WorldWideScience

Sample records for bicaudal d2 dynein

  1. Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate centrosome and nuclear positioning during mitotic entry.

    Directory of Open Access Journals (Sweden)

    Daniël Splinter

    Full Text Available BICD2 is one of the two mammalian homologues of the Drosophila Bicaudal D, an evolutionarily conserved adaptor between microtubule motors and their cargo that was previously shown to link vesicles and mRNP complexes to the dynein motor. Here, we identified a G2-specific role for BICD2 in the relative positioning of the nucleus and centrosomes in dividing cells. By combining mass spectrometry, biochemical and cell biological approaches, we show that the nuclear pore complex (NPC component RanBP2 directly binds to BICD2 and recruits it to NPCs specifically in G2 phase of the cell cycle. BICD2, in turn, recruits dynein-dynactin to NPCs and as such is needed to keep centrosomes closely tethered to the nucleus prior to mitotic entry. When dynein function is suppressed by RNA interference-mediated depletion or antibody microinjection, centrosomes and nuclei are actively pushed apart in late G2 and we show that this is due to the action of kinesin-1. Surprisingly, depletion of BICD2 inhibits both dynein and kinesin-1-dependent movements of the nucleus and cytoplasmic NPCs, demonstrating that BICD2 is needed not only for the dynein function at the nuclear pores but also for the antagonistic activity of kinesin-1. Our study demonstrates that the nucleus is subject to opposing activities of dynein and kinesin-1 motors and that BICD2 contributes to nuclear and centrosomal positioning prior to mitotic entry through regulation of both dynein and kinesin-1.

  2. 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

  3. BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures

    Science.gov (United States)

    Splinter, Daniël; Razafsky, David S.; Schlager, Max A.; Serra-Marques, Andrea; Grigoriev, Ilya; Demmers, Jeroen; Keijzer, Nanda; Jiang, Kai; Poser, Ina; Hyman, Anthony A.; Hoogenraad, Casper C.; King, Stephen J.; Akhmanova, Anna

    2012-01-01

    Cytoplasmic dynein is the major microtubule minus-end–directed cellular motor. Most dynein activities require dynactin, but the mechanisms regulating cargo-dependent dynein–dynactin interaction are poorly understood. In this study, we focus on dynein–dynactin recruitment to cargo by the conserved motor adaptor Bicaudal D2 (BICD2). We show that dynein and dynactin depend on each other for BICD2-mediated targeting to cargo and that BICD2 N-terminus (BICD2-N) strongly promotes stable interaction between dynein and dynactin both in vitro and in vivo. Direct visualization of dynein in live cells indicates that by itself the triple BICD2-N–dynein–dynactin complex is unable to interact with either cargo or microtubules. However, tethering of BICD2-N to different membranes promotes their microtubule minus-end–directed motility. We further show that LIS1 is required for dynein-mediated transport induced by membrane tethering of BICD2-N and that LIS1 contributes to dynein accumulation at microtubule plus ends and BICD2-positive cellular structures. Our results demonstrate that dynein recruitment to cargo requires concerted action of multiple dynein cofactors. PMID:22956769

  4. 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

  5. Cytoplasmic dynein nomenclature

    Science.gov (United States)

    Pfister, K. Kevin; Fisher, Elizabeth M.C.; Gibbons, Ian R.; Hays, Thomas S.; Holzbaur, Erika L.F.; McIntosh, J. Richard; Porter, Mary E.; Schroer, Trina A.; Vaughan, Kevin T.; Witman, George B.; King, Stephen M.; Vallee, Richard B.

    2005-01-01

    A variety of names has been used in the literature for the subunits of cytoplasmic dynein complexes. Thus, there is a strong need for a more definitive consensus statement on nomenclature. This is especially important for mammalian cytoplasmic dyneins, many subunits of which are encoded by multiple genes. We propose names for the mammalian cytoplasmic dynein subunit genes and proteins that reflect the phylogenetic relationships of the genes and the published studies clarifying the functions of the polypeptides. This nomenclature recognizes the two distinct cytoplasmic dynein complexes and has the flexibility to accommodate the discovery of new subunits and isoforms. PMID:16260502

  6. 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.

  7. Analyses of Dynein Heavy Chain Mutations Reveal Complex Interactions Between Dynein Motor Domains and Cellular Dynein Functions

    Science.gov (United States)

    Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Razafsky, David S.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

    2012-01-01

    Cytoplasmic dynein transports cargoes for a variety of crucial cellular functions. However, since dynein is essential in most eukaryotic organisms, the in-depth study of the cellular function of dynein via genetic analysis of dynein mutations has not been practical. Here, we identify and characterize 34 different dynein heavy chain mutations using a genetic screen of the ascomycete fungus Neurospora crassa, in which dynein is nonessential. Interestingly, our studies show that these mutations segregate into five different classes based on the in vivo localization of the mutated dynein motors. Furthermore, we have determined that the different classes of dynein mutations alter vesicle trafficking, microtubule organization, and nuclear distribution in distinct ways and require dynactin to different extents. In addition, biochemical analyses of dynein from one mutant strain show a strong correlation between its in vitro biochemical properties and the aberrant intracellular function of that altered dynein. When the mutations were mapped to the published dynein crystal structure, we found that the three-dimensional structural locations of the heavy chain mutations were linked to particular classes of altered dynein functions observed in cells. Together, our data indicate that the five classes of dynein mutations represent the entrapment of dynein at five separate points in the dynein mechanochemical and transport cycles. We have developed N. crassa as a model system where we can dissect the complexities of dynein structure, function, and interaction with other proteins with genetic, biochemical, and cell biological studies. PMID:22649085

  8. Subunit organization in cytoplasmic dynein subcomplexes

    Science.gov (United States)

    King, Stephen J.; Bonilla, Myriam; Rodgers, Michael E.; Schroer, Trina A.

    2002-01-01

    Because cytoplasmic dynein plays numerous critical roles in eukaryotic cells, determining the subunit composition and the organization and functions of the subunits within dynein are important goals. This has been difficult partly because of accessory polypeptide heterogeneity of dynein populations. The motor domain containing heavy chains of cytoplasmic dynein are associated with multiple intermediate, light intermediate, and light chain accessory polypeptides. We examined the organization of these subunits within cytoplasmic dynein by separating the molecule into two distinct subcomplexes. These subcomplexes were competent to reassemble into a molecule with dynein-like properties. One subcomplex was composed of the dynein heavy and light intermediate chains whereas the other subcomplex was composed of the intermediate and light chains. The intermediate and light chain subcomplex could be further separated into two pools, only one of which contained dynein light chains. The two pools had distinct intermediate chain compositions, suggesting that intermediate chain isoforms have different light chain–binding properties. When the two intermediate chain pools were characterized by analytical velocity sedimentation, at least four molecular components were seen: intermediate chain monomers, intermediate chain dimers, intermediate chain monomers with bound light chains, and a mixture of intermediate chain dimers with assorted bound light chains. These data provide new insights into the compositional heterogeneity and assembly of the cytoplasmic dynein complex and suggest that individual dynein molecules have distinct molecular compositions in vivo. PMID:11967380

  9. Single molecule analysis of cytoplasmic dynein motility

    Science.gov (United States)

    Yildiz, Ahmet

    2014-03-01

    Cytoplasmic dynein is a homodimeric AAA + motor that transports a multitude of cargos towards the microtubule (MT) minus end. The mechanism of dynein motility remains unclear, due to its large size (2.6 MDa) and the complexity of its structure. By tracking the stepping motion of both heads at nanometer resolution, we observed that dynein heads move independently along the MT, in contrast to hand over hand movement of kinesins and myosin. Stepping behavior of the heads varies as a function of interhead separation and establishing the basis of high variability in dynein step size. By engineering the mechanical and catalytic properties of the dynein motor domain, we show that a rigid linkage between monomers and dimerization between N-terminal tail domains are not essential for processive movement. Instead, dynein processivity minimally requires the linker domain of one active monomer to be attached to an inert MT tether retaining only the MT-binding domain. The release of a dynein monomer from the MT can be mediated either by nucleotide binding or external load. Nucleotide dependent release is inhibited by the tension on the linker domain at high interhead separations. Tension dependent release is highly asymmetric, with faster release towards the minus-end. Reversing the asymmetry of the MT binding interface results in plus end directed motility, even though the force was generated by the dynein motor activity. On the basis of these measurements, we propose a model that describes the basis of dynein processivity, directionality and force generation.

  10. Integrated Control of Axonemal Dynein AAA+ Motors

    Science.gov (United States)

    King, Stephen M.

    2012-01-01

    Axonemal dyneins are AAA+ enzymes that convert ATP hydrolysis to mechanical work. This leads to the sliding of doublet microtubules with respect to each other and ultimately the generation of ciliary/flagellar beating. However, in order for useful work to be generated, the action of individual dynein motors must be precisely controlled. In addition, cells modulate the motility of these organelles through a variety of second messenger systems and these signals too must be integrated by the dynein motors to yield an appropriate output. This review describes the current status of efforts to understand dynein control mechanisms and their connectivity focusing mainly on studies of the outer dynein arm from axonemes of the unicellular biflagellate green alga Chlamydomonas. PMID:22406539

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

    Science.gov (United States)

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

    2015-01-01

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

  12. A Mouse Neurodegenerative Dynein Heavy Chain Mutation Alters Dynein Motility and Localization in Neurospora crassa

    Science.gov (United States)

    Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

    2013-01-01

    Cytoplasmic dynein is responsible for the transport and delivery of cargoes in organisms ranging from humans to fungi. Dysfunction of dynein motor machinery due to mutations in dynein or its activating complex dynactin can result in one of several neurological diseases in mammals. The mouse Legs at odd angles (Loa) mutation in the tail domain of the dynein heavy chain has been shown to lead to progressive neurodegeneration in mice. The mechanism by which the Loa mutation affects dynein function is just beginning to be understood. In this work, we generated the dynein tail mutation observed in Loa mice into the Neurospora crassa genome and utilized cell biological and complementing biochemical approaches to characterize how that tail mutation affected dynein function. We determined that the Loa mutation exhibits several subtle defects upon dynein function in N. crassa that were not seen in mice, including alterations in dynein localization, impaired velocity of vesicle transport, and in the biochemical properties of purified motors. Our work provides new information on the role of the tail domain on dynein function and points out areas of future research that will be of interest to pursue in mammalian systems. PMID:22991199

  13. 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.

  14. 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...

  15. The ciliary inner dynein arm, I1 dynein, is assembled in the cytoplasm and transported by IFT before axonemal docking.

    Science.gov (United States)

    Viswanadha, Rasagnya; Hunter, Emily L; Yamamoto, Ryosuke; Wirschell, Maureen; Alford, Lea M; Dutcher, Susan K; Sale, Winfield S

    2014-10-01

    To determine mechanisms of assembly of ciliary dyneins, we focused on the Chlamydomonas inner dynein arm, I1 dynein, also known as dynein f. I1 dynein assembles in the cytoplasm as a 20S complex similar to the 20S I1 dynein complex isolated from the axoneme. The intermediate chain subunit, IC140 (IDA7), and heavy chains (IDA1, IDA2) are required for 20S I1 dynein preassembly in the cytoplasm. Unlike I1 dynein derived from the axoneme, the cytoplasmic 20S I1 complex will not rebind I1-deficient axonemes in vitro. To test the hypothesis that I1 dynein is transported to the distal tip of the cilia for assembly in the axoneme, we performed cytoplasmic complementation in dikaryons formed between wild-type and I1 dynein mutant cells. Rescue of I1 dynein assembly in mutant cilia occurred first at the distal tip and then proceeded toward the proximal axoneme. Notably, in contrast to other combinations, I1 dynein assembly was significantly delayed in dikaryons formed between ida7 and ida3. Furthermore, rescue of I1 dynein assembly required new protein synthesis in the ida7 × ida3 dikaryons. On the basis of the additional observations, we postulate that IDA3 is required for 20S I1 dynein transport. Cytoplasmic complementation in dikaryons using the conditional kinesin-2 mutant, fla10-1 revealed that transport of I1 dynein is dependent on kinesin-2 activity. Thus, I1 dynein complex assembly depends upon IFT for transport to the ciliary distal tip prior to docking in the axoneme.

  16. 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.

  17. A Unified Taxonomy for Ciliary Dyneins

    Science.gov (United States)

    Hom, Erik F.Y.; Witman, George B.; Harris, Elizabeth H.; Dutcher, Susan K.; Kamiya, Ritsu; Mitchell, David R.; Pazour, Gregory J.; Porter, Mary E.; Sale, Winfield S.; Wirschell, Maureen; Yagi, Toshiki; King, Stephen M.

    2011-01-01

    The formation and function of eukaryotic cilia/flagella require the action of a large array of dynein microtubule motor complexes. Due to genetic, biochemical, and microscopic tractability, Chlamydomonas reinhardtii has become the premier model system in which to dissect the role of dyneins in flagellar assembly, motility, and signaling. Currently, fifty-four proteins have been described as components of various Chlamydomonas flagellar dyneins or as factors required for their assembly in the cytoplasm and/or transport into the flagellum; orthologues of nearly all these components are present in other ciliated organisms including humans. For historical reasons, the nomenclature of these diverse dynein components and their corresponding genes, mutant alleles and orthologues has become extraordinarily confusing. Here, we unify Chlamydomonas dynein gene nomenclature and establish a systematic classification scheme based on structural properties of the encoded proteins. Furthermore, we provide detailed tabulations of the various mutant alleles and protein aliases that have been used and explicitly define the correspondence with orthologous components in other model organisms and humans. PMID:21953912

  18. 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

  19. Regulation of Cytoplasmic Dynein ATPase by Lis1

    Science.gov (United States)

    Mesngon, Mariano T.; Tarricone, Cataldo; Hebbar, Sachin; Guillotte, Aimee M.; Schmitt, E. William; Lanier, Lorene; Musacchio, Andrea; King, Stephen J.; Smith, Deanna S.

    2015-01-01

    Mutations in Lis1 cause classical lissencephaly, a developmental brain abnormality characterized by defects in neuronal positioning. Over the last decade, a clear link has been forged between Lis1 and the microtubule motor cytoplasmic dynein. Substantial evidence indicates that Lis1 functions in a highly conserved pathway with dynein to regulate neuronal migration and other motile events. Yeast two-hybrid studies predict that Lis1 binds directly to dynein heavy chains (Sasaki et al., 2000; Tai et al., 2002), but the mechanistic significance of this interaction is not well understood. We now report that recombinant Lis1 binds to native brain dynein and significantly increases the microtubule-stimulated enzymatic activity of dynein in vitro. Lis1 does this without increasing the proportion of dynein that binds to microtubules, indicating that Lis1 influences enzymatic activity rather than microtubule association. Dynein stimulation in vitro is not a generic feature of microtubule-associated proteins, because tau did not stimulate dynein. To our knowledge, this is the first indication that Lis1 or any other factor directly modulates the enzymatic activity of cytoplasmic dynein. Lis1 must be able to homodimerize to stimulate dynein, because a C-terminal fragment (containing the dynein interaction site but missing the self-association domain) was unable to stimulate dynein. Binding and colocalization studies indicate that Lis1 does not interact with all dynein complexes found in the brain. We propose a model in which Lis1 stimulates the activity of a subset of motors, which could be particularly important during neuronal migration and long-distance axonal transport. PMID:16481446

  20. 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...

  1. 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.

  2. BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures

    NARCIS (Netherlands)

    D. Splinter (Daniël); D.S. Razafsky (David); M.A. Schlager (Max); A. Serra-Marques (Andrea); I. Grigoriev (Ilya); J.A.A. Demmers (Jeroen); N. Keijzer (Nanda); K. Jiang (Kai); S. Poser; A. Hyman (Anthony); C.C. Hoogenraad (Casper); S.J. King (Stephen); A.S. Akhmanova (Anna)

    2012-01-01

    textabstractCytoplasmic dynein is the major microtubule minus-end-directed cellular motor. Most dynein activities require dynactin, but the mechanisms regulating cargo-dependent dynein-dynactin interaction are poorly understood. In this study, we focus on dynein-dynactin recruitment to cargo by the

  3. 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 ...

  4. 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.

  5. 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......-balancing scheme of elements into nodes is deterministic and general enough to be applied to other hierarchical tree-based overlays. This load-balancing mechanism is based on an innovative lazy weight-balancing mechanism, which is interesting in its own right....

  6. Analysis of the Dynein-Dynactin Interaction In Vitro and In Vivo

    Science.gov (United States)

    King, Stephen J.; Brown, Christa L.; Maier, Kerstin C.; Quintyne, Nicholas J.; Schroer, Trina A.

    2003-01-01

    Cytoplasmic dynein and dynactin are megadalton-sized multisubunit molecules that function together as a cytoskeletal motor. In the present study, we explore the mechanism of dynein-dynactin binding in vitro and then extend our findings to an in vivo context. Solution binding assays were used to define binding domains in the dynein intermediate chain (IC) and dynactin p150Glued subunit. Transient overexpression of a series of fragments of the dynein IC was used to determine the importance of this subunit for dynein function in mammalian tissue culture cells. Our results suggest that a functional dynein-dynactin interaction is required for proper microtubule organization and for the transport and localization of centrosomal components and endomembrane compartments. The dynein IC fragments have different effects on endomembrane localization, suggesting that different endomembranes may bind dynein via distinct mechanisms. PMID:14565986

  7. Phosphoregulation of an Inner Dynein Arm Complex in Chlamydomonas reinhardtii Is Altered in Phototactic Mutant Strains

    Science.gov (United States)

    King, Stephen J.; Dutcher, Susan K.

    1997-01-01

    To gain a further understanding of axonemal dynein regulation, mutant strains of Chlamydomonas reinhardtii that had defects in both phototactic behavior and flagellar motility were identified and characterized. ptm1, ptm2, and ptm3 mutant strains exhibited motility phenotypes that resembled those of known inner dynein arm region mutant strains, but did not have biochemical or genetic phenotypes characteristic of other inner dynein arm mutations. Three other mutant strains had defects in the f class of inner dynein arms. Dynein extracts from the pf9-4 strain were missing the entire f complex. Strains with mutations in pf9/ida1, ida2, or ida3 failed to assemble the f dynein complex and did not exhibit phototactic behavior. Fractionated dynein from mia1-1 and mia2-1 axonemes exhibited a novel f class inner dynein arm biochemical phenotype; the 138-kD f intermediate chain was present in altered phosphorylation forms. In vitro axonemal dynein activity was reduced by the mia1-1 and mia2-1 mutations. The addition of kinase inhibitor restored axonemal dynein activity concomitant with the dephosphorylation of the 138-kD f intermediate chain. Dynein extracts from uni1-1 axonemes, which specifically assemble only one of the two flagella, contained relatively high levels of the altered phosphorylation forms of the 138-kD intermediate chain. We suggest that the f dynein complex may be phosphoregulated asymmetrically between the two flagella to achieve phototactic turning. PMID:9008712

  8. A gradient of maternal Bicaudal-C controls vertebrate embryogenesis via translational repression of mRNAs encoding cell fate regulators.

    Science.gov (United States)

    Park, Sookhee; Blaser, Susanne; Marchal, Melissa A; Houston, Douglas W; Sheets, Michael D

    2016-03-01

    Vertebrate Bicaudal-C (Bicc1) has important biological roles in the formation and homeostasis of multiple organs, but direct experiments to address the role of maternal Bicc1 in early vertebrate embryogenesis have not been reported. Here, we use antisense phosphorothioate-modified oligonucleotides and the host-transfer technique to eliminate specifically maternal stores of both bicc1 mRNA and Bicc1 protein from Xenopus laevis eggs. Fertilization of these Bicc1-depleted eggs produced embryos with an excess of dorsal-anterior structures and overexpressed organizer-specific genes, indicating that maternal Bicc1 is crucial for normal embryonic patterning of the vertebrate embryo. Bicc1 is an RNA-binding protein with robust translational repression function. Here, we show that the maternal mRNA encoding the cell-fate regulatory protein Wnt11b is a direct target of Bicc1-mediated repression. It is well established that the Wnt signaling pathway is crucial to vertebrate embryogenesis. Thus, the work presented here links the molecular function of Bicc1 in mRNA target-specific translation repression to its biological role in the maternally controlled stages of vertebrate embryogenesis. PMID:26811381

  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. 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.

  11. 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.

  12. Genetic analysis of the cytoplasmic dynein subunit families.

    Directory of Open Access Journals (Sweden)

    K Kevin Pfister

    2006-01-01

    Full Text Available Cytoplasmic dyneins, the principal microtubule minus-end-directed motor proteins of the cell, are involved in many essential cellular processes. The major form of this enzyme is a complex of at least six protein subunits, and in mammals all but one of the subunits are encoded by at least two genes. Here we review current knowledge concerning the subunits, their interactions, and their functional roles as derived from biochemical and genetic analyses. We also carried out extensive database searches to look for new genes and to clarify anomalies in the databases. Our analysis documents evolutionary relationships among the dynein subunits of mammals and other model organisms, and sheds new light on the role of this diverse group of proteins, highlighting the existence of two cytoplasmic dynein complexes with distinct cellular roles.

  13. 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...

  14. Identification of the t Complex–encoded Cytoplasmic Dynein Light Chain Tctex1 in Inner Arm I1 Supports the Involvement of Flagellar Dyneins in Meiotic Drive

    Science.gov (United States)

    Harrison, Alistair; Olds-Clarke, Patricia; King, Stephen M.

    1998-01-01

    The cytoplasmic dynein light chain Tctex1 is a candidate for one of the distorter products involved in the non-Mendelian transmission of mouse t haplotypes. It has been unclear, however, how the t-specific mutations in this protein, which is found associated with cytoplasmic dynein in many tissues, could result in a male germ cell–specific phenotype. Here, we demonstrate that Tctex1 is not only a cytoplasmic dynein component, but is also present both in mouse sperm and Chlamydomonas flagella. Genetic and biochemical dissection of the Chlamydomonas flagellum reveal that Tctex1 is a previously undescribed component of inner dynein arm I1. Combined with the recent identification of another putative t complex distorter, Tctex2, within the outer dynein arm, these results support the hypothesis that transmission ratio distortion (meiotic drive) of mouse t haplotypes involves dysfunction of both flagellar inner and outer dynein arms but does not require the cytoplasmic isozyme. PMID:9490726

  15. 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.

  16. 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.

  17. 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...

  18. 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

  19. Functional Architecture of the Outer Arm Dynein Conformational Switch*

    Science.gov (United States)

    King, Stephen M.; Patel-King, Ramila S.

    2012-01-01

    Dynein light chain 1 (LC1/DNAL1) is one of the most highly conserved components of ciliary axonemal outer arm dyneins, and it associates with both a heavy chain motor unit and tubulin located within the A-tubule of the axonemal outer doublet microtubules. In a variety of model systems, lack of LC1 or expression of mutant forms leads to profound defects in ciliary motility, including the failure of the hydrodynamic coupling needed for ciliary metachronal synchrony, random stalling during the power/recovery stroke transition, an aberrant response to imposed viscous load, and in some cases partial failure of motor assembly. These phenotypes have led to the proposal that LC1 acts as part of a mechanical switch to control motor function in response to alterations in axonemal curvature. Here we have used NMR chemical shift mapping to define the regions perturbed by a series of mutations in the C-terminal domain that yield a range of phenotypic effects on motility. In addition, we have identified the subdomain of LC1 involved in binding microtubules and characterized the consequences of an Asn → Ser alteration within the terminal leucine-rich repeat that in humans causes primary ciliary dyskinesia. Together, these data define a series of functional subdomains within LC1 and allow us to propose a structural model for the organization of the dynein heavy chain-LC1-microtubule ternary complex that is required for the coordinated activity of dynein motors in cilia. PMID:22157010

  20. 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.

  1. Differential Light Chain Assembly Influences Outer Arm Dynein Motor Function

    Science.gov (United States)

    DiBella, Linda M.; Gorbatyuk, Oksana; Sakato, Miho; Wakabayashi, Ken-ichi; Patel-King, Ramila S.; Pazour, Gregory J.; Witman, George B.; King, Stephen M.

    2005-01-01

    Tctex1 and Tctex2 were originally described as potential distorters/sterility factors in the non-Mendelian transmission of t-haplotypes in mice. These proteins have since been identified as subunits of cytoplasmic and/or axonemal dyneins. Within the Chlamydomonas flagellum, Tctex1 is a subunit of inner arm I1. We have now identified a second Tctex1-related protein (here termed LC9) in Chlamydomonas. LC9 copurifies with outer arm dynein in sucrose density gradients and is missing only in those strains completely lacking this motor. Zero-length cross-linking of purified outer arm dynein indicates that LC9 interacts directly with both the IC1 and IC2 intermediate chains. Immunoblot analysis revealed that LC2, LC6, and LC9 are missing in an IC2 mutant strain (oda6-r88) that can assemble outer arms but exhibits significantly reduced flagellar beat frequency. This defect is unlikely to be due to lack of LC6, because an LC6 null mutant (oda13) exhibits only a minor swimming abnormality. Using an LC2 null mutant (oda12-1), we find that although some outer arm dynein components assemble in the absence of LC2, they are nonfunctional. In contrast, dyneins from oda6-r88, which also lack LC2, retain some activity. Furthermore, we observed a synthetic assembly defect in an oda6-r88 oda12-1 double mutant. These data suggest that LC2, LC6, and LC9 have different roles in outer arm assembly and are required for wild-type motor function in the Chlamydomonas flagellum. PMID:16195342

  2. Interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in Drosophila neurons.

    Science.gov (United States)

    del Castillo, Urko; Winding, Michael; Lu, Wen; Gelfand, Vladimir I

    2015-12-28

    In this study, we investigated how microtubule motors organize microtubules in Drosophila neurons. We showed that, during the initial stages of axon outgrowth, microtubules display mixed polarity and minus-end-out microtubules push the tip of the axon, consistent with kinesin-1 driving outgrowth by sliding antiparallel microtubules. At later stages, the microtubule orientation in the axon switches from mixed to uniform polarity with plus-end-out. Dynein knockdown prevents this rearrangement and results in microtubules of mixed orientation in axons and accumulation of microtubule minus-ends at axon tips. Microtubule reorganization requires recruitment of dynein to the actin cortex, as actin depolymerization phenocopies dynein depletion, and direct recruitment of dynein to the membrane bypasses the actin requirement. Our results show that cortical dynein slides 'minus-end-out' microtubules from the axon, generating uniform microtubule arrays. We speculate that differences in microtubule orientation between axons and dendrites could be dictated by differential activity of cortical dynein.

  3. Dynein modifiers in C. elegans: light chains suppress conditional heavy chain mutants.

    Directory of Open Access Journals (Sweden)

    Sean M O'Rourke

    2007-08-01

    Full Text Available Cytoplasmic dynein is a microtubule-dependent motor protein that functions in mitotic cells during centrosome separation, metaphase chromosome congression, anaphase spindle elongation, and chromosome segregation. Dynein is also utilized during interphase for vesicle transport and organelle positioning. While numerous cellular processes require cytoplasmic dynein, the mechanisms that target and regulate this microtubule motor remain largely unknown. By screening a conditional Caenorhabditis elegans cytoplasmic dynein heavy chain mutant at a semipermissive temperature with a genome-wide RNA interference library to reduce gene functions, we have isolated and characterized twenty dynein-specific suppressor genes. When reduced in function, these genes suppress dynein mutants but not other conditionally mutant loci, and twelve of the 20 specific suppressors do not exhibit sterile or lethal phenotypes when their function is reduced in wild-type worms. Many of the suppressor proteins, including two dynein light chains, localize to subcellular sites that overlap with those reported by others for the dynein heavy chain. Furthermore, knocking down any one of four putative dynein accessory chains suppresses the conditional heavy chain mutants, suggesting that some accessory chains negatively regulate heavy chain function. We also identified 29 additional genes that, when reduced in function, suppress conditional mutations not only in dynein but also in loci required for unrelated essential processes. In conclusion, we have identified twenty genes that in many cases are not essential themselves but are conserved and when reduced in function can suppress conditionally lethal C. elegans cytoplasmic dynein heavy chain mutants. We conclude that conserved but nonessential genes contribute to dynein function during the essential process of mitosis.

  4. 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

    2015-11-26

    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.

  5. Chlamydomonas axonemal dynein assembly locus ODA8 encodes a conserved flagellar protein needed for cytoplasmic maturation of outer dynein arm complexes.

    Science.gov (United States)

    Desai, Paurav B; Freshour, Judy R; Mitchell, David R

    2015-01-01

    The Chlamydomonas reinhardtii oda8 mutation blocks assembly of flagellar outer dynein arms (ODAs), and interacts genetically with ODA5 and ODA10, which encode axonemal proteins thought to aid dynein binding onto axonemal docking sites. We positionally cloned ODA8 and identified the gene product as the algal homolog of vertebrate LRRC56. Its flagellar localization depends on ODA5 and ODA10, consistent with genetic interaction studies, but phylogenomics suggests that LRRC56 homologs play a role in intraflagellar transport (IFT)-dependent assembly of outer row dynein arms, not axonemal docking. ODA8 distribution between cytoplasm and flagella is similar to that of IFT proteins and about half of flagellar ODA8 is in the soluble matrix fraction. Dynein extracted in vitro from wild type axonemes will rebind efficiently to oda8 mutant axonemes, without re-binding of ODA8, further supporting a role in dynein assembly or transport, not axonemal binding. Assays comparing preassembled ODA complexes from the cytoplasm of wild type and mutant strains show that dynein in oda8 mutant cytoplasm has not properly preassembled and cannot bind normally onto oda axonemes. We conclude that ODA8 plays an important role in formation and transport of mature dynein complexes during flagellar assembly.

  6. 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....

  7. N-Acetyl-D-Glucosamine Kinase Interacts with Dynein-Lis1-NudE1 Complex and Regulates Cell Division.

    Science.gov (United States)

    Sharif, Syeda Ridita; Islam, Ariful; Moon, Il Soo

    2016-09-01

    N-acetyl-D-glucosamine kinase (GlcNAc kinase or NAGK) primarily catalyzes phosphoryl transfer to GlcNAc during amino sugar metabolism. Recently, it was shown NAGK interacts with dynein light chain roadblock type 1 (DYNLRB1) and upregulates axo-dendritic growth, which is an enzyme activity-independent, non-canonical structural role. The authors examined the distributions of NAGK and NAGK-dynein complexes during the cell cycle in HEK293T cells. NAGK was expressed throughout different stages of cell division and immunocytochemistry (ICC) showed NAGK was localized at nuclear envelope, spindle microtubules (MTs), and kinetochores (KTs). A proximity ligation assay (PLA) for NAGK and DYNLRB1 revealed NAGK-dynein complex on nuclear envelopes in prophase cells and on chromosomes in metaphase cells. NAGK-DYNLRB1 PLA followed by Lis1/NudE1 immunostaining showed NAGK-dynein complexes were colocalized with Lis1 and NudE1 signals, and PLA for NAGK-Lis1 showed similar signal patterns, suggesting a functional link between NAGK and dynein-Lis1 complex. Subsequently, NAGK-dynein complexes were found in KTs and on nuclear membranes where KTs were marked with CENP-B ICC and nuclear membrane with lamin ICC. Furthermore, knockdown of NAGK by small hairpin (sh) RNA was found to delay cell division. These results indicate that the NAGK-dynein interaction with the involvements of Lis1 and NudE1 plays an important role in prophase nuclear envelope breakdown (NEB) and metaphase MT-KT attachment during eukaryotic cell division.

  8. N-Acetyl-D-Glucosamine Kinase Interacts with Dynein-Lis1-NudE1 Complex and Regulates Cell Division.

    Science.gov (United States)

    Sharif, Syeda Ridita; Islam, Ariful; Moon, Il Soo

    2016-09-01

    N-acetyl-D-glucosamine kinase (GlcNAc kinase or NAGK) primarily catalyzes phosphoryl transfer to GlcNAc during amino sugar metabolism. Recently, it was shown NAGK interacts with dynein light chain roadblock type 1 (DYNLRB1) and upregulates axo-dendritic growth, which is an enzyme activity-independent, non-canonical structural role. The authors examined the distributions of NAGK and NAGK-dynein complexes during the cell cycle in HEK293T cells. NAGK was expressed throughout different stages of cell division and immunocytochemistry (ICC) showed NAGK was localized at nuclear envelope, spindle microtubules (MTs), and kinetochores (KTs). A proximity ligation assay (PLA) for NAGK and DYNLRB1 revealed NAGK-dynein complex on nuclear envelopes in prophase cells and on chromosomes in metaphase cells. NAGK-DYNLRB1 PLA followed by Lis1/NudE1 immunostaining showed NAGK-dynein complexes were colocalized with Lis1 and NudE1 signals, and PLA for NAGK-Lis1 showed similar signal patterns, suggesting a functional link between NAGK and dynein-Lis1 complex. Subsequently, NAGK-dynein complexes were found in KTs and on nuclear membranes where KTs were marked with CENP-B ICC and nuclear membrane with lamin ICC. Furthermore, knockdown of NAGK by small hairpin (sh) RNA was found to delay cell division. These results indicate that the NAGK-dynein interaction with the involvements of Lis1 and NudE1 plays an important role in prophase nuclear envelope breakdown (NEB) and metaphase MT-KT attachment during eukaryotic cell division. PMID:27646688

  9. 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.

  10. Mutations in the gene encoding IFT dynein complex component WDR34 cause Jeune asphyxiating thoracic dystrophy.

    Science.gov (United States)

    Schmidts, Miriam; Vodopiutz, Julia; Christou-Savina, Sonia; Cortés, Claudio R; McInerney-Leo, Aideen M; Emes, Richard D; Arts, Heleen H; Tüysüz, Beyhan; D'Silva, Jason; Leo, Paul J; Giles, Tom C; Oud, Machteld M; Harris, Jessica A; Koopmans, Marije; Marshall, Mhairi; Elçioglu, Nursel; Kuechler, Alma; Bockenhauer, Detlef; Moore, Anthony T; Wilson, Louise C; Janecke, Andreas R; Hurles, Matthew E; Emmet, Warren; Gardiner, Brooke; Streubel, Berthold; Dopita, Belinda; Zankl, Andreas; Kayserili, Hülya; Scambler, Peter J; Brown, Matthew A; Beales, Philip L; Wicking, Carol; Duncan, Emma L; Mitchison, Hannah M

    2013-11-01

    Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery.

  11. 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...

  12. 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.

  13. M phase phosphorylation of cytoplasmic dynein intermediate chain and p150(Glued).

    Science.gov (United States)

    Huang, C Y; Chang, C P; Huang, C L; Ferrell, J E

    1999-05-14

    To understand how the dramatic cell biological changes of oocyte maturation are brought about, we have begun to identify proteins whose phosphorylation state changes during Xenopus oocyte maturation. Here we have focused on one such protein, p83. We partially purified p83, obtained peptide sequence, and identified it as the intermediate chain of cytoplasmic dynein. During oocyte maturation, dynein intermediate chain became hyperphosphorylated at the time of germinal vesicle breakdown and remained hyperphosphorylated throughout the rest of meiosis and early embryogenesis. p150(Glued), a subunit of dynactin that has been shown to bind to dynein intermediate chain, underwent similar changes in its phosphorylation. Both dynein intermediate chain and p150(Glued) also became hyperphosphorylated during M phase in XTC-2 cells and HeLa cells. Thus, two components of the dynein-dynactin complex undergo coordinated phosphorylation changes at two G2/M transitions (maturation in oocytes and mitosis in cells in culture) but remain constitutively in their M phase forms during early embryogenesis. Dynein intermediate chain and p150(Glued) phosphorylation may positively regulate mitotic processes, such as spindle assembly or orientation, or negatively regulate interphase processes such as minus-end-directed organelle trafficking.

  14. Dynein and dynactin leverage their bivalent character to form a high-affinity interaction.

    Directory of Open Access Journals (Sweden)

    Amanda E Siglin

    Full Text Available Cytoplasmic dynein and dynactin participate in retrograde transport of organelles, checkpoint signaling and cell division. The principal subunits that mediate this interaction are the dynein intermediate chain (IC and the dynactin p150(Glued; however, the interface and mechanism that regulates this interaction remains poorly defined. Herein, we use multiple methods to show the N-terminus of mammalian dynein IC, residues 10-44, is sufficient for binding p150(Glued. Consistent with this mapping, monoclonal antibodies that antagonize the dynein-dynactin interaction also bind to this region of the IC. Furthermore, double and triple alanine point mutations spanning residues 6 to 19 in the yeast IC homolog, Pac11, produce significant defects in spindle positioning. Using the same methods we show residues 381 to 530 of p150(Glued form a minimal fragment that binds to the dynein IC. Sedimentation equilibrium experiments indicate that these individual fragments are predominantly monomeric, but admixtures of the IC and p150(Glued fragments produce a 2:2 complex. This tetrameric complex is sensitive to salt, temperature and pH, suggesting that the binding is dominated by electrostatic interactions. Finally, circular dichroism (CD experiments indicate that the N-terminus of the IC is disordered and becomes ordered upon binding p150(Glued. Taken together, the data indicate that the dynein-dynactin interaction proceeds through a disorder-to-order transition, leveraging its bivalent-bivalent character to form a high affinity, but readily reversible interaction.

  15. 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.

  16. 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...

  17. 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.

  18. Kinetochore dynein generates a poleward pulling force to facilitate congression and full chromosome alignment

    Institute of Scientific and Technical Information of China (English)

    Yan Li; Wei Yu; Yun Liang; Xueliang Zhu

    2007-01-01

    For proper chromosome segregation, all kinetochores must achieve bipolar microtubule (MT) attachment and subsequently align at the spindle equator before anaphase onset. The MT minus end-directed motor dynein/dynactin binds kinetochores in prometaphase and has long been implicated in chromosome congression. Unfortunately, inactivation of dynein usually disturbs spindle organization, thus hampering evaluation of its kinetochore roles. Here we specifically eliminated kinetochore dynein/dynactin by RNAi-mediated depletion of ZW10, a protein essential for kinetochore localization of the motor. Time-lapse microscopy indicated markedly-reduced congression efficiency, though congressing chromosomes displayed similar velocities as in control cells. Moreover, cells frequently failed to achieve full chromosome alignment, despite their normal spindles. Confocal microcopy revealed that the misaligned kinetochores were monoori-ented or unattached and mostly lying outside the spindle, suggesting a difficulty to capture MTs from the opposite pole. Kinetochores on monoastral spindles were dispersed farther away from the pole and exhibited only mild oscillation. Furthermore, inactivating dynein by other means generated similar phenotypes. Therefore, kinetochore dynein produces on monooriented kinetochores a poleward pulling force, which may contribute to efficient bipolar attachment by facilitating their proper microtubule captures to promote congression as well as full chromosome alignment.

  19. Dynein mutations associated with hereditary motor neuropathies impair mitochondrial morphology and function with age.

    Science.gov (United States)

    Eschbach, Judith; Sinniger, Jérôme; Bouitbir, Jamal; Fergani, Anissa; Schlagowski, Anna-Isabel; Zoll, Joffrey; Geny, Bernard; René, Frédérique; Larmet, Yves; Marion, Vincent; Baloh, Robert H; Harms, Matthew B; Shy, Michael E; Messadeq, Nadia; Weydt, Patrick; Loeffler, Jean-Philippe; Ludolph, Albert C; Dupuis, Luc

    2013-10-01

    Mutations in the DYNC1H1 gene encoding for dynein heavy chain cause two closely related human motor neuropathies, dominant spinal muscular atrophy with lower extremity predominance (SMA-LED) and axonal Charcot-Marie-Tooth (CMT) disease, and lead to sensory neuropathy and striatal atrophy in mutant mice. Dynein is the molecular motor carrying mitochondria retrogradely on microtubules, yet the consequences of dynein mutations on mitochondrial physiology have not been explored. Here, we show that mouse fibroblasts bearing heterozygous or homozygous point mutation in Dync1h1, similar to human mutations, show profoundly abnormal mitochondrial morphology associated with the loss of mitofusin 1. Furthermore, heterozygous Dync1h1 mutant mice display progressive mitochondrial dysfunction in muscle and mitochondria progressively increase in size and invade sarcomeres. As a likely consequence of systemic mitochondrial dysfunction, Dync1h1 mutant mice develop hyperinsulinemia and hyperglycemia and progress to glucose intolerance with age. Similar defects in mitochondrial morphology and mitofusin levels are observed in fibroblasts from patients with SMA-LED. Last, we show that Dync1h1 mutant fibroblasts show impaired perinuclear clustering of mitochondria in response to mitochondrial uncoupling. Our results show that dynein function is required for the maintenance of mitochondrial morphology and function with aging and suggest that mitochondrial dysfunction contributes to dynein-dependent neurological diseases, such as SMA-LED.

  20. Three Members of the LC8/DYNLL Family Are Required for Outer Arm Dynein Motor Function

    Science.gov (United States)

    Tanner, Christopher A.; Rompolas, Panteleimon; Patel-King, Ramila S.; Gorbatyuk, Oksana; Wakabayashi, Ken-ichi; Pazour, Gregory J.

    2008-01-01

    The highly conserved LC8/DYNLL family proteins were originally identified in axonemal dyneins and subsequently found to function in multiple enzyme systems. Genomic analysis uncovered a third member (LC10) of this protein class in Chlamydomonas. The LC10 protein is extracted from flagellar axonemes with 0.6 M NaCl and cofractionates with the outer dynein arm in sucrose density gradients. Furthermore, LC10 is specifically missing only from axonemes of those strains that fail to assemble outer dynein arms. Previously, the oda12-1 insertional allele was shown to lack the Tctex2-related dynein light chain LC2. The LC10 gene is located ∼2 kb from that of LC2 and is also completely missing from this mutant but not from oda12-2, which lacks only the 3′ end of the LC2 gene. Although oda12-1 cells assemble outer arms that lack only LC2 and LC10, this strain exhibits a flagellar beat frequency that is consistently less than that observed for strains that fail to assemble the entire outer arm and docking complex (e.g., oda1). These results support a key regulatory role for the intermediate chain/light chain complex that is an integral and highly conserved feature of all oligomeric dynein motors. PMID:18579685

  1. 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.

  2. DRC3 connects the N-DRC to dynein g to regulate flagellar waveform

    Science.gov (United States)

    Awata, Junya; Song, Kangkang; Lin, Jianfeng; King, Stephen M.; Sanderson, Michael J.; Nicastro, Daniela; Witman, George B.

    2015-01-01

    The nexin-dynein regulatory complex (N-DRC), which is a major hub for the control of flagellar motility, contains at least 11 different subunits. A major challenge is to determine the location and function of each of these subunits within the N-DRC. We characterized a Chlamydomonas mutant defective in the N-DRC subunit DRC3. Of the known N-DRC subunits, the drc3 mutant is missing only DRC3. Like other N-DRC mutants, the drc3 mutant has a defect in flagellar motility. However, in contrast to other mutations affecting the N-DRC, drc3 does not suppress flagellar paralysis caused by loss of radial spokes. Cryo–electron tomography revealed that the drc3 mutant lacks a portion of the N-DRC linker domain, including the L1 protrusion, part of the distal lobe, and the connection between these two structures, thus localizing DRC3 to this part of the N-DRC. This and additional considerations enable us to assign DRC3 to the L1 protrusion. Because the L1 protrusion is the only non-dynein structure in contact with the dynein g motor domain in wild-type axonemes and this is the only N-DRC–dynein connection missing in the drc3 mutant, we conclude that DRC3 interacts with dynein g to regulate flagellar waveform. PMID:26063732

  3. Tuning microtubule-based transport via filamentous MAPs: the problem of dynein

    Science.gov (United States)

    Vershinin, Michael; Xu, Jing; Razafsky, David S.; King, Stephen J.; Gross, Steven P.

    2010-01-01

    We recently proposed that regulating the single-to-multiple motor transition was a likely strategy for regulating kinesin-based transport in vivo. Here, we use an in vitro bead assay coupled with an optical trap to investigate how this proposed regulatory mechanism affects dynein-based transport. We show that tau’s regulation of kinesin function can proceed without interfering with dynein-based transport. Surprisingly, at extremely high tau levels—where kinesin cannot bind microtubules—dynein can still contact microtubules. The difference between tau’s effects on kinesin- and dynein-based motility suggests that tau can be used to tune relative amounts of plus-end and minus-end directed transport. As in the case of kinesin, we find that the 3RS isoform of tau is a more potent inhibitor of dynein binding to microtubules. We show that this isoform-specific effect is not due to steric interference of tau’s projection domains, but rather due to tau’s interactions with the motor at the microtubule surface. Nonetheless, we do observe a modest steric interference effect of tau away from the microtubule and discuss the potential implications of this for molecular motor structure. PMID:18373727

  4. Kinesin-3 and dynein cooperate in long-range retrograde endosome motility along a nonuniform microtubule array

    NARCIS (Netherlands)

    Schuster, M.; Kilaru, S.; Fink, G.; Collemare, J.A.R.; Roger, Y.; Steinberg, G.

    2011-01-01

    The polarity of microtubules (MTs) determines the motors for intracellular motility, with kinesins moving to plus ends and dynein to minus ends. In elongated cells of Ustilago maydis, dynein is thought to move early endosomes (EEs) toward the septum (retrograde), whereas kinesin-3 transports them to

  5. 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

    Apoptosis is the process in which external or internal cues activate certain killing pathways in a cell to induce self-elimination. Apoptosis is a conserved key process required to modulate embryogenesis and for removal of damaged or superfluous cells. Dysregulation of apoptosis is implicated...... in the etiology of many diseases, including cancer, neurodegenerative, cardiovascular and autoimmune diseases. Several of the first genes found to regulate apoptosis were discovered in the nematode Caenorhabditis elegans. In this project, two different and tissue specific roles of C. elegans dynein light chain 1...... (dlc-1) in apoptosis are described. DLC-1 is a part of the motor complex dynein, which moves along microtubules inside the cell. DLC-1 has been demonstrated to have both dynein dependent and independent functions in mammalian cells, which is also apparent from the studies presented here. Specifically...

  6. 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)

  7. 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.

  8. 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_...

  9. The LC7 Light Chains of Chlamydomonas Flagellar Dyneins Interact with Components Required for Both Motor Assembly and Regulation

    Science.gov (United States)

    DiBella, Linda M.; Sakato, Miho; Patel-King, Ramila S.; Pazour, Gregory J.; King, Stephen M.

    2004-01-01

    Members of the LC7/Roadblock family of light chains (LCs) have been found in both cytoplasmic and axonemal dyneins. LC7a was originally identified within Chlamydomonas outer arm dynein and associates with this motor's cargo-binding region. We describe here a novel member of this protein family, termed LC7b that is also present in the Chlamydomonas flagellum. Levels of LC7b are reduced ∼20% in axonemes isolated from strains lacking inner arm I1 and are ∼80% lower in the absence of the outer arms. When both dyneins are missing, LC7b levels are diminished to <10%. In oda9 axonemal extracts that completely lack outer arms, LC7b copurifies with inner arm I1, whereas in ida1 extracts that are devoid of I1 inner arms it associates with outer arm dynein. We also have observed that some LC7a is present in both isolated axonemes and purified 18S dynein from oda1, suggesting that it is also a component of both the outer arm and inner arm I1. Intriguingly, in axonemal extracts from the LC7a null mutant, oda15, which assembles ∼30% of its outer arms, LC7b fails to copurify with either dynein, suggesting that it interacts with LC7a. Furthermore, both the outer arm γ heavy chain and DC2 from the outer arm docking complex completely dissociate after salt extraction from oda15 axonemes. EDC cross-linking of purified dynein revealed that LC7b interacts with LC3, an outer dynein arm thioredoxin; DC2, an outer arm docking complex component; and also with the phosphoprotein IC138 from inner arm I1. These data suggest that LC7a stabilizes both the outer arms and inner arm I1 and that both LC7a and LC7b are involved in multiple intradynein interactions within both dyneins. PMID:15304520

  10. 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.

  11. 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

  12. 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

  13. Understanding the Roles of Nudel/Lis1/Dynein Pathway in Cell Motility

    Institute of Scientific and Technical Information of China (English)

    Xie Lele; Zhu Xueliang

    2007-01-01

    @@ Under the support of multiple grants by NSFC, including General Program, Key Program, National Science Fund for Distinguished Young Scholars, and Fund for Creative Research Groups, the research group explored how the Nudel/Lis1/dynein pathway functions in cell motility.

  14. 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

  15. 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

  16. 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

  17. An Outer Arm Dynein Conformational Switch Is Required for Metachronal Synchrony of Motile Cilia in Planaria

    Science.gov (United States)

    Rompolas, Panteleimon; Patel-King, Ramila S.

    2010-01-01

    Motile cilia mediate the flow of mucus and other fluids across the surface of specialized epithelia in metazoans. Efficient clearance of peri-ciliary fluids depends on the precise coordination of ciliary beating to produce metachronal waves. The role of individual dynein motors and the mechanical feedback mechanisms required for this process are not well understood. Here we used the ciliated epithelium of the planarian Schmidtea mediterranea to dissect the role of outer arm dynein motors in the metachronal synchrony of motile cilia. We demonstrate that animals that completely lack outer dynein arms display a significant decline in beat frequency and an inability of cilia to coordinate their oscillations and form metachronal waves. Furthermore, lack of a key mechanosensitive regulatory component (LC1) yields a similar phenotype even though outer arms still assemble in the axoneme. The lack of metachrony was not due simply to a decrease in ciliary beat frequency, as reducing this parameter by altering medium viscosity did not affect ciliary coordination. In addition, we did not observe a significant temporal variability in the beat cycle of impaired cilia. We propose that this conformational switch provides a mechanical feedback system within outer arm dynein that is necessary to entrain metachronal synchrony. PMID:20844081

  18. CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms

    Science.gov (United States)

    Panizzi, Jennifer R.; Becker-Heck, Anita; Castleman, Victoria H.; Al-Mutairi, Dalal; Liu, Yan; Loges, Niki T.; Pathak, Narendra; Austin-Tse, Christina; Sheridan, Eamonn; Schmidts, Miriam; Olbrich, Heike; Werner, Claudius; Häffner, Karsten; Hellman, Nathan; Chodhari, Rahul; Gupta, Amar; Kramer-Zucker, Albrecht; Olale, Felix; Burdine, Rebecca D.; Schier, Alexander F.; O’Callaghan, Christopher; Chung, Eddie MK; Reinhardt, Richard; Mitchison, Hannah M.; King, Stephen M.; Omran, Heymut; Drummond, Iain A.

    2012-01-01

    Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation, and to establish laterality1. Cilia motility defects cause Primary Ciliary Dyskinesia (PCD, MIM 242650), a disorder affecting 1:15-30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive cilia bending2. Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD linked loci3. Here we show that the zebrafish cilia paralysis mutant schmalhanstn222 (smh) mutant encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a regulated gene. Screening 146 unrelated PCD families identified patients in six families with reduced outer dynein arms, carrying mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103 functions as a tightly bound, axoneme-associated protein. The results identify Ccdc103 as a novel dynein arm attachment factor that when mutated causes Primary Ciliary Dyskinesia. PMID:22581229

  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.

    2013-01-01

    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. 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

  1. Analysis of dynein intermediate chains, light intermediate chains and light chains in a cohort of hereditary peripheral neuropathies.

    Science.gov (United States)

    Tey, Shelisa; Ahmad-Annuar, Azlina; Drew, Alexander P; Shahrizaila, Nortina; Nicholson, Garth A; Kennerson, Marina L

    2014-10-01

    The cytoplasmic dynein heavy chain (DYNC1H1) gene has been increasingly associated with neurodegenerative disorders including axonal Charcot-Marie-Tooth disease (CMT2), intellectual disability and malformations of cortical development. In addition, evidence from mouse models (Loa, catabolite repressor-activator (Cra) and Sprawling (Swl)) has shown that mutations in Dync1h1 cause a range of neurodegenerative phenotypes with motor and sensory neuron involvement. In this current study, we examined the possible contribution of other cytoplasmic dynein subunits that bind to DYNC1H1 as a cause of inherited peripheral neuropathy. We focused on screening the cytoplasmic dynein intermediate, light intermediate and light chain genes in a cohort of families with inherited peripheral neuropathies. Nine genes were screened and ten variants were detected, but none was identified as pathogenic, indicating that cytoplasmic dynein intermediate, light intermediate and light chains are not a cause of neuropathy in our cohort.

  2. 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.

  3. 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

  4. 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...

  5. Transport and arrangement of the outer-dynein-arm docking complex in the flagella of Chlamydomonas mutants that lack outer dynein arms.

    Science.gov (United States)

    Wakabayashi, K; Takada, S; Witman, G B; Kamiya, R

    2001-04-01

    The outer dynein arms of Chlamydomonas flagella are attached to a precise site on the outer doublet microtubules and repeat at a regular interval of 24 nm. This binding is mediated by the outer dynein arm docking complex (ODA-DC), which is composed of three protein subunits. In this study, antibodies against the 83- and 62-kD subunits (DC83 and DC62) of the ODA-DC were used to analyze its state of association with outer arm components within the cytoplasm, and its localization in the axonemes of oda mutants. Immunoprecipitation indicates that DC83 and DC62 are preassembled within the cytoplasm, but that they are not associated with outer arm dynein. Both proteins are lost or greatly diminished in oda1 and oda3, mutants in the structural genes of DC62 and DC83, respectively, demonstrating that their association is necessary for their stable presence in the cytoplasm. Immunoelectron microscopy indicates that DC83 repeats at 24-nm intervals along the length of the doublet microtubules of oda6, which lacks outer arms; thus, outer arm periodicity may be determined by the ODA-DC. Flagellar regeneration and temporary dikaryon experiments indicate that the ODA-DC can be rapidly transported into the flagellum and assembled on the doublet microtubules independently of the outer arms and independently of flagellar growth. Unexpectedly, the intensity of ODA-DC labeling decreased toward the distal ends of axonemes of oda6 but not wild-type cells, suggesting that the outer arms reciprocally contribute to the assembly/stability of the ODA-DC.

  6. 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...

  7. 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.

  8. DYNC2LI1 mutations broaden the clinical spectrum of dynein-2 defects

    OpenAIRE

    K Kessler; Wunderlich, I.; Uebe, S; Falk, N.S.; Giessl, A; Brandstatter, J.H.; Popp, B.; Klinger, P; Ekici, A B; Sticht, H.; Dorr, H. G.; Reis, A; Roepman, R; Seemanova, E; Thiel, C T

    2015-01-01

    Skeletal ciliopathies are a heterogeneous group of autosomal recessive osteochondrodysplasias caused by defects in formation, maintenance and function of the primary cilium. Mutations in the underlying genes affect the molecular motors, intraflagellar transport complexes (IFT), or the basal body. The more severe phenotypes are caused by defects of genes of the dynein-2 complex, where mutations in DYNC2H1, WDR34 and WDR60 have been identified. In a patient with a Jeune-like phenotype we perfor...

  9. Nucleoporin translocated promoter region (Tpr) associates with dynein complex, preventing chromosome lagging formation during mitosis.

    Science.gov (United States)

    Nakano, Hiroshi; Funasaka, Tatsuyoshi; Hashizume, Chieko; Wong, Richard W

    2010-04-01

    Gain or loss of whole chromosomes is often observed in cancer cells and is thought to be due to aberrant chromosome segregation during mitosis. Proper chromosome segregation depends on a faithful interaction between spindle microtubules and kinetochores. Several components of the nuclear pore complex/nucleoporins play critical roles in orchestrating the rapid remodeling events that occur during mitosis. Our recent studies revealed that the nucleoporin, Rae1, plays critical roles in maintaining spindle bipolarity. Here, we show association of another nucleoporin, termed Tpr (translocated promoter region), with the molecular motors dynein and dynactin, which both orchestrate with the spindle checkpoints Mad1 and Mad2 during cell division. Overexpression of Tpr enhanced multinucleated cell formation. RNA interference-mediated knockdown of Tpr caused a severe lagging chromosome phenotype and disrupted spindle checkpoint proteins expression and localization. Next, we performed a series of rescue and dominant negative experiments to confirm that Tpr orchestrates proper chromosome segregation through interaction with dynein light chain. Our data indicate that Tpr functions as a spatial and temporal regulator of spindle checkpoints, ensuring the efficient recruitment of checkpoint proteins to the molecular motor dynein to promote proper anaphase formation.

  10. Dynein regulates epithelial polarity and the apical localization of stardust A mRNA.

    Science.gov (United States)

    Horne-Badovinac, Sally; Bilder, David

    2008-01-01

    Intense investigation has identified an elaborate protein network controlling epithelial polarity. Although precise subcellular targeting of apical and basolateral determinants is required for epithelial architecture, little is known about how the individual determinant proteins become localized within the cell. Through a genetic screen for epithelial defects in the Drosophila follicle cells, we have found that the cytoplasmic Dynein motor is an essential regulator of apico-basal polarity. Our data suggest that Dynein acts through the cytoplasmic scaffolding protein Stardust (Sdt) to localize the transmembrane protein Crumbs, in part through the apical targeting of specific sdt mRNA isoforms. We have mapped the sdt mRNA localization signal to an alternatively spliced coding exon. Intriguingly, the presence or absence of this exon corresponds to a developmental switch in sdt mRNA localization in which apical transcripts are only found during early stages of epithelial development, while unlocalized transcripts predominate in mature epithelia. This work represents the first demonstration that Dynein is required for epithelial polarity and suggests that mRNA localization may have a functional role in the regulation of apico-basal organization. Moreover, we introduce a unique mechanism in which alternative splicing of a coding exon is used to control mRNA localization during development.

  11. Dynein regulates epithelial polarity and the apical localization of stardust A mRNA.

    Directory of Open Access Journals (Sweden)

    Sally Horne-Badovinac

    2008-01-01

    Full Text Available Intense investigation has identified an elaborate protein network controlling epithelial polarity. Although precise subcellular targeting of apical and basolateral determinants is required for epithelial architecture, little is known about how the individual determinant proteins become localized within the cell. Through a genetic screen for epithelial defects in the Drosophila follicle cells, we have found that the cytoplasmic Dynein motor is an essential regulator of apico-basal polarity. Our data suggest that Dynein acts through the cytoplasmic scaffolding protein Stardust (Sdt to localize the transmembrane protein Crumbs, in part through the apical targeting of specific sdt mRNA isoforms. We have mapped the sdt mRNA localization signal to an alternatively spliced coding exon. Intriguingly, the presence or absence of this exon corresponds to a developmental switch in sdt mRNA localization in which apical transcripts are only found during early stages of epithelial development, while unlocalized transcripts predominate in mature epithelia. This work represents the first demonstration that Dynein is required for epithelial polarity and suggests that mRNA localization may have a functional role in the regulation of apico-basal organization. Moreover, we introduce a unique mechanism in which alternative splicing of a coding exon is used to control mRNA localization during development.

  12. Effect of catch bonding on transport of cellular cargo by dynein motors

    Science.gov (United States)

    Nair, Anil; Chandel, Sameep; Mitra, Mithun K.; Muhuri, Sudipto; Chaudhuri, Abhishek

    2016-09-01

    Recent experiments have demonstrated that dynein motors exhibit catch bonding behavior, in which the unbinding rate of a single dynein decreases with increasing force, for a certain range of force. Motivated by these experiments, we study the effect of catch bonding on unidirectional transport properties of cellular cargo carried by multiple dynein motors. We introduce a threshold force bond deformation (TFBD) model, consistent with the experiments, wherein catch bonding sets in beyond a critical applied load force. 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 plot in the parameter space of the catch bond strength and the stall force of the motor. This plot yields predictions that may be experimentally accessed by suitable modifications of motor transport and binding properties.

  13. An outer arm dynein light chain acts in a conformational switch for flagellar motility

    Science.gov (United States)

    Patel-King, Ramila S.

    2009-01-01

    A system distinct from the central pair–radial spoke complex was proposed to control outer arm dynein function in response to alterations in the mechanical state of the flagellum. In this study, we examine the role of a Chlamydomonas reinhardtii outer arm dynein light chain that associates with the motor domain of the γ heavy chain (HC). We demonstrate that expression of mutant forms of LC1 yield dominant-negative effects on swimming velocity, as the flagella continually beat out of phase and stall near or at the power/recovery stroke switchpoint. Furthermore, we observed that LC1 interacts directly with tubulin in a nucleotide-independent manner and tethers this motor unit to the A-tubule of the outer doublet microtubules within the axoneme. Therefore, this dynein HC is attached to the same microtubule by two sites: via both the N-terminal region and the motor domain. We propose that this γ HC–LC1–microtubule ternary complex functions as a conformational switch to control outer arm activity. PMID:19620633

  14. DYNC2LI1 mutations broaden the clinical spectrum of dynein-2 defects.

    Science.gov (United States)

    Kessler, Kristin; Wunderlich, Ina; Uebe, Steffen; Falk, Nathalie S; Gießl, Andreas; Brandstätter, Johann Helmut; Popp, Bernt; Klinger, Patricia; Ekici, Arif B; Sticht, Heinrich; Dörr, Helmuth-Günther; Reis, André; Roepman, Ronald; Seemanová, Eva; Thiel, Christian T

    2015-01-01

    Skeletal ciliopathies are a heterogeneous group of autosomal recessive osteochondrodysplasias caused by defects in formation, maintenance and function of the primary cilium. Mutations in the underlying genes affect the molecular motors, intraflagellar transport complexes (IFT), or the basal body. The more severe phenotypes are caused by defects of genes of the dynein-2 complex, where mutations in DYNC2H1, WDR34 and WDR60 have been identified. In a patient with a Jeune-like phenotype we performed exome sequencing and identified compound heterozygous missense and nonsense mutations in DYNC2LI1 segregating with the phenotype. DYNC2LI1 is ubiquitously expressed and interacts with DYNC2H1 to form the dynein-2 complex important for retrograde IFT. Using DYNC2LI1 siRNA knockdown in fibroblasts we identified a significantly reduced cilia length proposed to affect cilia function. In addition, depletion of DYNC2LI1 induced altered cilia morphology with broadened ciliary tips and accumulation of IFT-B complex proteins in accordance with retrograde IFT defects. Our results expand the clinical spectrum of ciliopathies caused by defects of the dynein-2 complex.

  15. Geometric Clutch model version 3: the role of the inner and outer arm dyneins in the ciliary beat.

    Science.gov (United States)

    Lindemann, Charles B

    2002-08-01

    The Geometric Clutch model of ciliary and flagellar beating uses the transverse force (t-force) that develops between the outer doublets of the axoneme as the regulator for activating and deactivating the dynein motors and organizing the flagellar beat. The version of the model described here adds detail to the formulations used in the two previous versions as follows: (1) In place of two opposing sets of dyneins, the new model has four sets of dyneins, corresponding to two sets on each side of the axoneme acting in series. (2) The four sets of dyneins are each subdivided into two ranks representing inner and outer arm dyneins. (3) The force produced by each dynein is governed by a force-velocity relationship that is independently specified for the inner and outer arms. Consistent with the original model, the new version of the Geometric Clutch model can simulate both the effective and recovery stroke phases of the ciliary beat using a single uniform algorithm. In addition, the new version can operate with the outer arms disabled. Under this condition, the simulation exhibits a beat pattern similar to the original but the beat frequency is reduced to approximately one third. These results are contingent on using force-velocity relationships for the inner and outer arms similar to those described by Brokaw [1999: Cell Motil. Cytoskeleton 42:134-148], where the inner arms contribute most of the driving force at low shear velocities. This constitutes the first examination of the effects of the force-velocity characteristics of dynein on a cilia-like beat in a theoretical framework. PMID:12112138

  16. 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...

  17. 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 (D2HGD...... idiopathic D-2-HGA manifests with normal D-2-HGDH activity and higher D-2-HG levels in body fluids compared with Type I patients. It remains possible that several classifications for idiopathic D-2-HGA patients with diverse genetic loci will be revealed in future studies....

  18. 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...... 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....

  19. 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...

  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. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Epidermal Growth Factor Stimulates Extracellular-Signal Regulated Kinase Phosphorylation of a Novel Site on Cytoplasmic Dynein Intermediate Chain 2

    Directory of Open Access Journals (Sweden)

    Andrew D. Catling

    2013-02-01

    Full Text Available Extracellular-signal regulated kinase (ERK signaling is required for a multitude of physiological and patho-physiological processes. However, the identities of the proteins that ERK phosphorylates to elicit these responses are incompletely known. Using an affinity purification methodology of general utility, here we identify cytoplasmic dynein intermediate chain 2 (DYNC1I-2, IC-2 as a novel substrate for ERK following epidermal growth factor receptor stimulation of fibroblasts. IC-2 is a subunit of cytoplasmic dynein, a minus-end directed motor protein necessary for transport of diverse cargos along microtubules. Emerging data support the hypothesis that post-translational modification regulates dynein but the signaling mechanisms used are currently unknown. We find that ERK phosphorylates IC-2 on a novel, highly conserved Serine residue proximal to the binding site for the p150Glued subunit of the cargo adapter dynactin. Surprisingly, neither constitutive phosphorylation nor a phosphomimetic substitution of this Serine influences binding of p150Glued to IC-2. These data suggest that ERK phosphorylation of IC-2 regulates dynein function through mechanisms other than its interaction with dynactin.

  7. Sensing the Mechanical State of the Axoneme and Integration of Ca2+ Signaling by Outer Arm Dynein

    Science.gov (United States)

    King, Stephen M.

    2010-01-01

    Axonemal dyneins have been demonstrated to monitor the mechanical state of the axoneme and must also alter activity in response to various signaling pathways. The central pair/radial spoke systems are clearly involved in controlling inner dynein arm function; however, the mechanisms by which the outer dynein arm transduces regulatory signals appear quite distinct at the molecular level. In Chlamydomonas, these regulatory components include thioredoxins involved in response to redox changes, molecules that tether the γ heavy chain motor unit to the A-tubule of the outer doublet and a Ca2+-binding protein that controls the structure of the γ heavy chain N-terminal domain. Together, these studies now suggest that the γ heavy chain acts as a key regulatory node for controlling outer arm function in response to alterations in curvature and ligand binding. Furthermore, they allow us to propose a testable molecular mechanism by which altered Ca2+ levels might lead to a change in ciliary waveform by controlling whether one heavy chain of outer arm dynein acts as a microtubule translocase or as an ATP-dependent brake that limits the amount of inter-doublet sliding. PMID:20186692

  8. Dynein light chain binding to a 3′-untranslated sequence mediates parathyroid hormone mRNA association with microtubules

    Science.gov (United States)

    Epstein, Eyal; Sela-Brown, Alin; Ringel, Israel; Kilav, Rachel; King, Stephen M.; Benashski, Sharon E.; Yisraeli, Joel K.; Silver, Justin; Naveh-Many, Tally

    2000-01-01

    The 3′-untranslated region (UTR) of mRNAs binds proteins that determine mRNA stability and localization. The 3′-UTR of parathyroid hormone (PTH) mRNA specifically binds cytoplasmic proteins. We screened an expression library for proteins that bind the PTH mRNA 3′-UTR, and the sequence of 1 clone was identical to that of the dynein light chain LC8, a component of the dynein complexes that translocate cytoplasmic components along microtubules. Recombinant LC8 binds PTH mRNA 3′-UTR, as shown by RNA electrophoretic mobility shift assay. We showed that PTH mRNA colocalizes with microtubules in the parathyroid gland, as well as with a purified microtubule preparation from calf brain, and that this association was mediated by LC8. To our knowledge, this is the first report of a dynein complex protein binding an mRNA. The dynein complex may be the motor that is responsible for transporting mRNAs to specific locations in the cytoplasm and for the consequent is asymmetric distribution of translated proteins in the cell. PMID:10683380

  9. Association of Lis1 with outer arm dynein is modulated in response to alterations in flagellar motility

    Science.gov (United States)

    Rompolas, Panteleimon; Patel-King, Ramila S.; King, Stephen M.

    2012-01-01

    The cytoplasmic dynein regulatory factor Lis1, which induces a persistent tight binding to microtubules and allows for transport of cargoes under high-load conditions, is also present in motile cilia/flagella. We observed that Lis1 levels in flagella of Chlamydomonas strains that exhibit defective motility due to mutation of various axonemal substructures were greatly enhanced compared with wild type; this increase was absolutely dependent on the presence within the flagellum of the outer arm dynein α heavy chain/light chain 5 thioredoxin unit. To assess whether cells might interpret defective motility as a “high-load environment,” we reduced the flagellar beat frequency of wild-type cells through enhanced viscous load and by reductive stress; both treatments resulted in increased levels of flagellar Lis1, which altered the intrinsic beat frequency of the trans flagellum. Differential extraction of Lis1 from wild-type and mutant axonemes suggests that the affinity of outer arm dynein for Lis1 is directly modulated. In cytoplasm, Lis1 localized to two punctate structures, one of which was located near the base of the flagella. These data reveal that the cell actively monitors motility and dynamically modulates flagellar levels of the dynein regulatory factor Lis1 in response to imposed alterations in beat parameters. PMID:22855525

  10. 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

  11. 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 ...

  12. The Oligomeric Outer Dynein Arm Assembly Factor CCDC103 Is Tightly Integrated within the Ciliary Axoneme and Exhibits Periodic Binding to Microtubules*

    Science.gov (United States)

    King, Stephen M.; Patel-King, Ramila S.

    2015-01-01

    CCDC103 is an ∼29-kDa protein consisting of a central RPAP3_C domain flanked by N- and C-terminal coiled coils. Defects in CCDC103 lead to primary ciliary dyskinesia caused by the loss of outer dynein arms. This protein is present along the entire length of the ciliary axoneme and does not require other dynein or docking complex components for its integration. Unlike other known dynein assembly factors within the axoneme, CCDC103 is not solubilized by 0.6 m NaCl and requires more chaotropic conditions, such as 0.5 m KI. Alternatively, it can be extracted using 0.3% sarkosyl. CCDC103 forms stable dimers and other oligomers in solution through interactions involving the central domain. The smallest particle observed by dynamic light scattering has a hydrodynamic diameter of ∼25 nm. Furthermore, CCDC103 binds microtubules directly, forming ∼9-nm diameter particles that exhibit a 12-nm spacing on the microtubule lattice, suggesting that there may be two CCDC103 units per outer arm dynein repeat. Although the outer dynein arm docking complex is necessary to form arrays of dyneins along microtubules, it is not sufficient to set up a single array in a precise location on each axonemal doublet. We propose that CCDC103 helps generate a high-affinity site on the doublets for outer arm assembly, either through direct interactions or indirectly, perhaps by modifying the underlying microtubule lattice. PMID:25572396

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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...

  18. 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 ...

  19. 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.

  20. Protein-Protein Interactions between Intermediate Chains and the Docking Complex of Chlamydomonas Flagellar Outer Arm Dynein

    Science.gov (United States)

    Ide, Takahiro; Owa, Mikito; King, Stephen M.; Kamiya, Ritsu; Wakabayashi, Ken-ichi

    2013-01-01

    Outer arm dynein (OAD) is bound to specific loci on outer-doublet-microtubules by interactions at two sites: via intermediate chain 1 (IC1) and the outer dynein arm docking complex (ODA-DC). Studies using Chlamydomonas mutants have suggested that the individual sites have rather weak affinities for microtubules, and therefore strong OAD attachment to microtubules is achieved by their cooperation. To test this idea, we examined interactions between IC1, IC2 (another intermediate chain) and ODA-DC using recombinant proteins. Recombinant IC1 and IC2 were found to form a 1:1 complex, and this complex associated with ODA-DC in vitro. Binding of IC1 to mutant axonemes revealed that there are specific binding sites for IC1. From these data, we propose a novel model of OAD-outer doublet association. PMID:23747306

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. Formin-mediated actin polymerization cooperates with Mushroom body defect (Mud)-Dynein during Frizzled-Dishevelled spindle orientation.

    Science.gov (United States)

    Johnston, Christopher A; Manning, Laurina; Lu, Michelle S; Golub, Ognjen; Doe, Chris Q; Prehoda, Kenneth E

    2013-10-01

    To position the mitotic spindle, cytoskeletal components must be coordinated to generate cortical forces on astral microtubules. Although the dynein motor is common to many spindle orientation systems, 'accessory pathways' are often also required. In this work, we identified an accessory spindle orientation pathway in Drosophila that functions with Dynein during planar cell polarity, downstream of the Frizzled (Fz) effector Dishevelled (Dsh). Dsh contains a PDZ ligand and a Dynein-recruiting DEP domain that are both required for spindle orientation. The Dsh PDZ ligand recruits Canoe/Afadin and ultimately leads to Rho GTPase signaling mediated through RhoGEF2. The formin Diaphanous (Dia) functions as the Rho effector in this pathway, inducing F-actin enrichment at sites of cortical Dsh. Chimeric protein experiments show that the Dia-actin accessory pathway can be replaced by an independent kinesin (Khc73) accessory pathway for Dsh-mediated spindle orientation. Our results define two 'modular' spindle orientation pathways and show an essential role for actin regulation in Dsh-mediated spindle orientation.

  6. A Chlamydomonas Homologue of the Putative Murine t Complex Distorter Tctex-2 Is an Outer Arm Dynein Light Chain

    Science.gov (United States)

    Patel-King, Ramila S.; Benashski, Sharon E.; Harrison, Alistair; King, Stephen M.

    1997-01-01

    Molecular analysis of a 19,000-Mr protein from the Chlamydomonas flagellum reveals that it is homologous to the t complex–encoded protein Tctex-2, which is a candidate for one of the distorter products that cause the extreme transmission ratio distortion (meiotic drive) of the murine t complex. The 19,000-Mr protein is extracted from the axoneme with 0.6 M NaCl and comigrates with the outer dynein arm in sucrose density gradients. This protein also is specifically missing in axonemes prepared from a mutant that does not assemble the outer arm. These data raise the possibility that Tctex-2 is a sperm flagellar dynein component. Combined with the recent identification of Tctex-1 (another distorter candidate) as a light chain of cytoplasmic dynein, these results lead to a biochemical model for how differential defects in spermiogenesis that result in the phenomenon of meiotic drive might be generated in wild-type vs t-bearing sperm. PMID:9166408

  7. Partially Functional Outer-Arm Dynein in a Novel Chlamydomonas Mutant Expressing a Truncated γ Heavy Chain▿

    Science.gov (United States)

    Liu, Zhongmei; Takazaki, Hiroko; Nakazawa, Yuki; Sakato, Miho; Yagi, Toshiki; Yasunaga, Takuo; King, Stephen M.; Kamiya, Ritsu

    2008-01-01

    The outer dynein arm of Chlamydomonas flagella contains three heavy chains (α, β, and γ), each of which exhibits motor activity. How they assemble and cooperate is of considerable interest. Here we report the isolation of a novel mutant, oda2-t, whose γ heavy chain is truncated at about 30% of the sequence. While the previously isolated γ chain mutant oda2 lacks the entire outer arm, oda2-t retains outer arms that contain α and β heavy chains, suggesting that the N-terminal sequence (corresponding to the tail region) is necessary and sufficient for stable outer-arm assembly. Thin-section electron microscopy and image analysis localize the γ heavy chain to a basal region of the outer-arm image in the axonemal cross section. The motility of oda2-t is lower than that of the wild type and oda11 (lacking the α heavy chain) but higher than that of oda2 and oda4-s7 (lacking the motor domain of the β heavy chain). Thus, the outer-arm dynein lacking the γ heavy-chain motor domain is partially functional. The availability of mutants lacking individual heavy chains should greatly facilitate studies on the structure and function of the outer-arm dynein. PMID:18487347

  8. 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...

  9. 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...

  10. 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.

  11. 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

  12. Transport of the outer dynein arm complex to cilia requires a cytoplasmic protein Lrrc6.

    Science.gov (United States)

    Inaba, Yasuko; Shinohara, Kyosuke; Botilde, Yanick; Nabeshima, Ryo; Takaoka, Katsuyoshi; Ajima, Rieko; Lamri, Lynda; Takeda, Hiroyuki; Saga, Yumiko; Nakamura, Tetsuya; Hamada, Hiroshi

    2016-07-01

    Lrrc6 encodes a cytoplasmic protein that is expressed specifically in cells with motile cilia including the node, trachea and testes of the mice. A mutation of Lrrc6 has been identified in human patients with primary ciliary dyskinesia (PCD). Mutant mice lacking Lrrc6 show typical PCD defects such as hydrocephalus and laterality defects. We found that in the absence of Lrrc6, the morphology of motile cilia remained normal, but their motility was completely lost. The 9 + 2 arrangement of microtubules remained normal in Lrrc6(-/-) mice, but the outer dynein arms (ODAs), the structures essential for the ciliary beating, were absent from the cilia. In the absence of Lrrc6, ODA proteins such as DNAH5, DNAH9 and IC2, which are assembled in the cytoplasm and transported to the ciliary axoneme, remained in the cytoplasm and were not transported to the ciliary axoneme. The IC2-IC1 interaction, which is the first step of ODA assembly, was normal in Lrrc6(-/-) mice testes. Our results suggest that ODA proteins may be transported from the cytoplasm to the cilia by an Lrrc6-dependent mechanism.

  13. CO Blocking of D-2 Dissociative Adsorption on Ru

    NARCIS (Netherlands)

    Ueta, H.; Groot, I. M. N.; Gleeson, M. A.; Stolte, S.; McBane, G. C.; Juurlink, L. B. F.; Kleyn, A. W.

    2008-01-01

    The influence of pre-adsorbed CO on the dissociative adsorption of D-2 on Ru(0001) is studied by molecular-beam techniques. We determine the initial dissociation probability of D-2 as a function of its kinetic energy for various CO pre-coverages between 0.00 and 0.67 monolayers (ML) at a surface tem

  14. 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 ...

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

    Science.gov (United States)

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

    2011-01-01

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

  16. 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...

  17. 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

  18. 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.

  19. 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...

  20. 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.

  1. 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)

  2. The lissencephaly protein Lis1 is present in motile mammalian cilia and requires outer arm dynein for targeting to Chlamydomonas flagella

    DEFF Research Database (Denmark)

    Pedersen, Lotte B; Rompolas, Panteleimon; Christensen, Søren T;

    2007-01-01

    Lissencephaly is a developmental brain disorder characterized by a smooth cerebral surface, thickened cortex and misplaced neurons. Classical lissencephaly is caused by mutations in LIS1, which encodes a WD-repeat protein involved in cytoplasmic dynein regulation, mitosis and nuclear migration. S...

  3. 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.

  4. 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

  5. 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)

  6. A model of flagellar and ciliary functioning which uses the forces transverse to the axoneme as the regulator of dynein activation.

    Science.gov (United States)

    Lindemann, C B

    1994-01-01

    Ciliary and flagellar motion is driven by the dynein-tubulin interaction between adjacent doublets of the axoneme, and the resulting sliding displacements are converted into axonemal bends that are propagated. When the axoneme is bent in the normal beating plane, force develops across the axoneme in the plane of the bend. This transverse force (t-force) has maximal effect on the interdoublet spacing of outer doublets 2-4 on one side of the axoneme and doublets 7-9 on the opposite side. Episodes of sliding originates as the t-force brings these doublets into closer proximity (allowing dynein bridges to form) and are terminated when these doublets are separated from each other by the t-force. A second factor, the adhesive force of the dynein-tubulin attachments (bridges), also acts to pull neighboring doublets closer together. This force resists termination of a sliding episode once initiated, and acts locally to give the population of dynein bridges a type of excitability. In other words, as bridges form, the probability of nearby bridges attaching is increased by a positive feedback exerted through the interdoublet spacing. A conceptual working hypothesis explaining the behavior of cilia and flagella is proposed based on the above concepts. Additionally, the feasibility of this proposed mechanism is demonstrated using a computer simulation. The simulation uses a Monte Carlo-type algorithm for dynein attachment and adhesive force, together with a geometric evaluation of the t-force on the key microtubule pairs. This model successfully develops spontaneous oscillations from any starting configuration (including a straight position). It is compatible with the physical dimensions, mechanical properties and bridge forces measured in real cilia and flagella. In operation, it exhibits many of the observed actions of cilia and flagella, most notably wave propagation and the ability to produce both cilia-like and flagella-like waveforms. PMID:7820864

  7. 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.

  8. 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

  9. 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...

  10. 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...

  11. 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%

  12. 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...

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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...

  18. 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

  19. 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

  20. 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

  1. The effects of Ca2+ and ADP on dynein switching during the beat cycle of reactivated bull sperm models.

    Science.gov (United States)

    Lesich, Kathleen A; dePinho, Tania G; Dionne, Benjamin J; Lindemann, Charles B

    2014-11-01

    Calcium regulation of flagellar motility is the basis for chemotaxis, phototaxis, and hyperactivation responses in eukaryotic flagellates and spermatozoa. Ca2+ is the internal messenger for these responses, but the coupling between Ca2+ and the motor mechanism that generates the flagellar beat is incompletely understood. We examined the effects of Ca2+ on the flagellar curvature at the switch-points of the beat cycle in bull sperm. The sperm were detergent extracted and reactivated with 0.1 mM adenosine triphosphate (ATP). With their heads immobilized and their tails beating freely it is possible to calculate the bending torque and the transverse force acting on the flagellum at the switch-points. An increase in the free Ca2+ concentration (pCa 8 to pCa 4) significantly decreased the development of torque and t-force in the principal bending direction, while having negligible effect on the reverse bend. The action of Ca2+ was more pronounced when the sperm were also treated with 4 mM adenosine diphosphate (ADP); it was sufficient to change the direction of bending that reaches the greater curvature. We also observed that the curvature of the distal half of the flagellum became locked in one direction in the presence of Ca2+ . This indicates that a subset of the dynein becomes continuously activated by Ca2+ and fails to switch with the beat cycle. Our evidence suggests this subset of dyneins is localized to doublets #1-4 of the axoneme. PMID:25355469

  2. 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

  3. 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.

  4. Bicaudal-D: Switching motors, cargo and direction

    NARCIS (Netherlands)

    G.D. Splinter (Daniël)

    2008-01-01

    textabstractScope of this thesis Transport of vesicles and organelles is an essential cellular process. Proteins like Rab GTPases, specialized adaptor proteins and motor proteins are involved in targeting and movement of cargos to their destination. This thesis describes the function of the mammalia

  5. 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...

  6. 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.

  7. 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...

  8. 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)

  9. 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...

  10. 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)

  11. Dynactin Is an Indispensable Helper for Dynein's Function in Intracellular Motility%Dynactin辅助dynein进行细胞内物质运输的研究进展

    Institute of Scientific and Technical Information of China (English)

    王圣柳; 孙飞

    2012-01-01

    Cytoplasmic dynein is a microtubule motor protein which is responsible for the majority of minus end microtubule-based intracellular motility. The cargoes of dynein include not only mRNA and protein, but also cell organelle and vesicle. Dynactin, a huge complex with Mw of 1.2 Mda, is necessary for dynein's function. The subunits composition and an overall structure model of the dynactin has been revealed based on biochemistry and immuno-electron microscopy. Since the initial discovery, it has become clear that dynactin links dynein to cargo and increases dynein processivity. Although how dynactin ineracts with dynein and how dynactin act as an adapter between dynein and cargoes remain unclear, a lot of achievements have been made in the last decade. We will review these progresses and share a perspective future in this field.%胞质动力蛋白(cytoplasmic dynein)是沿微管向负极运动的马达蛋白,参与细胞内多种物质的运输,运输的货物(cargo)小至信使RNA和蛋白质,大至细胞器和囊泡.动力蛋白只有与动力激活蛋白(dynactin)结合在一起时才有活性.动力激活蛋白是一个分子量为1.2 MDa的多亚基复合物,利用分子生物学和免疫电子显微镜技术,研究者已阐明了其亚基的组成信息,并得到了一个初步的结构模型.10年来,随着对各亚基功能研究的不断深入,研究者发现动力激活蛋白不仅可以增强动力蛋白在微管上的运动持续性,而且还可帮助其结合细胞内的其他成分.然而,动力激活蛋白与动力蛋白之间如何相互调节功能,动力激活蛋白作为接头蛋白如何控制货物在动力蛋白上的结合与解离,这两个核心问题尚未解决.本文就动力激活蛋白的亚基组成及其辅助动力蛋白发挥功能等研究成果进行总结,并对以后的研究趋势进行展望.

  12. Sliding of microtubules by a team of dynein motors: Understanding the effect of spatial distribution of motor tails and mutual exclusion of motor heads on microtubules

    Science.gov (United States)

    Singh, Hanumant Pratap; Takshak, Anjneya; Mall, Utkarsh; Kunwar, Ambarish

    2016-06-01

    Molecular motors are natural nanomachines that use the free energy released from ATP hydrolysis to generate mechanical forces. Cytoplasmic dynein motors often work collectively as a team to drive important processes such as axonal growth, proplatelet formation and mitosis, as forces generated by single motors are insufficient. A large team of dynein motors is used to slide cytoskeletal microtubules with respect to one another during the process of proplatelet formation and axonal growth. These motors attach to a cargo microtubule via their tail domains, undergo the process of detachment and reattachment of their head domains on another track microtubule, while sliding the cargo microtubule along the track. Traditional continuum/mean-field approaches used in the past are not ideal for studying the sliding mechanism of microtubules, as they ignore spatial and temporal fluctuations due to different possible distributions of motor tails on cargo filament, as well as binding/unbinding of motors from their track. Therefore, these models cannot be used to address important questions such as how the distribution of motor tails on microtubules, or how the mutual exclusion of motor heads on microtubule tracks affects the sliding velocity of cargo microtubule. To answer these, here we use a computational stochastic model where we model each dynein motor explicitly. In our model, we use both random as well as uniform distributions of dynein motors on cargo microtubule, as well as mutual exclusion of motors on microtubule tracks. We find that sliding velocities are least affected by the distribution of motor tails on microtubules, whereas they are greatly affected by mutual exclusion of motor heads on microtubule tracks. We also find that sliding velocity depends on the length of cargo microtubule if mutual exclusion among motor heads is considered.

  13. Structural-Functional Relationships of the Dynein, Spokes, and Central-Pair Projections Predicted from an Analysis of the Forces Acting within a Flagellum

    OpenAIRE

    Lindemann, Charles B.

    2003-01-01

    In the axoneme of eukaryotic flagella the dynein motor proteins form crossbridges between the outer doublet microtubules. These motor proteins generate force that accumulates as linear tension, or compression, on the doublets. When tension or compression is present on a curved microtubule, a force per unit length develops in the plane of bending and is transverse to the long axis of the microtubule. This transverse force (t-force) is evaluated here using available experimental evidence from s...

  14. 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...

  15. 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 ...

  16. 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.

  17. Transcription factor NF-kappaB is transported to the nucleus via cytoplasmic dynein/dynactin motor complex in hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Ilja Mikenberg

    Full Text Available BACKGROUND: Long-term changes in synaptic plasticity require gene transcription, indicating that signals generated at the synapse must be transported to the nucleus. Synaptic activation of hippocampal neurons is known to trigger retrograde transport of transcription factor NF-kappaB. Transcription factors of the NF-kappaB family are widely expressed in the nervous system and regulate expression of several genes involved in neuroplasticity, cell survival, learning and memory. PRINCIPAL FINDINGS: In this study, we examine the role of the dynein/dynactin motor complex in the cellular mechanism targeting and transporting activated NF-kappaB to the nucleus in response to synaptic stimulation. We demonstrate that overexpression of dynamitin, which is known to dissociate dynein from microtubules, and treatment with microtubule-disrupting drugs inhibits nuclear accumulation of NF-kappaB p65 and reduces NF-kappaB-dependent transcription activity. In this line, we show that p65 is associated with components of the dynein/dynactin complex in vivo and in vitro and that the nuclear localization sequence (NLS within NF-kappaB p65 is essential for this binding. CONCLUSION: This study shows the molecular mechanism for the retrograde transport of activated NF-kappaB from distant synaptic sites towards the nucleus.

  18. LC2, the Chlamydomonas Homologue of the t Complex-encoded Protein Tctex2, Is Essential for Outer Dynein Arm Assembly

    Science.gov (United States)

    Pazour, Gregory J.; Koutoulis, Anthony; Benashski, Sharon E.; Dickert, Bethany L.; Sheng, Hong; Patel-King, Ramila S.; King, Stephen M.; Witman, George B.

    1999-01-01

    Tctex2 is thought to be one of the distorter genes of the mouse t haplotype. This complex greatly biases the segregation of the chromosome that carries it such that in heterozygous +/t males, the t haplotype is transmitted to >95% of the offspring, a phenomenon known as transmission ratio distortion. The LC2 outer dynein arm light chain of Chlamydomonas reinhardtii is a homologue of the mouse protein Tctex2. We have identified Chlamydomonas insertional mutants with deletions in the gene encoding LC2 and demonstrate that the LC2 gene is the same as the ODA12 gene, the product of which had not been identified previously. Complete deletion of the LC2/ODA12 gene causes loss of all outer arms and a slow jerky swimming phenotype. Transformation of the deletion mutant with the cloned LC2/ODA12 gene restores the outer arms and rescues the motility phenotype. Therefore, LC2 is required for outer arm assembly. The fact that LC2 is an essential subunit of flagellar outer dynein arms allows us to propose a detailed mechanism whereby transmission ratio distortion is explained by the differential binding of mutant (t haplotype encoded) and wild-type dyneins to the axonemal microtubules of t-bearing or wild-type sperm, with resulting differences in their motility. PMID:10512883

  19. Dynein Light Chain LC8 Is Required for RNA Polymerase I-Mediated Transcription in Trypanosoma brucei, Facilitating Assembly and Promoter Binding of Class I Transcription Factor A.

    Science.gov (United States)

    Kirkham, Justin K; Park, Sung Hee; Nguyen, Tu N; Lee, Ju Huck; Günzl, Arthur

    2016-01-01

    Dynein light chain LC8 is highly conserved among eukaryotes and has both dynein-dependent and dynein-independent functions. Interestingly, LC8 was identified as a subunit of the class I transcription factor A (CITFA), which is essential for transcription by RNA polymerase I (Pol I) in the parasite Trypanosoma brucei. Given that LC8 has never been identified with a basal transcription factor and that T. brucei relies on RNA Pol I for expressing the variant surface glycoprotein (VSG), the key protein in antigenic variation, we investigated the CITFA-specific role of LC8. Depletion of LC8 from mammalian-infective bloodstream trypanosomes affected cell cycle progression, reduced the abundances of rRNA and VSG mRNA, and resulted in rapid cell death. Sedimentation analysis, coimmunoprecipitation of recombinant proteins, and bioinformatic analysis revealed an LC8 binding site near the N terminus of the subunit CITFA2. Mutation of this site prevented the formation of a CITFA2-LC8 heterotetramer and, in vivo, was lethal, affecting assembly of a functional CITFA complex. Gel shift assays and UV cross-linking experiments identified CITFA2 as a promoter-binding CITFA subunit. Accordingly, silencing of LC8 or CITFA2 resulted in a loss of CITFA from RNA Pol I promoters. Hence, we discovered an LC8 interaction that, unprecedentedly, has a basal function in transcription.

  20. 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/...

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

    Science.gov (United States)

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

    2012-09-24

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

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

    Directory of Open Access Journals (Sweden)

    Jin‑Chung Chen

    2012-09-01

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

  3. 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.

  4. 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

  5. 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...

  6. Structural-functional relationships of the dynein, spokes, and central-pair projections predicted from an analysis of the forces acting within a flagellum.

    Science.gov (United States)

    Lindemann, Charles B

    2003-06-01

    In the axoneme of eukaryotic flagella the dynein motor proteins form crossbridges between the outer doublet microtubules. These motor proteins generate force that accumulates as linear tension, or compression, on the doublets. When tension or compression is present on a curved microtubule, a force per unit length develops in the plane of bending and is transverse to the long axis of the microtubule. This transverse force (t-force) is evaluated here using available experimental evidence from sea urchin sperm and bull sperm. At or near the switch point for beat reversal, the t-force is in the range of 0.25-1.0 nN/ micro m, with 0.5 nN/ micro m the most likely value. This is the case in both beating and arrested bull sperm and in beating sea urchin sperm. The total force that can be generated (or resisted) by all the dyneins on one micron of outer doublet is also approximately 0.5 nN. The equivalence of the maximum dynein force/ micro m and t-force/ micro m at the switch point may have important consequences. Firstly, the t-force acting on the doublets near the switch point of the flagellar beat is sufficiently strong that it could terminate the action of the dyneins directly by strongly favoring the detached state and precipitating a cascade of detachment from the adjacent doublet. Secondly, after dynein release occurs, the radial spokes and central-pair apparatus are the structures that must carry the t-force. The spokes attached to the central-pair projections will bear most of the load. The central-pair projections are well-positioned for this role, and they are suitably configured to regulate the amount of axoneme distortion that occurs during switching. However, to fulfill this role without preventing flagellar bend formation, moveable attachments that behave like processive motor proteins must mediate the attachment between the spoke heads and the central-pair structure. PMID:12770914

  7. 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.

  8. Interstellar detection of c-C3D2

    CERN Document Server

    Spezzano, S; Schilke, P; Caselli, P; Menten, K M; McCarthy, M C; Bizzocchi, L; Trevino-Morales, S P; Aikawa, Y; Schlemmer, S

    2013-01-01

    We report the first interstellar detection of c-C3D2. The doubly deuterated cyclopropenylidene, a carbene, has been detected toward the starless cores TMC- 1C and L1544 using the IRAM 30m telescope. The J(Ka,Kc) = 3(0,3)-2(1,2), 3(1,3)-2(0,2), and 2(2,1)-1(1,0) transitions of this species have been observed at 3 mm in both sources. The expected 1:2 intensity ratio has been found in the 3(0,3)-2(1,2) and 3(1,3)-2(0,2) lines, belonging to the para and ortho species respectively. We also observed lines of the main species, c-C3H2, the singly deuterated c-C3HD, and the species with one 13C off of the principal axis of the molecule, c-H13CC2H. The lines of c-C3D2 have been observed with high signal to noise ratio, better than 7.5 sigma in TMC-1C and 9 sigma in L1544. The abundance of doubly deuterated cyclopropenylidene with respect to the normal species is found to be (0.4 - 0.8)% in TMC-1C and (1.2 - 2.1)% in L1544. The deuteration of this small hydrocarbon ring is analysed with a comprehensive gas-grain model, ...

  9. 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...

  10. 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.

  11. 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...

  12. Disseny d'un Battle Chess 3D (2)

    OpenAIRE

    Monné Roca, Marc; Ganyet, Josep M.

    2009-01-01

    Aquesta memòria descriu el projecte de final de carrera anomenat "Disseny d'un Battle Chess 3D (2)", que tracta de la creació, modelat i animació de peces per a un joc d'escacs en 3 dimensions amb certes temàtiques, i que posteriorment s'integren amb el projecte "Disseny d'un Battle Chess 3D (1)" per a formar un joc interactiu d'escacs en un applet de Java. Es descriuen les eines utilitzades, les fases de creació, tècniques simbòliques, mètodes més emprats, proves sotmeses, limitacions, i fin...

  13. 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.)

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

    Science.gov (United States)

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

    2007-02-15

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

  15. 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.)

  16. Mitosin/CENP-F is a conserved kinetochore protein subjected to cytoplasmic dynein-mediated poleward transport

    Institute of Scientific and Technical Information of China (English)

    ZHEN YE YANG; JING GUO; NING LI; MIN QIAN; SHENG NIAN WANG; XUE LIANG ZHU

    2003-01-01

    Mitosin/CENP-F is a human nuclear protein transiently associated with the outer kinetochore plate in M phase and is involved in M phase progression. LEK1 and CMF1, which are its murine and chicken orthologs, however, are implicated in muscle differentiation and reportedly not distributed at kinetochores.We therefore conducted several assays to clarify this issue. The typical centromere staining patterns were observed in mitotic cells from both human primary culture and murine, canine, and mink cell lines. A C-terminal portion of LEK1 also conferred centromere localization. Our analysis further suggests conserved kinetochore localization of mammalian mitosin orthologs. Moreover, mitosin was associated preferentially with kinetochores of unaligned chromosomes. It was also constantly transported from kinetochores to spindle poles by cytoplasmic dynein. These properties resemble those of other kinetochore proteins important for the spindle checkpoint, thus implying a role of mitosin in this checkpoint. Therefore, mitosin family may serve as multifunctional proteins involved in both mitosis and differentiation.

  17. Cooperative binding of the outer arm-docking complex underlies the regular arrangement of outer arm dynein in the axoneme

    Science.gov (United States)

    Owa, Mikito; Furuta, Akane; Usukura, Jiro; Arisaka, Fumio; King, Stephen M.; Witman, George B.; Kamiya, Ritsu; Wakabayashi, Ken-ichi

    2014-01-01

    Outer arm dynein (OAD) in cilia and flagella is bound to the outer doublet microtubules every 24 nm. Periodic binding of OADs at specific sites is important for efficient cilia/flagella beating; however, the molecular mechanism that specifies OAD arrangement remains elusive. Studies using the green alga Chlamydomonas reinhardtii have shown that the OAD-docking complex (ODA-DC), a heterotrimeric complex present at the OAD base, functions as the OAD docking site on the doublet. We find that the ODA–DC has an ellipsoidal shape ∼24 nm in length. In mutant axonemes that lack OAD but retain the ODA-DC, ODA-DC molecules are aligned in an end-to-end manner along the outer doublets. When flagella of a mutant lacking ODA-DCs are supplied with ODA-DCs upon gamete fusion, ODA-DC molecules first bind to the mutant axonemes in the proximal region, and the occupied region gradually extends toward the tip, followed by binding of OADs. This and other results indicate that a cooperative association of the ODA-DC underlies its function as the OAD-docking site and is the determinant of the 24-nm periodicity. PMID:24979786

  18. 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...

  19. 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...

  20. 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.

  1. 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...

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Brittany Ebersole

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

  4. 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.

  5. 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.

  6. 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.

  7. 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}.

  8. LC8 dynein light chain (DYNLL1) binds to the C-terminal domain of ATM-interacting protein (ATMIN/ASCIZ) and regulates its subcellular localization

    Energy Technology Data Exchange (ETDEWEB)

    Rapali, Peter [Dept. Biochemistry, Eoetvoes Lorand University, Budapest (Hungary); Garcia-Mayoral, Maria Flor [Dept. Biological Physical Chemistry, IQFR, CSIC, Madrid (Spain); Martinez-Moreno, Monica [Dept. Biochemistry and Molecular Biology I, Universidad Complutense, Madrid (Spain); Tarnok, Krisztian; Schlett, Katalin [Dept. Physiology and Neurobiology, Eoetvoes Lorand University, Budapest (Hungary); Albar, Juan Pablo [Proteomics Facility, CNB, CSIC, Madrid (Spain); Bruix, Marta [Dept. Biological Physical Chemistry, IQFR, CSIC, Madrid (Spain); Nyitray, Laszlo, E-mail: nyitray@elte.hu [Dept. Biochemistry, Eoetvoes Lorand University, Budapest (Hungary); Rodriguez-Crespo, Ignacio, E-mail: nacho@bbm1.ucm.es [Dept. Biochemistry and Molecular Biology I, Universidad Complutense, Madrid (Spain)

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer We have screened a human library with dynein light chain DYNLL1 (DLC8) as bait. Black-Right-Pointing-Pointer Dynein light chain DYNLL1 binds to ATM-kinase interacting protein (ATMIN). Black-Right-Pointing-Pointer ATMIN has 17 SQ/TQ motifs, a motif frequently found in DYNLL1-binding partners. Black-Right-Pointing-Pointer The two proteins interact in vitro, with ATMIN displaying at least five binding sites. Black-Right-Pointing-Pointer The interaction of ATMIN and DYNNL1 in transfected cells can also be observed. -- Abstract: LC8 dynein light chain (now termed DYNLL1 and DYNLL2 in mammals), a dimeric 89 amino acid protein, is a component of the dynein multi-protein complex. However a substantial amount of DYNLL1 is not associated to microtubules and it can thus interact with dozens of cellular and viral proteins that display well-defined, short linear motifs. Using DYNLL1 as bait in a yeast two-hybrid screen of a human heart library we identified ATMIN, an ATM kinase-interacting protein, as a DYNLL1-binding partner. Interestingly, ATMIN displays at least 18 SQ/TQ motifs in its sequence and DYNLL1 is known to bind to proteins with KXTQT motifs. Using pepscan and yeast two-hybrid techniques we show that DYNLL1 binds to multiple SQ/TQ motifs present in the carboxy-terminal domain of ATMIN. Recombinant expression and purification of the DYNLL1-binding region of ATMIN allowed us to obtain a polypeptide with an apparent molecular mass in gel filtration close to 400 kDa that could bind to DYNLL1 in vitro. The NMR data-driven modelled complexes of DYNLL1 with two selected ATMIN peptides revealed a similar mode of binding to that observed between DYNLL1 and other peptide targets. Remarkably, co-expression of mCherry-DYNLL1 and GFP-ATMIN mutually affected intracellular protein localization. In GFP-ATMIN expressing-cells DNA damage induced efficiently nuclear foci formation, which was partly impeded by the presence of mCherry-DYNLL1

  9. 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...

  10. 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...

  11. Identification of dynein light chain road block-1 as a novel interaction partner with the human reduced folate carrier.

    Science.gov (United States)

    Ashokkumar, Balasubramaniem; Nabokina, Svetlana M; Ma, Thomas Y; Said, Hamid M

    2009-09-01

    The reduced folate carrier (RFC) is a major folate transport system in mammalian cells. RFC is highly expressed in the intestine and believed to play a role in folate absorption. Studies from our laboratory and others have characterized different aspects of the intestinal folate absorption process, but little is known about possible existence of accessory protein(s) that interacts with RFC and influences its physiology and/or cell biology. We investigated this issue by employing a bacterial two-hybrid system to screen a BacterioMatch II human intestinal cDNA library using the large intracellular loop between transmembrane domains 6 and 7 of the human RFC (hRFC) as bait. Our screening has resulted in the identification of dynein light chain road block-1 (DYNLRB1) as an interacting partner with hRFC. Existence of a direct protein-protein interaction between hRFC and DYNLRB1 was confirmed by in vitro pull-down assay and in vivo mammalian two-hybrid luciferase assay and coimmunoprecipitation analysis. Furthermore, confocal imaging of live human intestinal epithelial HuTu-80 cells demonstrated colocalization of DYNLRB1 with hRFC. Coexpression of DYNLRB1 with hRFC led to a significant (P < 0.05) increase in folate uptake. On the other hand, inhibiting the endogenous DYNLRB1 with gene-specific small interfering RNA or pharmacologically with a specific inhibitor (vanadate) led to a significant (P < 0.05) decrease in folate uptake. This study demonstrates for the first time the identification of DYNLRB1 as an interacting protein partner with hRFC. Furthermore, DYNLRB1 appears to influence the function and cell biology of hRFC.

  12. 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.

  13. 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.

  14. 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

  15. Algorithms for enumerating and counting D2CS of some graphs

    CERN Document Server

    Reddy, P Venkata Subba

    2010-01-01

    A D2CS of a graph G is a set $S \\subseteq V(G)$ with $diam(G[S]) \\leq 2$. We study the problem of counting and enumerating D2CS of a graph. First we give an explicit formula for the number of D2CS in a complete k-ary tree, Fibonacci tree, binary Fibonacci tree and the binomial tree. Next we give an algorithm for enumerating and counting D2CS of a graph. We then give a linear time algorithm for finding all maximal D2CS in a strongly chordal graph.

  16. 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...

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

    Science.gov (United States)

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

    2013-06-01

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

  18. Late steps in cytoplasmic maturation of assembly-competent axonemal outer arm dynein in Chlamydomonas require interaction of ODA5 and ODA10 in a complex.

    Science.gov (United States)

    Dean, Anudariya B; Mitchell, David R

    2015-10-15

    Axonemal dyneins are multisubunit enzymes that must be preassembled in the cytoplasm, transported into cilia by intraflagellar transport, and bound to specific sites on doublet microtubules, where their activity facilitates microtubule sliding-based motility. Outer dynein arms (ODAs) require assembly factors to assist their preassembly, transport, and attachment to cargo (specific doublet A-tubule sites). In Chlamydomonas, three assembly factors--ODA5, ODA8, and ODA10--show genetic interactions and have been proposed to interact in a complex, but we recently showed that flagellar ODA8 does not copurify with ODA5 or ODA10. Here we show that ODA5 and ODA10 depend on each other for stability and coexist in a complex in both cytoplasmic and flagellar extracts. Immunofluorescence and immuno-electron microscopy reveal that ODA10 in flagella localizes strictly to a proximal region of doublet number 1, which completely lacks ODAs in Chlamydomonas. Studies of the in vitro binding of ODAs to axonemal doublets reveal a role for the ODA5/ODA10 assembly complex in cytoplasmic maturation of ODAs into a form that can bind to doublet microtubules.

  19. 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.)

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

    Science.gov (United States)

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

    2014-01-01

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

  1. 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).

  2. 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.

  3. 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.

  4. 17 CFR 270.12d2-1 - Definition of insurance company for purposes of sections 12(d)(2) and 12(g) of the Act.

    Science.gov (United States)

    2010-04-01

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

  5. 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.

  6. 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。

  7. 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

  8. 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.

  9. 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.

  10. THz spectroscopy of liquid H2O and D2O

    DEFF Research Database (Denmark)

    Rønne, C.; Åstrand, P.-O.; Keiding, S.R.

    1999-01-01

    We have measured and analyzed the dielectric (0.1-2 THz) response of liquid H2O and D2O from 270 to 365 K. The response has been modeled using a Debye model with a fast and a slow decay time. By shifting the temperature scale for the slow decay time of D2O by 7.2 K we find identical behavior for D2...

  11. 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...

  12. 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 ...

  13. 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…

  14. 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...

  15. 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...

  16. 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...

  17. 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

  18. 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

  19. 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.

  20. Chromosomal and Extrachromosomal Instability of the cyclin D2 Gene is Induced by Myc Overexpression

    Directory of Open Access Journals (Sweden)

    Sabine Mai

    1999-08-01

    Full Text Available We examined the expression of cyclins D1, D2, D3, and E in mouse B-lymphocytic tumors. Cyclin D2 mRNA was consistently elevated in plasmacytomas, which characteristically contain Myc-activating chromosome translocations and constitutive c-Myc mRNA and protein expression. We examined the nature of cyclin D2 overexpression in plasmacytomas and other tumors. Human and mouse tumor cell lines that exhibited c-Myc dysregulation displayed instability of the cyclin D2 gene, detected by Southern blot, fluorescent in situ hybridization (FISH, and in extrachromosomal preparations (Hirt extracts. Cyclin D2 instability was not seen in cells with low levels of c-Myc protein. To unequivocally demonstrate a role of c-Myc in the instability of the cyclin D2 gene, a Myc-estrogen receptor chimera was activated in two mouse cell lines. After 3 to 4 days of Myc-ERTm activation, instability at the cyclin D2 locus was seen in the form of extrachromosomal elements, determined by FISH of metaphase and interphase nuclei and of purified extrachromosomal elements. At the same time points, Northern and Western blot analyses detected increased cyclin D2 mRNA and protein levels. These data suggest that Myc-induced genomic instability may contribute to neoplasia by increasing the levels of a cell cycle—regulating protein, cyclin D2, via intrachromosomal amplification of its gene or generation of extrachromosomal copies.

  1. 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

  2. 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

  3. 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

  4. Cloning, characterization and expression of the D2 dopamine receptor from the tilapia pituitary.

    Science.gov (United States)

    Levavi-Sivan, Berta; Aizen, Joseph; Avitan, Ayelet

    2005-05-31

    A full-length cDNA encoding a dopamine receptor (DA-R) was obtained from the pituitary of tilapia (ta). This cDNA encodes a protein of 469 amino acids that exhibits the typical arrangement of GPCR. The taDA-R shows high similarity to the DA-Rs of mullet and fugu, and over 70% similarity to Xenopus, mouse and turkey D2 DA-Rs. Northern blot analysis revealed transcript for a single transcript in the pituitary, of approximately 3 kb. In a Southern analysis, the tilapia probe recognized specific bands in the genomic DNA of both mullet and catfish, suggesting high similarity between the corresponding genes. Phylogenetic analysis clearly aligned the taDA-D2-R with all vertebrate D2-like receptor sequences cloned to date, and it was therefore designated taDA-D2-R. taDA-D2-R was transiently expressed in COS-7 cells together with the reporter construct CRE-luciferase. Addition of the specific D2 dopamine agonists quinpirole or bromocriptine, in the presence of forskolin, led to a dose-dependent decrease in forskolin-induced cAMP levels. Both agonists yielded the same maximal inhibition (around 40%). However, the potency of taDA-D2-R for bromocriptine was higher than for quinpirole. As established for mammalian D2-like receptors, stimulation of the taDA-D2-R with quinpirole triggers pertussis-toxin-sensitive Gi/o-mediated, but not Gs-mediated signaling. In contrast to mammals, PCR analysis gave no evidence of alternative splicing in taDA-D2-R. Pharmacological and genetic manipulation of the taDA-D2-R should enable us to better define its physiological role and to further explore the usefulness of fish as a model system for understanding dopaminergic function in higher organisms. PMID:15876479

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

    Science.gov (United States)

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

    2016-01-01

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

  6. Estimating Dopamine D-2 Receptor Occupancy for Doses of 8 Antipsychotics : A Meta-Analysis

    NARCIS (Netherlands)

    Lako, Irene M.; van den Heuvel, Edwin R.; Knegtering, Henrikus; Bruggeman, Richard; Taxis, Katja

    2013-01-01

    Rationale: Dose equivalents based on dopamine D-2 receptor occupancy can be used to compare antipsychotics on D-2 receptor-mediated (adverse) effects such as extrapyramidal symptoms and altered emotional experiences. Previous meta-analyses modeling the dose-occupancy relationship hardly addressed po

  7. 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

  8. 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

  9. 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

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

    Science.gov (United States)

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

    2016-01-01

    Patients with malignant gliomas have a poor prognosis with average survival of less than 1 year. Whereas in other tumor entities the characteristics of tumor metabolism are successfully used for therapeutic approaches, such developments are very rare in brain tumors, notably in gliomas. One metabolic feature characteristic of gliomas, in particular diffuse astrocytomas and oligodendroglial tumors, is the variable content of D-2-hydroxyglutarate (D2HG), a metabolite that was discovered first in this tumor entity. D2HG is generated in large amounts due to various "gain-of-function" mutations in the isocitrate dehydrogenases IDH1 and IDH2. Meanwhile, D2HG has been detected in several other tumor entities, including intrahepatic bile-duct cancer, chondrosarcoma, acute myeloid leukemia, and angioimmunoblastic T-cell lymphoma. D2HG is barely detectable in healthy tissue (bioluminescence assay for determining D2HG in sections of snap-frozen tissue. The assay was verified independently by photometric tests and liquid chromatography/mass spectrometry. The novel technique allows the microscopically resolved determination of D2HG in a concentration range of 0-10 μmol/g tissue (wet weight). In combination with the already established bioluminescence imaging techniques for ATP, glucose, pyruvate, and lactate, the novel D2HG assay enables a comparative characterization of the metabolic profile of individual tumors in a further dimension.

  11. Stability of globular proteins in H2O and D2O

    NARCIS (Netherlands)

    Efimova, Y. M.; Haemers, S.; Wierczinski, B.; Norde, W.; van Well, A. A.

    2007-01-01

    In several experimental techniques D2O rather then H2O is often used as a solvent for proteins. Concerning the influence of the solvent on the stability of the proteins, contradicting results have been reported in literature. In this paper the influence of H2O-D2O solvent substitution on the stabili

  12. Selective poisoning of active sites for D-2 dissociation on platinum

    NARCIS (Netherlands)

    Hahn, C.; Shan, J. J.; Groot, I. M. N.; Kleyn, A. W.; Juurlink, L. B. F.

    2010-01-01

    We have examined the reactivity of D-2 on CO-precovered Pt(5 3 3) employing supersonic molecular beam techniques and compare our results to D-2 dissociation on the bare surface. At very low kinetic energy, reaction probability is reduced linearly with increasing CO-precoverage at step edges. Diffusi

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. Translational Modeling in Schizophrenia : Predicting Human Dopamine D2 Receptor Occupancy

    NARCIS (Netherlands)

    Johnson, Martin; Kozielska, Magdalena; Pilla Reddy, Venkatesh; Vermeulen, An; Barton, Hugh A; Grimwood, Sarah; de Greef, Rik; Groothuis, Geny M M; Danhof, Meindert; Proost, Johannes H

    2015-01-01

    OBJECTIVES: To assess the ability of a previously developed hybrid physiology-based pharmacokinetic-pharmacodynamic (PBPKPD) model in rats to predict the dopamine D2 receptor occupancy (D2RO) in human striatum following administration of antipsychotic drugs. METHODS: A hybrid PBPKPD model, previousl

  18. 26 CFR 53.4941(d)-2 - Specific acts of self-dealing.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Specific acts of self-dealing. 53.4941(d)-2 Section 53.4941(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED... those described in subparagraph (1) of this paragraph to a foundation manager in recognition of...

  19. 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.

  20. 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).

  1. CIE D2 and Developments of Photometry Radiometry%CIE D2和光辐射测量动态

    Institute of Scientific and Technical Information of China (English)

    潘建根

    2005-01-01

    本文简单介绍国际照明委员会(CIE)第二分部(D2)的主要工作范围,介绍CIE D2目前已成立的技术委员会(TC),已出版的标准和技术文件等出版物.同时,本文还介绍在光和辐射测量领域内国际较为关注的热点问题和最新发展动态.

  2. 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

  3. 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.

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

    Science.gov (United States)

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

    2015-03-01

    The prefrontal cortex houses representations critical for ongoing and future behavior expressed in the form of patterns of neural activity. Dopamine has long been suggested to play a key role in the integrity of such representations, with D2-receptor activation rendering them flexible but weak. However, it is currently unknown whether and how D2-receptor activation affects prefrontal representations in humans. In the current study, we use dopamine receptor-specific pharmacology and multivoxel pattern-based functional magnetic resonance imaging to test the hypothesis that blocking D2-receptor activation enhances prefrontal representations. Human subjects performed a simple reward prediction task after double-blind and placebo controlled administration of the D2-receptor antagonist amisulpride. Using a whole-brain searchlight decoding approach we show that D2-receptor blockade enhances decoding of reward signals in the medial orbitofrontal cortex. Examination of activity patterns suggests that amisulpride increases the separation of activity patterns related to reward versus no reward. Moreover, consistent with the cortical distribution of D2 receptors, post hoc analyses showed enhanced decoding of motor signals in motor cortex, but not of visual signals in visual cortex. These results suggest that D2-receptor blockade enhances content-specific representations in frontal cortex, presumably by a dopamine-mediated increase in pattern separation. These findings are in line with a dual-state model of prefrontal dopamine, and provide new insights into the potential mechanism of action of dopaminergic drugs. PMID:25740537

  5. 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

  6. 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...

  7. 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...

  8. Dynamic Alignment of D2 Enhanced by Two Few-cycle Pulses

    Institute of Scientific and Technical Information of China (English)

    Zeng-qiang Yang; Zhi-rong Guo; Bao-xiang Yin; Mao-zhu Sun

    2008-01-01

    Dynamic alignment of D2 induced by two few-cycle pulses was investigated by solving the time-dependent Schr(o)dinger equation numerically based on a rigid rotor model. The results show that alignment of D2 can be enhanced by two few-cycle pulses compared with the level achievable by a single fewcycle pulse as long as the time delay between two pulses is chosen properly, and the pulse duration of two lasers plays an important role in the aligning process of D2 molecules.

  9. 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...

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

    Science.gov (United States)

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

    2007-08-01

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

  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. 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.

  14. 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

  15. 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

  16. 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。

  17. 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...

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

    Science.gov (United States)

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

    2008-08-01

    Complete or almost complete hepatitis B virus (HBV) genomes were sequenced for 13 genotype A and 42 genotype D strains from the former USSR. The strains were classifiable within subgenotypes A2, D1, D2 and D3. Comparison of the deduced gene products for the four ORFs of 89 genotype D strains revealed 27 subgenotype-specific residues, and a region spanning residues 58-128 in the spacer region of the P gene could be used to distinguish between D1 and D4. This enabled the allocation to subgenotype of strains with partially sequenced genomes. D2 was dominating, while D3 was found in low frequency in the whole region. D1 was most prevalent in the Middle Asian Republics. Mean inter-subgenotype divergences between D1 and D2, D1 and D3 and D2 and D3 were 2.7, 3.4 and 3.4 %, respectively. The intra-subgenotype divergence was 0.4, 1.1, 1.0 and 1.8 % for A2, D1, D2 and D3, respectively. All D1 and D3 strains encoded subtype ayw2, whereas most D2 strains encoded ayw3. Two D2 strains encoded ayw4. Strains with identical S genes were closely related at the level of complete genomes and formed geographically specific clades with low intraclade divergences, possibly indicating past iatrogenic spread. It is not clear whether the finding of four subgenotypes in the area corresponds to separate introductions of the virus or to previous population migrations into the area. An earlier introduction of D3 compared with D2 was supported by its higher intra-subgenotype divergence, while the lower divergence within D1 is probably due to a more recent emergence. PMID:18632953

  19. 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...

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

    Science.gov (United States)

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

    2016-09-13

    Ice nucleation is of fundamental significance in many areas, including atmospheric science, food technology, and cryobiology. In this study, we investigated the ice-nucleation characteristics of picoliter-sized drops consisting of different D2O and H2O mixtures with and without the ice-nucleating bacteria Pseudomonas syringae. We also studied the effects of commonly used cryoprotectants such as ethylene glycol, propylene glycol, and trehalose on the nucleation characteristics of D2O and H2O mixtures. The results show that the median freezing temperature of the suspension containing 1 mg/mL of a lyophilized preparation of P. syringae is as high as -4.6 °C for 100% D2O, compared to -8.9 °C for 100% H2O. As the D2O concentration increases every 25% (v/v), the profile of the ice-nucleation kinetics of D2O + H2O mixtures containing 1 mg/mL Snomax shifts by about 1 °C, suggesting an ideal mixing behavior of D2O and H2O. Furthermore, all of the cryoprotectants investigated in this study are found to depress the freezing phenomenon. Both the homogeneous and heterogeneous freezing temperatures of these aqueous solutions depend on the water activity and are independent of the nature of the solute. These findings enrich our fundamental knowledge of D2O-related ice nucleation and suggest that the combination of D2O and ice-nucleating agents could be a potential self-ice-nucleating formulation. The implications of self-nucleation include a higher, precisely controlled ice seeding temperature for slow freezing that would significantly improve the viability of many ice-assisted cryopreservation protocols. PMID:27495973

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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...

  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. Agrobacterium VirD2 protein interacts with plant host cyclophilins.

    Science.gov (United States)

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

    1998-06-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  9. 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

  10. 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.

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

    Science.gov (United States)

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

    2013-08-01

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

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

    Science.gov (United States)

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

    2004-11-01

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

  13. 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

  14. 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.

  15. 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.

  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. 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...

  19. 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

    DEFF Research Database (Denmark)

    Itkonen, Suvi T.; Skaffari, Essi; Saaristo, Pilvi;

    2016-01-01

    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...

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Ansorg Anne

    2012-05-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

  3. 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

  4. 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

  5. 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.

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

    Science.gov (United States)

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

    2009-06-01

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

  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. 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

  9. Overexpression of the dynein light chain km23-1 in human ovarian carcinoma cells inhibits tumor formation in vivo and causes mitotic delay at prometaphase/metaphase.

    Science.gov (United States)

    Pulipati, Nageswara R; Jin, Qunyan; Liu, Xin; Sun, Baodong; Pandey, Manoj K; Huber, Jonathan P; Ding, Wei; Mulder, Kathleen M

    2011-08-01

    km23-1 is a dynein light chain that was identified as a TGFβ receptor-interacting protein. To investigate whether km23-1 controls human ovarian carcinoma cell (HOCC) growth, we established a tet-off inducible expression system in SKOV-3 cells in which the expression of km23-1 is induced upon doxycycline removal. We found that forced expression of km23-1 inhibited both anchorage-dependent and anchorage-independent growth of SKOV-3 cells. More importantly, induction of km23-1 expression substantially reduced the tumorigenicity of SKOV-3 cells in a xenograft model in vivo. Fluorescence-activated cell sorting analysis of SKOV-3 and IGROV-1 HOCCs demonstrated that the cells were accumulating at G2/M. Phospho-MEK, phospho-ERK and cyclin B1 were elevated, as was the mitotic index, suggesting that km23-1 suppresses HOCCs growth by inducing a mitotic delay. Immunofluorescence analyses demonstrated that the cells were accumulating at prometaphase/metaphase with increases in multipolar and multinucleated cells. Further, although the mitotic spindle assembly checkpoint protein BubR1 was present at the prometaphase kinetochore in Dox+/- cells, it was inappropriately retained at the metaphase kinetochore in Dox- cells. Thus, the mechanism by which high levels of km23-1 suppress ovarian carcinoma growth in vitro and inhibit ovary tumor formation in vivo appears to involve a BubR1-related mitotic delay.

  10. 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.

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

    Science.gov (United States)

    Nagai, Kenta; Watanabe, Kazuo

    2016-01-01

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

  12. 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

  13. 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.

  14. 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...... connection allows underlay operation with Successive Interference Cancellation (SIC) during the cellular downlink transmissions. We consider different ways to use SIC and investigate the trade-off between, on one hand, the achieved rate for the downlink cellular users and, on the other hand, the outage...

  15. 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.

  16. 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...

  17. 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;

    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...... the unaffected mother was a mosaic carrier....

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

    DEFF Research Database (Denmark)

    Kristensen, Anders S; Hansen, Kasper B; Naur, Peter;

    2016-01-01

    -term depression. Here, we investigate the pharmacology of the orthosteric binding site in GluD2 by examining the activity of analogs of D-Ser and GluN1 glycine site competitive antagonists at GluD2 receptors containing the lurcher mutation (GluD2(LC)), which promotes spontaneous channel activation. We identify...

  19. 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%.

  20. 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

  1. 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

  2. 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)

  3. 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.

  4. 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.)

  5. 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

  6. Magnetic field decoupling and 3D-2D crossover in Nb/Cu multilayers

    DEFF Research Database (Denmark)

    Krasnov, V.M.; Kovalev, A.E.; Oboznov, V.A.;

    1996-01-01

    Transport properties of Nb/Cu multilayers were measured along and across layers. Ir is shown that not only the temperature but also the magnetic field parallel to layers can effectively decouple layers and cause the three-to-two-dimensional (3D-2D) crossover. As a consequence of the 3D-2D crossover...... magnetic field and by the multiply branched I-V curves caused by flux-flow of Josephson vortices in the stacked superconductor-normal-metal-superconductor junctions composing the multilayer. By measurements across layers the ''breaking field'' at which the proximity induced superconductivity in the normal...

  7. 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

  8. 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.

  9. 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...

  10. 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.

  11. 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

  12. 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...

  13. 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...

  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. 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...

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

    Science.gov (United States)

    Yuzaki, Michisuke

    2013-11-01

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

  19. 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

    -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...

  20. 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)

  1. 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.

  2. Acidity Measurements with the Glass Electrode in H2O-D2O Mixtures

    DEFF Research Database (Denmark)

    Mikkelsen, K.; Nielsen, Sigurd Olaf

    1960-01-01

    . deuterium enriched samples. From the electromotive forces observed with a saturated KC1-H20 calomel electrode at 22° the relation between true p(DH) and apparent pH in 98% D2O is derived. p(DH) = apparent pH + 0.44. A possibility of determining the activities, an and aD, separately is considered from...

  3. 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.

  4. 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...

  5. 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.

  6. 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

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

    Science.gov (United States)

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

    2014-01-01

    The obesity epidemic is believed to be driven by a food environment that promotes consumption of inexpensive, convenient, high-calorie, palatable foods. Individual differences in obesity susceptibility or resistance to weight loss may arise due to alterations in the neurocircuitry supporting food reward and eating habits. In particular, dopamine signaling in the ventromedial striatum is thought to encode food reward and motivation, whereas dopamine in the dorsal and lateral striatum orchestrates the development of eating habits. We measured striatal dopamine D2-like receptor binding potential (D2BP) using positron emission tomography (PET) with [18F]fallypride in 43 human subjects with body mass indices (BMI) ranging from 18–45 kg/m2. Opportunistic eating behavior and BMI were both positively associated with D2BP in the dorsal and lateral striatum, whereas BMI was negatively associated with D2BP in the ventromedial striatum. These results suggest that obese people have alterations in dopamine neurocircuitry that may increase their susceptibility to opportunistic overeating while at the same time making food intake less rewarding, less goal-directed, and more habitual. Whether or not the observed neurocircuitry alterations pre-existed or occurred as a result of obesity development, they may perpetuate obesity given the omnipresence of palatable foods and their associated cues. PMID:25199919

  8. Prostaglandin D2 regulates joint inflammation and destruction in murine collagen-induced arthritis.

    NARCIS (Netherlands)

    Maicas Blasco, N.; Ibanez, L.; Alcaraz, M.J.; Ubeda, A.; Ferrandiz, M.L.

    2012-01-01

    OBJECTIVE: Prostaglandin D2 (PGD2) may exert proinflammatory or antiinflammatory effects in different biologic systems. Although this prostanoid and the enzymes responsible for its synthesis are up-regulated by interleukin-1beta (IL-1beta) in human chondrocytes in vitro, the role of PGD2 in arthriti

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

    Science.gov (United States)

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

    2008-05-01

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

  10. 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

  11. 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

  12. 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....

  13. Data of evolutionary structure change: 1AW2D-2VENA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1AW2D-2VENA 1AW2 2VEN D A --RHPVVMGNWKLNGSKEMVVDLLNGLNAELEGVTGVDV...RQLDAVINTQGVEALEGAIIAYEPIWAIGTGKAATAEDAQRIHAQIRAHIAEK-SEAVAKNVVIQYGGSVKPENAAAYFAQPDIDGALVGGAALDAKSFAAIAKAAAE...14> 2VEN A 2VENA...ndex> 2VEN A 2VENA E...x> 2 2VEN A

  14. Predicting dopamine D2 receptor occupancy in humans using a physiology-based approach

    NARCIS (Netherlands)

    Johnson, Martin; Kozielska, Magdalena; Pilla Reddy, Venkatesh; Vermeulen, An; Barton, Hugh A.; Grimwood, Sarah; de Greef, Rik; Groothuis, Genoveva; Danhof, Meindert; Proost, Johannes

    2011-01-01

    Objectives: A hybrid physiology-based pharmacokinetic and pharmacodynamic model (PBPKPD) was used to predict the time course of dopamine receptor occupancy (D2RO) in human striatum following the administration of antipsychotic (AP) drugs, using in vitro and in silico information. Methods: A hybrid P

  15. 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

  16. 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

  17. 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...

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

    DEFF Research Database (Denmark)

    Pilz, Florian; Yan, Shi; Grest, Daniel;

    2007-01-01

    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...

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 12 CFR Appendix D-2 to Part 208 - Interagency Guidelines Establishing Information Security Standards

    Science.gov (United States)

    2010-01-01

    ..., such as buildings, computer facilities, and records storage facilities to permit access only to... to detect actual and attempted attacks on or intrusions into customer information systems; g... (OTS). 2 12 CFR part 30, app. B (OCC); 12 CFR part 208, app. D-2 and part 225, app. F (Board); 12...

  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. AIMS D2DB simulation for DUV and EUV mask inspection

    Science.gov (United States)

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

    2012-02-01

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

  7. GAME THEORY BASED INTERFERENCE CONTROL AND POWER CONTROL FOR D2D COMMUNICATION IN CELLULAR NETWORKS

    Directory of Open Access Journals (Sweden)

    Fa-Bin Li

    2016-09-01

    Full Text Available With the current development of mobile communication services, people need personal communication of high speed, excellent service, high quality and low latency,however, limited spectrum resources become the most important factor to hamper improvement of cellular systems. As big amount of data traffic will cause greater local consumption of spectrum resources, future networks are required to have appropriate techniques to better support such forms of communication. D2D (Device-to-device communication technology in a cellular network makes full use of spectrum resources underlaying, reduces the load of the base station, minimizes transmit power of the terminals and the base stations, thereby enhances the overall throughput of the networks. Due to the use of multiplexing D2D UE (User equipment resources and spectrum, and the interference caused by the sharing of resources between adjacent cells, it has become a major factor affecting coexisting of cellular subscribers and D2D users. When D2D communication multiplexes the uplink resources, the base-stations are easily to be disturbed; when the downlink resources are multiplexed, the users of downlink are susceptible to interference. In order to build a high-efficient mobile network, we can meet the QoS requirements by controlling the power to suppress the interference between the base station and a terminal user.

  8. 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.

  9. VUV Fourier-transform absorption study of the Lyman and Werner bands in D-2

    NARCIS (Netherlands)

    Lange, de A.; Dickenson, G.D.; Salumbides, E.J.; Ubachs, W.M.G.; Oliveira, de N.; Joyeux, D.; Nahon, L.

    2012-01-01

    An extensive survey of the D-2 absorption spectrum has been performed with the high-resolution VUV Fourier-transform spectrometer employing synchrotron radiation. The frequency range of 90 000-119 000 cm (1) covers the full depth of the potential wells of the B (1)Sigma(+)(u), B' 1 Sigma(+)(u), and

  10. A non-linear representation of the d=2 so (4)-extended superconformal algebra

    NARCIS (Netherlands)

    Schoutens, K.

    1987-01-01

    We present a non-linear representation of the so(4)-extended d=2 superconformal algebra in terms of one boson and four Majorana fermions. The matter fields and the currents can be grouped into a single N=4 superfield. Breaking the supersymmetry to N=3 or N=2 leads to new representations of the N=3,2

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

    Science.gov (United States)

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

    2016-01-01

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

  12. 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_...

  13. Ecodriver. D2.4: Plan for using and disseminating knowledge_Public

    NARCIS (Netherlands)

    Winder, A.; et al

    2016-01-01

    The full D2.4 confidential deliverable describes the ecoDriver project’s key projected results and the plans for exploiting them. This public version omits the chapters on expoitoitable results and the project partners plans for exploiting them. This is the third year version of the deliverable repo

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

    Science.gov (United States)

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

    2011-05-18

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

  15. 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...

  16. 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.

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

    Science.gov (United States)

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

    2016-09-01

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

  18. Cryptomoschatone D2 from Cryptocarya mandioccana: cytotoxicity against human cervical carcinoma cell lines

    Directory of Open Access Journals (Sweden)

    CHRISTIANE PIENNA SOARES

    2010-06-01

    Full Text Available

    Among the substances isolated from Cryptocarya sp, some styrylpyrones, such as goniothalamin, demonstrate antiproliferative activity in a broad range of human cell lines. In the present study, we assessed the cytotoxicity of a styrylpyrone (cryptomoschatone D2, isolated from Cryptocarya mandiocanna, in HPV-infected (HeLa and SiHa and uninfected (C33A human cervical carcinoma cell lines and a human lung fibroblast line (MRC-5. The cytotoxicity was tested by the MTT assay. In this assay, cells were treated with cryptomoschatone D2 at 15, 30, 60 or 90 μM for 6, 24 or 48 hours, as well as for 6 hours followed by a post-treatment recovery period of 24, 48 or 72 hours. High cytotoxicity (dose- and timedependent was observed in HeLa, SiHa, C33A and MRC-5 cell lines. Although in general the styrylpyrone cytotoxicity was not significantly different among the cell lines tested, it was apparently stronger in HeLa and C33A than in MRC-5 and SiHa in the 24 or 48-hour treatments. Moreover, HeLa and SiHa were able to recover their ability to proliferate, in direct proportion to the post-treatment recovery time. On the other hand, C33A did not demonstrate a similar post-treatment recovery. We can conclude that cryptomoschatone D2 possesses high dose-dependent or time-dependent cytotoxicity. Keywords: Cell culture. Antiproliferative activity. Styrylpyrone, Cryptomoschatone D2. RESUMO Cryptomoscatona D2 de Cryptocarya mandioccana: atividade citotóxica contra linhagem celular de carcinoma cervical humano Dentre as substâncias isoladas de Cryptocarya sp, algumas estirilpironas, como a goniotalamina, apresentam atividade antiproliferativa em diferentes linhagens celulares. No presente estudo, foram avaliadas as atividades citotóxica de uma estirilpirona (criptomoscatona D2 isolada de Cryptocarya mandiocanna, em linhagens celulares de carcinoma cervical humano infectada por HPV (HeLa e SiHa, não infectada (C33A e fibroblasto pulmonar

  19. 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.

  20. 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

  1. 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).

  2. 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.

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

    Science.gov (United States)

    Merritt, Kathryn E.; Bachtell, Ryan K.

    2013-01-01

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

  4. 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-...

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

    Science.gov (United States)

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

    2016-04-14

    There is a need for food-based solutions for preventing vitamin D deficiency. Vitamin D3 (D3) is mainly used in fortified food products, although the production of vitamin D2 (D2) is more cost-effective, and thus may hold opportunities. We investigated the bioavailability of D2 from UV-irradiated yeast present in bread in an 8-week randomised-controlled trial in healthy 20-37-year-old women (n 33) in Helsinki (60°N) during winter (February-April) 2014. Four study groups were given different study products (placebo pill and regular bread=0 µg D2 or D3/d; D2 supplement and regular bread=25 µg D2/d; D3 supplement and regular bread=25 µg D3/d; and placebo pill and D2-biofortified bread=25 µg D2/d). Serum 25-hydroxyvitamin D2 (S-25(OH)D2) and serum 25-hydroxyvitamin D3 (S-25(OH)D3) concentrations were measured at baseline, midpoint and end point. The mean baseline total serum 25-hydroxyvitamin D (S-25(OH)D=S-25(OH)D2+S-25(OH)D3) concentration was 65·1 nmol/l. In repeated-measures ANCOVA (adjusted for baseline S-25(OH)D as total/D2/D3), D2-bread did not affect total S-25(OH)D (P=0·707) or S-25(OH)D3 (P=0·490), but increased S-25(OH)D2 compared with placebo (PD2 supplement was more effective than bread in increasing S-25(OH)D2 (PD2 and D3 supplementation increased total S-25(OH)D compared with placebo (P=0·030 and P=0·001, respectively), but D2 supplementation resulted in lower S-25(OH)D3 (PD2 from UV-irradiated yeast in bread was not bioavailable in humans. Our results support the evidence that D2 is less potent in increasing total S-25(OH)D concentrations than D3, also indicating a decrease in the percentage contribution of S-25(OH)D3 to the total vitamin D pool.

  6. 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)

    Stephan eSauer

    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

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. Longitudinal relaxation of ND4D2PO4 type antiferroelectrics. Piezoelectric resonance and sound attenuation

    Directory of Open Access Journals (Sweden)

    R.R. Levitskii

    2009-01-01

    Full Text Available Within the framework of the modified proton model with taking into account the interaction with the shear strain ε6, a dynamic dielectric response of ND4D2PO4 type antiferroelectrics is considered. Dynamics of the piezoelectric strain is taken into account. Experimentally observed phenomena of crystal clamping by high frequency electric field, piezoelectric resonance and microwave dispersion are described. Ultrasound velocity and attenuation are calculated. Character of behaviour of attenuation in the paraelectric phase and the existence of a cut-off frequency in the frequency dependence of attenuation are predicted. At the proper choice of the parameters, a good quantitative description of experimental data for longitudinal static dielectric, piezoelectric and elastic characteristics and sound velocity for ND4D2PO4 and NH4H2PO4 is obtained in the paraelectric phase.

  15. 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.

  16. Vertical D4-D2-D0 bound states on K3 fibrations and modularity

    DEFF Research Database (Denmark)

    Bouchard, Vincent; Creutzig, Thomas; Diaconescu, Duiliu-Emanuel;

    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 the...... theory. This leads to a new construction of vector valued modular forms which exhibits some of the features of a generalized Hecke transform.......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...

  17. 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)

  18. 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.

  19. 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。

  20. 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.

  1. 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).

  2. 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.

  3. 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...

  4. 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

  5. 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

  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. 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.

  8. 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

  9. 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.

  10. 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...

  11. 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.

  12. 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.

  13. 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...

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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. ...

  19. 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...

  20. 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....

  1. Gastric cancer surgery in cirrhotic patients: Result of gastrectomy with D2 lymph node dissection

    Institute of Scientific and Technical Information of China (English)

    Jun Ho Lee; Junuk Kim; Jae Ho Cheong; Woo Jin Hyung; Seung Ho Choi; Sung Hoon Noh

    2005-01-01

    AIM: To explore the feasibility of performing gastrectomy with D2 lymphadenectomy in gastric cancer patients with liver cirrhosis.METHODS: A total of 7 178 patients were admitted with a diagnosis of liver cirrhosis from January 1993 to December 2003. We reviewed the records of 142 patients who were diagnosed with liver cirrhosis and gastric adenocarcinoma during the same period. Gastrectomy with D2 lymph node dissection for carcinoma of the stomach was performed in 94 patients with histologically proven hepatic cirrhosis.RESULTS: All but 12 patients were classified as Child's class A. Only 35 patients (37.2%) were diagnosed with cirrhosis before operation. Seventy-three patients underwent a subtotal gastrectomy (77.7%) and 21 patients (22.3%)underwent a total gastrectomy, each with D2 or more lymph node dissection. Two patients (3.8%) who had prophylactic intra-operative drain placement, died of postoperative complications from hepatorenal failure with intractable ascites. Thirty-seven patients (39.4%) experienced postoperative complications. The extent of gastric resection did not influence the morbidity whereas serum aspartate aminotransferase level (P = 0.011) and transfusion did (P= 0.008). The most common postoperative complication was ascites (13.9%) followed by wound infection (10.6%).CONCLUSION: We concluded that the presence of compensated cirrhosis, i.e. Child class A, is not a contraindication against gastrectomy with D2 or more lymph node dissection, when curative resection for gastric cancer is possible. Hepatic reserve and meticulous hemostasis are the likely determinants of operative prognosis.

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

    Science.gov (United States)

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

    1986-01-01

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

  3. 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.

  4. 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

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

    Science.gov (United States)

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

    2014-09-01

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

  6. 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.

  7. 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

  8. 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.

  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. 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.

  11. 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.

  12. 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

  13. Striatal D1 and D2 signaling differentially predict learning from positive and negative outcomes.

    Science.gov (United States)

    Cox, Sylvia M L; Frank, Michael J; Larcher, Kevin; Fellows, Lesley K; Clark, Crystal A; Leyton, Marco; Dagher, Alain

    2015-04-01

    The extent to which we learn from positive and negative outcomes of decisions is modulated by the neurotransmitter dopamine. Dopamine neurons burst fire in response to unexpected rewards and pause following negative outcomes. This dual signaling mechanism is hypothesized to drive both approach and avoidance behavior. Here we test a prediction deriving from a computational reinforcement learning model, in which approach is mediated via activation of the direct cortico-striatal pathway due to striatal D1 receptor stimulation, while avoidance occurs via disinhibition of indirect pathway striatal neurons secondary to a reduction of D2 receptor stimulation. Using positron emission tomography with two separate radioligands, we demonstrate that individual differences in human approach and avoidance learning are predicted by variability in striatal D1 and D2 receptor binding, respectively. Moreover, transient dopamine precursor depletion improved learning from negative outcomes. These findings support a bidirectional modulatory role for striatal dopamine in reward and avoidance learning via segregated D1 and D2 cortico-striatal pathways.

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

    CERN Document Server

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

    2012-01-01

    An extensive survey of the D2 absorption spectrum has been performed with the high-resolution VUV Fourier-transform spectrometer of the DESIRS beamline at the SOLEIL synchrotron. The frequency range of 90 000-119 000 cm-1 covers the full depth of the potential wells of the B 1{\\Sigma}+u, B' 1{\\Sigma}+u, and C 1{\\Pi}u electronic states up to the D(1s) + D(2\\ell) dissociation limit. Improved level energies of rovibrational levels have been determined up to respectively v = 51, v = 13, and v = 20. Highest resolution is achieved by probing absorption in a molecular gas jet with slit geometry, as well as in a liquid helium cooled static gas cell, resulting in line widths of ~0.35 cm-1. Extended calibration methods are employed to extract line positions of D2 lines at absolute accuracies of 0.03 cm-1. The D1{\\Pi}u and B" 1{\\Sigma}+u electronic states correlate with the D(1s) + D(3\\ell) dissociation limit, but support a few vibrational levels below the second dissociation limit, respectively v = 0-3 and v = 0-1, and...

  15. 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)

  16. 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.

  17. 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

  18. Rice Blast Resistance of Transgenic Rice Plants with Pi-d2 Gene

    Institute of Scientific and Technical Information of China (English)

    CHEN De-xi; CHEN Xue-wei; LEI Cai-lin; MA Bing-tian; WANG Yu-ping; LI Shi-gui

    2010-01-01

    Resistance to rice blast of transgenic rice lines harboring rice blast resistance gene Pi-d2 transformed from three different expression vectors of pCB6.3kb, pCB5.3kb and pZH01-2.72kb were analyzed. Nine advanced-generation transgenic rice lines with Pi-d2 gene displayed various resistance to 39 rice blast strains, and the highest disease-resistant frequency reached 91.7%. Four early-generation homozygous transgenic lines with Pi-d2 gene exhibited resistance to more than 81.5% of 58 rice blast strains, showing the characteristic of wide-spectrum resistance. The transgenic embryonic calli selected by the crude toxin of rice blast fungus showed that the callus induction rate of immature embryo from transgenic rice plants decreased as the concentration of crude toxin in the culture medium increased. When the concentration of crude toxin reached 40%, the callus induction rate of immature embryo from transgenic lines was 49.3%, and that of the receptor control was 5%. The disease incidence of neck blast of the transgenic rice lines in fields under induction was 0% to 50%, indicating that the rice blast resistance of transgenic rice lines is much higher than that of the receptor control.

  19. 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...

  20. 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...

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

    Science.gov (United States)

    Park, Kicheon; Pan, Yingtian

    2013-01-01

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

  2. 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

  3. 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

  4. 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

  5. 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 ...

  6. 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...

  7. 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

  8. 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

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

    Science.gov (United States)

    Tomasi, D; Wang, G-J; Volkow, N D

    2016-01-01

    Sleep deprivation (SD) disrupts dopamine (DA) signaling and impairs attention. However, the interpretation of these concomitant effects requires a better understanding of dopamine's role in attention processing. Here we test the hypotheses that D2/D3 receptors (D2/D3R) in dorsal and ventral striatum would distinctly regulate the activation of attention regions and that, by decreasing D2/D3, SD would disrupt these associations. We measured striatal D2/D3R using positron emission tomography with [11C]raclopride and brain activation to a visual attention (VA) task using 4-Tesla functional magnetic resonance imaging. Fourteen healthy men were studied during rested wakefulness and also during SD. Increased D2/D3R in striatum (caudate, putamen and ventral striatum) were linearly associated with higher thalamic activation. Subjects with higher D2/D3R in caudate relative to ventral striatum had higher activation in superior parietal cortex and ventral precuneus, and those with higher D2/D3R in putamen relative to ventral striatum had higher activation in anterior cingulate. SD impaired the association between striatal D2/D3R and VA-induced thalamic activation, which is essential for alertness. Findings suggest a robust DAergic modulation of cortical activation during the VA task, such that D2/D3R in dorsal striatum counterbalanced the stimulatory influence of D2/D3R in ventral striatum, which was not significantly disrupted by SD. In contrast, SD disrupted thalamic activation, which did not show counterbalanced DAergic modulation but a positive association with D2/D3R in both dorsal and ventral striatum. The counterbalanced dorsal versus ventral striatal DAergic modulation of VA activation mirrors similar findings during sensorimotor processing (Tomasi et al., 2015) suggesting a bidirectional influence in signaling between the dorsal caudate and putamen and the ventral striatum. PMID:27219347

  10. 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

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

    Science.gov (United States)

    Rosales, Antonio; Rodríguez-García, Ignacio

    2016-01-01

    Cp2TiCl/D2O/Mn is an efficient combination, sustainable and cheap reagent that mediates the D-atom transfer from D2O to different functional groups and can contribute to the synthesis of new deuterated organic compounds under friendly experimental conditions and with great economic advantages. PMID:27559410

  12. Predicting treatment response in Schizophrenia: the role of stratal and frontal dopamine D2/D3 receptor binding potential

    DEFF Research Database (Denmark)

    Wulff, Sanne; Nørbak-Emig, Henrik; Nielsen, Mette Ødegaard;

    2014-01-01

    the ligand [123]IBZM (123labeled iodbenzamid) to examine the binding potential (BP) of dopamine D2/D3 receptors in striatum. Patients were treated with amisulpride for six weeks. In the EPIcohort we included 25 patients. The ligand [123I]epidepride was used for quantification of extrastriatal dopamine D2/D3...

  13. Adsorbed Layers of D2, H2, O2, and 3He on Graphite Studied by Neutron Scattering

    DEFF Research Database (Denmark)

    Nielsen, Mourits; McTague, J. P.; Ellenson, W. D.

    1977-01-01

    The phase diagrams of adsorbed monolayers of D2, H2, O2, and 3He on graphite have been measured by neutron diffraction. H2 and D2-layers have a registered √3 structure at low coverages, and at monolayer completion they have a dense triangular structure, which is incommensurate with the substrate...

  14. 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. PMID:27559410

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  2. 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.

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

    Science.gov (United States)

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

    2014-01-01

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

  4. 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.

  5. 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

  6. 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

  7. 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

    2016-06-08

    Fifth Generation (5G) wireless systems are expected to connect an avalanche of "smart" objects disseminated from the largest "Smart City" to the smallest "Smart Home". In this vision, Long Term Evolution-Advanced (LTE-A) is deemed to play a fundamental role in the Internet of Things (IoT) arena providing a large coherent infrastructure and a wide wireless connectivity to the devices. However, since LTE-A was originally designed to support high data rates and large data size, novel solutions are required to enable an efficient use of radio resources to convey small data packets typically exchanged by IoT applications in "smart" environments. On the other hand, the typically high energy consumption required by cellular communications is a serious obstacle to large scale IoT deployments under cellular connectivity as in the case of Smart City scenarios. Network-assisted Device-to-Device (D2D) communications are considered as a viable solution to reduce the energy consumption for the devices. The particular approach presented in this paper consists in appointing one of the IoT smart devices as a collector of all data from a cluster of objects using D2D links, thus acting as an aggregator toward the eNodeB. By smartly adapting the Modulation and Coding Scheme (MCS) on the communication links, we will show it is possible to maximize the radio resource utilization as a function of the total amount of data to be sent. A further benefit that we will highlight is the possibility to reduce the transmission power when a more robust MCS is adopted. A comprehensive performance evaluation in a wide set of scenarios will testify the achievable gains in terms of energy efficiency and resource utilization in the envisaged D2D-based IoT data collection.

  8. 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.

  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. 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.

  11. 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

  12. 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

  13. 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.

  14. Partner of η2(1645) in the 11D2 Meson Nonet

    Institute of Scientific and Technical Information of China (English)

    FENG Xue-Chao; JIANG Feng-Chun

    2007-01-01

    In the (qq) quark model, the states π2(1670) and η2(1645) are assigned as the 11D2 meson nonet. The partner of state η2 (1645) needs further confirmation in the experiments. We employ the meson-meson mixing and the Regge trajectory methods to calculate the mass of the partner of state η2 (1645) to be 1879.8 MeV and 1863 ± 24 MeV respectively. We also calculate the strong decay width in the 3Po decay model. These predictions can be compared with experiments in the future.

  15. A faster method for 3D/2D medical image registration - a simulation study

    Energy Technology Data Exchange (ETDEWEB)

    Birkfellner, Wolfgang [CARCAS-Switzerland, University Hospitals Basel and Zurich (Switzerland); Wirth, Joachim [CARCAS-Switzerland, University Hospitals Basel and Zurich (Switzerland); Burgstaller, Wolfgang [CARCAS-Switzerland, University Hospitals Basel and Zurich (Switzerland); Baumann, Bernard [CARCAS-Switzerland, University Hospitals Basel and Zurich (Switzerland); Staedele, Harald [CARCAS-Switzerland, University Hospitals Basel and Zurich (Switzerland); Hammer, Beat [Department of Reconstructive Surgery, University Hospital Basel (Switzerland); Gellrich, Niels Claudius [Department of Oral and Maxillofacial Surgery, University of Freiburg (Germany); Jacob, Augustinus Ludwig [CARCAS-Switzerland, University Hospitals Basel and Zurich (Switzerland); Regazzoni, Pietro [CARCAS-Switzerland, University Hospitals Basel and Zurich (Switzerland); Messmer, Peter [CARCAS-Switzerland, University Hospitals Basel and Zurich (Switzerland)

    2003-08-21

    3D/2D patient-to-computed-tomography (CT) registration is a method to determine a transformation that maps two coordinate systems by comparing a projection image rendered from CT to a real projection image. Iterative variation of the CT's position between rendering steps finally leads to exact registration. Applications include exact patient positioning in radiation therapy, calibration of surgical robots, and pose estimation in computer-aided surgery. One of the problems associated with 3D/2D registration is the fact that finding a registration includes solving a minimization problem in six degrees of freedom (dof) in motion. This results in considerable time requirements since for each iteration step at least one volume rendering has to be computed. We show that by choosing an appropriate world coordinate system and by applying a 2D/2D registration method in each iteration step, the number of iterations can be grossly reduced from n{sup 6} to n{sup 5}. Here, n is the number of discrete variations around a given coordinate. Depending on the configuration of the optimization algorithm, this reduces the total number of iterations necessary to at least 1/3 of it's original value. The method was implemented and extensively tested on simulated x-ray images of a tibia, a pelvis and a skull base. When using one projective image and a discrete full parameter space search for solving the optimization problem, average accuracy was found to be 1.0 {+-} 0.6 (deg.) and 4.1 {+-} 1.9 (mm) for a registration in six parameters, and 1.0 {+-} 0.7 (deg.) and 4.2 {+-} 1.6 (mm) when using the 5 + 1 dof method described in this paper. Time requirements were reduced by a factor 3.1. We conclude that this hardware-independent optimization of 3D/2D registration is a step towards increasing the acceptance of this promising method for a wide number of clinical applications.

  16. 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.

  17. 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.)

  18. 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

  19. Towards the quantization of the non-relativistic D2-brane in the Pure Spinor Formalism

    CERN Document Server

    Herrera-Aguilar, A

    2015-01-01

    The non-relativistic D2-brane is treated in the framework of pure spinor formalism. The fermionic constraints corresponding to the rescaled fermionic coordinates are given. Two commuting spinor fields are introduced, each one corresponding to a fermionic constraint. A BRST charge is constructed via the ansatz proposed by Nathan Berkovits. The nilpotency of the BRST charge leads to a set of constraints for the two spinor fields including pure spinor constraints. A nontrivial solution is given for one of the spinor fields.

  20. Inverse problem from the discrete spectrum in the D = 2 dimensional space

    International Nuclear Information System (INIS)

    Considering the Schrödinger equation in the D = 2 dimensional space, we propose a method to determine a circular symmetric potential from its discrete spectrum. The approach is based on the relationships between the moments of the ground state density and the lowest excitation energy of each angular momentum. The required condition for a unique answer is the knowledge of all the lowest eigenvalues. In principle, it means an infinite number of moments to be known. As we shall show, reasonable accuracy can be reached in practice with a finite set of moments. Two illustrative examples are presented. (paper)

  1. Dopamine-transporter SPECT and Dopamine-D2-receptor SPECT in basal ganglia diseases

    International Nuclear Information System (INIS)

    The basal ganglia comprise a group of subcortical nuclei, which are essential for motor control. Dysfunction of these areas, especially in dopaminergic transmission, results in disordered movement and neurological diseases such as Parkinson's disease, Wilson's disease, or Huntington disease. Positron emission tomography and single photon emission computed tomography (SPECT) have enhanced the understanding of the underlying pathophysiology, but they much more contribute to the early differential diagnosis of patients suffering from Parkinsonian syndrome in routine care. The present article provides dopamine transporter and D2 receptor SPECT findings in selected movement disorders. (orig.)

  2. Multiparametric family of collapse solutions of critical nonlinear Schrodinger equation for dimensionality D = 2

    International Nuclear Information System (INIS)

    The system of three equations, describing the collapse of the critical nonlinear Schroedinger equation for the D = 2 dimensionality is obtained. The above system of equations supposes the five-parametric family of solutions. The tunneling processes are practically insignificant everywhere, with the exception of the exponentially narrow area near the collapse point. The relationship of the initial data with the condition of the collapse origination is studied. The separatrix, separating the collapse areas and the areas of expansion without origination of the peculiarity at the time finite period, is identified

  3. Absolute Frequency Measurements of the D1 and D2 Transitions in Aatomic Li

    Science.gov (United States)

    Sheets, Donal; Almaguer, Jose; Baron, Jacob; Elgee, Peter; Rowan, Michael; Stalnaker, Jason

    2014-05-01

    We present preliminary results from our measurements of the D1 and D2 transitions in Li. The data were obtained from a collimated atomic beam excited by light from an extended cavity diode laser. The frequency of the diode laser was stabilized to an optical frequency comb, providing absolute frequency measurement and control of the excitation laser frequency. These measurements will provide a stringent test of atomic structure calculations and yield information about the nuclear structure. We also discuss plans to extend the technique to other high-lying states in lithium. Funded by the NIST Precision Measurements Grant and NSF Award #1305591.

  4. Wear Properties of TiN Coating Formed on AISI D2 Surface

    OpenAIRE

    ÇEĞİL, Özkan; KILINÇ, Bülent; Şen, Şaduman

    2014-01-01

    In this work, the wear test of uncoated and titanium nitride coated AISI D2 cold work tool steel against silicon nitride ball was realized at 0.3 m/s sliding speed and under the loads of 2.5N, 5N and 10N. Steel samples were nitrided at 575°C for 8 h in the first step of the coating process, and then titanium nitride coating was performed by pack diffusion coating in a powder mixture consisting of ferro-titanium, ammonium chloride and alumina at 1000°C for 2h. Nitro-titanized samples were char...

  5. SANS contrast in iota-carrageenan gels and solutions in D2O

    DEFF Research Database (Denmark)

    Mischenko, N.; Denef, B.; Mortensen, K.;

    1997-01-01

    SANS of Na+-iota-carrageenan in D2O/saline solutions was measured as a function of concentration, temperature and type of counterions (K+ or Na+). High and low scattering-contrasted gels and solutions were detected. High contrast is caused by aggregation of low-hydrated chains at high concentration...... of carrageenan in the presence of gel-promoting counterions. The aggregates do not disappear at 60 degrees C, although at this temperature the molecules should partially lose their ordered conformation. The network formation, observed by SANS, does not happen in high-contrast system immediately after cooling...

  6. 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.

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

    OpenAIRE

    Schmidts, M.; Hou, Y; Cortes, C.R.; Mans, D. A.; Huber, C.; Boldt, K.; M. Patel; Van Reeuwijk, J; Plaza, J.M.; Beersum, S.E.C; Yap, Z.M.; Letteboer, S.J.F.; Taylor, S. P.; Herridge, W; Johnson, C A

    2015-01-01

    ARTICLE Received 1 Oct 2014 | Accepted 31 Mar 2015 | Published 5 June 2015 TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport Miriam Schmidts1,2,3,4,*, Yuqing Hou5,*, Claudio R. Corte´s6, Dorus A. Mans2,3, Celine Huber7, Karsten Boldt8, Mitali Patel1, Jeroen van Reeuwijk2,3, Jean-Marc Plaza9, Sylvia E.C. van Beersum2,3, Zhi Min Yap1, Stef J.F. Letteboer2,3, S Paige Taylor10, Warren Herridge11, Colin A. Johns...

  8. Phospholipase D2 mediates signaling by ATPase class I type 8B membrane 1[S

    OpenAIRE

    Chen, Frank; Ghosh, Ayantika; Shneider, Benjamin L.

    2013-01-01

    Functional defects in ATPase class I type 8B membrane 1 (ATP8B1 or familial intrahepatic cholestasis 1, FIC1) lead to cholestasis by mechanism(s) that are not fully understood. One proposed pathophysiology involves aberrant signaling to the bile acid sensor, the farnesoid X receptor (FXR), via protein kinase C ζ (PKCζ). The following cell line-based studies investigated whether phospholipase D2 may transduce a signal from FIC1 to FXR. PLD2 gain of function led to activation of the bile salt e...

  9. Tribology of nitriding layer, TiN coatings and their complex on AISI D2 steel

    Institute of Scientific and Technical Information of China (English)

    WANG Ke-sheng; ZHANG De-yuan; DONG Ding-fu

    2004-01-01

    The sliding wear and impact wear resistances of D2 steel with nitriding layer, PVD titanium nitride coating and their duplex treatment were investigated. The experimental results suggest that the duplex treatment has the best sliding and impact wear resistances under experimental conditions. And the wear resistance of PVD titanium nitride is better than that of nitriding. The impact wear resistance and wear mechanism of all three surface layers remain unchanged under impact load of 0.2 J or 1 J. All samples end with the same symptom of flaking.

  10. Kinetic Model of Hypophosphite Oxidation on a Nickel Electrode in D2O Solution

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Kinetic model of hypophosphite oxidation on a nickel electrode was studied in D2Osolution in order to reach a better understanding of the oxidation mechanism. In the model the electrooxidation of hypophosphite undergo a H abstraction of hypophosphite from the P-H bond to form the phosphorus-centered radical PHO2-, which subsequently is electrochemically reacted with water to form the final product, phosphite. The kinetic equations were derived, and the kinetic parameters were obtained from a comparison of experimental results and the kinetic equations. The process of hypophosphite electrooxidation could be well simulated by this model

  11. The reactions of neutral iron clusters with D2O: Deconvolution of equilibrium constants from multiphoton processes

    International Nuclear Information System (INIS)

    The chemical reactions of neutral iron clusters with D2O are studied in a continuous flow tube reactor by molecular beam sampling and time-of-flight mass spectrometry with laser photoionization. Product distributions are invariant to a four-fold change in reaction time demonstrating that equilibrium is attained between free and adsorbed D2O. The observed negative temperature dependence is consistent with an exothermic, molecular addition reaction at equilibrium. Under our experimental conditions, there is significant photodesorption of D2O (Fe/sub n/(D2O)/sub m/ + hν → Fe/sub n/ + m D2O) along with ionization due to absorption of multiple photons from the ionizing laser. Using a simple model based on a rate equation analysis, we are able to quantitatively deconvolute this desorption process from the equilibrium constants. 8 refs., 1 fig

  12. On mode selection and power control for uplink D2D communication in cellular networks

    KAUST Repository

    Ali, Konpal Shaukat

    2015-06-08

    Device-to-device (D2D) communication enables users lying in close proximity to bypass the cellular base station (BS) and transmit to one another directly. This offloads traffic from the cellular network, improves spatial frequency reuse and energy efficiency in the network. We present a comprehensive and tractable analytical framework for D2D-enabled uplink cellular networks with two different flexible mode-selection schemes. The power-control cutoff thresholds of the two communication modes have been decoupled unlike past work on the subject. We find that for a given network, an optimal value exists not only for the biased mode selection criterion, but also for r, the ratio of the power-control cutoff thresholds of the two communication modes, which maximizes spatial spectral efficiency. Also, r turns out to be a more robust parameter for optimizing network performance. Further, it is shown that the second scheme, which prioritizes spatial frequency reuse over the per-user achievable performance compared to the first scheme, achieves almost the same overall network performance; thereby trading per user performance to serve a larger number of users.

  13. A Precision Measurement of the Neutron Twist-3 Matrix Element $d_2^n$: Probing Color Forces

    CERN Document Server

    Posik, M; 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; Nuruzzaman,; 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

    2014-01-01

    Double-spin asymmetries and absolute cross sections were measured at large Bjorken $x$ (0.25 $ \\le x \\le $ 0.90), in both the deep-inelastic and resonance regions, by scattering longitudinally polarized electrons at beam energies of 4.7 and 5.9 GeV from a transversely and longitudinally polarized $^3$He target. In this dedicated experiment, the spin structure function $g_2$ on $^3$He was determined with precision at large $x$, and the neutron twist-three matrix element $d_2^n$ was measured at $\\left$ of 3.21 and 4.32 GeV$^2$/$c^2$, with an absolute precision of about $10^{-5}$. Our results are found to be in agreement with lattice QCD calculations and resolve the disagreement found with previous data at $\\left =$ 5 GeV$^2$/$c^2$. Combining $d_2^n$ and a newly extracted twist-four matrix element, $f_2^n$, the average neutron color electric and magnetic forces were extracted and found to be of opposite sign and about 60 MeV/fm in magnitude.

  14. Infrared Spectroscopy of the H2/HD/D2-O2 Van Der Waals Complexes

    Science.gov (United States)

    Raston, Paul; Bunn, Hayley

    2016-06-01

    Hydrogen is the most abundant element in the universe and oxygen is the third, so understanding the interaction between the two in their different forms is important to understanding astrochemical processes. The interaction between H2 and O2 has been explored in low energy scattering experiments and by far infrared synchrotron spectroscopy of the van der Waals complex. The far infrared spectra suggest a parallel stacked average structure with seven bound rotationally excited states. Here, we present the far infrared spectrum of HD/D2-O2 and the mid infrared spectrum of H2-O2 at 80 K, recorded at the infrared beamline facility of the Australian Synchrotron. We observed 'sharp' peaks in the mid infrared region, corresponding to the end over end rotation of H2-O2, that are comparatively noisier than analogous peaks in the far infrared where the synchrotron light is brightest. The larger reduced mass of HD and D2 compared to H2 is expected to result in more rotational bound states and narrower bands. The latest results in our ongoing efforts to explore this system will be presented. Y. Kalugina, et al., Phys. Chem. Chem. Phys. 14, 16458 (2012) S. Chefdeville et al. Science 341, 1094 (2013) H. Bunn et al. ApJ 799, 65 (2015)

  15. Niobium boride layers deposition on the surface AISI D2 steel by a duplex treatment

    Science.gov (United States)

    Kon, O.; Pazarlioglu, S.; Sen, S.; Sen, U.

    2015-03-01

    In this paper, we investigated the possibility of deposition of niobium boride layers on the surface of AISI D2 steel by a duplex treatment. At the first step of duplex treatment, boronizing was performed on AISI D2 steel samples at 1000oC for 2h and then pre-boronized samples niobized at 850°C, 900°C and 950°C using thermo-reactive deposition method for 1-4 h. The presence of the niobium boride layers such as NbB, NbB2 and Nb3B4 and also iron boride phases such as FeB, Fe2B were examined by X-ray diffraction analysis. Scanning electron microscope (SEM) and micro-hardness measurements were realized. Experimental studies showed that the depth of the coating layers increased with increasing temperature and times and also ranged from 0.42 µm to 2.43 µm, depending on treatment time and temperature. The hardness of the niobium boride layer was 2620±180 HV0.005.

  16. The FLO Diffusive 1D-2D Model for Simulation of River Flooding

    Directory of Open Access Journals (Sweden)

    Costanza Aricò

    2016-05-01

    Full Text Available An integrated 1D-2D model for the solution of the diffusive approximation of the shallow water equations, named FLO, is proposed in the present paper. Governing equations are solved using the MArching in Space and Time (MAST approach. The 2D floodplain domain is discretized using a triangular mesh, and standard river sections are used for modeling 1D flow inside the section width occurring with low or standard discharges. 1D elements, inside the 1D domain, are quadrilaterals bounded by the trace of two consecutive sections and by the sides connecting their extreme points. The water level is assumed to vary linearly inside each quadrilateral along the flow direction, but to remain constant along the direction normal to the flow. The computational cell can share zero, one or two nodes with triangles of the 2D domain when lateral coupling occurs and more than two nodes in the case of frontal coupling, if the corresponding section is at one end of the 1D channel. No boundary condition at the transition between the 1D-2D domain has to be solved, and no additional variable has to be introduced. Discontinuities arising between 1D and 2D domains at 1D sections with a top width smaller than the trace of the section are properly solved without any special restriction on the time step.

  17. Far infrared spectrum of Methanol-D2 in the lowest torsional state (e0)

    Science.gov (United States)

    Mukhopadhyay, Indra

    2016-03-01

    The infrared (IR) and far infrared (FIR) absorption spectra have been measured for the Methanol-D1 and D2 species in the wave number range of 20-1200 cm-1 at the Justus Liebig Universität in Giessen, Germany using a Brüker Fourier Transform spectrometer at a resolution of 0.002 cm-1. The spectra looked very complicated but analyses were possible for the lower lying states. At higher wave number regions spectra of few vibrational fundamental modes were visible. In this communication, the details of the assignments and analyses of the lowest lying internal rotational state (e0) for Methanol-D2 are reported. A catalog of about 900 assigned spectral lines has been prepared and is made available from the author to conserve space. As application of this work, it was possible to assign some optically pumped FIR laser lines to quantum states. The results should be useful for "radio astronomers" and in the field of optically pumped FIR and Sub-millimeter Wave (SMMW) lasers which are used in Tokamaks for plasma diagnostics and as local oscillators in radio detection from space.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Kessler, R.M.; Ansari, M.S.; de Paulis, T.; Schmidt, D.E.; Clanton, J.A.; Smith, H.E.; Manning, R.G.; Gillespie, D.; Ebert, M.H. (Vanderbilt University School of Medicine, Nashville, TN (USA))

    1991-08-01

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

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

    International Nuclear Information System (INIS)

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