of studies have suggested the importance of cortical dopamine (DA) transmission in the pathophysiology of schizophrenia. The putative alteration of striatal D(2) receptor density in schizophrenia has been studied intensely, although extrastriatal DA activity may be more relevant for behavioral symptoms. The aim of this study was to explore extrastriatal D(2/3) density in drug-naive schizophrenic patients. We studied the extrastriatal D(2/3) receptor binding with a novel high-affinity single-photon emission tomography ligand epidepride in seven drug-naive schizophrenic patients and seven matched controls. The symptoms were rated with Positive and Negative Syndrome Scale for Schizophrenia. The findings indicated an extremely low D(2/3) receptor binding among patients in temporal cortex in both hemispheres when compared with controls (effect size 2.0-2.3), and the D(2/3) levels had negative correlations with general psychopathological (r from -0.86 to -0.90) and negative (r from -0.37 to -0.55) schizophrenic symptoms. These results support the previous hypothesis on dysfunction of mesocortical DA function behind the cognitive and negative symptoms in schizophrenia. PMID:12740603

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

    Science.gov (United States)

    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. PMID:26314311

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

    International Nuclear Information System (INIS)

    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

  6. Modeling key interactions between dopamine D2 receptor second extracellular loop and arylpiperazine ligands

    Directory of Open Access Journals (Sweden)

    Šukalović Vladimir

    2012-01-01

    Full Text Available Second extracellular loop (ecl2 of dopamine (DA D2 receptor is an essential part of dopaminergic ligands binding pocket. To form a part of the ligand binding surface it has to fold down into the transmembrane domain of the DA receptor. The current study describes the modeling of the D2 DA receptor ecl2 and its interactions with arylpiperazine ligands. In order to model D2 DA receptor ecl2, the number of arylpiperazine ligands was used to propose pharmacophore model. D2 DA receptor ecl2 model was built using Accelrys Discovery Studio. To test the proposed model, docking analysis was performed and key amino acid residues were determined. Proposed receptor-ligand iteractions were rationalized and compared with measured binding affinity. It is shown that D2 DA receptor ecl2 significantly participates in receptor-ligand complex formation through aromatic, hydrophobic and polar interaction. Taking them in account would benefit GPCR molecular modeling and facilitate the design of novel active compounds.

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

    Directory of Open Access Journals (Sweden)

    Xiong Wang

    2014-01-01

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

  8. The infrared spectrum of the Ne-C2D2 complex

    Science.gov (United States)

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

    2015-11-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Evans, Barbara R [ORNL; Bali, Garima [Georgia Institute of Technology, Atlanta; Reeves, David T [ORNL; O' Neill, Hugh Michael [ORNL; Sun, Qining [Georgia Institute of Technology, Atlanta; Shah, Riddhi S [ORNL; Ragauskas, Arthur [Georgia Institute of Technology, Atlanta

    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.

  10. Interaction with Dopamine D2 Receptor Enhances Expression of Transient Receptor Potential Channel 1 at the Cell Surface

    OpenAIRE

    Hannan, Meredith A.; Kabbani, Nadine; Paspalas, Constantinos D.; Levenson, Robert

    2008-01-01

    Receptor signaling is mediated by direct protein interaction with various types of cytoskeletal, adapter, effector, and additional receptor molecules. In brain tissue and in cultured neurons, activation of dopamine D2 receptors (D2Rs) has been found to impact cellular calcium signaling. Using a yeast two-hybrid approach, we have uncovered a direct physical interaction between the D2R and the transient receptor potential channel (TRPC) subtypes 1, 4 and 5. The TRPC/D2R interaction was further ...

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

    Science.gov (United States)

    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

  12. The infrared-induced temperature distributions of solid D2 ices

    Institute of Scientific and Technical Information of China (English)

    Bi Peng; Xie Duan; Lin Wei; Wang Kai; Liu Jiang-Ping; Tang Yong-Jian; Yang Xiang-Dong

    2013-01-01

    A specific-wavelength infrared (IR) light (λ =3140 nm) was irradiated into a solid D2 ice prepared in a cylinder target cell.The temperature in the solid D2 ice oscillated periodicaily with a high amplitude when irradiated by the IR light.The temperature oscillation has been well explained based on the two-dimensional heat transfer theory plus the IR-irradiation effect.The transmission optical imaging reveals that such a temperature oscillation is favorable to recrystallize the solid D2 ice from multicrystal to quasi single crystal.This suggests an efficient method to layer the solid hydrogen-isotope ice for the inertial-confinement-fusion (ICF) experiments.

  13. Synergistic extraction of uranium from acidic sulfate leach liquor using D2EHPA mixed with TOPO

    International Nuclear Information System (INIS)

    Uranium extraction from sulfate leach liquor acid by D2EHPA and TOPO mixture in kerosene was investigated. The effect of different factors affecting the extraction mechanism such as sulfate leach liquor acid, D2EHPA and TOPO concentrations and temperature have been studied. The mathematical treatment for the obtained date suggested that the composition of synergistic extraction species is (UO2(D)2T). The logarithm of the apparent equilibrium constant, log Kex, of synergistic extraction reaction has been evaluated, to be 3.35 ± 0.1. The effect of temperature on extraction process was investigated and the apparent values of the thermodynamics parameters (∆H, ∆G and ∆S) were 38.2 kJ/mol, -19.1 kJ/mol and 192.5 J/mol respectively. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Sokoloff, P.; Riou, J.F.; Martres, M.P.; Schwartz, J.C. (Centre Paul Broca, Paris (France))

    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.

  15. Analysis of the crystal structure of a tetragonal RbD2PO4 single crystal

    International Nuclear Information System (INIS)

    Tetragonal RbD2PO4 single crystals, which are colorless and transparent, are synthesized from tetragonal RbH2PO4 crystals. A ferroelectric transition temperature was found to be 235 K from the temperature dependence of the structure factor F0 in neutron diffraction. Deuteriums in a paraelectric phase are in disordered array. Hydrogen bonds in the monoclinic structure form two-dimensional array in the bc plane, but in the tetragonal structure these display three-dimensional array. The distribution of deuterium was studied by Fourier analysis method. The crystal structure of tetragonal RbD2PO4 at a paraelectric phase was analyzed on the basis of neutron diffraction experiments, and the movement for PO4 tetrahedral was studied. The results for the tetragonal RbD2PO4 were compared with those for the monoclinic structure. (Y. Kazumata)

  16. Revealing the inner structure of the newly observed $D_2^*(3000)$

    CERN Document Server

    Wang, Jun-Zhang; Song, Qin-Tao; Liu, Xiang; Matsuki, Takayuki

    2016-01-01

    Stimulated by the recent observation of the $D_2^\\ast(3000)$, we study the decay behaviors of the $3P$ and $2F$ charmed mesons in the present work. By comparing the masses and decay properties of the $3^3P_2$ and $2^3F_2$ charmed mesons with the observation of the $D_2^\\ast(3000)$, we conclude that the most possible assignment of the $D_2^\\ast(3000)$ is the $3^3P_2$ charmed meson, while the assignment of the $2^3F_2$ charmed meson could not be fully exclude. The results of the unobserved $3P$ and $2F$ charmed mesons in this work could provide some fundamental information of searching for these charmed mesons in the further experiments by LHCb and forthcoming Belle II.

  17. Can Full Duplex reduce the discovery time in D2D Communication?

    DEFF Research Database (Denmark)

    Gatnau, Marta; Berardinelli, Gilberto; Mahmood, Nurul Huda;

    2016-01-01

    Device-to-device (D2D) communication is considered as one of the key technologies to support new types of services, such as public safety and proximity-based applications. D2D communication requires a discovery phase, i.e., the node awareness procedure prior to the communication phase. Conventional...... half duplex transmission may not be sufficient to provide fast discovery and cope with the strict latency targets of future 5G services. On the other hand, in-band full duplex, by allowing simultaneous transmission and reception, may complete the discovery phase faster. In this paper, the potential of...... full duplex in providing fast discovery for the next 5th generation (5G) system supporting D2D communication is investigated. A design for such system is presented and evaluated via simulations, showing that full duplex can accelerate the discovery phase by supporting a higher transmission probability...

  18. Charge-induced effects in the spectra of mixtures of solid H2, D2, HD

    International Nuclear Information System (INIS)

    Proton-beam irradiation of mixtures of solid hydrogens, specifically H2 in D2 and H2 in HD, were studied using infrared absorption spectroscopy. Mixture ratios from 5-50% H2 in D2 near 4.2 K represent the ratios of most interest. This study allows direct comparison of the Stark-shifted lines (caused by negative charges, Q1- of H2 and D2 in the same sample. These lines occur in different spectral regions but were thought to have a common cause. Analysis of spectral intensities, as well as timing behaviour as the proton beam is turned off, indicates that the mechanisms giving rise to charge-induced effects are somewhat more complicated than previously thought. (author)

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

    Science.gov (United States)

    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.

  20. The D2G2 project: a new software tool for nuclear engineering design in Canada

    Energy Technology Data Exchange (ETDEWEB)

    Rheaume, P.; Lefebvre, J.F.; Roy, R.; Koclas, J. [Ecole Polytechnique de Montreal, Nuclear Engineering Inst., Montreal, Quebec (Canada)]. E-mail: pascal.rheaume@polymtl.ca; jean-francois.lefebvre@polymtl.ca

    2004-07-01

    Nowadays, high quality neutronic simulation codes are readily available. The open source software suite DRAGON/DONJON is a good example. It is free, it has proven quality and correctness over the years and is still developed and maintained at Ecole Polytechnique de Montreal. However, most simulation codes have the following weaknesses: limited usability, poor maintainability, no internal data standardization and poor portability. The D2G2 project is a software development initiative which aims to create an upper layer software tool that annihilates the weakness of classic simulation codes. This paper presents D2G2Client's and D2G2Server's principal capabilities, how they interact and the libraries they use. (author)

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

    Science.gov (United States)

    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

  2. Novel cases of D-2-hydroxyglutaric aciduria with IDH1 or IDH2 mosaic mutations identified by amplicon deep sequencing

    DEFF Research Database (Denmark)

    Nota, Benjamin; Hamilton, Eline M; Sie, Daoud; Ozturk, Senay; van Dooren, Silvy J M; Ojeda, Matilde R Fernandez; Jakobs, Cornelis; Christensen, Ernst; Kirk, Edwin P; Sykut-Cegielska, Jolanta; Lund, Allan M; van der Knaap, Marjo S; Salomons, Gajja S

    2013-01-01

    Mosaic IDH1 mutations are described as the cause of metaphyseal chondromatosis with increased urinary excretion of D-2-hydroxyglutarate (MC-HGA), and mutations in IDH2 as the cause of D-2-hydroxyglutaric aciduria (D-2HGA) type II. Mosaicism for IDH2 mutations has not previously been reported as a...

  3. Examining the role of dopamine D2 and D3 receptors in Pavlovian conditioned approach behaviors.

    Science.gov (United States)

    Fraser, Kurt M; Haight, Joshua L; Gardner, Eliot L; Flagel, Shelly B

    2016-05-15

    Elucidating the neurobiological mechanisms underlying individual differences in the extent to which reward cues acquire the ability to act as incentive stimuli may contribute to the development of successful treatments for addiction and related disorders. We used the sign-tracker/goal-tracker animal model to examine the role of dopamine D2 and D3 receptors in the propensity to attribute incentive salience to reward cues. Following Pavlovian training, wherein a discrete lever-cue was paired with food reward, rats were classified as sign- or goal-trackers based on the resultant conditioned response. We examined the effects of D2/D3 agonists, 7-OH-DPAT (0.01-0.32mg/kg) or pramipexole (0.032-0.32mg/kg), the D2/D3 antagonist raclopride (0.1mg/kg), and the selective D3 antagonist, SB-277011A (6 or 24mg/kg), on the expression of sign- and goal-tracking conditioned responses. The lever-cue acquired predictive value and elicited a conditioned response for sign- and goal-trackers, but only for sign-trackers did it also acquire incentive value. Following administration of either 7-OH-DPAT, pramipexole, or raclopride, the performance of the previously acquired conditioned response was attenuated for both sign- and goal-trackers. For sign-trackers, the D2/D3 agonist, 7-OH-DPAT, also attenuated the conditioned reinforcing properties of the lever-cue. The selective D3 antagonist did not affect either conditioned response. Alterations in D2/D3 receptor signaling, but not D3 signaling alone, transiently attenuate a previously acquired Pavlovian conditioned response, regardless of whether the response is a result of incentive motivational processes. These findings suggest activity at the dopamine D2 receptor is critical for a reward cue to maintain either its incentive or predictive qualities. PMID:26909847

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

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, R.M.; Mason, N.S.; Ansari, M.S. [Vanderbilt Univ., Nashville, TN (United States)] [and others

    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.

  5. Dopamine inhibits reproduction in female zebrafish (Danio rerio) via three pituitary D2 receptor subtypes.

    Science.gov (United States)

    Fontaine, Romain; Affaticati, Pierre; Yamamoto, Kei; Jolly, Cécile; Bureau, Charlotte; Baloche, Sylvie; Gonnet, Françoise; Vernier, Philippe; Dufour, Sylvie; Pasqualini, Catherine

    2013-02-01

    In many teleosts, the stimulatory control of gonadotrope axis by GnRH is opposed by an inhibitory control by dopamine (DA). The functional importance of this inhibitory pathway differs widely from one teleostean species to another. The zebrafish (Danio rerio) is a teleost fish that has become increasingly popular as an experimental vertebrate model. However, the role of DA in the neuroendocrine control of its reproduction has never been studied. Here the authors evaluated in sexually regressed female zebrafish the effects of in vivo treatments with a DA D2 receptor (D2-R) antagonist domperidone, or a GnRH agonist, alone and in combination, on the pituitary level of FSHβ and LHβ transcripts, the gonadosomatic index, and the ovarian histology. Only the double treatment with GnRH agonist and domperidone could induce an increase in the expression of LHβ, in the gonadosomatic index, and a stimulation of ovarian vitellogenesis, indicating that removal of dopaminergic inhibition is required for the stimulatory action of GnRH and reactivation of ovarian function to occur. Using double immunofluorescent staining on pituitary, the authors showed in this species the innervation of LH cells by tyrosine-hydroxylase immunoreactive fibers. Finally, using in situ hybridization and immunofluorescence, the authors showed that the three subtypes of zebrafish DA D2-R (D2a, D2b, and D2c) were expressed in LH-producing cells, suggesting that they all may be involved in mediating this inhibition. These results show for the first time that, in zebrafish, DA has a direct and potent inhibitory action capable of opposing the stimulatory effect of GnRH in the neuroendocrine control of reproduction. PMID:23295741

  6. SPECT imaging of D2 dopamine receptors and endogenous dopamine release in mice

    International Nuclear Information System (INIS)

    The dopamine D2 receptor (D2R) is important in the mediation of addiction. [123I]iodobenzamide (IBZM), a SPECT ligand for the D2R, has been used for in vivo studies of D2R availability in humans, monkeys, and rats. Although mouse models are important in the study of addiction, [123I]IBZM has not been used in mice SPECT studies. This study evaluates the use of [123I]IBZM for measuring D2R availability in mice. Pharmacokinetics of [123I]IBZM in mice were studied with pinhole SPECT imaging after intravenous (i.v.) injection of [123I]IBZM (20, 40, and 70 MBq). In addition, the ability to measure the release of endogenous dopamine after amphetamine administration with [123I]IBZM SPECT was investigated. Thirdly, i.v. administration, the standard route of administration, and intraperitoneal (i.p.) administration of [123I]IBZM were compared. Specific binding of [123I]IBZM within the mouse striatum could be clearly visualized with SPECT. Peak specific striatal binding ratios were reached around 90 min post-injection. After amphetamine administration, the specific binding ratios of [123I]IBZM decreased significantly (-27.2%; n=6; p=0.046). Intravenous administration of [123I]IBZM led to significantly higher specific binding than i.p. administration of the same dose. However, we found that i.v. administration of a dose of 70 MBq [123I]IBZM might result in acute ethanol intoxication because ethanol is used as a preparative aid for the routine production of [123I]IBZM. Imaging of D2R availability and endogenous dopamine release in mice is feasible using [123I]IBZM single pinhole SPECT. Using commercially produced [123I]IBZM, a dose of 40 MBq injected i.v. can be recommended. (orig.)

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

    Directory of Open Access Journals (Sweden)

    David C. Nieman

    2013-12-01

    Full Text Available 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(OHD2 456% and decreased 25(OHD3 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(OHD2 and decreased 25(OHD3, had no effect on muscle function tests, and amplified muscle damage markers in NASCAR pit crew athletes following eccentric exercise.

  8. A new esterase EstD2 isolated from plant rhizosphere soil metagenome.

    Science.gov (United States)

    Lee, Myung Hwan; Hong, Kyung Sik; Malhotra, Shweta; Park, Ji-Hye; Hwang, Eul Chul; Choi, Hong Kyu; Kim, Young Sup; Tao, Weixin; Lee, Seon-Woo

    2010-11-01

    Soil metagenome constitutes a reservoir for discovering novel enzymes from the unculturable microbial diversity. From three plant rhizosphere metagenomic libraries comprising a total of 142,900 members of recombinant plasmids, we obtained 14 recombinant fosmids that exhibited lipolytic activity. A selected recombinant plasmid, pFLP-2, which showed maximum lipolytic activity, was further analyzed. DNA sequence analysis of the subclone in pUC119, pELP-2, revealed an open reading frame of 1,191 bp encoding a 397-amino-acid protein. Purified EstD2 exhibited maximum enzymatic activity towards p-nitrophenyl butyrate, indicating that it is an esterase. Purified EstD2 showed optimal activity at 35 °C and at pH 8.0. The K(m) and K(cat) values were determined to be 79.4 μM and 120.5/s, respectively. The esterase exhibited an increase in enzymatic activity in the presence of 15% butanol and 15% methanol. Phylogenetic analysis revealed that the lipolytic protein EstD2 may be a member of a novel family of lipolytic enzymes. Several hypothetical protein homologs of EstD2 were found in the database. A hypothetical protein from Phenylobacterium zucineum HLK1, a close homolog of EstD2, displayed lipolytic activity when the corresponding gene was expressed in Escherichia coli. Our results suggest that the other hypothetical protein homologs of EstD2 might also be members of this novel family. PMID:20683720

  9. EVALUATION OF N-RATIO IN SELECTING PATIENTS FOR ADJUVANT CHEMORADIOTHERAPY AFTER D2-GASTRECTOMY

    Directory of Open Access Journals (Sweden)

    Wilson Luiz da COSTA JUNIOR

    2013-12-01

    Full Text Available Context Whether adjuvant chemoradiotherapy may contribute to improve survival outcomes after D2-gastrectomy remains controvertial. Objective To explore the clinical utility of N-Ratio in selecting gastric cancer patients for adjuvant chemoradiotherapy after D2-gastrectomy. Methods A retrospective cohort study was carried out on gastric cancer patients who underwent D2-gastrectomy alone or D2-gastrectomy plus adjuvant chemoradiotherapy (INT-0116 protocol at the Hospital A. C. Camargo from September 1998 to December 2008. Statistical analysis were performed using multiple conventional methods, such as c-statistic, adjusted Cox's regression and stratified survival analysis. Results Our analysis involved 128 patients. According to c-statistic, the N-Ratio (i.e., as a continuous variable presented “area under ROC curve” (AUC of 0.713, while the number of metastatic nodes presented AUC of 0.705. After categorization, the cut-offs provide by Marchet et al. displayed the highest discriminating power – AUC value of 0.702. This N-Ratio categorization was confirmed as an independent predictor of survival using multivariate analyses. There also was a trend of better survival by adding of adjuvant chemoradiotherapy only for patients with milder degrees of lymphatic spread – 5-year survival of 23.1% vs 66.9%, respectively (HR = 0.426, 95% CI 0.150–1.202; P = 0.092. Conclusions This study confirms the N-Ratio as a tool to improve the lymph node metastasis staging in gastric cancer and suggests the cut-offs provided by Marchet et al. as the best way for its categorization after a D2-gastrectomy. In these settings, the N-Ratio appears a useful tool to select patients for adjuvant chemoradiotherapy, and the benefit of adding this type of adjuvancy to D2-gastrectomy is suggested to be limited to patients with milder degrees of lymphatic spread (i.e., NR2, 10%–25%.

  10. R2d2 Drives Selfish Sweeps in the House Mouse.

    Science.gov (United States)

    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. Effects of D2O on biochemical parameters of normal cells and tumour cells

    International Nuclear Information System (INIS)

    The influence of high temperatures (Hyperthermia) on normal tissue and Ehrlich-Ascites tumour cells ('ATZ') was examined under several conditions with regard to the application of deuterium oxide as a stabilising factor. It was proven that the DNA-synthesis of normal tissue (liver, mouse) is not sensitive to temperature. This effect of hyperthermia only occurs when the tissue is damaged, e.g. by trypsinising. The influence of hyperthermia on several biochemical parameters and on morphological changes of the Ascites cells was examined. The findings show that deuterium oxide (D2O) is able to reduce both the thermal and the ureal denaturation of enzymes. Thus tests were carried out to find out if D2O also reduces toxic influence in complicated biological systems. The assumption of high D2O concentrations to prevent several reactions was confirmed. When the Ascites tumour cells in the H2O-buffer were exposed to the damaging influence of hyperthermia, the high degree of damage was seen with the decreasing DNA synthesis, reduced aerobic glycose capacity, a drop in the ATP values and breakdown of the permeability of the membrane. Deuterium oxide was able under high temperature (from appr. 440C on) to reduce the degree of damage to DNA synthesis, while auto-effects (inhibition of synthesis) of D2O predominate in the lower region. Aerobic glycolysis was damaged in both cases to the same degree, however. In D2O after hyperthermia the ATP-level dropped faster than in H2O. D2O not only reduces the thermal denaturation of the Ascites tumour cells, but it also eliminates the toxic influence of the zytostaticum TRENIMONsup(R) (under 380 or 460C incubation). (orig./AJ)

  12. Pion transfer from hydrogen to deuterium in H2+D2 gas mixtures

    International Nuclear Information System (INIS)

    The transfer of negative pions from pionic hydrogen to deuterium has been investigated in gas mixtures of H2 and D2 as a function of the D2 concentration. The concentration dependence of the transfer rate was fitted using a phenomenological model with two parameters. For C → ∞ (32±3)% of the pions undergo transfer. The fitted parameters reflect the ratio of pion capture to pion transfer in collisions of pionic hydrogen with protons or deuterons. No pressure dependence for pion transfer was found. (Author) 33 refs., 3 tabs., 7 figs

  13. Dependence of metal partition coefficients in D2EHPA capacity on extraction from acid solutions

    International Nuclear Information System (INIS)

    In devising solvent-extraction schemes for extracting the transplutonium elements (TPE), one usually employs the partition coefficients K/sub p/ for trace amounts; when the results are transferred to weighable amounts of the elements, there are difficulties because one lacks capacity characteristics for the extractants under the conditions used. They have determined the capacity of D2EHPA over a wide range in acidity (0.001-2 mole/liter) in relation to dysprosium (the analog of californium) in the system formed by D2EHPA with nitric acid by saturating a set volume of the extractant with dysprosium in nitric acid containing the necessary amount of free acid

  14. Surface reactions of metal clusters. II. Reactivity surveys with D2, N2, and CO

    OpenAIRE

    Morse, M. D.; Gausic, M. E.; Heath, J. R.; Smalley, R. E.

    1985-01-01

    Reactions on the surface of a variety of transition metal clusters have been studied in the gas phase at near room temperature using a newly developed fast-flow reaction device. Initial examples of the use of this device are provided by survey studies of the reactivity of iron, cobalt, nickel, copper, and niobium clusters in contact with low concentrations of D2, N2 and CO. Dissociative chemisorption of D2 is found to occur with dramatic sensitivity to cluster size in the cases of iron, cobal...

  15. 123I-epidepride: an imaging agent for dopamine D2 receptor

    International Nuclear Information System (INIS)

    123I-epidepride, 123I-(s)-N-[(l-ethyl-2-pyrrolidinyl) methyl]-5-iodo-2,3-dimethoxybenzamide, is a potent imaging agent for SPECT of dopamine D2 receptor. With high affinity (Kd = 24 pmol/L) and relatively low lipophilicity (lg Kw = 2.05), it is suitable for imaging in striated and extra-striated. In addition, it has high value in imaging of dopamine D2 receptors in pituitary adenoma, and it can serve as a predictor for response to dopamine agonist treatment

  16. Temporal cortex dopamine D2/3 receptor binding in major depression.

    Science.gov (United States)

    Lehto, Soili M; Kuikka, Jyrki; Tolmunen, Tommi; Hintikka, Jukka; Viinamäki, Heimo; Vanninen, Ritva; Haatainen, Kaisa; Koivumaa-Honkanen, Heli; Honkalampi, Kirsi; Tiihonen, Jari

    2008-06-01

    The aim of this study was to assess the dopamine function of the temporal cortex in major depressive disorder using [(123)I]epidepride to image D(2/3) receptor binding sites. Ten major depressives and 10 healthy controls were selected from a general population sample for single-photon emission computed tomography imaging. Among the major depressives there was a strong bilateral correlation between the scores on the 21-item Hamilton Depression Rating Scale and D(2/3) receptor binding. Dopaminergic abnormalities may be present in the temporal cortices of major depressives. PMID:18588596

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

    OpenAIRE

    Yoon, Ye Ran; Baik, Ja-Hyun

    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 leve...

  18. D2 gas-filled blisters on deuterium-bombarded tungsten

    International Nuclear Information System (INIS)

    Most of spherical blisters formed by deuterium (D) bombardment (38 eV/D) up to 3 x 1024 D/m2 at 300 K on polycrystalline tungsten are fully elastic deformations. This has been proven by opening individual blisters with a focused ion beam and in situ observation of their complete relaxation by scanning electron microscopy. The D2 gas filling is confirmed by observing simultaneously the D2 puff. The gas pressure is causal for the stability of such spherical blisters after implantation and the gas release leads to sudden relaxation. The dilatation of the blister cap by trapped D can be excluded as cause for the blisters.

  19. Corrosion Behavior of TiN Coated AISI D2 Steel

    OpenAIRE

    ÇEĞİL, Özkan; Şen, Şaduman

    2014-01-01

    In this study, the corrosion behaviors of nitride and titanium nitride (TiN) layers deposited on AISI D2 steel samples are reported. Steel was at first nitrided in a nitrogen and ammonia atmosphere at 575 °C for 8 h and then titanium nitride coating treatment was performed in the powder mixture consisting of ferro-titanium, ammonium chloride and alumina at 1000°C for 2h by pack diffusion coating. TiN coating layer thickness realized on the AISI D2 steel is 6,71 ± 0,9 μm. The hardness of TiN l...

  20. Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

    Directory of Open Access Journals (Sweden)

    John Li

    2013-12-01

    Full Text Available The total synthesis of the endogenous inflammation resolving eicosanoid resolvin D2 (1 is described. The key steps involved a Wittig reaction between aldehyde 5 and the ylide derived from phosphonium salt 6 to give enyne 17 and condensation of the same ylide with aldehyde 7 to afford enyne 11. Desilylation of 11 followed by hydrozirconation and iodination gave the vinyl iodide 4 and Sonogashira coupling between this compound and enyne 3 provided alkyne 18. Acetonide deprotection, partial reduction and ester hydrolysis then gave resolvin D2 (1.

  1. Genetic contributions to avoidance-based decisions: striatal D2 receptor polymorphisms.

    Science.gov (United States)

    Frank, M J; Hutchison, K

    2009-11-24

    Individuals differ in their tendencies to seek positive decision outcomes or to avoid negative ones. At the neurobiological level, our model suggests that phasic changes in dopamine support learning to reinforce good decisions via striatal D1 receptors, and to avoid maladaptive choices via striatal D2 receptors. Accordingly, in a previous study individual differences in positive and negative learning were strongly modulated by two genetic polymorphisms factors related to striatal D1 and D2 function, respectively. Nevertheless, whereas the role for dopamine in positive learning is relatively well accepted, that in learning to avoid negative outcomes is more controversial. Here we further explore D2-receptor-related genetic contributions to probabilistic avoidance in humans, in light of recent data showing that particular DRD2 polymorphisms are associated with functional modulation of receptor expression [Zhang Y, Bertolino A, Fazio L, Blasi G, Rampino A, Romano R, Lee M-LT, Xiao T, Papp A, Wang D, Sadée W (2007) Polymorphisms in human dopamine d2 receptor gene affect gene expression, splicing, and neuronal activity during working memory. Proc Natl Acad Sci U S A 104(51):20552-20557]. We find that a promoter polymorphism rs12364283 associated with transcription and D2 receptor density was strongly and selectively predictive of avoidance-based decisions. Two further polymorphisms (rs2283265 and rs1076560) associated with relatively reduced presynaptic relative to postsynaptic D2 receptor expression were predictive of relative impairments in negative compared to positive decisions. These previously undocumented effects of DRD2 polymorphisms were largely independent of those we reported previously for the C957T polymorphism (rs6277) associated with striatal D2 density. In contrast, effects of the commonly studied Taq1A polymorphism on reinforcement-based decisions were due to indirect association with C957T. Taken together these findings suggest multiple D2-dependent

  2. Tracking the photodissociation probability of D$_2^+$ induced by linearly chirped laser pulses

    CERN Document Server

    Csehi, András; Cederbaum, Lorenz S; Vibók, Ágnes

    2016-01-01

    In the presence of linearly varying frequency chirped laser pulses the photodissociation dynamics of D$_2^+$ is studied theoretically after ionization of D$_{2}$ . As a completion of our recent work (J. Chem. Phys. 143, 014305 (2015)) a comprehensive dependence on the pulse duration and delay time is presented in terms of total dissociation probabilities. Our numerical analysis carried out in the recently introduced light-induced conical intersection (LICI) framework clearly shows the effects of the changing position of the LICI which is induced by the frequency modulation of the chirped laser pulses. This impact is presented for positively, negatively and zero chirped short pulses.

  3. Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI

    DEFF Research Database (Denmark)

    Sander, Christin Y; Hooker, Jacob M; Catana, Ciprian;

    2013-01-01

    This study employed simultaneous neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to demonstrate the relationship between changes in receptor occupancy measured by PET and changes in brain activity inferred by fMRI. By administering the D2/D3...... responses and receptor occupancies. The distinct CBV magnitudes between putamen and caudate at matched occupancies approximately matched literature differences in basal dopamine levels, suggesting that the relative fMRI measurements reflect basal D2/D3 dopamine receptor occupancy. These results can provide...

  4. Effects of Lactobacillus acidophilus D2/CSL on laying hen performance

    OpenAIRE

    Luigi Guidobono Cavalchini; Carla Orsi; Viviana Ferrazzi; Stefano Marelli; Maria Grazia Mangiagalli; Alberto Giardini; Daniele Gallazzi

    2010-01-01

    In order to evaluate the effects of dietary addition of probiotic strain Lactobacillus acidophilus D2/CSL on hen performance and egg quality, 160 commercial Hy-Line Brown pullets, 17 weeks old, were divided in control group (C) (N=80) and treated group (T) (N=80), with 4 alternate replicates of 20 animals each per group. C was fed with a “standard diet”, whereas the T group received the same diet with an inclusion of 1x109 CFU kg-1 of Lactobacillus acidophilus D2/CSL (freeze dried...

  5. Neurotensin Triggers Dopamine D2 Receptor Desensitization through a Protein Kinase C and β-Arrestin1-dependent Mechanism*

    OpenAIRE

    Thibault, Dominic; Albert, Paul R.; Pineyro, Graciela; Trudeau, Louis-Éric

    2011-01-01

    The peptide neurotensin (NT) is known to exert a potent excitatory effect on the dopaminergic system by inhibiting D2 dopamine (DA) receptor (D2R) function. This regulation is dependent on activation of PKC, a well known effector of the type 1 NT receptor (NTR1). Because PKC phosphorylation of the D2R has recently been shown to induce its internalization, we hypothesized that NT acts to reduce D2R function through heterologous desensitization of the D2R. In the present study, we first used HE...

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

    Science.gov (United States)

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

    2016-06-01

    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

  7. 17 CFR 270.27d-2 - Insurance company undertaking in lieu of segregated trust account.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Insurance company undertaking....27d-2 Insurance company undertaking in lieu of segregated trust account. (a) Any depositor of or... company (as defined in section 2(a)(17) of the Act) undertakes in writing to guarantee the performance...

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

    Science.gov (United States)

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

  9. Determination of high-energy radiation doses with Agfa-Gevaert Structurix D2p films

    International Nuclear Information System (INIS)

    A linear dependence of the optical density of Agfa-Gevaert Structurix D2p films on the dose and energy of radiation obtained in electron linacs in the range between 0,1 and 1 Gy is studied. The accuracy of the photometric method is estimated and the conditions of the photochemical processing are described. 4 figs., 1 tab., 2 refs. (author)

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

    Science.gov (United States)

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

    2016-01-01

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

  11. Extraction of La and Nd Concentrate Product of Monazite Sand Treatment byD2EHPA

    International Nuclear Information System (INIS)

    Extraction of La and Nd concentrate product of monazite sand treatment byD2EHPA have done. The mayor element contained in monazite sand were Ce, Laand Nd. After separation of Ce, was obtained La and Nd concentrate. Theextraction process using D2EHPA to separate La and Nd. The extraction feed oraqueous phase was La and Nd concentrate in HNO3. The parameter influencewere time and rate of agitation, acidity of feed and concentration of D2EHPAin kerosene. The best yield was obtained at extraction of 10 ml of feed inHNO3 0.2M, was extracted by 10 ml of D2EHPA in kerosene along 10 minuteswith the rate of agitation was 400 rpm. At this condition was obtaineddistribution coefficient (Kd) of La =10.34, Kd Ce =0.58, Kd Nd = 0.24 andseparation factor of (FS) La-Ce 27.21, FS of La-Nd = 43.08 and FS of Ce-Nd2.42. (author)

  12. Intensity dependence of the attosecond control of the dissociative ionization of D2

    International Nuclear Information System (INIS)

    Light-field driven electron localization in deuterium molecules in intense near single-cycle laser fields is studied as a function of the laser intensity. The emission of D+ ions from the dissociative ionization of D2 is interrogated with single-shot carrier–envelope phase (CEP)-tagged velocity map imaging. We explore the reaction for an intensity range of (1.0–2.8) × 1014 W cm−2, where laser-driven electron recollision leads to the population of excited states of D2+. Within this range we find the onset of dissociation from 3σ states of D2+ by comparing the experimental data to quantum dynamical simulations including the first eight states of D2+. We find that dissociation from the 3σ states yields D+ ions with kinetic energies above 8 eV. Electron localization in the dissociating molecule is identified through an asymmetry in the emission of D+ ions with respect to the laser polarization axis. The observed CEP-dependent asymmetry indicates two mechanisms for the population of 3σ states: (1) excitation by electron recollision to the lower excited states, followed by laser-field excitation to the 3σ states, dominating at low intensities, and (2) direct excitation to the 3σ states by electron recollision, playing a role at higher intensities. (paper)

  13. Three-dimensional wave packet dynamics of H2 + D2 reaction

    International Nuclear Information System (INIS)

    Research highlights: → Three-dimensional wave packet dynamics of H2(v1 = high) + D2(v2 = low) reaction. → Competitive processes were studied on the BMKP and ASP potential energy surfaces. → Orientation of the cold diatom did not greatly affect the reaction processes. → Orientation of the hot diatom had a significant effect on the reaction processes. → Reaction probabilities for H2 + D2 reaction were compared with H2 + H2 reaction. - Abstract: Initial state selected time-dependent wave packet calculations were carried out for the H2(v1 = high) + D2(v2 = low) reaction within a three degrees of freedom model. The probabilities for different competitive processes were studied on two realistic global potential energy surfaces (PESs) - BMKP and ASP. The orientation of the cold diatom did not greatly affect the reaction processes, while the orientation of the hot diatom had a significant effect. The BMKP surface generally gave lower energy thresholds than the ASP surface, except for the collision induced dissociation (CID) within the TII geometry where the hot diatom comes in head-on perpendicular to the cold diatom. Isotopic substitution effects were studied on the recent BMKP PES. The H2 + D2 reaction was more effective for CID and showed more structured probability curves for single exchange reaction (SE) and three-body complex formation (3BC) than the H2 + H2 reaction.

  14. 17 CFR 240.12d2-1 - Suspension of trading.

    Science.gov (United States)

    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...

  15. Measurements of $d_{2}^{n}$ and $A_{1}^{n}$: Probing the neutron spin structure

    CERN Document Server

    Flay, D; Parno, D S; Allada, K; Armstrong, W; 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; Oh, Y; Peng, J C; Qian, X; Qiang, Y; Rakhman, A; Riordan, S; Saha, A; Sawatzky, B; Shabestari, M H; Shahinyan, A; Širca, S; Solvignon, P; Subedi, R; Sulkosky, V; Tobias, 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

    2016-01-01

    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 $d_2$ 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_...

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

    Directory of Open Access Journals (Sweden)

    Jihye Kim

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

  17. Structure and Properties of Burnished and Nitrided AISI D2 Tool Steel

    Directory of Open Access Journals (Sweden)

    Daniel TOBOŁA

    2015-11-01

    Full Text Available D2 belongs to traditional steels, frequently used in metalworking industry. Shot peening and nitriding are known to improve the wear resistance of D2. In this work we focus on processes of slide burnishing and industrial low temperature gas nitriding. The D2 steel specimens were first subjected to heat treatments (HT prescribed by the manufacturer, turning (T, then burnishing (B and nitriding (N. The reason for turning was achieving appropriate surface roughness. Deformation induced in slide burnishing can be better controlled then in shot peening because of deterministic nature of this process. Four different paths to prepare surfaces were employed: HT + T, HT + T + B, HT + T + N, HT + T + B + N. D2 steel is very sensitive to the final finishing, wear rates vary up to 300 %. Two of our procedures (HT + T + N and HT + T + B + N are much superior to the others. Moreover, in the HT + T + N case, apparently the surface fatigue scaling off takes place.DOI: http://dx.doi.org/10.5755/j01.ms.21.4.7224

  18. Vacuum squeezed light for atomic memories at the D2 cesium line

    CERN Document Server

    Burks, Sidney; Giacobino, Elisabeth; Laurat, Julien; Ortalo, Jérémie; Jia, Xiaojun; Villa, Fabrizio; Chuimmo, Antonino

    2008-01-01

    We report the experimental generation of squeezed light at 852 nm, locked on the Cesium D2 line. 50% of noise reduction down to 50 kHz has been obtained with a doubly resonant optical parametric oscillator operating below threshold, using a periodically-polled KTP crystal. This light is directly utilizable with Cesium atomic ensembles for quantum networking applications

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

    Science.gov (United States)

    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.

  20. High-pressure phase relations of CsD2PO4

    International Nuclear Information System (INIS)

    The high-pressure phase diagram of CsD2PO4 to 4.5 GPa and temperatures between 0 and 4700C is reported. Comparisons are made with CsH2PO4 and correlated with the isotope effect on the high-temperature high-pressure phase relations of KH2PO4

  1. Production of neutron and tritium from D2O electrolysis with palladium cathode

    International Nuclear Information System (INIS)

    Anomalous neutron burst and an increase in tritium concentration were observed simultaneously from heavy water electrolysis with palladium cathode. Considered with previous experiment results, we presumed that production of neutron and tritium from D2O electrolysis depends heavily on the constitution and the state of each cathode. (author)

  2. Fall and Rise of a D$_2$O Ice Cube in Liquid H$_2$O

    Indian Academy of Sciences (India)

    2016-05-01

    The demonstration described in this article is to show thatwhile H$_2$O ice floats in water, D$_2$O ice sinks in water, provingthe higher density of ‘heavy water’. This experiment can bedone in a classroom or in an auditoriam.

  3. D2O system and oil hydraulic system of fuelling machine

    International Nuclear Information System (INIS)

    Two of the most important supporting systems in CANDU fuel handling system--D2O supply and control system and oil hydraulic system are described, focusing on design requirements, major function, system structure and the main work flow of the two systems individually so as to briefly and concisely present the two typical CANDU systems

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

    Science.gov (United States)

    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. PMID:27196975

  5. Solvent extraction of copper and zinc from bioleaching solutions with LIX984 and D2EHPA

    Institute of Scientific and Technical Information of China (English)

    LAN Zhuo-yue; HU Yue-hua; LIU Jian-she; WANG Jun

    2005-01-01

    The solvent extraction of copper and zinc from the bioleaching solutions of low-grade sulfide ores with LIX984 and D2EHPA was investigated. The influences of extractant content, aqueous pH value, phase ratio and equilibration time on metals extraction were studied. The results show that LIX984 has a higher selectivity for copper than for iron, zinc and other metals, and has the copper extraction rate above 97%,while the zinc and iron extraction rate is less than 1.6% respectively. Zinc extraction is carried out following the copper extraction from the raffinate. The zinc extraction with di(2-ethylhexyl) phosphoric acid(D2EHPA) is low due to its poor cation exchange. A sodium salt of D2EHPA is used and the zinc extraction rate is enhanced to above 98%. Though iron (Ⅲ) is strongly extracted before the extraction of zinc by D2EHPA, it is difficult to strip iron from the organic phase by sulfuric acid. The zinc stripping rate is above 99% with 100 g/L sulfuric acid, while that of iron is 0.16%. Hence, the separation of zinc from iron can be achieved by the selective stripping.

  6. Utilizing Semantic Interpretation of Junctions for 3D-2D Pose Estimation

    DEFF Research Database (Denmark)

    Pilz, Florian; Yan, Shi; Grest, Daniel; Pugeault, Nicolas; Kalkan, Sinan; Krüger, Norbert

    In this paper we investigate the quality of 3D-2D pose estimates using hand labeled line and point correspondences. We select point correspondences from junctions in the image, allowing to construct a meaningful interpretation about how the junction is formed, as proposed in e.g. [1], [2], [3]. We...

  7. Production of the excited charm mesons D1 and D*2 at HERA

    International Nuclear Information System (INIS)

    The production of the excited charm mesons D1(2420) and D*2(2460) in ep collisions has been measured with the ZEUS detector at HERA using an integrated luminosity of 373 pb-1. The masses of the neutral and charged states, the widths of the neutral states, and the helicity parameter of D1(2420)0 were determined and compared with other measurements and with theoretical expectations. The measured helicity parameter of the D01 allows for some mixing of S- and D-waves in its decay to D*±π-+. The result is also consistent with a pure D-wave decay. Ratios of branching fractions of the two decay modes of the D*2(2460)0 and D*2(2460)± states were measured and compared with previous measurements. The fractions of charm quarks hadronising into D1 and D*2 were measured and are consistent with those obtained in e+e- annihilations.

  8. Improper activation of D1 and D2 receptors leads to excess noise in prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Michael eAvery

    2015-03-01

    Full Text Available The dopaminergic system has been shown to control the amount of noise in the prefrontal cortex (PFC and likely plays an important role in working memory and the pathophysiology of schizophrenia. We developed a model that takes into account the known receptor distributions of D1 and D2 receptors, the changes these receptors have on neuron response properties, as well as identified circuitry involved in working memory. Our model suggests that D1 receptor under-stimulation in supragranular layers gates internal noise into the PFC leading to cognitive symptoms as has been proposed in attention disorders, while D2 over-stimulation gates noise into the PFC by over-activation of cortico-striatal projecting neurons in infragranular layers. We apply this model in the context of a memory-guided saccade paradigm and show deficits similar to those observed in schizophrenic patients. We also show set-shifting impairments similar to those observed in rodents with D1 and D2 receptor manipulations. We discuss how the introduction of noise through changes in D1 and D2 receptor activation may account for many of the symptoms of schizophrenia depending on where this dysfunction occurs in the PFC.

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

    International Nuclear Information System (INIS)

    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 [3H]DA, modulation of [3H]-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 [3H]spiperone binding assays. 31 references, 2 figures, 1 table

  10. On Secondary Electron Emission from Solid H2 and D2

    DEFF Research Database (Denmark)

    Schou, Jørgen; Sørensen, H.

    The emission of secondary electrons from solid hydrogen (H2 , D2, T2) is often considered to be of importance for the interaction between a fusion plasma and pellets of solid hydrogens. A set-up was therefore built for studies of interactions between energetic particles and solid hydrogens. Studi...

  11. On Secondary Electron Emission from Solid H2 and D2

    DEFF Research Database (Denmark)

    Schou, Jørgen; Sørensen, H.

    1978-01-01

    solid H2 is always 0.65-0.70 times that for solid D2. This difference is attributed to different losses to vibrational states in H2 and D2 for the low energy electrons. Measurements were also made on solid para-H2 with both electrons and hydrogen ions. There was no difference from the results for normal......The emission of secondary electrons from solid hydrogen (H2 , D2, T2) is often considered to be of importance for the interaction between a fusion plasma and pellets of solid hydrogens. A set-up was therefore built for studies of interactions between energetic particles and solid hydrogens. Studies...... of secondary electron emission (SEE) from solid H2 and D2 were made for incidence of electrons up to 3 keV and for incidence of ions of hydrogen, deuterium, and helium up to 10 keV. The measurements were made for normal incidence, and in some cases also for oblique incidence. The SEE coefficients for...

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

    DEFF Research Database (Denmark)

    Urbain, Paul; Jakobsen, Jette

    2015-01-01

    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 mushrooms and comparable to levels found...

  13. Neutron scattering from NiCl2/D2O - hard-sphere approach

    International Nuclear Information System (INIS)

    The main feature of the nickel-nickel partial structure factor derived from neutron scattering data for a solution of NiCl2 in D2O are discussed within the framework of a model in which both ions are strongly hydrated and in which the interaction between the hydrated ions is represented by a hard-sphere potential. (author)

  14. Intensity dependence of the attosecond control of the dissociative ionization of D2

    Science.gov (United States)

    Li, H.; Alnaser, A. S.; Tong, X. M.; Betsch, K. J.; Kübel, M.; Pischke, T.; Förg, B.; Schötz, J.; Süßmann, F.; Zherebtsov, S.; Bergues, B.; Kessel, A.; Trushin, S. A.; Azzeer, A. M.; Kling, M. F.

    2014-06-01

    Light-field driven electron localization in deuterium molecules in intense near single-cycle laser fields is studied as a function of the laser intensity. The emission of D+ ions from the dissociative ionization of D2 is interrogated with single-shot carrier-envelope phase (CEP)-tagged velocity map imaging. We explore the reaction for an intensity range of (1.0-2.8) × 1014 W cm-2, where laser-driven electron recollision leads to the population of excited states of D2+. Within this range we find the onset of dissociation from 3σ states of D2+ by comparing the experimental data to quantum dynamical simulations including the first eight states of D2+. We find that dissociation from the 3σ states yields D+ ions with kinetic energies above 8 eV. Electron localization in the dissociating molecule is identified through an asymmetry in the emission of D+ ions with respect to the laser polarization axis. The observed CEP-dependent asymmetry indicates two mechanisms for the population of 3σ states: (1) excitation by electron recollision to the lower excited states, followed by laser-field excitation to the 3σ states, dominating at low intensities, and (2) direct excitation to the 3σ states by electron recollision, playing a role at higher intensities.

  15. Dopamine D2-receptors in human narcolepsy. A SPECT study with 123I-IB

    International Nuclear Information System (INIS)

    Increased dopamine D2 receptor binding in basal ganglia has been reported in human narcolepsy. These studies have been based on post-mortem material of 8 patients, most of them also medicated for narcolepsy. We studied six narcoleptics without stimulant or anticataplectic medication. The patients had an unambiguous history of cataplexy, and they were also studied polygraphically. Single photon emission computed tomography (SPECT) imaging was performed. The D2 receptor density wad determined by using 123I-iodobenzamide (IBZM). The control subjects were 8 unmedicated Parkinson patients with one-sided (hemiparkinsonian) clinical symptoms. The D2 receptor density in them is known to be normal or somewhat increased compared to healthy normals. The striatum/frontal D2 activity ratio was 1.331 ± 0.084 (with phantom study correction 2.101 ± 0.300) in the narcoleptic patients, and in the parkinsonian controls 1.321 ± 0.052 (2.067 ± 0.185) for the asymptomatic side and 1.335 ± 0.025 (2.117 ± 0.090) for the symptomatic side (i.e. contralateral to the side with the clinical extrapyramidal signs). There was no statistical difference between the groups or between the symptomatic and asymptomatic side in the Parkinson patients. Thus, our results differ from the earlier post-mortem studies. (au) (28 refs.)

  16. Coordinated Precoding for D2D Communications Underlay Uplink MIMO Cellular Networks

    Directory of Open Access Journals (Sweden)

    Bing Fang

    2016-01-01

    Full Text Available We study the coordinated precoding problem for device-to-device (D2D communications underlay multiple-input multiple-output (MIMO cellular networks. The system model considered here constitutes multiple D2D user pairs attempting to share the uplink radio resources of a cellular network. We first formulate the coordinated precoding problem for the D2D user pairs as a sum-rate maximization (SRM problem, which is subject to a total interference power constraint imposed to protect the base station (BS and individual transmit power budgets available for each D2D user pair. Since the formulated SRM problem is nonconvex in general, we reformulate it as a difference convex- (DC- type programming problem, which can be iteratively solved by employing the famous successive convex approximation (SCA method. Moreover, a proximal-point-based regularization approach is also pursued here to ensure the convergence of the proposed algorithm. Interestingly, the centralized precoding algorithm can also lend itself to a distributed implementation. By introducing a price-based interference management mechanism, we reformulate the coordinated precoding problem as a Stackelberg game. Then, a distributed precoding algorithm is developed based on the concept of Stackelberg equilibrium (SE. Finally, numerical simulations are also provided to demonstrate the proposed algorithms. Results show that our algorithms can converge fast to a satisfactory solution with guaranteed convergence.

  17. Network-Assisted Device-to-Device (D2D) Direct Proximity Discovery with Underlay Communication

    DEFF Research Database (Denmark)

    Pratas, Nuno; Popovski, Petar

    2015-01-01

    announces its interest in establishing a D2D connection) or monitor (which listens for the transmissions from the announcers). Traditionally, the announcers transmit their messages over dedicated channel resources. In contrast, inspired by recent advances on receivers with multiuser decoding capabilities...

  18. Thermal behavior of TAXN and TCDXM D2 collimator mask, Finite element studies

    CERN Document Server

    Sklariks, Stepans

    2015-01-01

    The objective of this project was to perform thermal loading simulations of TCDXM (D2 collimator mask) and TAXN so as to allow the preliminary evaluation of the suitability of the given parts for the upcoming high luminosity upgrade that is to be performed in LHC in the nearest future.

  19. Bioanalysis and pharmacokinetics of the dopamine D2 agonist N-0923

    NARCIS (Netherlands)

    Swart, Pieter Jacob

    1992-01-01

    This thesis describes the bioanalysis and pharmacokinetics of the S(-) enantiomer (N-0923) of the selective and potent dopamine D2 agonist 2-(N-propyl-N-2-thienylethyl-amino)-5-hydroxytetralin, N-0437 which has possible applications in the treatment of Parkinson’s disease. The R(+) enantiomer (N-092

  20. Underlay of low-rate machine-type D2D links on downlink cellular links

    DEFF Research Database (Denmark)

    Pratas, Nuno K.; Popovski, Petar

    2014-01-01

    Wireless cellular networks feature two emerging technological trends: direct Device-to-Device (D2D) communications and Machine-Type Communications (MTC). MTC devices (MTDs) pose new challenges to the cellular network, such as low transmission power and massive access that can lead to overload of...... the radio interface. In this paper we explore the opportunity opened by D2D links for supporting Low-rate Low-power MTDs that are connected to a nearby device, such as an on-body MTD connected to a mobile phone that acts as a relay towards the Base Station (BS). The low-rate requirement for this D2D...... probability for the MTC link. The results show that SIC is an important enabler of low-power underlay D2D transmission for low-rate machine-type traffic; however, it may incur a significant rate penalty for the cellular users when trying to meet the outage requirements of the MTC link....

  1. Frontostriatal involvement in task switching depends on genetic differences in D2 receptor density

    NARCIS (Netherlands)

    Stelzel, C.; Basten, U.; Montag, C.; Reuter, M.; Fiebach, C.J.

    2010-01-01

    Recent studies suggest an association of dopamine D2 receptor (DRD2) availability with flexibility in reward-based learning. We extend these results by demonstrating an association of genetically based differences in DRD2 density with the ability to intentionally switch between nonrewarded tasks: no

  2. Voluminous D2 source for intense cold neutron beam production at the ESS

    DEFF Research Database (Denmark)

    Klinkby, Esben Bryndt; Batkov, K.; Mezei, F.;

    2014-01-01

    target for the complementary needs of certain fundamental physics experiments. To facilitate experiments depending on the total number of neutrons in a sizable beam, the option of a voluminous D2 moderator, in a large cross-section extraction guide is discussed and its neutronic performance is assessed....

  3. Reduced striatal dopamine D2/3 receptor availability in Body Dysmorphic Disorder.

    Science.gov (United States)

    Vulink, Nienke C; Planting, Robin S; Figee, Martijn; Booij, Jan; Denys, Damiaan

    2016-02-01

    Though the dopaminergic system is implicated in Obsessive Compulsive and Related Disorders (OCRD), the dopaminergic system has never been investigated in-vivo in Body Dysmorphic Disorder (BDD). In line with consistent findings of reduced striatal dopamine D2/3 receptor availability in Obsessive Compulsive Disorder (OCD), we hypothesized that the dopamine D2/3 receptor availability in the striatum will be lower in patients with BDD in comparison to healthy subjects. Striatal dopamine D2/3 receptor Binding Potential (BPND) was examined in 12 drug-free BDD patients and 12 control subjects pairwise matched by age, sex, and handedness using [(123)I]iodobenzamide Single Photon Emission Computed Tomography (SPECT; bolus/constant infusion technique). Regions of interest were the caudate nucleus and the putamen. BPND was calculated as the ratio of specific striatal to binding in the occipital cortex (representing nonspecific binding). Compared to controls, dopamine D2/3 receptor BPND was significantly lower in BDD, both in the putamen (p=0.017) and caudate nucleus (p=0.022). This study provides the first evidence of a disturbed dopaminergic system in BDD patients. Although previously BDD was classified as a separate disorder (somatoform disorder), our findings give pathophysiological support for the recent reclassification of BDD to the OCRD in DSM-5. PMID:26711686

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

    Science.gov (United States)

    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

  5. 维生素D2脂质体凝胶剂的体外透皮扩散%Diffusion of liposomal vitamin D2 gel dosage form through rat skin in vitro

    Institute of Scientific and Technical Information of China (English)

    齐宪荣; 王培玉; 唐干益; 米谷芳芝; 永井恒司

    2001-01-01

    目的:本文探讨了包封于脂质体中的维生素D2体外透皮扩散能力的变化。方法:将维生素D2包封于脂质体中,并进一步制备成羧甲基纤维素钠的凝胶剂,与未包封于脂质体中的维生素D2的羧甲基纤维素钠凝胶剂比较,进行了大鼠离体皮肤的扩散实验,比较不同类型的脂质体对维生素D2透皮的影响。结果:维生素D2在游离状态下,不易进入皮肤层。维生素D2脂质体可使维生素D2在皮肤层中滞留,而且多室脂质体凝胶剂比单室脂质体凝胶剂在皮肤层中维生素D2的滞留量多。结论:脂质体作为维生素D2皮肤局部给药的载体,能够提高对皮肤的穿透力。%OBJECTIVE To investigate the changes of liposomal vitamin D2 inpermeability through the rat skin in vitro. METHODS The rat skin diffusion of liposomal vitamin D2 in carboxymethylcellulose-sodium gel dosage form through was compared with non-liposomal vitamin D2 in the gel dosage form in vitro. RESULTS The permeability of non-liposomal vitamin D2 through the rat skin was poor.When vitamin D2 entrapped in liposomes, the permeability of vitamin D2 through skin increased and deposited in skin. The multilamellar vesicles detained a higher amount of vitamin D2 than the unilamillar vesicles in skin. The amount of vitamin D2 in the receiver cell did not increase significantly.CONCLUSIONS Liposomes can be used as a carrier of vitamin D2 in topical application that increase the permeability through the rat skin.

  6. Radioiodination of central nerves system dopamine D2 receptor imaging agent. IBZM preparation and preclinical study

    International Nuclear Information System (INIS)

    To study preparation of central nerves system dopamine D2 imaging agent 131I-IBZM and its preclinical investigation, peracetic acid was used as the oxidant for preparing radioiodinated 125I-IBZM and 131I-IBZM, D2 binding properties of IBZM were examined by in vitro binding saturation analysis, rat whole body and regional brain biodistribution, rat brain autoradiography and rabbit SPECT static imaging, etc. The results are: 1. The radiolabelling yields of 125I-IBZM and 131I-IBZM were 84.18% +- 3.06% and 78.50% +- 3.47%. The radiochemical purity were over 95% after being isolated by HPLC; and were over 90% after being isolated by organic extraction. 2. Scatchard plot of D2 receptor saturation binding analysis showed: Kd = 0.53 +- 0.06 nmol/L, Bmax = 466.45 +- 45.88 fmol/mg protein. 3. The rat brain autoradiography and analysis showed that there was high 125I-IBZM uptake in striatal area 2 hr after injection, the striatal/cerebellum ratio was 6.22 +- 0.48; the high 125-IBZM uptake can be blocked by haloperidol--a special dopamine D2 receptor antagonist. 4. 131I-IBZM rat biodistribution and rabbit SPECT planar imaging showed good initial brain uptake and retention, the initial uptake of rat brain was 1.893 +- 0.147% ID/g at 2 min and 1.044 +- 0.135% ID/g at 60 min. The results showed that the radioiodinated IBZM had high affinity, saturation and specificity to rat's and rabbit's central nerves system dopamine D2 receptors

  7. Multivariate cluster analysis of dynamic iodine-123 iodobenzamide SPET dopamine D2receptor images in schizophrenia

    International Nuclear Information System (INIS)

    This paper describes the application of a multivariate statistical technique to investigate striatal dopamine D2receptor concentrations measured by iodine-123 iodobenzamide (123I-IBZM) single-photon emission tomography (SPET). This technique enables the automatic segmentation of dynamic nuclear medicine images based on the underlying time-activity curves present in the data. Once the time-activity curves have been extracted, each pixel can be mapped back on to the underlying distribution, considerably reducing image noise. Cluster analysis has been verified using computer simulations and phantom studies. The technique has been applied to SPET images of dopamine D 2receptors in a total of 20 healthy and 20 schizophrenic volunteers (22 male, 18 female), using the ligand 123I-IBZM. Following automatic image segmentation, the concentration of striatal dopamine D 2receptors shows a significant left-sided asymmetry in male schizophrenics compared with male controls. The mean left-minus-right laterality index for controls is -1.52 (95% CI -3.72-0.66) and for patients 4.04 (95% CI 1.07-7.01). Analysis of variance shows a case-by-sex-by-side interaction, with F=10.01, P=0.005. We can now demonstrate that the previously observed male sex-specific D 2receptor asymmetry in schizophrenia, which had failed to attain statistical significance, is valid. Cluster analysis of dynamic nuclear medicine studies provides a powerful tool for automatic segmentation and noise reduction of the images, removing much of the subjectivity inherent in region-of-interest analysis. The observed striatal D 2asymmetry could reflect long hypothesized disruptions in dopamine-rich cortico-striatal-limbic circuits in schizophrenic males. (orig.). With 4 figs., 2 tabs

  8. Initial d2 dopamine receptor sensitivity predicts cocaine sensitivity and reward in rats.

    Directory of Open Access Journals (Sweden)

    Kathryn E Merritt

    Full Text Available 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.

  9. Homeostatic regulation of excitatory synapses on striatal medium spiny neurons expressing the D2 dopamine receptor.

    Science.gov (United States)

    Thibault, Dominic; Giguère, Nicolas; Loustalot, Fabien; Bourque, Marie-Josée; Ducrot, Charles; El Mestikawy, Salah; Trudeau, Louis-Éric

    2016-05-01

    Striatal medium spiny neurons (MSNs) are contacted by glutamatergic axon terminals originating from cortex, thalamus and other regions. The striatum is also innervated by dopaminergic (DAergic) terminals, some of which release glutamate as a co-transmitter. Despite evidence for functional DA release at birth in the striatum, the role of DA in the establishment of striatal circuitry is unclear. In light of recent work suggesting activity-dependent homeostatic regulation of glutamatergic terminals on MSNs expressing the D2 DA receptor (D2-MSNs), we used primary co-cultures to test the hypothesis that stimulation of DA and glutamate receptors regulates the homeostasis of glutamatergic synapses on MSNs. Co-culture of D2-MSNs with mesencephalic DA neurons or with cortical neurons produced an increase in spines and functional glutamate synapses expressing VGLUT2 or VGLUT1, respectively. The density of VGLUT2-positive terminals was reduced by the conditional knockout of this gene from DA neurons. In the presence of both mesencephalic and cortical neurons, the density of synapses reached the same total, compatible with the possibility of a homeostatic mechanism capping excitatory synaptic density. Blockade of D2 receptors increased the density of cortical and mesencephalic glutamatergic terminals, without changing MSN spine density or mEPSC frequency. Combined blockade of AMPA and NMDA glutamate receptors increased the density of cortical terminals and decreased that of mesencephalic VGLUT2-positive terminals, with no net change in total excitatory terminal density or in mEPSC frequency. These results suggest that DA and glutamate signaling regulate excitatory inputs to striatal D2-MSNs at both the pre- and postsynaptic level, under the influence of a homeostatic mechanism controlling functional output of the circuit. PMID:25782435

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-10-25

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

  12. Role of ventral pallidal D2 dopamine receptors in the consolidation of spatial memory.

    Science.gov (United States)

    Péczely, László; Ollmann, Tamás; László, Kristóf; Kovács, Anita; Gálosi, Rita; Kertes, Erika; Zagorácz, Olga; Kállai, Veronika; Karádi, Zoltán; Lénárd, László

    2016-10-15

    The role of dopamine (DA) receptors in spatial memory consolidation has been demonstrated in numerous brain regions, among others in the nucleus accumbens which innervates the ventral pallidum (VP). The VP contains both D1 and D2 DA receptors. We have recently shown that the VP D1 DA receptor activation facilitates consolidation of spatial memory in Morris water maze test. In the present study, the role of VP D2 DA receptors was investigated in the same paradigm. In the first experiment, the D2 DA receptor agonist quinpirole was administered into the VP of male Wistar rats in three doses (0.1, 1.0 or 5.0μg, respectively in 0.4μl physiological saline). In the second experiment, the D2 DA receptor antagonist sulpiride was applied to elucidate whether it can antagonise the effects of quinpirole. The antagonist (4.0μg, dissolved in 0.4μl physiological saline) was microinjected into the VP either by itself or prior to 1.0μg agonist treatment. Control animals received saline in both experiments. The two higher doses (1.0 and 5.0μg) of the agonist accelerated memory consolidation relative to controls and increased the stability of the consolidated memory against extinction. Sulpiride pretreatment antagonised the effects of quinpirole. In addition, the antagonist microinjected into the VP immediately after the second conditioning trial impaired learning functions. The present data provide evidences for the important role of VP D2 DA receptors in the consolidation and stabilization of spatial memory. PMID:27392640

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

    Science.gov (United States)

    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).

  14. In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland

    OpenAIRE

    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.

    2013-01-01

    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-...

  15. Link between D1 and D2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain

    International Nuclear Information System (INIS)

    Dopamine receptor types D1 and D2 can oppose enhance each other's actions for electrical, biochemical, and psychomotor effects. The authors report a D1-D2 interaction in homogenized tissue as revealed by ligand binding. D2 agonists lowered the binding of [3H]raclopride to D2 receptors in striatal and anterior pituitary tissues. Pretreating the tissue with the D1-selective antagonist SCH 23390 prevented the agonist-induced decrease in [3H]raclopride binding to D2 sites in the striatum but not in the anterior pituitary, which has no D1 receptors. Conversely, a dopamine-induced reduction in the binding of [3H]SCH 23390 to D1 receptors could be prevented by the D2-selective antagonist eticlopride. Receptor photolabeling experiments confirmed both these D1-D2 interactions. The blocking effect by SCH 23390 was similar to that produced by a nonhydrolyzable guanine nucleotide analogue, and SCH 23390 reduced the number of agonist-labeled D2 receptors in the high-affinity state. Thus, the D1-D2 link may be mediated by guanine nucleotide-binding protein components. The link may underlie D1-D2 interactions influencing behavior, since the link was missing in over half the postmortem striata from patients with schizophrenia and Huntington disease (both diseases that show some hyperdopamine signs) but was present in human control, Alzheimer, and Parkinson striata

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Gifford, A.N.; Gatley, S.J.; Shea, C. [Brookhaven National Lab., Upton, NY (United States)

    1996-05-01

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

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

    Science.gov (United States)

    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

  19. Jahn-Teller Distortion and Electronic Spectra of C80n(D2,Ih)%C80n(D2,Ih)的Jahn-Teller畸变和电子光谱

    Institute of Scientific and Technical Information of China (English)

    吴师; 滕启文

    2005-01-01

    用INDO系列方法研究C80n(D2,Ih)的Jahn-Teller畸变,表明C80(D2)比C80(Ih)稳定,与实验一致;C80n(D2)未发生Jahn-Teller畸变, C80n(Ih)的部分离子发生明显的Jahn-Teller畸变,电荷对C80(Ih)稳定性有显著影响.首次计算其电子光谱,不仅得到C80(D2)与实验一致的吸收峰,还预测了C80n(D2,Ih)的电子光谱,对电子跃迁进行理论指认.C80n(D2)光谱与C80(D2)相比发生吸收峰红移,而C80n(Ih)光谱与C80(Ih)相比发生吸收峰兰移,其原因是C80n(D2)的LUMO-HOMO能隙比C80(D2)小,而C80n(Ih)的能隙则比C80(Ih)的能隙大.

  20. Studies on the crystalline acetylene-d2 by thermal neutron powder diffraction technique

    International Nuclear Information System (INIS)

    The two crystalline phases of acetylene-d2, C2D2, have been investigated by thermal neutron powder diffraction technique. The crystal structure studies of the orthorhombic low phase at 4.2 K, 77 K and 109 K and of the cubic structure at 150.5 K, as well as investigations on molecular motion and lattice parameter dependence on temperature in the orthorhombic phase along with a report concerning with the orthorhombic-cubic solid phase transition have been published ealier. In the thesis, the reported studies are presented under a main title. A short description of the experimental details is given, and the results and discrepancies of the studies are discussed. (author)

  1. AFM surface imaging of AISI D2 tool steel machined by the EDM process

    International Nuclear Information System (INIS)

    The surface morphology, surface roughness and micro-crack of AISI D2 tool steel machined by the electrical discharge machining (EDM) process were analyzed by means of the atomic force microscopy (AFM) technique. Experimental results indicate that the surface texture after EDM is determined by the discharge energy during processing. An excellent machined finish can be obtained by setting the machine parameters at a low pulse energy. The surface roughness and the depth of the micro-cracks were proportional to the power input. Furthermore, the AFM application yielded information about the depth of the micro-cracks is particularly important in the post treatment of AISI D2 tool steel machined by EDM

  2. AFM surface imaging of AISI D2 tool steel machined by the EDM process

    Energy Technology Data Exchange (ETDEWEB)

    Guu, Y.H. [Department of Mechanical Engineering, National United University, 1 Lien Da, Kung-Ching Li, Miaoli 360, Taiwan (China)]. E-mail: yhorng@nuu.edu.tw

    2005-04-15

    The surface morphology, surface roughness and micro-crack of AISI D2 tool steel machined by the electrical discharge machining (EDM) process were analyzed by means of the atomic force microscopy (AFM) technique. Experimental results indicate that the surface texture after EDM is determined by the discharge energy during processing. An excellent machined finish can be obtained by setting the machine parameters at a low pulse energy. The surface roughness and the depth of the micro-cracks were proportional to the power input. Furthermore, the AFM application yielded information about the depth of the micro-cracks is particularly important in the post treatment of AISI D2 tool steel machined by EDM.

  3. Microstructure evolution and texture development in a friction stir-processed AISI D2 tool steel

    Science.gov (United States)

    Yasavol, N.; Abdollah-zadeh, A.; Vieira, M. T.; Jafarian, H. R.

    2014-02-01

    Crystallographic texture developments during friction stir processing (FSP) of AISI D2 tool were studied with respect to grain sizes in different tool rotation rates. Comparison of the grain sizes in various rotation rates confirmed that grain refinement occurred progressively in higher rotation rates by severe plastic deformation. It was found that the predominant mechanism during FSP should be dynamic recovery (DRV) happened concurrently with continuous dynamic recrystallization (CDRX) caused by particle-stimulated nucleation (PSN). The developed shear texture relates to the ideal shear textures of D1 and D2 in bcc metals. The prevalence of highly dense arrangement of close-packed planes of bcc and the lowest Taylor factor showed the lowest compressive residual stress which is responsible for better mechanical properties compared with the grain-precipitate refinement.

  4. Tool life and surface roughness of ceramic cutting tool when turning AISI D2 tool steel

    International Nuclear Information System (INIS)

    The tool life of physical vapor deposition (PVD) titanium nitride (TiN) coated ceramic when turning AISI D2 tool steel of hardness 54-55 HRC was investigated. The experiments were conducted at various cutting speed and feed rate combinations with constant depth of cut and under dry cutting condition. The tool life of the cutting tool for all cutting conditions was obtained. The tool failure mode and wear mechanism were also investigated. The wear mechanism that is responsible for the wear form is abrasion and diffusion. Flank wear and crater wear are the main wear form found when turning AISI D2 grade hardened steel with 54-55 HRC using KY 4400 ceramic cutting tool. Additionally catastrophic failure is observed at cutting speed of 183 m/min and feed rate of 0.16 mm/ rev. (author)

  5. The polarization of F1 strings into D2 branes "Aut Caesar aut nihil"

    CERN Document Server

    Bena, I

    2003-01-01

    We give matrix and supergravity descriptions of type IIA F-strings polarizing into cylindrical D2 branes. When a RR four-form field strength F_4 is turned on in a supersymmetric fashion (with 4 supercharges), a complete analysis of the solutions reveals the existence of a moduli space of F1 -> D2 polarizations (Caesar) for some fractional strengths of the perturbation, and of no polarization whatsoever (nihil) for all other strengths of the perturbation. This is a very intriguing phenomenon, whose physical implications we can only speculate about. In the matrix description of the polarization we use the Non-Abelian Born-Infeld action in an extreme regime, where the commutators of the fields are much larger than 1. The validity of the results we obtain, provides a direct confirmation of this action, although is does not confirm or disprove the symmetrized trace prescription.

  6. Novel Method Fusing (2D) 2 LDA with Multichannel Model for Face Recognition

    Institute of Scientific and Technical Information of China (English)

    Xia Liu∗; Yang Cao; Yu Cao; Bo Wang

    2015-01-01

    A fusion method of Gabor features and (2D)2LDA for face feature extraction is proposed in this paper. Gabor filters are utilized to extract multi⁃direction and multi⁃scale features from facial image to employ its robust performance for illumination, expressional variability and other factors. The extracted features have the defect of high dimension and redundancy data. (2D)2LDA is implemented to reduce the dimension of Gabor features and select effective feature data. Finally, the nearest neighbor classifier is used to classify characteristics and complete face recognition. The experiments are implemented by using ORL database and Yale database respectively. The experimental results show that the proposed method significantly reduces the dimension of Gabor features and decrease the influence of other factors. The proposed method acquires excellent recognition accuracy and has light architectures as well.

  7. The alignment of the radio structure and magnetic field in three D2 quasars

    International Nuclear Information System (INIS)

    The radio structures and magnetic fields in the components of the D2 quasars 3C 273, 345 and 454.3 are found to be misaligned by typically 200 with the main axes of the sources. However, the direction of the magnetic field within a given component agrees with the structural elongation of that component. The misalignments in the nuclei of these D2 quasars are in sharp contrast with the situation in the nuclei of D1 sources, which are found to be strictly aligned with the main axis. The 'super-luminal' proper motions in 3C 273 and 345 are in directions closely parallel to the magnetic field vectors in the nuclei of these sources. (author)

  8. Synthesis and 131I labelling of epidepride as a dopamine D2 receptor imaging agent

    International Nuclear Information System (INIS)

    S-(-)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2, 3-dimethoxybenzamide (Epidepride) and its iodine labeling precursor S-(-)-N-[(1-Ethyl-2-pyrrolidinyl)methyl]-5-tributyltin-2, 3-dimethoxybenzamide are synthesized from 3-methoxy salicylic acid. The labeling precursor is labeled with 131I by hydrogen peroxide method, and 131I-epidepride is gained, its radiolabelling yield (RLY) and the radiochemical purity (RCP) are all over 95%. The RCP of 131I-epidepride is over 90% under 4 degree C after 15 days. 131I-epidepride has high affinity to dopamine D2 receptor. The striatal uptake can be blocked completely by spiperone. The striatum and cerebellum uptake ratio can reach 237 at 320 min in rats. The results show that 131I-epidepride may be used as a dopamine D2 receptor imaging agent for SPECT

  9. Complex Quantum Network Manifolds in Dimension $d>2$ are Scale-Free

    CERN Document Server

    Bianconi, Ginestra

    2015-01-01

    In quantum gravity, several approaches have been proposed until now for the quantum description of discrete geometries. These theoretical frameworks include loop quantum gravity, causal dynamical triangulations, causal sets, quantum graphity, and energetic spin networks. Most of these approaches describe discrete spaces as homogeneous network manifolds. Here we define Complex Quantum Network Manifolds (CQNM) describing the evolution of quantum network states, and constructed from growing simplicial complexes of dimension $d$. We show that in $d=2$ CQNM are homogeneous networks while for $d>2$ they are scale-free i.e. they are characterized by large inhomogeneities of degrees like most complex networks. From the self-organized evolution of CQNM quantum statistics emerge spontaneously. Here we define the generalized degrees associated with the $\\delta$-faces of the $d$-dimensional CQNMs, and we show that the statistics of these generalized degrees can either follow Fermi-Dirac, Boltzmann or Bose-Einstein distri...

  10. Sputtering of W and Al in D2/O2 plasma cleaning discharge

    International Nuclear Information System (INIS)

    Ion sputtering of W, Al, and Be (in several experiments) in a low pressure DC discharge in D2/O2 mixtures was studied. Ion energy was varied by electrical biasing of the samples from −100 to −600 V with respect to the plasma. At a bias of −100 V the sputtering yields peaked with an addition of 2–4 mol.% oxygen reaching (4 ± 0.5) × 10−3, (12 ± 1) × 10−3, and (20 ± 2) × 10−3 Me at./ion for W, Al, and Be, respectively. It is supposed that chemical nature of W, Al, and Be sputtering in D2/O2 plasma is caused by formation of weakly bound surface oxides and hydroxides under impinging of reactive deuterated ions (D3O+, D3+)

  11. Diagnostic use of secondary proton spectra for D2-filled inertial confinement fusion targets (abstract)

    International Nuclear Information System (INIS)

    The use of measured spectra of secondary fusion protons for studying physical characteristics of D2-filled inertial confinement fusion capsules is described theoretically and demonstrated with data from implosions in the OMEGA 60-beam laser facility. Spectra were acquired with a magnet-based charged-particle spectrometer and with a range-filter-based spectrometer utilizing filters and CR39 nuclear track detectors. Measurement of mean proton energy makes possible the study of a capsule's total areal density (ρR), since that is what affects the energy loss suffered by protons as they pass through fuel and shell while leaving the capsule. Details of specific shots will be presented. It is also shown that similar techniques should prove useful for diagnosis of future experiments with cryogenic D2-filled capsules

  12. Dopamine signaling in food addiction: role of dopamine D2 receptors

    Directory of Open Access Journals (Sweden)

    Ja-Hyun Baik

    2013-11-01

    Full Text Available Dopamine (DA regulates emotional and motivationalbehavior through the mesolimbic dopaminergic pathway.Changes in DA signaling in mesolimbic neurotransmission arewidely believed to modify reward-related behaviors and aretherefore closely associated with drug addiction. Recentevidence now suggests that as with drug addiction, obesitywith compulsive eating behaviors involves reward circuitry ofthe brain, particularly the circuitry involving dopaminergicneural substrates. Increasing amounts of data from humanimaging studies, together with genetic analysis, havedemonstrated that obese people and drug addicts tend to showaltered expression of DA D2 receptors in specific brain areas,and that similar brain areas are activated by food-related anddrug-related cues. This review focuses on the functions of theDA system, with specific focus on the physiological interpretationand the role of DA D2 receptor signaling in foodaddiction. [BMB Reports 2013; 46(11: 519-526

  13. High current pulsed electron beam modification on fretting wear behavior of D2 die steel

    International Nuclear Information System (INIS)

    The author studied the effect of high current pulsed electron beam (HCPEB) treatment on fretting wear ability of D2 die steel. It is shown that the most pronounced structural changes occur in the near-surface region, where the energy deposition is at its maximum. The fretting tests under dry condition were carried out on both treated and untreated specimens. The HCPEB treatment increases the fretting wear resistance significantly, and the improvement is further enhanced by surface pre-alloying by TiN and Cr. SEM analysis of the wear scars showed that the fretting wear mechanism of Cr coating is adhesive and oxidation wear, that of the TiN coating and non-coating D2 die steel is particle detachment through the propagation and fracture of fatigue microcracks on surface, and slight adhesive and oxidation wear is found, its wear mechanism is more complex

  14. DEVELOPMENT OF COUPLED 1D-2D MATHEMATICAL MODELS FOR TIDAL RIVERS

    Institute of Scientific and Technical Information of China (English)

    XU Zu-xin; YIN Hai-long

    2004-01-01

    Some coupled 1D-2D hydrodynamic and water quality models depicting tidal water bodies with complex topography were presented. For the coupled models, finite element method was used to solve the governing equations so as to study tidal rivers with complex topography. Since the 1D and 2D models were coupled, the principle of model coupling was proposed to account appropriately for the factors of water level, flow and pollutant flux and the related dynamical behavior was simulated. Specifically the models were used to probe quantitative pollution contribution of receiving water from neighboring Jiangsu and Zhejiang Provinces to the pollution in the Huangpu River passing through Shanghai City. Numerical examples indicated that the developed coupled 1D-2D models are applicable in tidal river network region of Shanghai.

  15. D2和W1工具钢的动态再结晶

    Institute of Scientific and Technical Information of China (English)

    郭永铭

    2002-01-01

    在900~1150℃温度范围(对D2)和900~1200℃温度范围(对W1)内以0.1、1和4S-1的应变率对高碳、高Cr冷作模具钢(D2)和一种水硬碳素工具钢(W1)进行了连续热扭曲试验。应力一应变(σ-ε)曲线上升到峰值应力σp,然后倾斜下降到一稳定状态值σss。

  16. Secondary electron emission from solid HD and a solid H2-D2 mixture

    DEFF Research Database (Denmark)

    Sørensen, H.; Børgesen, P.; Hao-Ming, Chen;

    1983-01-01

    Secondary electron emission from solid HD and a solid 0.6 H2 + 0.4 D2 mixture has been studied for electron and hydrogen ion bombardment at primary energies from 0.5 to 3 keV and 2 to 10 keV/amu, respectively. The yield for solid HD is well explained by a simple stoichiometric model of the low......-energy stopping power for the internal secondaries. The secondary electron yield from the mixture is somewhat larger than the expected value, but lies between the values for pure solid H2 and D2. The secondary electron emission coefficient for solid tritium may be determined from a linear extrapolation of the...

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

    CERN Document Server

    Aali-Javanangrouh, M

    2016-01-01

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

  18. Resonances in the reaction ortho- and para- D2 + H at temperatures below 10 K

    Science.gov (United States)

    Simbotin, I.; Côté, R.

    2016-05-01

    In a previous study we reported cross sections for the reaction H2 + D in the temperature regime 10-6 D2 + H for vibrationally excited ortho- and para- D2, and compare and contrast these results with those for H2 + D. We remark that this benchmark system is a prototypical example of reactions with a strong barrier, which have very small cross sections in the cold and ultracold regimes. However, shape resonances can enhance the reaction cross sections by orders of magnitude for temperatures around and below T = 1 K. Moreover, resonant features would provide stringent tests for quantum chemistry calculations of potential energy surfaces. Partial support from the US Army Research Office (Grant No. W911NF-13-1-0213).

  19. Achieving energy efficiency in LTE with joint D2D communications and green networking techniques

    KAUST Repository

    Yaacoub, Elias E.

    2013-07-01

    In this paper, the joint operation of cooperative device-to-device (D2D) communications and green cellular communications is investigated. An efficient approach for grouping mobile terminals (MTs) into cooperative clusters is described. In each cluster, MTs cooperate via D2D communications to share content of common interest. Furthermore, an energy-efficient technique for putting BSs in sleep mode in an LTE cellular network is presented. Finally, both methods are combined in order to ensure green communications for both the users\\' MTs and the operator\\'s BSs. The studied methods are investigated in the framework of OFDMA-based state-of-the-art LTE cellular networks, while taking into account intercell interference and resource allocation. © 2013 IEEE.

  20. Energy-efficient Joint Power Allocation and Channel Selection for D2D Communications

    Directory of Open Access Journals (Sweden)

    Guifang Ma

    2015-08-01

    Full Text Available Device-to-device (D2D communications have gained great attentions due to the potential and numerous benefits for cellular networks. However,it also brings tremendous resource allocation challenges for the sake of the constraint of battery life. Up to now, there are limited works attempt to prolong the battery life by improving the energy efficiency (EE. In this paper, we study how to perform resource allocation to increase EE in a interference limited environment under a noncooperative game model. Each D2D pair can reuse all or part of the channel resources allocated to cellular users. An energy-efficient joint power allocation and channel selection is proposed by employing the nonlinear fractional programming. We obtain the optimal power allocation and channel selection through an iterative algorithm called Dinkelbach method. Finally, the algorithm proposed in this paper is verified by simulation.

  1. L-DOPA reverses the elevated density of D2 dopamine receptors in Parkinson's diseased striatum

    International Nuclear Information System (INIS)

    Striatal dopamine receptors werde studied using [3H]-spiperone in postmortem tissues of thirty-six patients with Parkinson's Disease. Each tissue was analyzed by the receptor saturation method. In non-treated patients, the D2 dopamine receptor density was elevated in the caudate nucleus and putamen compared to controls. In L-DOPA-treated patients, the receptor density was the same as controls. The dissociation constant for [3H]-spiperone was similar in all groups. The elevated density of D2 receptors in non-treated patients may indicate dopaminergic supersensitivity in this disease. The elevated density was reversed with dopamine agonist therapy, but the density was not lower than control tissues. (Author)

  2. Cloning and identification of an Ubiquitinconjugatingenzyme E2 D2 gene fromJapanese lamprey Lampetra japonica

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation.Ubiquitin-conjugating enzyme E2 D2 is a protein that is encoded by the UBE2D2 gene. Here, we report a lamprey (LaUBE2D2) gene which contained 441-bp open reading frame (ORF) encoding 147 amino acids with a typical UBC domain. Real-time PCR assay showed that the highest expression of the protein inadult lamprey was in the leukocytes, the lowest expression was in the skin, kidney and liver. The high conservation in amino acid sequence of the LaUBE2D2protein with the UBE2D2s from Homo sapiens, Danio rerio, Oreochromis niloticus and Takifugu rubripes, implied that it had similar function with UBE2D2proteins from other species.

  3. In vitro activity of 79 antimicrobial agents against Corynebacterium group D2.

    OpenAIRE

    García-Rodriguez, J A; García Sánchez, J E; Muñoz Bellido, J L; Nebreda Mayoral, T; García Sánchez, E; García García, I

    1991-01-01

    Corynebacterium group D2 (CGD2) is involved in urinary tract infections in patients with underlying predisposing factors. This microorganism is highly resistant to a number of antimicrobial agents. We tested the activities of 79 antimicrobial agents against CGD2. beta-Lactams, aminoglycosides, and macrolides were ineffective. Fluorinated quinolones showed irregular activities, ofloxacin being the most active one. Doxycycline, rifampin, and mainly glycopeptides (vancomycin and teicoplanin) wer...

  4. Rapid anti-depressant and anxiolytic actions following dopamine D1-D2 receptor heteromer inactivation.

    Science.gov (United States)

    Shen, Maurice Y F; Perreault, Melissa L; Bambico, Francis R; Jones-Tabah, Jace; Cheung, Marco; Fan, Theresa; Nobrega, José N; George, Susan R

    2015-12-01

    A role for the mesolimbic dopaminergic system in the pathophysiology of depression has become increasingly evident. Specifically, brain-derived neurotrophic factor (BDNF) has been shown to be elevated in the nucleus accumbens of depressed patients and to positively contribute to depression-like behaviour in rodents. The dopamine D1-D2 receptor heteromer exhibits significant expression in NAc and has also been shown to enhance BDNF expression and signalling in this region. We therefore examined the effects of D1-D2 heteromer stimulation in rats by SKF 83959, or its inactivation by a selective heteromer-disrupting TAT-D1 peptide on depression- and anxiety-like behaviours in non-stressed animals and in animals exposed to chronic unpredictable stress. SKF 83959 treatment significantly enhanced the latency to immobility in the forced swim test, increased the latency to drink condensed milk and reduced total milk consumption in the novelty-induced hypophagia test, and additionally reduced the total time spent in the open arms in the elevated plus maze test. These pro-depressant and anxiogenic effects of SKF 83959 were consistently abolished or attenuated by TAT-D1 peptide pre-treatment, signifying the behaviours were mediated by the D1-D2 heteromer. More importantly, in animals exposed to chronic unpredictable stress (CUS), TAT-D1 peptide treatment alone induced significant and rapid anxiolytic and antidepressant-like effects in two tests for CUS-induced anhedonia-like reactivity and in the novelty-suppressed feeding test. Together these findings indicate a positive role for the D1-D2 heteromer in mediating depression- and anxiety-like behaviours and suggest its possible value as a novel therapeutic target. PMID:26431907

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

    OpenAIRE

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

    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 pa...

  6. Absolute measurement of the ultrafast nonlinear electronic and rovibrational response in H$_2$ and D$_2$

    CERN Document Server

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

    2015-01-01

    The electronic, rotational, and vibrational components of the ultrafast optical nonlinearity in H$_2$ and D$_2$ are measured directly and absolutely at intensities up to the ionization threshold of $\\sim$10$^{14}$ W/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.

  7. Nonsequential double ionization of D2 molecules with intense 20-fs pulses

    DEFF Research Database (Denmark)

    Sakai, H.; Larsen, J.J.; Wendt-Larsen, I.;

    2003-01-01

    The kinetic-energy distribution of D+ fragments obtained from the ionization of D2 molecules with intense 20-fs pulses includes a high-energy component extending up to ˜10 eV. These fragments are only present for linearly, or slightly elliptically, polarized light. Both the maximum kinetic......-energy and the ellipticity dependence are consistent with nonsequential double ionization caused by recollision....

  8. D2-brane as the wormhole and the number of the universes

    Science.gov (United States)

    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.

  9. Evaluation of prostaglandin D2 as a CSF leak marker: implications in safe epidural anesthesia

    Directory of Open Access Journals (Sweden)

    Kondabolu S

    2011-07-01

    Full Text Available Sirish Kondabolu, Rishimani Adsumelli, Joy Schabel, Peter Glass, Srinivas PentyalaDepartment of Anesthesiology, School of Medicine, Stony Brook Medical Center, Stony Brook, New York, USABackground: It is accepted that there is a severe risk of dural puncture in epidural anesthesia. Of major concern to anesthesiologists is unintentional spinal block. Reliable identification of cerebrospinal fluid (CSF from the aspirate is crucial for safe epidural anesthesia. The aim of this study was to determine whether prostaglandin D2 could be clinically used as a marker for the detection of CSF traces.Methods: After obtaining Institutional Review Board approval and patient consent, CSF was obtained from patients undergoing spinal anesthesia, and blood, urine, and saliva were obtained from normal subjects and analyzed for prostaglandin D2 (PGD. CSF (n=5 samples were diluted with local anesthetic (bupivacaine, normal saline and blood in the ratios of 1:5 and 1:10. PGD levels in the CSF samples were analyzed with a PGD-Methoxime (MOX EIA Kit (Cayman Chemicals, MI. This assay is based on the conversion of PGD to a stable derivative, which is analyzed with antiserum specific for PGD-MOX. Results: Different concentrations of pure PGD-MOX conjugate were analyzed by EIA and a standard curve was derived. PGD levels in CSF and CSF with diluents were determined and the values were extrapolated onto the standard curve. Our results show a well-defined correlation for the presence of PGD both in straight CSF samples and in diluted CSF (dilution factor of 1:5 and 1:10. Conclusion: Prostaglandin D2 was reliably identified in CSF by enzyme-linked immunosorbent assay when diluted with local anesthetic, saline, and serum, and can be used as a marker to identify the presence of CSF in epidural aspirates.Keywords: epidural, cerebrospinal fluid, leak, marker, prostaglandin D2

  10. Production of 4He in D2-Loaded Palladium-Carbon Catalyst II

    International Nuclear Information System (INIS)

    Measurements of He, 3He/4He, Ne and 13 other components (H2, HD, D2, CH4, H2O, HDO, D2O, N2, CO, C2H6, O2, Ar, and CO2) in four samples of gas from SRI International (SRI) are reported. Three samples were collected from SRI Case-type stainless steel cells containing ∼10 g of Pd/C catalyst initially loaded with ∼3 atm D2 at ∼200 deg. C, and the fourth sample (not identified) was stated to be a control. Case and the SRI researchers have claimed to observe 4He in concentrations of ∼100 parts per million (ppm) and up to 11 ppm, respectively, produced in these cells via the fusion reaction D + D = 4He + 23.8 MeV. Others found no evidence for 4He addition that cannot be readily explained by leaks from the atmosphere into the SRI cells. One sample appears to be identical in composition to air, and the other three have been seriously affected by leak(s) into and from the SRI cells. The rare gas 'forensic' evidence includes 3He/4He ratios and He and Ne concentrations that are almost identical to air values. The samples also show high N2 (a primary indicator of air), low O2, and high CO and CO2 due to reaction of incoming atmospheric O2 with C in the catalyst. In two samples, the original D2 (or H2) has almost completely disappeared by outflow through the leak(s). These results have obvious implications concerning the validity of the excess 4He concentrations claimed by Case and the SRI researchers

  11. Nucleus Accumbens D2/3 Receptors Predict Trait Impulsivity and Cocaine Reinforcement

    OpenAIRE

    Dalley, Jeffrey W.; Fryer, Tim D; Brichard, Laurent; Robinson, Emma S J; Theobald, David E. H.; Lääne, Kristjan; Peña, Yolanda; Murphy, Emily R.; Shah, Yasmene; Probst, Katrin; Abakumova, Irina; Aigbirhio, Franklin I.; Richards, Hugh K.; Hong, Young; Baron, Jean-Claude

    2007-01-01

    Stimulant addiction is often linked to excessive risk taking, sensation seeking, and impulsivity, but in ways that are poorly understood. We report here that a form of impulsivity in rats predicts high rates of intravenous cocaine self-administration and is associated with changes in dopamine (DA) function before drug exposure. Using positron emission tomography, we demonstrated that D2/3 receptor availability is significantly reduced in the nucleus accumbens of impulsive rats that were never...

  12. Repeated apomorphine administration alters dopamine D1 and D2 receptor densities in pigeon basal telencephalon

    OpenAIRE

    Acerbo, Martin J.; Výboh, Pavel; Košťál, Ľubor; Kubíková, Ľubica; Delius, Juan

    2005-01-01

    When pigeons are repeatedly administered a dose of apomorphine they show an increasing behavioral response, much as rodents do. In birds this expresses itself in an augmented pecking response. This sensitization is assumed to be largely due to a conditioning process. Here we present evidence that sensitization is accompanied by an alteration of the D1 to D2 dopamine receptor densities. An experimental group of pigeons was repeatedly injected with apomorphine, and a control group with saline. ...

  13. Information on the gauge principle from an N=1/2, D=2 supersymmetric model

    International Nuclear Information System (INIS)

    The gauge principle does not only work to generate interactions. It potentially yields an abundance of gauge-potential fields transforming under the same local symmetry group. In order to show evidences of this property this work gauge-covariantizes an N = 1/2, D = 2 supersymmetric theory. Then, by relaxing the so-called conventional constraint, a second gauge-potential field naturally emerges. (author)

  14. Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

    OpenAIRE

    John Li; May May Leong; Alastair Stewart; Mark A. Rizzacasa

    2013-01-01

    The total synthesis of the endogenous inflammation resolving eicosanoid resolvin D2 (1) is described. The key steps involved a Wittig reaction between aldehyde 5 and the ylide derived from phosphonium salt 6 to give enyne 17 and condensation of the same ylide with aldehyde 7 to afford enyne 11. Desilylation of 11 followed by hydrozirconation and iodination gave the vinyl iodide 4 and Sonogashira coupling between this compound and enyne 3 provided alkyne 18. Acetonide deprotection, partial red...

  15. Attosecond xuv pulses for complete mapping of the time-dependent wave packets of D2+

    International Nuclear Information System (INIS)

    We have shown that the whole time-dependent vibrational wave packet of D2+ ions can be reconstructed from the kinetic energy release of the D+ ion pairs when it is probed with an attosecond xuv pulse. Such a full interrogation of the wave packet will pave the way for controlling the generation of tailor-designed wave packets for favorable chemical reaction paths, as well as for probing the time evolution of their interaction with the medium

  16. D2 lymphadenectomy is not only safe but necessary in the era of neoadjuvant chemotherapy

    Directory of Open Access Journals (Sweden)

    Shrikhande Shailesh V

    2013-02-01

    Full Text Available Abstract Background Patients with locally advanced resectable gastric cancers are increasingly offered neoadjuvant chemotherapy (NACT following the MAGIC and REAL-2 trials. However, information on the toxicity of NACT, its effects on perioperative surgical outcomes and tumor response is not widely reported in literature. Methods Analysis of a prospective database of gastric cancer patients undergoing radical D2 gastrectomy over 2 years was performed. Chemotherapy-related toxicity, perioperative outcomes and histopathological responses to NACT were analyzed. The data is presented and compared to a cohort of patients undergoing upfront surgery in the same time period. Results In this study, 139 patients (42 female and 97 male patients, median age 53 years with gastric adenocarcinoma received NACT. Chemotherapy-related toxicity was noted in 32% of patients. Of the 139 patients, 129 underwent gastrectomy with D2 lymphadenectomy, with 12% morbidity and no mortality. Major pathological response of primary tumor was noted in 22 patients (17%. Of these 22 patients, lymph node metastases were noted in 12 patients. The median blood loss and lymph node yield was not significantly different to the 62 patients who underwent upfront surgery. Patients who underwent upfront surgery were older (58 vs. 52 years, P P P  Conclusions Perioperative outcomes of gastrectomy with D2 lymphadenectomy for locally advanced, resectable gastric cancer were not influenced by NACT. The number of lymph nodes harvested was unaltered by NACT but, more pertinently, metastases to lymph nodes were noted even in patients with a major pathological response of the primary tumor. D2 lymphadenectomy should be performed in all patients irrespective of the degree of response to NACT.

  17. D2 lymphadenectomy is not only safe but necessary in the era of neoadjuvant chemotherapy

    OpenAIRE

    Shrikhande Shailesh V; Barreto Savio G; Talole Sanjay D; Vinchurkar Kumar; Annaiah Somashekar; Suradkar Kunal; Mehta Shaesta; Goel Mahesh

    2013-01-01

    Abstract Background Patients with locally advanced resectable gastric cancers are increasingly offered neoadjuvant chemotherapy (NACT) following the MAGIC and REAL-2 trials. However, information on the toxicity of NACT, its effects on perioperative surgical outcomes and tumor response is not widely reported in literature. Methods Analysis of a prospective database of gastric cancer patients undergoing radical D2 gastrectomy over 2 years was performed. Chemotherapy-related toxicity, perioperat...

  18. Characterization of dopamine D1 and D2 receptor-expressing neurons in the mouse hippocampus.

    Science.gov (United States)

    Gangarossa, Giuseppe; Longueville, Sophie; De Bundel, Dimitri; Perroy, Julie; Hervé, Denis; Girault, Jean-Antoine; Valjent, Emmanuel

    2012-12-01

    The hippocampal formation is part of an anatomical system critically involved in learning and memory. Increasing evidence suggests that dopamine plays an important role in learning and memory as well as in several forms of synaptic plasticity. However, the precise identification of neuronal populations expressing D1 or D2 dopamine receptors within the hippocampus is still lacking. To clarify this issue, we used BAC transgenic mice expressing enhanced green fluorescent protein (EGFP) under the control of the promoter of dopamine D1 or D2 receptors. In Drd1a-EGFP mice, sparse GFP-expressing neurons were detected among glutamatergic projecting neurons of the granular layer of the dentate gyrus and GABAergic interneurons located in the hilus. A dense immunofluorescence was observed in the outer and medial part of the molecular layer of the dentate gyrus as well as in the inner part of the molecular layer of CA1 corresponding to the terminals of pyramidal neurons of the entorhinal cortex defining the perforant and the temporo-ammonic pathway respectively. Finally, scattered D1 receptor-expressing neurons were also identified as GABAergic interneurons in the CA3/CA1 fields of the hippocampus. In Drd2-EGFP transgenic mice, GFP was exclusively detected in the glutamatergic mossy cells located in the polymorphic layer of the dentate gyrus. This pattern was confirmed in Drd2-Cre mice crossed with NLS-LacZ-Tau(mGFP) :LoxP and RCE:LoxP reporter lines. Our results demonstrate that D1 and D2 receptor-expressing neurons are strictly segregated in the mouse hippocampus. By clarifying the identity of D1 and D2 receptor-expressing neurons in the hippocampus, this study establishes a basis for future investigations aiming at elucidating their roles in the hippocampal network. PMID:22777829

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

    Science.gov (United States)

    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.

  20. D2 brane as the wormhole and the number of the universes

    CERN Document Server

    Gusin, Pawel

    2016-01-01

    We construct wormhole-like solutions in the type IIA string theory. These solutions represent wormholes in four-dimensions and are given by the D2 branes within appropraited 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 the type IIA theory leads to the dynamic wormhole. We also speculate about the number of universes and the cosmological constant.

  1. Vertical D4-D2-D0 bound states on K3 fibrations and modularity

    CERN Document Server

    Bouchard, Vincent; Diaconescu, Duiliu-Emanuel; Doran, Charles; Quigley, Callum; Sheshmani, Artan

    2016-01-01

    An explicit formula is derived for the generating function of vertical D4-D2-D0 bound states on smooth K3 fibered Calabi-Yau threefolds, generalizing previous results of Gholampour and Sheshmani. It is also shown that this formula satisfies strong modularity properties, as predicted by string theory. This leads to a new construction of vector valued modular forms which exhibits some of the features of a generalized Hecke transform.

  2. Dissociative ionization of H2 and D2 by electron impact near threshold

    NARCIS (Netherlands)

    Boesten, L.G.J.; Heideman, H.G.M.

    1980-01-01

    We have studied the dissciative ionization of H2 and D2 by electron impact. It is found that in the vicinity of the 2Σ+g dissociation threshold of H+2 (18.08 eV) a significant fraction of the produced protons originates from the process e + H2 → H− + H+ + e (threshold at 17.34 eV). Similar results a

  3. Time-Dependence of Risperidone and Asenapine Sensitization and Associated D2 receptor Mechanism

    OpenAIRE

    Gao, Jun; LI Ming

    2013-01-01

    When an antipsychotic drug is given repeatedly and intermittently, there is often a long-term increase in its behavioral efficacy, termed antipsychotic sensitization. With the passage of time, the magnitude of antipsychotic sensitization may increase or decrease depending on the principle of Time-Dependent Sensitization (TDS) or memory decay, respectively. In the present study, we examined the time-dependent feature and possible dopamine D2 receptor mechanism of sensitization induced by the a...

  4. Fatores prognósticos nas gastrectomias com linfadenectomia D2 por adenocarcinoma gástrico Prognostic factors in D2 gastrectomy for gastric adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Osvaldo Antonio Prado Castro

    2009-09-01

    Full Text Available RACIONAL: A disseminação linfática é significativamente mais prevalente do que a hematogênica no câncer gástrico e assim torna-se importante o tratamento loco-regional, ou seja, a ressecção cirúrgica associada à linfadenectomia, preferencialmente do tipo D2. OBJETIVO: Avaliar a sobrevivência global nos pacientes submetidos à gastrectomia D2 por adenocarcinoma gástrico; determinar os principais fatores prognósticos e definir variáveis que possuam valor prognóstico independente. MÉTODOS: Estudo prospectivo em 125 pacientes submetidos à gastrectomia D2, entre agosto de 1997 e outubro de 2005. A técnica adotada seguiu rigorosamente o protocolo proposto pelo Centro Nacional de Câncer de Tóquio. RESULTADOS: Havia 73 homens e 52 mulheres com idades que variaram de 28 a 84 anos (média de 58,96 ± 14,01. Setenta por cento das lesões situavam-se na porção distal do estômago, 20% eram proximais e 10% ocupavam os três segmentos anatômicos do órgão. Os estádios estavam assim distribuídos: I - 37 casos (29,6%, II - 20 casos (16%, III - 37 casos (29,6%, e IV - 31 casos (24,8%. Realizou-se 87 gastrectomias subtotais e 38 totais. A morbidade total foi de 26,4%, constituindo-se predominantemente de fístulas e complicações pulmonares. A letalidade foi de 9,6%. Após seguimento médio de 48 meses, 68 (54,4% pacientes tinham falecido, representando sobrevivência global de 45,6%. As análises univariada e multivariada revelaram que: tumores que acometiam grandes segmentos do estômago, lesões que acometiam além da serosa (T3 ou T4, comprometimento neoplásico em mais de sete linfonodos (N2 ou N3, presença de metástases à distância (M1 e o estádio III e IV da doença, estavam relacionados diretamente com pior prognóstico. CONCLUSÃO: Menos da metade dos pacientes encontrava-se vivo após seguimento médio de quatro anos; o estádio TNM isolado constituiu-se no principal fator prognóstico, sendo que a extensão do

  5. Pramipexole, a dopamine D2 autoreceptor agonist, decreases the extracellular concentration of dopamine in vivo.

    Science.gov (United States)

    Carter, A J; Müller, R E

    1991-07-23

    Pramipexole (SND 919) is a dopamine D2 autoreceptor agonist which is structurally related to talipexole (B-HT 920), a potential antipsychotic agent. The aim of this study was to investigate the effects of pramipexole on the extracellular concentration of dopamine in vivo. Dopamine and its metabolites, 3,4-dihydrophenylacetic acid and homovanillic acid, were measured in the anterior striatum of freely moving rats by microdialysis and high-performance liquid chromatography with electrochemical detection. Pramipexole (30 and 100 micrograms/kg) caused long-lasting decreases in the extracellular concentrations of dopamine and its metabolites. Talipexole (30 micrograms/kg) produced similar effects. Sulpiride (5 mg/kg), a selective dopamine D2 antagonist, caused a transient increase in the concentration of dopamine and long-lasting increases in the concentrations of its metabolites; it also reversed the effects of pramipexole. SCH-23390 (100 micrograms/kg), a selective dopamine D1 receptor antagonist, caused a transient increase in the concentration of dopamine but did not affect the concentrations of the metabolites. SCH-23390 failed to reverse the effects of pramipexole. These results indicate that pramipexole reduces the extracellular concentrations of dopamine and its metabolites in vivo through a reversible interaction with the dopamine D2 receptor. PMID:1685123

  6. Temperature dependence of structure and density for D2O confined in MCM-41-S

    International Nuclear Information System (INIS)

    Using neutron diffraction, we have tracked the temperature dependence of structural properties for heavy water confined in the nanoporous silica matrix MCM-41-S. By observing the correlation peak corresponding to the pore-pore distance, which is determined by the scattering contrast between the silica and the water, we monitored the density of the confined water. Concurrently, we studied the prominent first diffraction peak of D2O at ≈1.8 Å-1, which furnishes information on the microscopic arrangement of the water molecules. The data show the presence of a density maximum at ≈275 K (±10 K), a property similar to bulk water, and the occurrence of a density minimum at ≈180 K (±10 K). The prominent diffraction peak of D2O is found to shift and sharpen over a wide T range from 200 to 270 K, reflecting structural changes that are strongly correlated with the changes in density. We also observe the continuous formation of external ice, arising from water expelled from the pores while expansion takes place within the pores. An efficient method for monitoring the density of the confined D2O using a triple-axis spectrometer is demonstrated. (paper)

  7. The adsorption of H2O and D2O on porous polystyrene adsorbents

    International Nuclear Information System (INIS)

    The adsorption of H2O and D2O on porous polymers, Chromosorb-102 (styrene-divinylbenzene copolymer) and MN-200 (super cross-linked polystyrene), was studied by gas chromatography. Test adsorbates used to study the properties of the surface of these polymers were n-alkanes (C6 C9), C6H6, and the polar compounds CHCl3, CH3NO2, CH3CN, (CH3)2CO, C2H5COOCH3, and (C2H5)2O. The experimental data on the retention of the sorbates were used to determine the contributions of dispersion and specific intermolecular interactions to the total energy of adsorption for the systems studied. The electron donor KD and electron acceptor KA characteristics of the surfaces of Chromosorb-102 and MN-200 were determined. The KD and KA values obtained allow these polymers to be classified as weakly specific adsorbents with the predominance of electron acceptor properties. The adsorption isotherms of H2O and D2O were measured at 55, 67, and 80 deg C. The dependences of the isosteric heats of adsorption Qst on adsorption values were determined. The conclusion was drawn that H2O interacted with the surface of the polymers by the adsorption mechanism, whereas absorption likely made a noticeable contribution to the retention of D2O

  8. Laparoscopic D2 radical gastrectomy plus complete mesogastrium excision with membrane anatomy

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Objective:By employing video laparoscopy, we further demonstrated that mesogastrium, covered by Proper Fascia with anterior surface (A) and posterior surface (P) extends towards and fuses with the “mesogastrium bed”. Therefore, D2 lymphadenectomy plus complete mesogastrium excision (CME) is proposed as a novel approach to en bloc for advanced gastric cancer.Methods: This study was approved by the Tongji Hospital Ethics Committee.Results:A total of 54 patients underwent laparoscopic D2+CME with membrane anatomy. hTe mean number of retrieved regional lymph nodes was 35.04±10.70 (range, 14-55 lymph nodes). The mean volume of blood loss was 12.44±22.89 mL. No operative complication was observed during hospitalization.Conclusion:We believe that the laparoscopic D2 plus CME can minimize the differences in the number of lymph nodes harvested, and substantially reduce the intraoperative blood losses and surgery-related injuries in advanced gastric cancer patients.

  9. Search for cold fusion using Pd-D2O cells and Ti-D mixtures

    Science.gov (United States)

    Hill, John C.; Stassis, C.; Shinar, J.; Goldman, A. I.; Folkerts, R.; Schwellenbach, D. D.; Peterson, D. T.; Widrig, C.; Porter, M.; Benesh, C. J.; Vary, J. P.

    1990-09-01

    We have searched for cold fusion produced in an electrolytic cell with Pd cathode and Pt anode. The electrolyte was 0.1 molar LiOD in 99.8% D2O. A 2-mm rod of polycrystalline Pd and a 4-mm rod of single crystal Pd were used. No radiation was detected above background by a BF3 neutron and Ge γ-X detector. The D2 loading of the Pd was 0.8 D per Pd atom reaching saturation after 4 hours. We also attempted to duplicate the work of Scaramuzzi and co-workers on the Ti-D2 system. Both powder and pieces of Ti were used. The material was cycled several times between 1100 K and 77 K. No neutron, γ- or x-ray emission above background was observed. The results of a barrier penetration calculation for H-like atoms are presented. The high fusion rates reported for PdD x . are much larger than those expected from theoretical calculations on these systems.

  10. Glycosyltransferase GLT8D2 Positively Regulates ApoB100 Protein Expression in Hepatocytes

    Directory of Open Access Journals (Sweden)

    Yu-Tao Zhan

    2013-10-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is characterized by triglyceride (TG accumulation in hepatocytes. Very low density lipoprotein (VLDL is a major secretory product of the liver that transports endogenously synthesized TG. Disrupted VLDL secretion may contribute to the accumulation of TG in hepatocytes. ApoB100 (apolipoprotein B100 is a glycoprotein and an essential protein component of VLDL. Its glycosylation may affect VLDL assembly and secretion. However, which glycosyltransferase catalyzes apoB100 glycosylation is unknown. In this study, we cloned the GLT8D2 (glycosyltransferase 8 domain containing 2 gene from HepG2 cells and generated a series of plasmids for in vitro studies of its molecular functions. We discovered that GLT8D2 was localized in the ER, interacted with apoB100, and positively regulated the levels of apoB100 protein in HepG2 cells. Based on these results, we propose that GLT8D2 is a glycosyltransferase of apoB100 that regulates apoB100 levels in hepatocytes.

  11. Homology modeling of dopamine D2 and D3 receptors: molecular dynamics refinement and docking evaluation.

    Directory of Open Access Journals (Sweden)

    Chiara Bianca Maria Platania

    Full Text Available 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 D(3 (hD(3 receptor has been recently solved. Based on the hD(3 receptor crystal structure we generated dopamine D(2 and D(3 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 hD(3 and hD(2L receptors was differentiated by means of MD simulations and D(3 selective ligands were discriminated, in terms of binding energy, by docking calculation. Robust correlation of computed and experimental K(i was obtained for hD(3 and hD(2L 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.

  12. Device-Relaying in Cellular D2D Networks: A Fairness Perspective

    KAUST Repository

    Chaaban, Anas

    2015-10-24

    Device-to-Device (D2D) communication is envisioned to play a key role in 5G networks as a technique for meeting the demand for high data rates. In a cellular network, D2D allows not only direct communication between users, but also device relaying. In this paper, a simple instance of device-relaying is investigated, and its impact on fairness among users is studied. Namely, a cellular network consisting of two D2D-enabled users and a base-station (BS) is considered. Thus, the users who want to establish communication with the BS can act as relays for each other’s signals. While this problem is traditionally considered in the literature as a multiple-access channel with cooperation in the uplink, and a broadcast channel with cooperation in the downlink, we propose a different treatment of the problem as a multi-way channel. A simple communication scheme is proposed, and is shown to achieve significant gain in terms of fairness (measured by the symmetric rate supported) in comparison to the aforementioned traditional treatment.

  13. Effects of Lactobacillus acidophilus D2/CSL on laying hen performance

    Directory of Open Access Journals (Sweden)

    Luigi Guidobono Cavalchini

    2010-01-01

    Full Text Available In order to evaluate the effects of dietary addition of probiotic strain Lactobacillus acidophilus D2/CSL on hen performance and egg quality, 160 commercial Hy-Line Brown pullets, 17 weeks old, were divided in control group (C (N=80 and treated group (T (N=80, with 4 alternate replicates of 20 animals each per group. C was fed with a “standard diet”, whereas the T group received the same diet with an inclusion of 1x109 CFU kg-1 of Lactobacillus acidophilus D2/CSL (freeze dried cells. The experimental trial lasted 39 weeks after one week of acclimatization. Hen performance and egg quality (egg production, FCR, egg specific gravity, shell thickness, Haugh Units were recorded. The results show a higher overall egg production (P<0.01 and better FCR (Kg feed intake/Kg saleable eggs (P<0.05 in the T birds, but no statistically significant differences were observed in egg weight. The eggs from the T birds were characterized by a higher specific gravity (ESG (P<0.01 and albumen viscosity (Haugh Units (P<0.05. No significant differences in egg shell thickness were recorded. In conclusion, Lactobacillus acidophilus D2/CSL improved some important parameters in laying hen performance and egg quality.

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

    Directory of Open Access Journals (Sweden)

    Joan Segura

    Full Text Available 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. Crystallization and preliminary X-ray analysis of d-2-hydroxyacid dehydrogenase from Haloferax mediterranei

    International Nuclear Information System (INIS)

    The d-2-hydroxyacid dehydrogenase from Haloferax mediterranei has been crystallized in two different forms. Diffraction data have been collected to 1.9 Å resolution for the non-productive ternary complex of the enzyme and to 2.7 Å for the selenomethionyl derivative. d-2-Hydroxyacid dehydrogenase (D2-HDH) from Haloferax mediterranei has been overexpressed in Escherichia coli, solubilized in 8 M urea and refolded by rapid dilution. The protein was purified and crystallized by the hanging-drop vapour-diffusion method using ammonium sulfate or PEG 3350 as precipitant. Two crystal forms representing the free enzyme and the nonproductive ternary complex with α-ketohexanoic acid and NAD+ grew under these conditions. Crystals of form I diffracted to beyond 3.0 Å resolution and belonged to the monoclinic space group P21, with unit-cell parameters a = 66.0, b = 119.6, c = 86.2 Å, β = 96.3°. Crystals of form II diffracted to beyond 2.0 Å resolution and belonged to the triclinic space group P1, with unit-cell parameters a = 66.5, b = 75.2, c = 77.6 Å, α = 109.1, β = 107.5, γ = 95.9°. The calculated values for VM and analysis of the self-rotation and self-Patterson functions suggest that the asymmetric unit in both crystal forms contains two dimers related by pseudo-translational symmetry

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

    Science.gov (United States)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Quantum Dynamics Study of the Isotopic Effect on Capture Reactions: HD, D2 + CH3

    Science.gov (United States)

    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.

  19. Object recognition impairment and rescue by a dopamine D2 antagonist in hyperdopaminergic mice.

    Science.gov (United States)

    França, Arthur S C; Muratori, Larissa; Nascimento, George Carlos; Pereira, Catia Mendes; Ribeiro, Sidarta; Lobão-Soares, Bruno

    2016-07-15

    Genetically-modified mice without the dopamine transporter (DAT) are hyperdopaminergic, and serve as models for studies of addiction, mania and hyperactive disorders. Here we investigated the capacity for object recognition in mildly hyperdopaminergic mice heterozygous for DAT (DAT +/-), with synaptic dopaminergic levels situated between those shown by DAT -/- homozygous and wild-type (WT) mice. We used a classical dopamine D2 antagonist, haloperidol, to modulate the levels of dopaminergic transmission in a dose-dependent manner, before or after exploring novel objects. In comparison with WT mice, DAT +/- mice showed a deficit in object recognition upon subsequent testing 24h later. This deficit was compensated by a single 0.05mg/kg haloperidol injection 30min before training. In all mice, a 0.3mg/kg haloperidol injected immediately after training impaired object recognition. The results indicate that a mild enhancement of dopaminergic levels can be detrimental to object recognition, and that this deficit can be rescued by a low dose of a D2 dopamine receptor antagonist. This suggests that novel object recognition is optimal at intermediate levels of D2 receptor activity. PMID:27059337

  20. Cognitive and Energy Harvesting-Based D2D Communication in Cellular Networks: Stochastic Geometry Modeling and Analysis

    OpenAIRE

    Sakr, Ahmed Hamdi; Hossain, Ekram

    2014-01-01

    While cognitive radio enables spectrum-efficient wireless communication, radio frequency (RF) energy harvesting from ambient interference is an enabler for energy-efficient wireless communication. In this paper, we model and analyze cognitive and energy harvesting-based D2D communication in cellular networks. The cognitive D2D transmitters harvest energy from ambient interference and use one of the channels allocated to cellular users (in uplink or downlink), which is referred to as the D2D c...

  1. Developmental Profile of the Aberrant Dopamine D2 Receptor Response in Striatal Cholinergic Interneurons in DYT1 Dystonia

    OpenAIRE

    Giuseppe Sciamanna; Annalisa Tassone; Giuseppina Martella; Georgia Mandolesi; Francesca Puglisi; Dario Cuomo; Grazia Madeo; Giulia Ponterio; David George Standaert; Paola Bonsi; Antonio Pisani

    2011-01-01

    BACKGROUND: DYT1 dystonia, a severe form of genetically determined human dystonia, exhibits reduced penetrance among carriers and begins usually during adolescence. The reasons for such age dependence and variability remain unclear. METHODS AND RESULTS: We characterized the alterations in D2 dopamine receptor (D2R) signalling in striatal cholinergic interneurons at different ages in mice overexpressing human mutant torsinA (hMT). An abnormal excitatory response to the D2R agonist quinpirole w...

  2. Motor activity following the administration of selective D-1 and D-2 dopaminergic drugs to normal common marmosets

    OpenAIRE

    Löschmann, P A; Smith, L A; Klaus W. Lange; Jaehnig, P.; Jenner, P.; Marsden, C. D.

    1991-01-01

    In normal common marmosets administration of the D-1/D-2 agonist apomorphine or the selective D-2 agonist quinpirole caused a dose-dependent increase in motor activity and induced stereotyped behaviour. Both the selective D-2 antagonist raclopride and the selective D-1 antagonist SCH 23390 inhibited normal locomotor activity and induced catalepsy. Quinpirole- and apomorphine-induced motor activity were potently inhibited by pretreatment with raclopride. The effects of quinpirole, but not apom...

  3. Striatal dopamine D2/3 receptor availability increases after long-term bariatric surgery-induced weight loss.

    Science.gov (United States)

    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

  4. Dopamine D2 receptor activates extracellular signal-regulated kinase through the specific region in the third cytoplasmic loop.

    Science.gov (United States)

    Takeuchi, Yusuke; Fukunaga, Kohji

    2004-06-01

    To investigate whether the third cytoplasmic loop and the C-terminal cytoplasmic tail of dopamine D(2) receptor (D2R) are involved in extracellular signal-regulated kinase (ERK) activation and subsequent regulation of transcription factors, we established NG108-15 cells stably expressing D2LR and D2SR deleted 40 amino acid residues in the third cytoplasmic loop (NGD2LR-3rd-dele and NGD2SR-3rd-dele) or the C-terminal cytoplasmic tail (NGD2LR-C-dele and NGD2SR-C-dele) and evaluated these receptors' functions using luciferase reporter gene assay. Immunocytochemical studies showed similar intracellular distributions of D2LR-3rd-dele and D2SR-3rd-dele to D2LR and D2SR, respectively. Quinpirole-induced inhibition of forskolin-induced cyclic AMP responsive element (CRE) activation was not affected by the deletion of 40 amino acid residues. However, nuclear factor-kappa B (NF-kappaB) activation by D2R-3rd-dele was largely attenuated compared to that by D2R. Similarly, ERK or serum-responsive element (SRE) activation by quinpirole treatment was totally abolished in NGD2R-3rd-dele cells. Moreover, D2R-C-dele was diffusely distributed or clustered in the cell bodies and lost the receptor functions. Taken together, the 40 amino acid residues in the third cytoplasmic loop are essential for the ERK activation but not for inhibition of adenylyl cyclase through Gi/o proteins. In addition, the C-terminal cytoplasmic tail is essential for membrane association of D2Rs to elicit the receptor functions. PMID:15189353

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

    OpenAIRE

    Kim, Hyoung-Il; Hur, Hoon; Kim, Youn Nam; Lee, Hyuk-Joon; Kim, Min-Chan; Han, Sang-Uk; Hyung, Woo Jin

    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 stud...

  6. Potent activation of dopamine D3/D2 heterodimers by the antiparkinsonian agents, S32504, pramipexole and ropinirole.

    Science.gov (United States)

    Maggio, Roberto; Scarselli, Marco; Novi, Francesca; Millan, Mark J; Corsini, Giovanni U

    2003-11-01

    Recombinant, human dopamine D3 and D2 receptors form functional heterodimers upon co-expression in COS-7 cells. Herein, actions of the antiparkinsonian agents, S32504, ropinirole and pramipexole, at D3/D2L heterodimers were compared to their effects at the respective monomers and at split, chimeric D3trunk/D2tail and D2trunk/D3tail receptors: the trunk incorporated transmembrane domains (TDs) I-V and the tail TDs VI and VII. In binding assays with the antagonist [3H]nemonapride, all agonists were potent ligands of D3 receptors showing, respectively, 100-, 18- and 56-fold lower affinity at D2L receptors, mimicking the selective D3 receptor antagonist, S33084 (100-fold). At D3trunk/D2tail receptors, except for ropinirole, all drugs showed lower affinities than at D3 sites, whereas for D2trunk/D3tail receptors, affinities of all drugs were higher than at D2L sites. The proportion of high affinity binding sites recognized by S32504, pramipexole and ropinirole in membranes derived from cells co-expressing D3 and D2L sites was higher than in an equivalent mixture of membranes from cells expressing D3 or D2L sites, consistent with the promotion of heterodimer formation. In contrast, the percentage of high and low affinity sites (biphasic isotherms) recognized by S33084 was identical. Functional actions were determined by co-transfection of a chimeric adenylyl cyclase (AC)-V/VI insensitive to D3 receptors. Accordingly, D3 receptor-transfected cells were irresponsive whereas, in D2L receptor-transfected cells, agonists suppressed forskolin-stimulated cAMP production with modest potencies. In cells co-transfected with D3 and D2L receptors, S32504, ropinirole and pramipexole potently suppressed AC-V/VI with EC50s 33-, 19- and 11-fold lower than at D2L receptors, respectively. S32504 also suppressed AC-V/VI activity at split D3trunk/D2tail and D2trunk/D3tail chimeras transfected into COS-7 cells. In conclusion, antiparkinson agents behave as potent agonists at D3/D2

  7. Relationship between Dose, Drug Levels, and D2 Receptor Occupancy for the Atypical Antipsychotics Risperidone and Paliperidone

    OpenAIRE

    Muly, E.C.; Votaw, J. R.; Ritchie, J.; Howell, L.L.

    2012-01-01

    Blockade of D2 family dopamine receptors (D2Rs) is a fundamental property of antipsychotics, and the degree of striatal D2R occupancy has been related to antipsychotic and motor effects of these drugs. Recent studies suggest the D2R occupancy of antipsychotics may differ in extrastriatal regions compared with the dorsal striatum. We studied this issue in macaque monkeys by using a within-subjects design. [18F]fallypride positron emission tomography scans were obtained on four different doses ...

  8. UvrD2 Is Essential in Mycobacterium tuberculosis, but Its Helicase Activity Is Not Required ▿

    OpenAIRE

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

    2011-01-01

    UvrD is an SF1 family helicase involved in DNA repair that is widely conserved in bacteria. Mycobacterium tuberculosishas two annotated UvrD homologues; here we investigate the role of UvrD2. The uvrD2gene at its native locus could be knocked out only in the presence of a second copy of the gene, demonstrating that uvrD2is essential. Analysis of the putative protein domain structure of UvrD2 shows a distinctive domain architecture, with an extended C terminus containing an HRDC domain normall...

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

    Science.gov (United States)

    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

  10. UV-dependent production of 25-hydroxyvitamin D2 in the recombinant yeast cells expressing human CYP2R1

    International Nuclear Information System (INIS)

    Highlights: •We produce 25-hydroxyvitamin D in the recombinant yeast expressing human CYP2R1. •Vitamin D2 is produced in yeast from endogenous ergosterol with UV irradiation. •We produce 25-hydroxyvitamin D2 in the recombinant yeast without added substrate. -- Abstract: CYP2R1 is known to be a physiologically important vitamin D 25-hydroxylase. We have successfully expressed human CYP2R1 in Saccharomyces cerevisiae to reveal its enzymatic properties. In this study, we examined production of 25-hydroxylated vitamin D using whole recombinant yeast cells that expressed CYP2R1. When vitamin D3 or vitamin D2 was added to the cell suspension of CYP2R1-expressing yeast cells in a buffer containing glucose and β-cyclodextrin, the vitamins were converted into their 25-hydroxylated products. Next, we irradiated the cell suspension with UVB and incubated at 37 °C. Surprisingly, the 25-hydroxy vitamin D2 was produced without additional vitamin D2. Endogenous ergosterol was likely converted into vitamin D2 by UV irradiation and thermal isomerization, and then the resulting vitamin D2 was converted to 25-hydroxyvitamin D2 by CYP2R1. This novel method for producing 25-hydroxyvitamin D2 without a substrate could be useful for practical purposes

  11. Ultrafast energy and charge transfer in D2O/Ru(0001)

    International Nuclear Information System (INIS)

    Thin D2O layers on a Ru(0001) surface experiencing energy transfer from the photoexcited metal and charge confinement after UV illumination were studied with surface-sensitive optical techniques and in a time-resolved manner to gain a microscopic understanding of the fundamental processes within this system. The intrinsically interface-sensitive sum frequency generation (SFG) vibrational spectroscopy is employed to investigate the surface structure of an ice film grown on the Ru(0001) substrate with different thickness and thus with different interaction strength with the metal. The vibrational signatures of thicker ice samples show characteristic differences between the surfaces of amorphous and crystalline ice, but the structure of the wetting layer is significantly influenced by the metal and distinctly different from that of ice, which leads to the pronounced hydrophobic properties of the first water adlayer. The number of hydrogen bonds between this wetting layer and further multilayers is shown to be considerably limited, which most probably gives rise to the Stranski-Krastanov growth mechanism. In the present work, the reason for the stabilization is consistently explained. After an electron is excited from the metal into the (D2O) ice layer by an intense, ultrashort UV (4.66 eV) laser pulse and stabilized at its surface, the SFG vibrational spectrum in the OD stretch region is changed dramatically. Electron injection resonantly enhances the SFG signal up to a factor of 103, particularly in the frequency range of vibrations involved in hydrogen bonding. The signal from the ice surface is simultaneously overwhelmed by the contribution from the bulk. The observed changes do not spontaneously reverse back to the original state on a timescale of several hours and strongly depend on the D2O structure, since no change in the sum-frequency spectra of thin amorphous ice layers can be observed under otherwise identical conditions. The screening occurs on a timescale

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

    Science.gov (United States)

    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

  13. Saccharomyces cerevisiae Forms d-2-Hydroxyglutarate and Couples Its Degradation to d-Lactate Formation via a Cytosolic Transhydrogenase.

    Science.gov (United States)

    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. PMID:26774271

  14. Palmitoylation on the carboxyl terminus tail is required for the selective regulation of dopamine D2 versus D3 receptors.

    Science.gov (United States)

    Zhang, Xiaowei; Le, Hang Thi; Zhang, Xiaohan; Zheng, Mei; Choi, Bo-Gil; Kim, Kyeong-Man

    2016-09-01

    Dopamine D2 receptor (D2R) and D3 receptor (D3R) possess highly conserved amino acid sequences but this study showed that D3R was more extensively palmitoylated than D2R. Based on this finding, the molecular basis of this selective palmitoylation of D3R was determined and the roles of palmitoylation in the regulation of D3R functions were investigated. D3R was palmitoylated on the cysteine residue on its carboxyl terminus tail, the last amino acid residue of D3R, and an exchange of the carboxyl terminus tail between D2R and D3R (D2R-D3C and D3R-D2C) resulted in the switching of the palmitoylation phenotype. When the consensus site for palmitoylation was mutated or the palmitoylation of D3R was inhibited by treatment with 2-bromopalmitate (2BP), a palmitoylation blocker, cell-surface expression, PKC-mediated endocytosis, agonist affinity, and agonist-induced tolerance of D3R were all inhibited. However, these changes were not observed when D3R palmitoylation was inhibited by replacing its carboxyl tail with that of D2R (D3R-D2C) or when the palmitoylation of D2R-D3C was inhibited by treatment with 2BP. Overall, this study shows that D3R is palmitoylated more extensively than D2R even though the carboxyl terminus tails of D2R and D3R are highly homologous, and thus provides a new clue regarding the consensus sequence for palmitoylation. This study also shows that palmitoylation controls various functionalities of D3R only when the receptor is in the intact D3R configuration. PMID:27349735

  15. Optogenetics reveals a role for accumbal medium spiny neurons expressingdopamine D2 receptors in cocaine-induced behavioral sensitization

    Directory of Open Access Journals (Sweden)

    Shelly Sooyun eSong

    2014-10-01

    Full Text Available Long-lasting, drug-induced adaptations within the nucleus accumbens (NAc have beenproposed to contribute to drug-mediated addictive behaviors. Here we have used anoptogenetic approach to examine the role of NAc medium spiny neurons (MSNs expressingdopamine D2 receptors (D2R in cocaine-induced behavioral sensitization. Adeno-associatedviral vectors coding channelrhodopsin-2 (ChR2 were delivered into the NAc of D2R-Cretransgenic mice. This allowed us to selectively photostimulate D2R-MSNs in NAc. D2RMSNsform local inhibitory circuits, because photostimulation of D2R-MSN evokedinhibitory postsynaptic currents in neighboring MSNs. Photostimulation of NAc D2R-MSNin vivo affected neither the initiation nor the expression of cocaine-induced behavioralsensitization. However, photostimulation during the drug withdrawal period attenuatedexpression of cocaine-induced behavioral sensitization. These results show that D2R-MSNsof NAc play a key role in withdrawal-induced plasticity and may contribute to relapse aftercessation of drug abuse.

  16. Antagonism of the prostaglandin D2 receptor CRTH2 attenuates asthma pathology in mouse eosinophilic airway inflammation

    DEFF Research Database (Denmark)

    Uller, Lena; Mathiesen, Jesper Mosolff; Alenmyr, Lisa;

    2007-01-01

    BACKGROUND: Mast cell-derived prostaglandin D2 (PGD2), may contribute to eosinophilic inflammation and mucus production in allergic asthma. Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), a high affinity receptor for prostaglandin D2, mediates trafficking of TH2-cells...... inflammation even to the extent that this mechanism can explain the efficacy of ramatroban Udgivelsesdato: february...

  17. Leptin Increases Striatal Dopamine D2 Receptor Binding in Leptin-Deficient Obese (ob/ob) Mice

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. A preliminary PET evaluation of the new dopamine D2 receptor agonist [11C]MNPA in cynomolgus monkey

    International Nuclear Information System (INIS)

    This study describes the preliminary positron emission tomography (PET) evaluation of a dopamine D2-like receptor agonist (R)-2-11CH3O-N-n-propylnorapomorphine ([11C]MNPA), as a potential new radioligand for in vivo imaging of the high-affinity state of the dopamine D2 receptor (D2R). MNPA is a selective D2-like receptor agonist with a high affinity (K i=0.17 nM). [11C]MNPA was successfully synthesized by direct O-methylation of (R)-2-hydroxy-NPA using [11C]methyl iodide and was evaluated in cynomolgus monkeys. This study included baseline PET experiments and a pretreatment study using unlabeled raclopride (1 mg/kg). High uptake of radioactivity was seen in regions known to contain high D2R, with a maximum striatum-to-cerebellum ratio of 2.23±0.21 at 78 min and a maximum thalamus-to-cerebellum ratio of 1.37±0.06 at 72 min. The pretreatment study demonstrated high specific binding to D2R by reducing the striatum-to-cerebellum ratio to 1.26 at 78 min. This preliminary study indicates that the dopamine agonist [11C]MNPA has potential as an agonist radioligand for the D2-like receptor and has potential for examination of the high-affinity state of the D2R in human subjects and patients with neuropsychiatric disorders

  19. Mechanism-Based Pharmacokinetic-Pharmacodynamic Modeling of the Dopamine D-2 Receptor Occupancy of Olanzapine in Rats

    NARCIS (Netherlands)

    Johnson, Martin; Kozielska, Magdalena; Reddy, Venkatesh Pilla; Vermeulen, An; Li, Cheryl; Grimwood, Sarah; de Greef, Rik; Groothuis, Geny M. M.; Danhof, Meindert; Proost, Johannes H.

    2011-01-01

    A mechanism-based PK-PD model was developed to predict the time course of dopamine D-2 receptor occupancy (D2RO) in rat striatum following administration of olanzapine, an atypical antipsychotic drug. A population approach was utilized to quantify both the pharmacokinetics and pharmacodynamics of ol

  20. Análisis del promotor del gen del receptor de prosatglandina D2, PTGDR en pacientes con asma

    OpenAIRE

    García Solaesa, Virginia

    2012-01-01

    [ES] Esta tesis presenta un análisis del promotor del gen del receptor del prosatglandina D2, PTGDR en pacientes con asma. [ES]This thesis presents an analysis of gene promoter prosatglandina D2 receptor, PTGDR in patients with asthma.

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

    Science.gov (United States)

    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.

  2. Occupancy of pramipexole (Sifrol) at cerebral dopamine D2/3 receptors in Parkinson's disease patients.

    Science.gov (United States)

    Deutschländer, Angela; la Fougère, Christian; Boetzel, Kai; Albert, Nathalie L; Gildehaus, Franz-Josef; Bartenstein, Peter; Xiong, Guoming; Cumming, Paul

    2016-01-01

    Whereas positron emission tomography (PET) with the antagonist ligand [(18)F]fallypride reveals the composite of dopamine D2 and D3 receptors in brain, treatment of Parkinson's disease (PD) patients with the D3-prefering agonist pramipexole should result in preferential occupancy in the nucleus accumbens, where the D3-subtype is most abundant. To test this prediction we obtained pairs of [(18)F]fallypride PET recordings in a group of nine PD patients, first in a condition of treatment as usual with pramipexole (ON-Sifrol; 3 × 0.7 mg p.d.), and again at a later date, after withholding pramipexole 48-72 h (OFF-Sifrol); in that condition the serum pramipexole concentration had declined by 90% and prolactin levels had increased four-fold, in conjunction with a small but significant worsening of PD motor symptoms. Exploratory comparison with historical control material showed 14% higher dopamine D2/3 availability in the more-affected putamen of patients OFF medication. On-Sifrol there was significant (p ˂ 0.01) occupancy at [(18)F]fallypride binding sites in globus pallidus (8%) thalamus (9%) and substantia nigra (19%), as well as marginally significant occupancy in frontal and temporal cortex of patients. Contrary to expectation, comparison of ON- and OFF-Sifrol results did not reveal any discernible occupancy in nucleus accumbens, or elsewhere in the extended striatum; present methods should be sensitive to a 10% change in dopamine D2/3 receptor availability in striatum; the significant findings elsewhere in the basal ganglia and in cerebral cortex are consistent with a predominance of D3 receptors in those structures, especially in substantia nigra, and imply that therapeutic effects of pramipexole may be obtained at sites outside the extended striatum. PMID:27408789

  3. Energy Efficient IoT Data Collection in Smart Cities Exploiting D2D Communications

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2016-03-29

    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

  5. Electroacupuncture-Induced Neuroprotection against Cerebral Ischemia in Rats: Role of the Dopamine D2 Receptor

    Directory of Open Access Journals (Sweden)

    Ming-Shu Xu

    2013-01-01

    Full Text Available Background. Cerebral ischemia is known to produce brain damage and related behavioural deficits, including memory deficits and motor disorders. Evidence shows that EA significantly promotes recovery of neurological function and thus improves quality of life. Objective. Evidence exists for the involvement of catecholamines in human neuroplasticity. A better understanding of dopaminergic (DAergic modulation in this process will be important. Methods. A total of 72 adult male Sprague-Dawley (SD rats were divided into 6 groups: normal, model, EA, spiperone group, EA + spiperone group, and pergolide. The middle cerebral artery occlusion (MCAO model was used in all 6 groups except the normal group. A behavioural assessment was conducted at 1, 3, 5, and 7 days after MCAO. The percent of brain infarct area was also determined 7 days after MCAO. Tyrosine hydroxylase (TH and growth-associated protein 43 (GAP-43 fluorescence double labeling was performed in the striatum. Results. In this study, we found that EA at Fengchi (GB20 acupoints resulted in marked improvements based on a behavioural assessment. Both TTC staining and GAP-43 immunofluorescence labeling results showed that EA treatment reduced ischemia injury and promoted neuroplasticity compared with the model group. The D2R-selective agonist, pergolide, showed similar results, but these results were reversed by the D2R-selective antagonist, spiperone. We also found that there were more colocalization and expression of GAP-43 and TH in the EA and pergolide groups than those in the other groups. Conclusion. These results suggest that the neuroplasticity induced by EA was mediated by D2 autoreceptors in DAergic neurons.

  6. Energy Efficient IoT Data Collection in Smart Cities Exploiting D2D Communications

    Directory of Open Access Journals (Sweden)

    Antonino Orsino

    2016-06-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  8. Energy Efficient IoT Data Collection in Smart Cities Exploiting D2D Communications.

    Science.gov (United States)

    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

  9. Intestinal tumor suppression in ApcMin/+ mice by prostaglandin D2 receptor PTGDR

    International Nuclear Information System (INIS)

    Our earlier work showed that knockout of hematopoietic prostaglandin D synthase (HPGDS, an enzyme that produces prostaglandin D2) caused more adenomas in ApcMin/+ mice. Conversely, highly expressed transgenic HPGDS allowed fewer tumors. Prostaglandin D2 (PGD2) binds to the prostaglandin D2 receptor known as PTGDR (or DP1). PGD2 metabolites bind to peroxisome proliferator-activated receptor γ (PPARG). We hypothesized that Ptgdr or Pparg knockouts may raise numbers of tumors, if these receptors take part in tumor suppression by PGD2. To assess, we produced ApcMin/+ mice with and without Ptgdr knockouts (147 mice). In separate experiments, we produced ApcMin/+ mice expressing transgenic lipocalin-type prostaglandin D synthase (PTGDS), with and without heterozygous Pparg knockouts (104 mice). Homozygous Ptgdr knockouts raised total numbers of tumors by 30–40% at 6 and 14 weeks. Colon tumors were not affected. Heterozygous Pparg knockouts alone did not affect tumor numbers in ApcMin/+ mice. As mentioned above, our Pparg knockout assessment also included mice with highly expressed PTGDS transgenes. ApcMin/+ mice with transgenic PTGDS had fewer large adenomas (63% of control) and lower levels of v-myc avian myelocytomatosis viral oncogene homolog (MYC) mRNA in the colon. Heterozygous Pparg knockouts appeared to blunt the tumor-suppressing effect of transgenic PTGDS. However, tumor suppression by PGD2 was more clearly mediated by receptor PTGDR in our experiments. The suppression mechanism did not appear to involve changes in microvessel density or slower proliferation of tumor cells. The data support a role for PGD2 signals acting through PTGDR in suppression of intestinal tumors

  10. Time-Dependence of Risperidone and Asenapine Sensitization and Associated D2 receptor Mechanism

    Science.gov (United States)

    Gao, Jun; Li, Ming

    2013-01-01

    When an antipsychotic drug is given repeatedly and intermittently, there is often a long-term increase in its behavioral efficacy, termed antipsychotic sensitization. With the passage of time, the magnitude of antipsychotic sensitization may increase or decrease depending on the principle of Time-Dependent Sensitization (TDS) or memory decay, respectively. In the present study, we examined the time-dependent feature and possible dopamine D2 receptor mechanism of sensitization induced by the antipsychotics risperidone and asenapine in the conditioned avoidance response test. Well-trained male adult Sprague-Dawley rats were first repeatedly treated with risperidone (1.0 mg/kg) or asenapine (0.2 mg/kg) and tested for avoidance response daily for 5 consecutive days. Eight, 18 or 38 days after the 5th drug treatment, all rats were retested drug-free to assess the residual impact of prior risperidone or asenapine treatment. Drug-pretreated rats had significantly lower avoidance than vehicle-pretreated ones on this test, and the group differences increased with the passage of time. In the subsequent drug challenge test at 10, 20 or 40 days after the 5th drug treatment, all rats were injected with a low dose of risperidone (0.3 mg/kg) or asenapine (0.1 mg/kg). Drug-pretreated rats again made significantly less avoidances than controls, confirming the drug-induced sensitization effect. Finally, in the quinpirole (a D2/3 receptor agonist, 1.0 mg/kg, sc)-induced hyperlocomotion test, risperidone-pretreated rats exhibited a significantly higher level of motor activity than the vehicle-pretreated ones. These findings suggest that risperidone and asenapine sensitization is long-lasting, follows the TDS principle, and is likely mediated by D2 receptor supersensitivity. PMID:24103641

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

    Directory of Open Access Journals (Sweden)

    Hanne L. Kristensen

    2012-04-01

    Full Text Available 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.

  12. CRYOGENIC AND STRESS RELIEF THERMAL TREATMENTS IN AN AISI D2 STEEL

    OpenAIRE

    Paula Fernanda da Silva Farina; Alexandre Bellegard Farina; Celso Antonio Barbosa; Helio Goldenstein

    2012-01-01

    The effects of cryogenic treatments on an AISI D2 cold work tool steel using X-ray diffraction from syncronton radiation are studied. The aim of this work is to verify the effects of: i) time at cryogenic temperatures (3, 10 and 30 hours); ii) cryogenic temperatures (–80°C and –196°C); iii) stress relief heat treatment (130°C) before cryogenic treatments; iv) effect of double tempering at 520°C for 2 hours each time, after cryogenic treatment at –196°C for 30 hours, with and witho...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. Exact solutions to D=2 Supersymmetric Yang-Mills Quantum Mechanics with SU(3) gauge group

    CERN Document Server

    Korcyl, Piotr

    2009-01-01

    In this article we present the cut Fock space approach to the D=d+1=2, Supersymmetric Yang-Mills Quantum Mechanics (SYMQM). We start by briefly introducing the main features of the framework. We concentrate on those properties of the method which make it a convenient set up not only for numerical calculations but also for analytic computations. In the main part of the article a sample of results are discussed, namely, analytic and numerical analysis of the D=2, SYMQM systems with SU(2) and SU(3) gauge symmetry.

  15. Study of Carbide Evolution During Thermo-Mechanical Processing of AISI D2 Tool Steel

    Science.gov (United States)

    Bombac, D.; Fazarinc, M.; Podder, A. Saha; Kugler, G.

    2013-03-01

    The microstructure of a cold-worked tool steel (AISI D2) with various thermo-mechanical treatments was examined in the current study to identify the effects of these treatments on phases. X-ray diffraction was used to identify phases. Microstructural changes such as spheroidization and coarsening of carbides were studied. Thermodynamic calculations were used to verify the results of the differential thermal analysis. It was found that soaking temperature and time have a large influence on dissolution, precipitation, spheroidization, and coalescence of carbides present in the steel. This consequently influences the hot workability and final properties.

  16. Moessbauer studies of a martensitic transformation and of cryogenic treatments of a D2 tool steel

    Energy Technology Data Exchange (ETDEWEB)

    Costa, B. F. O., E-mail: benilde@ci.uc.pt [University of Coimbra, CEMDRX, Department of Physics (Portugal); Blumers, M. [University Mainz, Institute of Inorganic Chemistry (Germany); Kortmann, A. [Ingpuls GmbH (Germany); Theisen, W. [Ruhr-Universitaet Bochum, Institute of Materials (Germany); Batista, A. C. [University of Coimbra, CEMDRX, Department of Physics (Portugal); Klingelhoefer, G. [University Mainz, Institute of Inorganic Chemistry (Germany)

    2013-04-15

    A D2 tool steel X153CrVMo12 with composition C1.53 Cr12 V0.95 Mo0.80 Mn0.40(wt% Fe balanced) was studied by use of Moessbauer spectroscopy and X-ray diffraction. It was observed that the study of carbides by X-ray diffraction was difficult while Moessbauer spectroscopy gives some light on the process occurring during cryogenic treatment. With the increase of the martensitic phase the carbides decrease and are dissolved in solid solution of martensite as well as the chromium element.

  17. Molecule-cluster collisions: Reaction of D2 with Ni13

    International Nuclear Information System (INIS)

    The reactive channel (dissociative adsorption of the molecule on the cluster) of the D2 + Ni13 collision system is studied via quasiclassical molecular dynamics simulations. The effects of the initial rovibrational state of the molecule and of the cluster structure are examined. Pronounced mode-selectivity of the reaction and a strong structure-reactivity correlation are found. A technique to analyze cluster-molecule complex (''resonance'') formation is presented and used to characterize the direct vs indirect reaction pathways, the probability of formation of reactive resonances and their lifetimes

  18. Tube of (Circle F, D0, D2) Bound State in Melvin Background

    OpenAIRE

    Huang, Wung-Hong

    2004-01-01

    By using the Born-Infeld action we show that the $m$ circular fundamental strings, $n$ D2-branes and $k$ D0-branes could become a tubular bound state which is prevented from collapsing by the magnetic force in the Melvin background. However, if the ratio $m/n$ is larger then a critical value the tube will become unstable and collapse to zero radius. We make analyses to find the critical value and tube radius therein. The tube configurations we found are different from the well known tubular b...

  19. On the vibrational properties of CsD2PO4 crystal

    International Nuclear Information System (INIS)

    Lattice dynamics simulation of CsD2PO4 crystal is performed in a quasiharmonic approximation using the atomistic potential involving Coulomb, short-range, covalent, van der Waals and hydrogen-bonded interactions. The phonon dispersion relations, partial density of states, velocities of ultrasonic waves and atomic displacement parameters are calculated both in the paraelectric and ferroelectric phases. The obtained data enable us to give a detailed description of the observed Raman and IR spectra and to determine the eventual local symmetry of the PO4 groups. (copyright 2007 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  20. Neutron-scattering study of the ferroelectric phase transition in CsD2PO4

    International Nuclear Information System (INIS)

    A neutron-scattering study of the ferroelectric transition in CsD2PO4 has yielded quasi-elastic diffuse distributions of intensity typical of a one-dimensional system with chainlike ordering parallel to the ferroelectric b axis of this monoclinic crystal. Therefore, despite such suggestive similarities as the large isotope shift in T/sub c/, the transition is quite different from that of tetragonal KD2PO4 where the diffuse scattering clearly exhibits characteristics of three-dimensional dipolar interactions