Sample records for 2x devices

  1. Manufacturability of 2x-nm devices with EUV tool (United States)

    Tawarayama, Kazuo; Nakajima, Yumi; Kyoh, Suigen; Aoyama, Hajime; Matsunaga, Kentaro; Magoshi, Shunko; Tanaka, Satoshi; Hayashi, Yumi; Mori, Ichiro


    Due to the promising development status of EUVL as a practical lithography technology for the 2x-nm node, we are continuing to evaluate its process liability using the EUV1 at Selete, which has an Off-Axis illumination capability. The resolution limit of the EUV1 for L&S patterns is currently 18 nm for dipole illumination, and 16 nm for aggressive dipole illumination. This study examined the critical points of EUVL for device manufacturing through wafer processes. The yield obtained from electrical measurements indicates the maturity of the technology, including the resist process, the tool, and the mask. Optimization of the resist and RIE processes significantly improved the yield. The final yields obtained from electrical measurements were 100% for hp 30 nm, 70% for hp 28 nm, and 40% for hp 26 nm. These results demonstrate EUV lithography to be a practical technology that is now suitable for 2x nm semiconductor manufacture.

  2. MEMS/ECD Method for Making Bi(2-x)Sb(x)Te3 Thermoelectric Devices (United States)

    Lim, James; Huang, Chen-Kuo; Ryan, Margaret; Snyder, G. Jeffrey; Herman, Jennifer; Fleurial, Jean-Pierre


    A method of fabricating Bi(2-x)Sb(x)Te3-based thermoelectric microdevices involves a combination of (1) techniques used previously in the fabrication of integrated circuits and of microelectromechanical systems (MEMS) and (2) a relatively inexpensive MEMS-oriented electrochemical-deposition (ECD) technique. The present method overcomes the limitations of prior MEMS fabrication techniques and makes it possible to satisfy requirements.

  3. A simple synthesis of Ag{sub 2+x}Se nanoparticles and their thin films for electronic device applications

    Energy Technology Data Exchange (ETDEWEB)

    Vo, Duc Quy; Dung, Dang Duc; Cho, Sunglae; Kim, Sunwook [School of Chemical Engineering, University of Ulsan, Ulsan (Korea, Republic of)


    A simple method to synthesize silver selenide nanoparticles has been proposed. By changing the ratio of Se-oleylamine complex and silver acetate in the reacting mixture at different temperatures, both size and stoichiometry of the silver selenide particles could be successfully controlled. The size of the nanoparticles was adjusted by changing reaction temperatures. The synthesized silver selenide nanoparticles showed size changes from 3 to 10 nm when the corresponding reaction temperatures were 40-100 .deg. C, respectively. In addition to the size change, the stoichiometry of the synthesized nanoparticles (Ag{sub 2+x}Se) could be adjusted by simply varying the ratio of Ag to Se precursors. Through XPS analyses the x value in Ag{sub 2+x}Se was determined, and it changed between 0.54 and −0.03 by varying Ag/Se ratio from 2/0.75 to 2/4. The optical property of the nonstoichiometric Ag{sub 2+x}Se nanoparticles was different from that of stoichiometric Ag{sub 2}Se nanoparticles, but showed the plasmon absorption of Ag-Ag network. The plasmon absorption was decreased with the increased concentration of the Se precursor. Finally, the Ag{sub 2+x}Se thin film in this work showed large magnetoresistance and successfully applied to prepare high-performance Schottky diode. The Ag{sub 2.06}Se film exhibited the magnetoresistance effect up to 0.9% at only 0.8 T at room temperature. The voltage drop and breakdown voltage of the Schottky diode were 0.5 V and 9.3 V, respectively.

  4. Anomalous elastic properties of RF-sputtered amorphous TeO2+x thin film for temperature-stable SAW device applications. (United States)

    Dewan, Namrata; Sreenivas, Kondepudy; Gupta, Vinay


    The anomalous elastic properties of TeO2+x thin films deposited by rf diode sputtering on substrates at room temperature have been studied. The deposited films are amorphous, and IR spectroscopy reveals the formation of Te-O bond. X-ray photoelectron spectroscopy confirms the variation in the stoichiometry of TeO2+x film from x=0 to 1 with an increase in the oxygen percentage in processing gas composition. The elastic parameters of the films in comparison to the reported values for TeO2+x single crystal are found to be low. However, the temperature coefficients of elastic parameters of all deposited films exhibit anomalous behavior showing positive values for TC(C11) in the range (32.0 to 600.0)x10(-4) degrees C(-1) and TC(C44)=(35.0 to 645.5)x10(-4) degrees C(-1) against the negative values TC(C11)=-2.7x10(-4) degrees C(-1) and TC(C44)=-0.73x10(-4) degrees C(-1) reported for TeO2+x single crystal. The variation in the elastic parameters and their temperature coefficients is correlated with the change in the three-dimensional network of Te-O bonding. The anomalous elastic properties of the TeO2+x films grown in 100% O2 are useful for potential application in the design of temperature stable surface acoustic wave devices.

  5. The effect of oxygen vacancies on the electrical properties of TiO2-x Re-RAM switching devices (United States)

    Benkraouda, Maamar


    The main goal of this work is to contribute toward an accurate determination of the electronic properties of Resistance random access memory (Re-RAM) using the density functional theory, which is the current state of the art method that employs high accuracy, it can treat a few hundred atoms on medium sized PC. All the fundamental properties are studied as a function of the mole fraction. The density of states arising from vacancy distribution, the electron transport and formation energy are analyzed. Using controllable mole fraction, various intermediate resistance states are induced. Oxygen vacancy has a considerable effect on the electrical properties of most transition metal oxides such as TiOx Re-RAM devices. The presence of oxygen vacancies is linked to the on-state conduction and resistance switching mechanism. Hydrogen is a ubiquitous impurity in most semiconductors, insertion of hydrogen atoms will remove some of defect states which were induced by oxygen vacancies; this will obviously have an effect on the conductive path, because hydrogen in the vacancy site results in the rupture of conductive channel by localizing electrons, the conductivity may decrease in this case.

  6. Coulomb repulsion in (TMTSF)2X and (TMTTF)2X

    DEFF Research Database (Denmark)

    Mortensen, Kell; Engler, E. M.


    On the basis of studies of transport properties of (TMTSF)2 X, (TMTTF)2X and their binary alloys the authors discuss the role of on-site Coulomb repulsion relative to the transfer integrals. In TMTTF-salts U/ta are believed to be large, resulting in a Hubbard gap, whereas U/ta in TMTSF-salts are ...

  7. AFM imaging reveals the assembly of a P2X receptor complex containing P2X2, P2X4 and P2X6 subunits



    Seven P2X purinergic receptor subunits have been identified: P2X1-P2X7. All except P2X6 assemble as homotrimers, and six heteromeric receptors (P2X1/2, P2X1/4, P2X1/5, P2X2/3, P2X2/6 and P2X4/6) have been described. In addition, P2X4 homomers associate with P2X2 or P2X7 homomers as dimers of trimers. The various P2X receptors show individual functional properties, suggesting distinct physiological roles. The overlapping expression of P2X2, P2X4 and P2X6 subunits has been shown in different ce...

  8. Evidence for functional P2X4/P2X7 heteromeric receptors. (United States)

    Guo, Chang; Masin, Marianela; Qureshi, Omar S; Murrell-Lagnado, Ruth D


    The cytolytic ionotropic ATP receptor P2X7 has several important roles in immune cell regulation, such as cytokine release, apoptosis, and microbial killing. Although P2X7 receptors are frequently coexpressed with another subtype of P2X receptor, P2X4, they are believed not to form heteromeric assemblies but to function only as homomers. Both receptors play a role in neuropathic pain; therefore, understanding how they coordinate the cellular response to ATP is important for the development of effective pain therapies. Here, we provide biochemical and electrophysiological evidence for an association between P2X4 and P2X7 that increases the diversity of receptor currents mediated via these two subtypes. The heterologously expressed receptors were coimmunoprecipitated from human embryonic kidney (HEK) 293 cells, and the endogenous P2X4 and P2X7 receptors were similarly coimmunoprecipitated from bone marrow-derived macrophages. In HEK293 cells, the fraction of P2X4 receptors biotinylated at the plasma membrane increased 2-fold in the presence of P2X7 although there was no change in overall expression. Coexpression of a dominant-negative P2X4 mutant (C353W) with P2X7, inhibited P2X7 receptor mediated currents by greater than 2-fold, whereas a nonfunctional but non-dominant-negative mutant (S341W) did not. Coexpression of P2X4S341W with P2X7 produced a current that was potentiated by ivermectin and inhibited by 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5-triphosphate (TNP-ATP), whereas expression of P2X7 alone produced a current that was insensitive to both of these compounds at the concentrations used. These results demonstrate a structural and functional interaction between P2X4 and P2X7, which suggests that they associate to form heteromeric receptors.

  9. P2X receptors in epithelia

    DEFF Research Database (Denmark)

    Leipziger, Jens Georg


    P2X receptors are ubiquitously expressed in all epithelial tissues but their functional roles are less well studied. Here we review the current state of knowledge by focusing on functional effects of P2X receptor in secretory and in absorptive tissues. In glandular tissue like the parotid gland...

  10. Stability of Fuzzy S^2 x S^2 x S^2 in IIB Type Matrix Models

    CERN Document Server

    Kaneko, H; Tomino, D


    We study the stability of fuzzy S^2 x S^2 x S^2 backgrounds in three different IIB type matrix models with respect to the change of the spins of each S^2 at the two loop level. We find that S^2 x S^2 x S^2 background is metastable and the effective action favors a single large S^2 in comparison to the remaining S^2 x S^2 in the models with Myers term. On the other hand, we find that a large S^2 x S^2 in comparison to the remaining S^2 is favored in IIB matrix model itself. We further study the stability of fuzzy S^2 x S^2 background in detail in IIB matrix model with respect to the scale factors of each S^2 as well. In this case, we find unstable directions which lower the effective action away from the most symmetric fuzzy S^2 x S^2 background.

  11. LTE Radiated Data Throughput Measurements, Adopting MIMO 2x2 Reference Antennas

    DEFF Research Database (Denmark)

    Szini, Istvan Janos; Pedersen, Gert Frølund; Barrio, Samantha Caporal Del;


    Long Term Evolution (LTE) requires Multiple Input Multiple Output (MIMO) antenna systems. Consequently a new over-the-air (OTA) test methodology need to be created to make proper assessment of LTE devices radiated performance. The antenna specific parameters i.e. total antenna efficiency, gain im...... performance, ruling out the LTE devices unknown MIMO 2x2 antenna performance....

  12. Scanning Tunneling Microscopy of SILICON(100) 2 X 1 (United States)

    Hubacek, Jerome S.


    The Si(100) 2 x 1 surface, a technologically important surface in microelectronics and silicon molecular beam epitaxy (MBE), has been studied with the scanning tunneling microscope (STM) to attempt to clear up the controversy that surrounds previous studies of this surface. To this end, an ultra-high vacuum (UHV) STM/surface science system has been designed and constructed to study semiconductor surfaces. Clean Si(100) 2 x 1 surfaces have been prepared and imaged with the STM. Atomic resolution images probing both the filled states and empty states indicate that the surface consists of statically buckled dimer rows. With electronic device dimensions shrinking to smaller and smaller sizes, the Si-SiO_2 interface is becoming increasingly important and, although it is the most popular interface used in the microelectronics industry, little is known about the initial stages of oxidation of the Si(100) surface. Scanning tunneling microscopy has been employed to examine Si(100) 2 x 1 surfaces exposed to molecular oxygen in UHV. Ordered rows of bright and dark spots, rotated 45^circ from the silicon dimer rows, appear in the STM images, suggesting that the Si(100)-SiO_2 interface may be explained with a beta -cristobalite(100) structure rotated by 45^ circ on the Si(100) surface.

  13. The P2X7 receptor

    DEFF Research Database (Denmark)

    Kvist, Torben Madsen; Schwarz, Peter; Jørgensen, Niklas Rye


    from an increase in bone resorption and the pro-inflammatory cytokines tumor necrosis factor alpha and interleukin 1 beta and has been shown to not only mediate the inflammatory response but also to strongly stimulate bone degradation. The purinergic P2X7 receptor is central in the processing...... receptor in immune-mediated bone loss and -osteoporosis....

  14. Representations by $x_1^2+2x_2^2+x_3^2+x_4^2+x_1x_3+x_1x_4+x_2x_4$

    CERN Document Server

    Eum, Ick Sun; Shin, Dong Hwa; Yoon, Dong Sung


    Let $r_Q(n)$ be the representation number of a nonnegative integer $n$ by the quaternary quadratic form $Q=x_1^2+2x_2^2+x_3^2+x_4^2+x_1x_3+x_1x_4+x_2x_4$. We prove the identity $r_Q(p^2n)=r_Q(p^2)r_Q(n)/r_Q(1)$ for any prime $p$ different from 13 and any positive integer $n$ prime to $p$, which was conjectured in [Eum et al, A modularity criterion for Klein forms, with an application to modular forms of level 13, J. Math. Anal. Appl. 375 (2011), 28--41]. We explicitly determine $r_Q(n^2)$ for any positive integer $n$, too.

  15. Lymphocytes from P2X7-deficient mice exhibit enhanced P2X7 responses


    Simon R.J. Taylor; Gonzalez-Begne, Mireya; Sojka, Dorothy K.; Richardson, Jill C.; Sheardown, Steven A.; Harrison, Stephen M; Pusey, Charles D.; Tam, Frederick W. K.; Elliott, James I


    The purinergic receptor P2X7 is expressed on immune cells, and its stimulation results in the release of IL-1β from macrophages. Its absence, as evidenced from the analysis of two independent strains of P2X7-deficient mice, results in reduced susceptibility to inflammatory disease, and the molecule is an important, potential therapeutic target in autoimmunity. However, P2X7 has also been detected in several neuronal cell types, although its function and even its presence in these cells are hi...

  16. Mouse Leydig cells express multiple P2X receptor subunits



    ATP acts on cellular membranes by interacting with P2X (ionotropic) and P2Y (metabotropic) receptors. Seven homomeric P2X receptors (P2X1–P2X7) and seven heteromeric receptors (P2X1/2, P2X1/4, P2X1/5, P2X2/3, P2X2/6, P2X4/6, P2X4/7) have been described. ATP treatment of Leydig cells leads to an increase in [Ca2+]i and testosterone secretion, supporting the hypothesis that Ca2+ signaling through purinergic receptors contributes to the process of testosterone secretion in these cells. Mouse Ley...

  17. Optical and infrared properties of tetramethyltetraselenafulvalene [(TMTSF)2X] and tetramethyltetrathiafulvalene [(TMTTF)2X] compounds

    DEFF Research Database (Denmark)

    Jacobsen, Claus Schelde; Tanner, D. B.; Bechgaard, K.


    to extract information on transfer integrals. Measurements of infrared reflectance provide information on the energy of charge-transfer processes and on electron-molecular vibration coupling. Far-infrared measurements allow comparison with low-frequency transport properties, and give clues to the transport......The electronic structure of the organic conductors bis-tetramethyltetraselenafulvalene-X [(TMTSF)2X] and bis-tetramethyltetrathiafulvalene-X [(TMTTF)2X] has been investigated by means of polarized optical and infrared reflectance measurements. Analysis of plasma edges in reflectance is used...... of the order 0.18-0.20 eV. No b-axis plasma edge is observable. The infrared conductivity spectra of the materials consist of a broad electronic band with superimposed vibrational fine structure. The band is centered at 300 cm-1 in the best (TMTSF)2X conductors and at 2200 cm-1 in (TMTTF)2PF6, an organic...

  18. LHC phenomenology of general SU(2)xSU(2)xU(1) models

    CERN Document Server

    Ježo, Tomáš; Schienbein, Ingo


    General SU(2)xSU(2)xU(1) models represent a well-motivated intermediate step towards the unification of the Standard Model gauge groups. Based on a recent global analysis of low-energy and LEP constraints of these models, we perform numerical scans of their various signals at the LHC. We show that total cross sections for lepton and third-generation quark pairs, while experimentally easily accessible, provide individually only partial information about the model realized in Nature. In contrast, correlations of these cross sections in the neutral and charged current channels may well lead to a unique identification.

  19. Paroxetine suppresses recombinant human P2X7 responses


    Dao-Ung, Phuong; Skarratt, Kristen; Fuller, Stephen; Stokes, Leanne


    P2X7 receptor (P2X7) activity may link inflammation to depressive disorders. Genetic variants of human P2X7 have been linked with major depression and bipolar disorders, and the P2X7 knockout mouse has been shown to exhibit anti-depressive-like behaviour. P2X7 is an ATP-gated ion channel and is a major regulator of the pro-inflammatory cytokine interleukin 1β (IL-1β) secretion from monocytes and microglia. We hypothesised that antidepressants may elicit their mood enhancing effects in part vi...

  20. Distribution of the purinegic receptors P2X(4) and P2X(6) during rat gut development. (United States)

    García-Alcocer, Guadalupe; Padilla, Karla; Rodríguez, Angelina; Miledi, Ricardo; Berumen, Laura C


    The purinergic receptors P2X(4) and P2X(6) are ion channels activated by ATP. These receptors are present in the gastrointestinal tract, and they are involved in synaptic transmission, taste sensation, and pain, among other functions. In this work, we studied the distribution of P2X(4) and P2X(6) receptors in proximal and distal regions of the gut newborn and adult rats. Using immunohistochemistry, purinergic receptors were found in gut epithelial cells and capillary vessels. In both proximal and distal regions of newborn rats, we observed P2X(4) signal in epithelial cells, whereas P2X(6) was present in capillary vessels in the proximal region and to a lesser extent in the distal region. In both regions of adult gut, we observed P2X(4) and P2X(6) immunostain in the capillary vessels. Semi-quantification indicated a significant difference in the amount of P2X(4) between proximal regions, whereas the P2X(6) content of both newborn regions differed from that in adult proximal gut. We conclude that P2X(4) and P2X(6) purinoreceptors are present in the gut from birth and that they are differentially distributed among regions.

  1. P2X receptors: New players in cancer pain

    Institute of Scientific and Technical Information of China (English)

    Alessia; Franceschini; Elena; Adinolfi


    Pain is unfortunately a quite common symptom for cancer patients. Normally pain starts as an episodic experience at early cancer phases to become chronic in later stages. In order to improve the quality of life of oncological patients, anti-cancer treatments are often accompanied by analgesic therapies. The P2 X receptor are adenosine triphosphate(ATP) gated ion channels expressed by several cells including neurons, cancer and immune cells. Purinergic signaling through P2 X receptors recently emerged as possible common pathway for cancer onset/growth and pain sensitivity. Indeed, tumor microenvironment is rich in extracellular ATP, which has a role in both tumor development and pain sensation. The study of the different mechanisms by which P2 X receptors favor cancer progression and relative pain, represents an interesting challenge to design integrated therapeutic strategies for oncological patients. This review summarizes recent findings linking P2 X receptors and ATP to cancer growth, progression and related pain. Special attention has been paid to the role of P2X2, P2X3, P2X4 and P2X7 in the genesisof cancer pain and to the function of P2X7 in tumor growth and metastasis. Therapeutic implications of the administration of different P2 X receptor blockers to alleviate cancer-associated pain sensations contemporarily reducing tumor progression are also discussed.

  2. ATP induces P2X7 receptor-independent cytokine and chemokine expression through P2X1 and P2X3 receptors in murine mast cells. (United States)

    Bulanova, Elena; Budagian, Vadim; Orinska, Zane; Koch-Nolte, Friedrich; Haag, Friedrich; Bulfone-Paus, Silvia


    Extracellular ATP mediates a diverse array of biological responses in many cell types and tissues, including immune cells. We have demonstrated that ATP induces purinergic receptor P2X(7) mediated membrane permeabilization, apoptosis, and cytokine expression in murine mast cells (MCs). Here, we report that MCs deficient in the expression of the P2X(7) receptor are resistant to the ATP-induced membrane permeabilization and apoptosis. However, ATP affects the tyrosine phosphorylation pattern of P2X(7)knockout cells, leading to the activation of ERK1/2. Furthermore, ATP induces expression of several cytokines and chemokines in these cells, including IL-4, IL-6, IFN-gamma, TNF-alpha, RANTES, and MIP-2, at the mRNA level. In addition, the release of IL-6 and IL-13 to cell-conditioned medium was confirmed by ELISA. The ligand selectivity and pharmacological profile indicate the involvement of two P2X family receptors, P2X(1) and P2X(3). Thus, depending on genetic background, particular tissue microenvironment, and ATP concentration, MCs can presumably engage different P2X receptor subtypes, which may result in functionally distinct biological responses to extracellular nucleotides. This finding highlights a novel level of complexity in the sophisticated biology of MCs and may facilitate the development of new therapeutic approaches to modulate MC activities.

  3. P2X7 Receptors in Neurological and Cardiovascular Disorders

    Directory of Open Access Journals (Sweden)

    Stephen D. Skaper


    Full Text Available P2X receptors are ATP-gated cation channels that mediate fast excitatory transmission in diverse regions of the brain and spinal cord. Several P2X receptor subtypes, including P2X7, have the unusual property of changing their ion selectivity during prolonged exposure to ATP, which results in a channel pore permeable to molecules as large as 900 daltons. The P2X7 receptor was originally described in cells of hematopoietic origin, and mediates the influx of Ca2+ and Na+ and Ca2+ and Na+ ions as well as the release of proinflammatory cytokines. P2X7 receptors may affect neuronal cell death through their ability to regulate the processing and release of interleukin-1, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7 receptors provides an inflammatory stimulus, and P2X7 receptor-deficient mice have substantially attenuated inflammatory responses, including models of neuropathic and chronic inflammatory pain. Moreover, P2X7 receptor activity, by regulating the release of proinflammatory cytokines, may be involved in the pathophysiology of depression. Apoptotic cell death occurs in a number of vascular diseases, including atherosclerosis, restenosis, and hypertension, and may be linked to the release of ATP from endothelial cells, P2X7 receptor activation, proinflammatory cytokine production, and endothelial cell apoptosis. In this context, the P2X7 receptor may be viewed as a gateway of communication between the nervous, immune, and cardiovascular systems.

  4. Generalized Measure of Departure from No Three-Factor Interaction Model for 2 x 2 x K Contingency Tables

    Directory of Open Access Journals (Sweden)

    Yohei Ban


    Full Text Available For 2 x 2 x K contingency tables, Tomizawa considered a Shannon entropy type measure to represent the degree of departure from a log-linear model of no three-factor interaction (the NOTFI model. This paper proposes a generalization of Tomizawa's measure for 2 x 2 x K tables. The measure proposed is expressed by using Patil-Taillie diversity index or Cressie-Read power-divergence. A special case of the proposed measure includes Tomizawa's measure. The proposed measure would be useful for comparing the degrees of departure from the NOTFI model in several tables.

  5. The role of P2X receptors in bone biology

    DEFF Research Database (Denmark)

    Jørgensen, N R; Syberg, S; Ellegaard, M


    come from studies on murine knockout models and from pharmacologic studies on cells and animals. More recently, the role of P2X receptors in human bone diseases has been documented. Loss-of-functions polymorphisms in the P2X7 receptorare associated with bone loss and increased fracture risk. Very...

  6. The role of P2X receptors in bone biology

    DEFF Research Database (Denmark)

    Jørgensen, N R; Syberg, S; Ellegaard, M


    receptors regulate bone metabolism and especially for the P2X7 receptor an impressive amount of evidence has now documented its expression in osteoblasts, osteoclasts, and osteocytes as well as important functional roles in proliferation, differentiation, and function of the cells of bone. Key evidence has...... come from studies on murine knockout models and from pharmacologic studies on cells and animals. More recently, the role of P2X receptors in human bone diseases has been documented. Loss-of-functions polymorphisms in the P2X7 receptorare associated with bone loss and increased fracture risk. Very...... recently a report from a genetic study in multiple myeloma demonstrated that decreased P2X7 receptor function was associated with increased risk of developing multiple myeloma. In contrast, the risk of developing myeloma bone disease and subsequent vertebral fractures was increased in subjects carrying P2X...

  7. P2X7 receptors: channels, pores and more. (United States)

    Volonté, C; Apolloni, S; Skaper, S D; Burnstock, G


    Purine nucleotides are well established as extracellular signaling molecules. P2X7 receptors (P2X7Rs) are members of the family of ionotropic ATP-gated receptors. Their activity can be found in a limited number of cell types, but is readily detectable in cells of hemopoietic lineage including macrophages, microglia, and certain lymphocytes, and mediates the influx of Ca2+ and Na+ as well as the release of pro-inflammatory cytokines. Amongst P2X receptors, P2X7Rs behave as a bifunctional molecule. The binding of ATP induces within milliseconds the opening of a channel selective for small cations, and within seconds a larger pore opens which allows permeation by molecules with a mass of up to 900 Da. In humans at least, the P2RX7 gene is highly polymorphic, and genetic differences within P2X7R affect receptor pore formation and channel function. ATP can act as a neurotransmitter, while the presence of P2X7Rs on immune cells suggests that they also regulate immune function and inflammatory responses. In addition, activation of the P2X7R has dramatic cytotoxic properties. The role of extracellular ATP and purinoceptors in cytokine regulation and neurological disorders is, in fact, the focus of a rapidly expanding area of research. P2X7Rs may affect neuronal cell death by regulating the processing and release of interleukin-1β, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7Rs provides an inflammatory stimulus, and P2X7R-deficient mice display a marked attenuation of inflammatory responses, including models of neuropathic and chronic inflammatory pain. Moreover, P2X7R activity, by regulating the release of pro-inflammatory cytokines, may be involved in the pathophysiology of neuropsychiatric disorders. The P2X7R may thus represent a critical communication link between the nervous and immune systems, while providing a target for therapeutic exploitation. In this review we discuss current biology and pharmacology of the P2X

  8. Observation of Considerable Upconversion Enhancement Induced by Cu2-xS Plasmon Nanoparticles. (United States)

    Zhou, Donglei; Liu, Dali; Xu, Wen; Yin, Ze; Chen, Xu; Zhou, Pingwei; Cui, Shaobo; Chen, Zhanguo; Song, Hongwei


    Localized surface plasmon resonances (LSPRs) are achieved in heavily doped semiconductor nanoparticles (NPs) with appreciable free carrier concentrations. In this paper, we present the photonic, electric, and photoelectric properties of plasmonic Cu2-xS NPs/films and the utilization of LSPRs generated from semiconductor NPs as near-infrared antennas to enhance the upconversion luminescence (UCL) of NaYF4:Yb(3+),Er(3+) NPs. Our results suggest that the LSPRs in Cu2-xS NPs originate from ligand-confined carriers and that a heat treatment resulted in the decomposition of ligands and oxidation of Cu2-xS NPs; these effects led to a decrease of the Cu(2+)/Cu(+) ratio, which in turn resulted in the broadening, decrease in intensity, and red-shift of the LSPRs. In the presence of a MoO3 spacer, the UCL intensity of NaYF4:Yb(3+),Er(3+) NPs was substantially improved and exhibited extraordinary power-dependent behavior because of the energy band structure of the Cu2-xS semiconductor. These findings provide insights into the nature of LSPR in semiconductors and their interaction with nearby emitters and highlight the possible application of LSPR in photonic and photoelectric devices.

  9. P2X7 receptors in cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Hui-Yu Bai; Ai-Ping Li


    Cerebral ischemia is one of the most common diseases resulting in death and disability in aged people.It leads immediately to rapid energy failure,ATP depletion,and ionic imbalance,which increase extracellular ATP levels and accordingly activate P2X7 receptors.These receptors are ATP-gated cation channels and widely distributed in nerve cells,especially in the immunocompetent cells of the brain.Currently,interest in the roles of P2X7 receptors in ischemic brain injury is growing.In this review,we discuss recent research progress on the actions of P2X7 receptors,their possible mechanisms in cerebral ischemia,and the potential therapeutic value of P2X7 receptor antagonists which may provide a new target both for clinical and for research purposes.

  10. Alaska Gravity Data per 2 x 4 min Cell (96) (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This 2' x 4' gravity density grid for Alaska displays the distribution of about 1.1 million terrestrial and marine gravity data held in the National Geodetic Survey...

  11. The role of P2X receptors in bone biology

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Syberg, S; Ellegaard, M


    Bone is a highly dynamic organ, being constantly modeled and remodeled in order to adapt to the changing need throughout life. Bone turnover involves the coordinated actions of bone formation and bone degradation. Over the past decade great effort has been put into the examination of how P2X...... receptors regulate bone metabolism and especially for the P2X7 receptor an impressive amount of evidence has now documented its expression in osteoblasts, osteoclasts, and osteocytes as well as important functional roles in proliferation, differentiation, and function of the cells of bone. Key evidence has...... come from studies on murine knockout models and from pharmacologic studies on cells and animals. More recently, the role of P2X receptors in human bone diseases has been documented. Loss-of-functions polymorphisms in the P2X7 receptorare associated with bone loss and increased fracture risk. Very...

  12. J-2X Test Articles Using FDM Process (United States)

    Anderson, Ted; Ruf, Joe; Steele, Phil


    This viewgraph presentation gives a brief history of the J-2X engine, along with detailed description of the material demonstrator and test articles that were created using Fused Deposition Modeling (FDM) process.

  13. Manipulation of P2X Receptor Activities by Light Stimulation

    Directory of Open Access Journals (Sweden)

    Sang Seong Kim


    Full Text Available P2X receptors are involved in amplification of inflammatory responses in peripheral nociceptive fibers and in mediating pain-related signals to the CNS. Control of P2X activation has significant importance in managing unwanted hypersensitive neuron responses. To overcome the limitations of chemical ligand treatment, optical stimulation methods of optogenetics and photoswitching achieve efficient control of P2X activation while allowing specificity at the target site and convenient stimulation by light illumination. There are many potential applications for photosensitive elements, such as improved uncaging methods, photoisomerizable ligands, photoswitches, and gold nanoparticles. Each technique has both advantages and downsides, and techniques are selected according to the purpose of the application. Technical advances not only provide novel approaches to manage inflammation or pain mediated by P2X receptors but also suggest a similar approach for controlling other ion channels.

  14. Work function of bulk-insulating topological insulator Bi2-xSbxTe3-ySey (United States)

    Takane, Daichi; Souma, Seigo; Sato, Takafumi; Takahashi, Takashi; Segawa, Kouji; Ando, Yoichi


    Recent discovery of bulk insulating topological insulator (TI) Bi2-xSbxTe3-ySey paved a pathway toward practical device application of TIs. For realizing TI-based devices, it is necessary to contact TIs with a metal. Since the band-bending at the interface dominates the character of devices, knowledge of TIs' work function is of essential importance. We have determined the compositional dependence of the work function in Bi2-xSbxTe3-ySey by high-resolution photoemission spectroscopy. The obtained work-function values (4.95-5.20 eV) track the energy shift of the surface chemical potential seen by angle-resolved photoemission spectroscopy. The present result serves as a useful guide for developing TI-based electronic devices.

  15. Entanglement of 2xK quantum systems

    CERN Document Server

    Lozinski, A; Zyczkowski, K; Wellens, T; Lozinski, Artur; Buchleitner, Andreas; Zyczkowski, Karol; Wellens, Thomas


    We derive an analytical expression for the lower bound of the concurrence of mixed quantum states of composite 2xK systems. In contrast to other, implicitly defined entanglement measures, the numerical evaluation of our bound is straightforward. We explicitly evaluate its tightness for general mixed states of 2x3 systems, and identify a large class of states where our expression gives the exact value of the concurrence.

  16. P2X1 receptors and the endothelium

    Directory of Open Access Journals (Sweden)

    LS Harrington


    Full Text Available Adenosine triphosphate (ATP is now established as a principle vaso-active mediator in the vasculature. Its actions on arteries are complex, and are mediated by the P2X and P2Y receptor families. It is generally accepted that ATP induces a bi-phasic response in arteries, inducing contraction via the P2X and P2Y receptors on the smooth muscle cells, and vasodilation via the actions of P2Y receptors located on the endothelium. However, a number of recent studies have placed P2X1 receptors on the endothelium of some arteries. The use of a specific P2X1 receptor ligand, a, b methylene ATP has demonstrated that P2X1 receptors also have a bi-functional role. The actions of ATP on P2X1 receptors is therefore dependant on its location, inducing contraction when located on the smooth muscle cells, and dilation when expressed on the endothelium, comparable to that of P2Y receptors.

  17. Chemical pressure induced change in multiferroicity of Bi1+2xGd2x/2Fe1-2xO3 bulk ceramics (United States)

    Pradhan, S. K.; Sahu, D. R.; Rout, P. P.; Das, S. K.; Pradhan, A. K.; Srinivasu, V. V.; Roul, B. K.


    We have optimized Gd ion substitution in BiFeO3 (BFO) and observed prominently change in structural, electrical and magnetic behavior of Bi1+2xGd2x/2Fe1-2xO3 ceramics synthesized through slow step sintering schedule. It is observed that with the increase in concentration of Gd (x=0.1), original structure of BFO is transformed from rhombohedral R3c space group to orthorhombic Pn21a space group. Surprisingly, unit cell volume is drastically contracted (35% for x=0.2) and the sintered specimen showed enhanced room temperature ferromagnetic behavior although the original BFO is normally G-type antiferromagnetic in nature at 643 K. It is expected that intrinsic chemical pressure within the bulk body built by the substitution of Gd in presence of excess bismuth greatly supported through unidirectional movement of electrical dipole moment with in each individual domain as a result of which suppression of leakage current with enhanced dielectric and ferroelectric hysteresis is observed.

  18. Extracellular ATP and P2X7 receptors in neurodegeneration. (United States)

    Le Feuvre, Rosalind; Brough, David; Rothwell, Nancy


    Neuronal injury and cell death in the central nervous system (CNS) are underlying features of neurodegenerative disorders. However, our understanding of the fundamental mechanisms involved is still limited. Inflammatory processes mediated by cytokines, and interleukin-1 (IL-1) in particular, play a significant role in neuronal death following pathological insults. Despite this growing area of research, very little is known about the factors regulating the expression, cleavage and release of interleukin-1 in the brain. Recent studies on immune cells demonstrate that extracellular ATP can act as a potent stimulus for the maturation and release of interleukin-1beta, via activation of P2X7 receptors. Stimulation of P2X7 receptors with ATP has dramatic cytotoxic properties and a wider role in neurodegenerative processes is possible. This review discusses the potential involvement of extracellular ATP and P2X7 receptors as regulators of interleukin-1-mediated neuropathologies and thus as a mediator of cell death following pathological insults.

  19. Influence of Defect States on Charge Transport in CuInSe2-xSx Quantum Dot Films (United States)

    Yun, Hyeong Jin; Fidler, Andrew; Lim, Jaehoon; Fuhr, Addis; Pietryga, Jeffrey; Keene, Sam; Law, Matt; Klimov, Victor; CenterAdvanced Solar Photophysics Team

    CuInSe2-xSx quantum dots (QDs) are environmental-friendly alternatives to Cd- or Pb-based QDs for solar energy applications. The key to using QD thin films in opto-electronic devices like solar cells is understanding their charge-transport properties, which are known to be influenced by defects that can serve as carrier traps. Here, we combine field effect transistor (FET) and ultrafast transient photocurrent (u-TPC) measurements to obtain a more complete picture of the nature and role of trap sates in CuInSe2-xSx QD thin films. FET devices employing indium contacts exhibit n-type transport with electron mobility of 5.34 ×10-4 cm2/Vs, but they also indicate high concentrations of electrons in the films. Early-time dynamical signatures revealed in u-TPC suggest that this high carrier density arises from the presence of trap states in CuInSe2-xSx QDs. In order to reduce the density of trap states, atomic layer deposition was used to infill the CuInSe2-xSx-based devices with amorphous alumina, which results in both higher FET mobilities, and a reduction in trap-related decay signatures in u-TPC measurements.

  20. Maltodextrin and fat preference deficits in "taste-blind" P2X2/P2X3 knockout mice. (United States)

    Sclafani, Anthony; Ackroff, Karen


    Adenosine triphosphate is a critical neurotransmitter in the gustatory response to the 5 primary tastes in mice. Genetic deletion of the purinergic P2X2/P2X3 receptor greatly reduces the neural and behavioral response to prototypical primary taste stimuli. In this study, we examined the behavioral response of P2X double knockout mice to maltodextrin and fat stimuli, which appear to activate additional taste channels. P2X double knockout and wild-type mice were given 24-h choice tests (vs. water) with ascending concentrations of Polycose and Intralipid. In Experiment 1, naive double knockout mice, unlike wild-type mice, were indifferent to dilute (0.5-4%) Polycose solutions but preferred concentrated (8-32%) Polycose to water. In a retest, the Polycose-experienced double knockout mice, like wild-type mice, preferred all Polycose concentrations. In Experiment 2, naive double knockout mice, unlike wild-type mice, were indifferent to dilute (0.313-2.5%) Intralipid emulsions but preferred concentrated (5-20%) Intralipid to water. In a retest, the fat-experienced double knockout mice, like wild-type mice, strongly preferred 0.313-5% Intralipid to water. These results indicate that the inherent preferences of mice for maltodextrin and fat are dependent upon adenosine triphosphate taste cell signaling. With experience, however, P2X double knockout mice develop strong preferences for the nontaste flavor qualities of maltodextrin and fat conditioned by the postoral actions of these nutrients.

  1. P2X7受体功能的调控%Regulation of P2X7 Receptor Function

    Institute of Scientific and Technical Information of China (English)

    张海燕; 郑国光



  2. P2X7 receptors in satellite glial cells mediate high functional expression of P2X3 receptors in immature dorsal root ganglion neurons

    Directory of Open Access Journals (Sweden)

    Chen Yong


    Full Text Available Abstract Background The purinergic P2X3 receptor (P2X3R expressed in the dorsal root ganglion (DRG sensory neuron and the P2X7 receptor (P2X7R expressed in the surrounding satellite glial cell (SGC are two major receptors participating in neuron-SGC communication in adult DRGs. Activation of P2X7Rs was found to tonically reduce the expression of P2X3Rs in DRGs, thus inhibiting the abnormal pain behaviors in adult rats. P2X receptors are also actively involved in sensory signaling in developing rodents. However, very little is known about the developmental change of P2X7Rs in DRGs and the interaction between P2X7Rs and P2X3Rs in those animals. We therefore examined the expression of P2X3Rs and P2X7Rs in postnatal rats and determined if P2X7R-P2X3R control exists in developing rats. Findings We immunostained DRGs of immature rats and found that P2X3Rs were expressed only in neurons and P2X7Rs were expressed only in SGCs. Western blot analyses indicated that P2X3R expression decreased while P2X7R expression increased with the age of rats. Electrophysiological studies showed that the number of DRG neurons responding to the stimulation of the P2XR agonist, α,β-meATP, was higher and the amplitudes of α,β-meATP-induced depolarizations were larger in immature DRG neurons. As a result, P2X3R-mediated flinching responses were much more pronounced in immature rats than those found in adult rats. When we reduced P2X7R expression with P2X7R-siRNA in postnatal and adult rats, P2X3R-mediated flinch responses were greatly enhanced in both rat populations. Conclusions These results show that the P2X7R expression increases as rats age. In addition, P2X7Rs in SGCs exert inhibitory control on the P2X3R expression and function in sensory neurons of immature rats, just as observed in adult rats. Regulation of P2X7R expression is likely an effective way to control P2X3R activity and manage pain relief in infants.

  3. The P2X7 Receptor-Interleukin-1 Liaison (United States)

    Giuliani, Anna Lisa; Sarti, Alba C.; Falzoni, Simonetta; Di Virgilio, Francesco


    Interleukin-1β (IL-1β) plays a central role in stimulation of innate immune system and inflammation and in several chronic inflammatory diseases. These include rare hereditary conditions, e.g., auto-inflammatory syndromes, as well as common pathologies, such as type II diabetes, gout and atherosclerosis. A better understanding of IL-1β synthesis and release is particularly relevant for the design of novel anti-inflammatory drugs. One of the molecules mainly involved in IL-1β maturation is the P2X7 receptor (P2X7R), an ATP-gated ion channel that chiefly acts through the recruitment of the NLRP3 inflammasome-caspase-1 complex. In this review, we will summarize evidence supporting the key role of the P2X7R in IL-1β production, with special emphasis on the mechanism of release, a process that is still a matter of controversy. Four different models have been proposed: (i) exocytosis via secretory lysosomes, (ii) microvesicles shedding from plasma membrane, (iii) release of exosomes, and (iv) passive efflux across a leaky plasma membrane during pyroptotic cell death. All these models involve the P2X7R. PMID:28360855

  4. The role of P2X receptors in bone biology

    DEFF Research Database (Denmark)

    Jørgensen, N R; Syberg, S; Ellegaard, M


    Bone is a highly dynamic organ, being constantly modeled and remodeled in order to adapt to the changing need throughout life. Bone turnover involves the coordinated actions of bone formation and bone degradation. Over the past decade great effort has been put into the examination of how P2X rece...

  5. The contribution of valence unstable ytterbium states into kinetic properties of YbNi{sub 2-x}Ge{sub 2+x} and YbCu{sub 2-x}Si{sub 2+x}

    Energy Technology Data Exchange (ETDEWEB)

    Kuzhel, B.C. [Department of Physics, Ivan Franko National University of Lviv, 50 Dragomanow Str., 79005, Lviv (Ukraine)]. E-mail:; Shcherba, I.D. [Department of Physics, Ivan Franko National University of Lviv, 50 Dragomanow Str., 79005, Lviv (Ukraine); Institute of Techniques, Academy of Pedagogy, Podchorozych 2, 30-084, Krakow (Poland); Kravchenko, I.I. [Department of Physics, University of Florida, P.O. Box 118440, Gainesville, FL 32611 (United States)]. E-mail:


    The intermetalic YbNi{sub 2-x}Ge{sub 2+x} (-0.25>=x>=0.25) and YbCu{sub 2-x}Si{sub 2+x} (-0.20>=x>=0.20) alloy systems (CeGa{sub 2}Al{sub 2} -type crystal structure) were studied by measuring X-ray absorption and diffraction at room temperatures as well as electrical resistivity and thermopower in the 4.2-300K temperature range. The temperature dependence of the contribution of valence unstable Yb ions to the total electrical resistance has been analyzed. The qualitative estimation of this contribution has been performed by utilizing the following equation:{delta}{rho}{sub Yb}(T)={rho}{sub exp}(T)-{rho}{sub YbCu{sub 2}Ge{sub 2}}(T)-{delta}{rho}{sub 4.2K},where {delta}{rho}{sub YbCu{sub 2}Ge{sub 2}}(T) is the temperature dependence of YbCu{sub 2}Ge{sub 2} electrical resistance, {delta}{rho}{sub 4.2}={rho}{sub 4.2}(exp)-{rho}{sub 4.2}(YbCu{sub 2}Ge{sub 2})

  6. Aligned Interference Neutralization and the Degrees of Freedom of the 2x2x2 Interference Channel

    CERN Document Server

    Gou, Tiangao; Jeon, Sang-Woon; Chung, Sae-Young


    We show that the 2x2x2 interference channel, i.e., the multihop interference channel formed by concatenation of two 2-user interference channels achieves the min-cut outer bound value of 2 DoF, for almost all values of channel coefficients, for both time-varying or fixed channel coefficients. The key to this result is a new idea, called aligned interference neutralization, that provides a way to align interference terms over each hop in a manner that allows them to be cancelled over the air at the last hop.

  7. Ac Impedance Spectroscopic Studies on Li2xPb2xBaP2O7 (United States)

    Vijayakumar, M.; Selvasekarapandian, S.


    The complex diphosphate (P2O7)4- ions have been used as a building blocks in wide variety of crystal phases for a wide spectrum of physical and chemical properties. Lithium barium diphsophate doped with lead {Li2-xPb2xBaP2O7 (x = 0, 0.2 & 0.4)} has been prepared by solid state reaction method The conductivity is found to be decreasing with the doping of lead. The lithium ion dynamics parameters such as hopping frequency and relaxation frequency were calculated from the frequency dependent conductivity and modulus analysis.

  8. 力竭运动对大鼠大脑P2X2、P2X4和P2X6受体表达的影响%Effect of Exhaustive Exercise on the Expression of Brain P2X2,P2X4,and P2X6 Receptors in Rats

    Institute of Scientific and Technical Information of China (English)

    周未艾; 李硕; 陈海涛


    目的:探讨一次和反复力竭游泳运动后大鼠大脑ATP受体P2X之三个亚型P2X2、P2X4和P2X6的时相性变化特点.方法:健康成年雄性SD大鼠68只,分为一次力竭游泳运动组和反复力竭游泳运动组及安静对照组,反复力竭组大鼠每日负重3%体重进行力竭游泳运动,共训练2周.运动组分别于力竭运动后即刻、4小时、12小时和24小时取材,采用实时荧光定量PCR方法测定力竭运动后大鼠P2X2、P2X4和P2X6受体亚型mRNA水平.结果:(1)反复力竭运动后12小时组P2X2相对表达率达到峰值,与反复力竭其它各组及安静对照组、一次力竭12小时组均有显著差异(P<0.01).(2)一次力竭即刻组P2X4相对表达率与安静对照组、4小时组、12小时组比较有显著统计学差异(分别为P< 0.01、P<0.05、P< 0.01).(3)反复力竭运动后12小时组P2X6相对表达率达到峰值.结论:3种受体亚型在一次力竭运动和反复力竭运动后12小时出现峰值或峰值趋势,提示在力竭运动后12小时,这3种P2X受体亚型所参与的中枢神经生理生化活动在此时可能会达到一个活跃期.%Objective The main purpose of this study is to investigate the variation in P2X2,P2X4 and P2X6 receptors in rats brain at different time points after single bout exhaustive exercise and repeated exhaustive exercise. Methods Sixty-eight male SD rats were divided randomly into the single bout exhaustive swimming group (SE), repeated exhausting swimming (RE), and sedentary group (C). The rats in group RE with weight-bearing 3% of body weight swan to exhaustion each day for a total of two weeks. The brain tissue of the rats was removed at 0 hr,4 hr,12 hr and 24 hr after the last exhaustive swimming. The mRNA levels of P2X2,P2X4 and P2X6 receptors in the brain tissue were observed through real-time quantitative PCR method. Results (l)The peak relative expression rate of the P2X2 in the group RE revealed at 12 hr after exhaustive

  9. Activation of P2X7 receptors in glial satellite cells reduces pain through downregulation of P2X3 receptors in nociceptive neurons


    Chen, Yong; Zhang, Xiaofei; Wang, Congying; Li, Guangwen; Gu, Yanping; Huang, Li-Yen Mae


    Purinergic ionotropic P2X7 receptors (P2X7Rs) are closely associated with excitotoxicity and nociception. Inhibition of P2X7R activation has been considered as a potentially useful strategy to improve recovery from spinal cord injury and reduce inflammatory damage to trauma. The physiological functions of P2X7Rs, however, are poorly understood, even though such information is essential for making the P2X7R an effective therapeutic target. We show here that P2X7Rs in satellite cells of dorsal ...

  10. P2X7 Receptor and Polykarion Formation


    Falzoni, Simonetta; Chiozzi, Paola; Ferrari, Davide; Buell, Gary; Di Virgilio, Francesco


    Cell fusion is a central phenomenon during the immune response that leads to formation of large elements called multinucleated giant cells (MGCs) of common occurrence at sites of granulomatous inflammation. We have previously reported on the involvement in this event of a novel receptor expressed to high level by mononuclear phagocytes, the purinergic P2X7 receptor. Herein, we show that blockade of this receptor by a specific monoclonal antibody prevents fusion in ...

  11. P2X7 receptors mediate ischemic damage to oligodendrocytes. (United States)

    Domercq, Maria; Perez-Samartin, Alberto; Aparicio, David; Alberdi, Elena; Pampliega, Olatz; Matute, Carlos


    Brain ischemia leading to stroke is a major cause of disability in developed countries. Therapeutic strategies have most commonly focused on protecting neurons from ischemic damage. However, ischemic damage to white matter causes oligodendrocyte death, myelin disruption, and axon dysfunction, and it is partially mediated by glutamate excitotoxicity. We have previously demonstrated that oligodendrocytes express ionotropic purinergic receptors. The objective of this study was to investigate the role of purinergic signaling in white matter ischemia. We show that, in addition to glutamate, enhanced ATP signaling during ischemia is also deleterious to oligodendrocytes and myelin, and impairs white matter function. Thus, ischemic oligodendrocytes in culture display an inward current and cytosolic Ca(2+) overload, which is partially mediated by P2X7 receptors. Indeed, oligodendrocytes release ATP after oxygen and glucose deprivation through the opening of pannexin hemichannels. Consistently, ischemia-induced mitochondrial depolarization as well as oxidative stress culminating in cell death are partially reversed by P2X7 receptor antagonists, by the ATP degrading enzyme apyrase and by blockers of pannexin hemichannels. In turn, ischemic damage in isolated optic nerves, which share the properties of brain white matter, is greatly attenuated by all these drugs. Ultrastructural analysis and electrophysiological recordings demonstrated that P2X7 antagonists prevent ischemic damage to oligodendrocytes and myelin, and improved action potential recovery after ischemia. These data indicate that ATP released during ischemia and the subsequent activation of P2X7 receptor is critical to white matter demise during stroke and point to this receptor type as a therapeutic target to limit tissue damage in cerebrovascular diseases.

  12. ATP, P2X receptors and pain pathways. (United States)

    Ding, Y; Cesare, P; Drew, L; Nikitaki, D; Wood, J N


    A role for ATP in nociception and pain induction was proposed on the basis of human psychophysical experiments shortly after the formulation of the purinergic hypothesis. Following the pharmacological definition of distinct P2X and P2Y purinergic receptor subtypes by Burnstock and his collaborators, molecular cloning studies have identified the gene products that underlie the effects of ATP on peripheral sensory neurons. One particular receptor, P2X(3), is of particular interest in the context of pain pathways, because it is relatively selectively expressed at high levels by nociceptive sensory neurons. Evidence that this receptor may play a role in the excitation of sensory neurons has recently been complemented by studies that suggest an additional presynaptic role in the regulation of glutamate release from primary afferent neurons in the dorsal horn of the spinal cord. In this brief review, we discuss the present state of knowledge of the role of ATP in pain induction through its action on peripheral P2X receptors.

  13. Electroacupuncture diminishes P2X2 and P2X3 purinergic receptor expression in dorsal root ganglia of rats with visceral hypersensitivity

    Institute of Scientific and Technical Information of China (English)

    Zhijun Weng; Luyi Wu; Yuan Lu; Lidong Wang; Linying Tan; Ming Dong; Yuhu Xin


    Electroacupuncture at Shangjuxu (ST37) and Tianshu (ST25) can improve visceral hypersensitivity in rats. Colorectal distension was used to establish a rat model of chronic visceral hypersensitivity. Immunohistochemistry was used to detect P2X2 and P2X3 receptor expression in dorsal root ganglia from rats with chronic visceral hypersensitivity. Results demonstrated that abdominal withdrawal reflex scores obviously increased following establishment of the model, indicating visceral hypersensitivity. Simultaneously, P2X2 and P2X3 receptor expression increased in dorsal root ganglia. After bilateral electroacupuncture at Shangjuxu and Tianshu, abdominal withdrawal reflex scores and P2X2 and P2X3 receptor expression decreased in rats with visceral hypersensitivity. These results indicated that electroacupuncture treatment improved visceral hypersensitivity in rats with irritable bowel syndrome by reducing P2X2 and P2X3 receptor expression in dorsal root ganglia.

  14. Robust optimization of 2x2 multimode interference couplers with fabrication uncertainties (United States)

    Rehman, Samee ur; Langelaar, Matthijs; Van Keulen, Fred


    In this paper, we propose a novel design-for-manufacture strategy for integrated photonics which specifically addresses the commonly encountered scenario in which probability distributions of the manufacturing variations are not available, however their bounds are known. The best design point for the device, in the presence of these uncertainties, can be found by applying robust optimization. This is performed by minimizing the maximum realizable value of the objective with respect to the uncertainty set so that an optimum is found whose performance is relatively immune to fabrication variations. Instead of applying robust optimization directly on a computationally expensive simulation model of the integrated photonic device, we construct a cheap surrogate model by uniformly sampling the simulated device at different values of the design variables and interpolating the resulting objective using a Kriging metamodel. By applying robust optimization on the constructed surrogate, the global robust optimum can be found at low computational cost. As an illustration of the method's general applicability, we apply the robust optimization approach on a 2x2 multimode interference (MMI) coupler. We robustly minimize the imbalance in the presence of uncertainties arising from variations in the fabricated design geometry. For this example device, we also study the influence of the number of sample points on the quality of the metamodel and on the robust optimization process.

  15. Chronic administration of the selective P2X3, P2X2/3 receptor antagonist, A-317491, transiently attenuates cancer-induced bone pain in mice

    DEFF Research Database (Denmark)

    Hansen, Rikke Rie; Nasser, Arafat; Falk, Sarah;


    The purinergic P2X3 and P2X2/3 receptors are in the peripheral nervous system almost exclusively confined to afferent sensory neurons, where they are found both at peripheral and central synapses. The P2X3 receptor is implicated in both neuropathic and inflammatory pain. However, the role of the ...

  16. Double P2X2/P2X3 Purinergic Receptor Knockout Mice Do Not Taste NaCl or the Artificial Sweetener SC45647 (United States)

    Eddy, Meghan C.; Eschle, Benjamin K.; Barrows, Jennell; Hallock, Robert M.; Finger, Thomas E.


    The P2X ionotropic purinergic receptors, P2X2 and P2X3, are essential for transmission of taste information from taste buds to the gustatory nerves. Mice lacking both P2X2 and P2X3 purinergic receptors (P2X2/P2X3Dbl−/−) exhibit no taste-evoked activity in the chorda tympani and glossopharyngeal nerves when stimulated with taste stimuli from any of the 5 classical taste quality groups (salt, sweet, sour, bitter, and umami) nor do the mice show taste preferences for sweet or umami, or avoidance of bitter substances (Finger et al. 2005. ATP signaling is crucial for communication from taste buds to gustatory nerves. Science. 310[5753]:1495–1499). Here, we compare the ability of P2X2/P2X3Dbl−/− mice and P2X2/P2X3Dbl+/+ wild-type (WT) mice to detect NaCl in brief-access tests and conditioned aversion paradigms. Brief-access testing with NaCl revealed that whereas WT mice decrease licking at 300 mM and above, the P2X2/P2X3Dbl−/− mice do not show any change in lick rates. In conditioned aversion tests, P2X2/P2X3Dbl−/− mice did not develop a learned aversion to NaCl or the artificial sweetener SC45647, both of which are easily avoided by conditioned WT mice. The inability of P2X2/P2X3Dbl−/− mice to show avoidance of these taste stimuli was not due to an inability to learn the task because both WT and P2X2/P2X3Dbl−/− mice learned to avoid a combination of SC45647 and amyl acetate (an odor cue). These data suggest that P2X2/P2X3Dbl−/− mice are unable to respond to NaCl or SC45647 as taste stimuli, mirroring the lack of gustatory nerve responses to these substances. PMID:19833661

  17. The 2X-HI disks of spiral galaxies

    CERN Document Server

    Koribalski, B S


    The outskirts of galaxies - especially the very extended HI disks of galaxies - are strongly affected by their local environment. I highlight the giant 2X-HI disks of nearby galaxies (M 83, NGC 3621, and NGC 1512), studied as part of the Local Volume HI Survey (LVHIS), their kinematics and relation to XUV disks, signatures of tidal interactions and accretion events, the MHI - DHI relation as well as the formation of tidal dwarf galaxies. - Using multi-wavelength data, I create 3D visualisations of the gas and stars in galaxies, with the shape of their warped disks obtained through kinematic modelling of their HI velocity fields.

  18. Aqueous Rechargeable Alkaline CoxNi2-xS2/TiO2 Battery. (United States)

    Liu, Jilei; Wang, Jin; Ku, Zhiliang; Wang, Huanhuan; Chen, Shi; Zhang, Lili; Lin, Jianyi; Shen, Ze Xiang


    An electrochemical energy storage system with high energy density, stringent safety, and reliability is highly desirable for next-generation energy storage devices. Here an aqueous rechargeable alkaline CoxNi2-xS2 // TiO2 battery system is designed by integrating two reversible electrode processes associated with OH(-) insertion/extraction in the cathode part and Li ion insertion/extraction in the anode part, respectively. The prototype CoxNi2-xS2 // TiO2 battery is able to deliver high energy/power densities of 83.7 Wh/kg at 609 W/kg (based on the total mass of active materials) and good cycling stabilities (capacity retention 75.2% after 1000 charge/discharge cycles). A maximum volumetric energy density of 21 Wh/l (based on the whole packaged cell) has been achieved, which is comparable to that of a thin-film battery and better than that of typical commercial supercapacitors, benefiting from the unique battery and hierarchical electrode design. This hybrid system would enrich the existing aqueous rechargeable LIB chemistry and be a promising battery technology for large-scale energy storage.

  19. 10 Years of Car-2-X Communication - a Success Story? (United States)

    Wischhof, Lars; Ebner, André


    For more than ten years, car-2-x communication has been a major topic of research in the scientific community and an important development focus for the automotive industry. First, this article takes a retrospective look at the evolution of car-2-x and the two different communication paradigms: decentralized car-2-car communication and centralized cellular solutions. Afterwards, a comparison of their technical advantages and limitations is presented, respectively. The result shows that in order to implement safety-relevant applications, car-2-car communication has strong advantages compared to cellular technologies but requires high market penetration. However, its introduction solely for safety applications is difficult since the required penetration will not be achieved until several years after initial deployment. Therefore, car-2-car communication must provide a benefit to the customer, even in the phase of market introduction. For this purpose, the article outlines an approach called SODAD (Segment-Oriented Data Abstraction and Dissemination). It offers a possibility to introduce decentralized vehicular applications with early customer benefit, in order to enable safety applications based on car-2-car communication on a long term.

  20. Evolutionary Markovian Strategies in 2 x 2 Spatial Games

    CERN Document Server

    Fort, H; Fort, Hugo; Sicardi, Estrella


    Evolutionary spatial 2 x 2 games between heterogeneous agents are analyzed using different variants of cellular automata (CA). Agents play repeatedly against their nearest neighbors 2 x 2 games specified by a rescaled payoff matrix with two parameteres. Each agent is governed by a binary Markovian strategy (BMS) specified by 4 conditional probabilities [p_R, p_S, p_T, p_P] that take values 0 or 1. The initial configuration consists in a random assignment of "strategists" among the 2^4= 16 possible BMS. The system then evolves within strategy space according to the simple standard rule: each agent copies the strategy of the neighbor who got the highest payoff. Besides on the payoff matrix, the dominant strategy -and the degree of cooperation- depend on i) the type of the neighborhood (von Neumann or Moore); ii) the way the cooperation state is actualized (deterministically or stochastichally); and iii) the amount of noise measured by a parameter epsilon. However a robust winner strategy is [1,0,1,1].

  1. Residual Chemosensory Capabilities in Double P2X2/P2X3 Purinergic Receptor Null Mice: Intraoral or Postingestive Detection? (United States)

    Hallock, Robert M.; Tatangelo, Marco; Barrows, Jennell


    Mice lacking the purinergic receptors, P2X2 and P2X3 (P2X2/P2X3Dbl−/−), exhibit essentially no tastant-evoked activity in the chorda tympani and glossopharyngeal nerves and substantial loss of tastant-evoked behavior as measured in long-term intake experiments. To assess whether the residual chemically driven behaviors in these P2X2/P2X3Dbl−/− mice were attributable to postingestive detection or oropharyngeal detection of the compounds, we used brief access lickometer tests to assess the behavioral capabilities of the P2X2/P2X3Dbl−/− animals. The P2X2/P2X3Dbl−/− mice showed avoidance to high levels (10 mM quinine and 10–30 mM denatonium benzoate) of classical “bitter”-tasting stimuli in 24-h, 2-bottle preference tests but minimal avoidance of these substances in the lickometer tests, suggesting that the strong avoidance in the intake tests was largely mediated by post-oral chemosensors. Similarly, increases in consumption of 1 M sucrose by P2X2/P2X3Dbl−/− mice in long-term intake tests were not mirrored by increases in consumption of sucrose in lickometer tests, suggesting that sucrose detection in these mice is mediated by postingestive consequences. In contrast, in brief access tests, P2X2/P2X3Dbl−/− mice avoided citric acid and hydrochloric acid at the same concentrations as their wild-type counterparts, indicating that these weak acids activate oropharyngeal chemoreceptors. PMID:19833662

  2. Differential gene expression patterns and colocalization of ATP-gated P2X6/P2X4 ion channels during rat small intestine ontogeny. (United States)

    Padilla, Karla; Gonzalez-Mendoza, David; Berumen, Laura C; Escobar, Jesica E; Miledi, Ricardo; García-Alcocer, Guadulupe


    Gene coding for ATP-gated receptor ion channels (P2X1-7) has been associated with the developmental process in various tissues; among these ion channel subtypes, P2X6 acts as a physiological regulator of P2X4 receptor functions when the two receptors form heteroreceptors. The P2X4 receptor is involved in pain sensation, the inflammatory process, and body homeostasis by means of Mg(2+) absorption through the intestine. The small intestine is responsible for the absorption and digestion of nutrients; throughout its development, several gene expressions are induced that are related to nutrients received, metabolism, and other intestine functions. Previous work has shown a differential P2X4 and P2X6 protein distribution in the small intestine of newborn and adult rats; however, it is not well-known at what age the change in the relationship between the gene and protein expression occurs and whether or not these receptors are colocalized. In this work, we evaluate P2X4 and P2X6 gene expression patterns by qPCR from embryonic (E18, P0, P7, P17, P30) to adult age in rat gut, as well as P2X6/P2X4 colocalization using qRT-PCR and confocal immunofluorescence in proximal and distal small intestine sections. The results showed that P2X6 and P2X4 gene expression levels of both receptors decreased at the embryonic-perinatal transition, whereas from ages P17 to P30 (suckling-weaning transition) both receptors increased their gene expression levels. Furthermore, P2X4 and P2X6 proteins were expressed in a different way during rat small intestine development, showing a higher colocalization coefficient at age P30 in both intestine regions. Those results suggest that purinergic receptors may play a role in intestinal maturation, which is associated with age and intestinal region.

  3. Electric field effect on superconductivity in La2-xSrxCuO4 (United States)

    Dubuis, G.; Bollinger, A. T.; Pavuna, D.; Božović, I.


    We demonstrate a method to tune the carrier concentration of a high temperature superconductor over a wide range, using an applied electric field. Thin film devices were made in an electrical double layer transistor configuration utilizing an ionic liquid. In this way, the surface carrier density in La2-xSrxCuO4 films can be varied between 0.01 and 0.14 carriers per Cu atom with a resulting change in critical temperature of 25 K (˜70% of the maximum critical temperature in this compound). This allows one to study a large segment of the cuprate phase diagram without altering the level of disorder. We used this method [A. T. Bollinger et al., Nature 472, 458-460 (2011)] to study the quantum critical point at the superconductor to insulator phase transition on the underdoped side of superconducting dome, and concluded that this transition is driven by quantum phase fluctuations and Cooper pair delocalization.

  4. A tiled CCD detector with 2x2 array and tapered fibre optics for electron microscopy

    CERN Document Server

    Faruqi, A R; Cattermole, D M; Stubbings, S


    Charge coupled devices (CCD)-based detectors have made a major impact on data collection in electron microscopy over the past few years. There have been a number of successful applications of CCDs in electron crystallography of two-dimensional protein crystal arrays but high-resolution imaging has been hampered by the relatively poor spatial resolution (and fewer independent pixels) compared to film. A partial solution to this problem, presented in this paper, are to design detectors with larger effective pixel sizes and with more pixels. A CCD detector with a much greater number of 'independent' pixels, achieved by tiling a 2x2 array of CCDs, each of which has 1242x1152 pixels is described here. The sensitive area of the detector, using fibre optics with a demagnification of 2.5 : 1, is 140x130 mm sup 2; the pixel size is 56 mu m square and there is a total of approx 2500x2300 pixels.

  5. A Truncated P2X7 Receptor Variant (P2X7-j) Endogenously Expressed in Cervical Cancer Cells Antagonizes the Full-length P2X7 Receptor through Hetero-oligomerization*


    Feng, Ying-Hong; LI Xin; Wang, Liqin; Zhou, Lingying; Gorodeski, George I.


    A truncated naturally occurring variant of the human receptor P2X7 was identified in cancer cervical cells. The novel protein (P2X7-j), a polypeptide of 258 amino acids, lacks the entire intracellular carboxyl terminus, the second transmembrane domain, and the distal third of the extracellular loop of the full-length P2X7 receptor. The P2X7-j was expressed in the plasma membrane; it showed diminished ligand-binding and channel function capacities and failed to form pores and mediate apoptosis...

  6. P2X7受体在肿瘤中的表达及其意义%P2X7 receptor and its significances in tumor

    Institute of Scientific and Technical Information of China (English)



    P2X7受体(P2X7R)是P2X家族受体的一员,分布于多种组织,参与细胞信号转导、炎症反应等多种生理功能.传统普遍认为,P2X7R是细胞毒性核苷酸受体的典型代表.近来,大量研究结果却证实,P2X7R还具有促进细胞增殖活性.P2X7R表达及功能异常与多种实体瘤及血液系统肿瘤相关.阐明P2X7R在肿瘤发生、发展中的作用对肿瘤的诊断、治疗及预后评估起重要的作用.%P2X7 receptor(P2X7R),a member of P2X receptors,is distributed to many tissues and plays an important role in cell signaling transduction,inflammatory reaction and so on.In the past,the P2X7R is often taken as an epitome of cytotoxic receptors.Over the years,numerous experiments have led us to adopt a new view,that P2X7R is a growth-promoting receptor.The abnormal expression and function of P2X7R are closely related to many solid tumors and hematological neoplasms.Thus,the better understanding of P2X7R in cancer opens promising perspectives for the diagnosis,treatments and prognostic evaluation of neoplasms.

  7. SU(2) x U(1) vacuum and the Centauro events (United States)

    Kazanas, D.; Balasubrahmanyan, V. K.; Streitmatter, R. E.


    It is proposed that the fireballs invoked to explain the Centauro events are bubbles of a metastable superdense state of nuclear matter, created in high energy (E approximately 10 to the 15th power eV) cosmic ray collisions at the top of the atmosphere. If these bubbles are created with a Lorentz factor gamma approximately equals 10 at their CM frame, the objections against the origin of these events in cosmic ray interactions are overcome. A relationship then between their lifetime, tau, and the threshold energy for bubble formation, E sub th, appears to be insensitive to the value of tau and always close to E sub th approximately 10 to 15th power eV. Finally it is speculated that these bubbles might be manifestations of the SU(2) x U(1) false vacuum excited in these collisions. The absence of in the Centauro events is then explained by the decay modes of these excitations.

  8. Semiconductivity in YBa2 - xSrxCu3Oy (United States)

    Uluǧ, A.; Uluǧ, B.; Şener, E.


    Structural and electrical properties of YBa2-xSrxCu3Oy prepared under ambient oxygen pressure were systematically investigated for 0≤x≤2.0. Samples with high Sr contents, x≥1.7, showed semiconductive properties with an activation energy of ˜150 meV at high temperature, T≥80 K. At low temperatures, T≤80 K, activation energy dropped to ˜3.00 and ˜0.85 meV for x=1.7-1.8 and x=1.9-2.0, respectively. It is argued that YSr2Cu3Oy is likely to have a tetragonal structure and that the disorder introduced by Sr substitution affects electrical conduction, which involves charge hopping between the CuO chains at high Sr contents.

  9. Thermodynamics of fission products in UO2+-x

    Energy Technology Data Exchange (ETDEWEB)

    Nerikar, Pankaj V [Los Alamos National Laboratory


    The stabilities of selected fission products - Xe, Cs, and Sr - are investigated as a function of non-stoichiometry x in UO{sub 2{+-}x}. In particular, density functional theory (OFT) is used to calculate the incorporation and solution energies of these fission products at the anion and cation vacancy sites, at the divacancy, and at the bound Schottky defect. In order to reproduce the correct insulating state of UO{sub 2}, the DFT calculations are performed using spin polarization and with the Hubbard U tenn. In general, higher charge defects are more soluble in the fuel matrix and the solubility of fission products increases as the hyperstoichiometry increases. The solubility of fission product oxides is also explored. CS{sub 2}O is observed as a second stable phase and SrO is found to be soluble in the UO{sub 2} matrix for all stoichiometries. These observations mirror experimentally observed phenomena.

  10. Trophic Activity of Human P2X7 Receptor Isoforms A and B in Osteosarcoma


    Giuliani, A.L.; Colognesi, D.; T. Ricco; Roncato, C.; Capece, M.; Amoroso, F; Wang, Q. G.; Marchi, E.; Gartland, A.; Di Virgilio, F; Adinolfi, E.


    The P2X7 receptor (P2X7R) is attracting increasing attention for its involvement in cancer. Several recent studies have shown a crucial role of P2X7R in tumour cell growth, angiogenesis and invasiveness. In this study, we investigated the role of the two known human P2X7R functional splice variants, the full length P2X7RA and the truncated P2X7RB, in osteosarcoma cell growth. Immunohistochemical analysis of a tissue array of human osteosarcomas showed that forty-four, of a total fifty-four tu...

  11. Discovery of P2X7 receptor-selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states


    Donnelly-Roberts, D L; Jarvis, M F


    ATP-sensitive P2X7 receptors are localized on cells of immunological origin including peripheral macrophages and glial cells in the CNS. Activation of P2X7 receptors leads to rapid changes in intracellular calcium concentrations, release of the proinflammatory cytokine interleukin-1β and following prolonged agonist exposure, the formation of cytolytic pores in plasma membranes. Both the localization and functional consequences of P2X7 receptor activation indicate a role in inflammatory proces...

  12. Improvement in efficiency of solar cell by removing Cu2-xSe from CIGS film surface

    Institute of Scientific and Technical Information of China (English)

    Li Wei; Sun Yun; Liu Wei; Li Feng-Yan; Zhou Lin


    CIGS thin films are deposited by sputtering and selenization.The synthesis of semiconducting polycrystalline thin films and characteristics of devices based on the CIGS absorbing layers are investigated.Their microstructures are characterized by X-ray diffraction and Raman spectroscopy.The results reveal that there exist metallic Cu2-xSe compounds in CIGS film surfaces and the compounds are thought to be responsible for the degradation of the open circuit voltage of solar cells.The optimization of selenization temperature profile and copper content in the precursor surfaces is studied,concluding that the conversion efficiency may be improved by removing metallic Cu2-xSe compounds from the surfaces of CIGS thin films.

  13. Flexible subunit stoichiometry of functional human P2X2/3 heteromeric receptors. (United States)

    Kowalski, Maria; Hausmann, Ralf; Schmid, Julia; Dopychai, Anke; Stephan, Gabriele; Tang, Yong; Schmalzing, Günther; Illes, Peter; Rubini, Patrizia


    The aim of the present work was to clarify whether heterotrimeric P2X2/3 receptors have a fixed subunit stoichiometry consisting of one P2X2 and two P2X3 subunits as previously suggested, or a flexible stoichiometry containing also the inverse subunit composition. For this purpose we transfected HEK293 cells with P2X2 and P2X3 encoding cDNA at the ratios of 1:2 and 4:1, and analysed the biophysical and pharmacological properties of the generated receptors by means of the whole-cell patch-clamp technique. The concentration-response curves for the selective agonist α,β-meATP did not differ from each other under the two transfection ratios. However, co-expression of an inactive P2X2 mutant and the wild type P2X3 subunit and vice versa resulted in characteristic distortions of the α,β-meATP concentration-response relationships, depending on which subunit was expressed in excess, suggesting that HEK293 cells express mixtures of (P2X2)1/(P2X3)2 and (P2X2)2/(P2X3)1 receptors. Whereas the allosteric modulators H+ and Zn2+ failed to discriminate between the two possible heterotrimeric receptor variants, the α,β-meATP-induced responses were blocked more potently by the competitive antagonist A317491, when the P2X2 subunit was expressed in deficit of the P2X3 subunit. Furthermore, blue-native PAGE analysis of P2X2 and P2X3 subunits co-expressed in Xenopus laevis oocytes and HEK293 cells revealed that plasma membrane-bound P2X2/3 receptors appeared in two clearly distinct heterotrimeric complexes: a (P2X2-GFP)2/(P2X3)1 complex and a (P2X2-GFP)1/(P2X3)2 complex. These data strongly indicate that the stoichiometry of the heteromeric P2X2/3 receptor is not fixed, but determined in a permutational manner by the relative availability of P2X2 and P2X3 subunits.

  14. Design and Verification of MIMO 2x2 Reference Antennas

    DEFF Research Database (Denmark)

    Szini, Istvan Janos; Pedersen, Gert Frølund; Estrada, J.;


    The development and initial discussion of a reference MIMO 2×2 antenna concept has been presented in [1]. The reference antenna concept has been created to eliminate the uncertainties linked to the unknown antenna performance of the few LTE MIMO 2×2 reference devices or golden standards currently...

  15. The second transmembrane domain of P2X7 contributes to dilated pore formation.

    Directory of Open Access Journals (Sweden)

    Chengqun Sun

    Full Text Available Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2 with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors.

  16. Endothelial P2X7 receptors’ expression is reduced by schistosomiasis


    Oliveira, Suellen D’Arc dos Santos; Coutinho-Silva, Robson; Silva, Claudia Lucia Martins


    Endothelial cells control vascular tone, permeability and leukocyte transmigration and are modulated by pro-inflammatory mediators. Schistosomiasis is an intravascular disease associated with inflammation, therefore altering endothelial cells’ phenotype. Purinergic P2X7 receptors (P2X7R) play an important role in inflammation; however, the impact of the disease upon endothelial P2X7R function or expression has not been explored. Using ethidium bromide uptake to investigate P2X7R function, we ...

  17. The second transmembrane domain of P2X7 contributes to dilated pore formation. (United States)

    Sun, Chengqun; Heid, Michelle E; Keyel, Peter A; Salter, Russell D


    Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors.

  18. Effects of antidepressants on P2X7 receptors. (United States)

    Wang, Wei; Xiang, Zheng-Hua; Jiang, Chun-Lei; Liu, Wei-Zhi; Shang, Zhi-Lei


    Antidepressants including paroxetine, fluoxetine and desipramine are commonly used for treating depression. P2×7 receptors are member of the P2X family. Recent studies indicate that these receptors may constitute a novel potential target for the treatment of depression. In the present study, we examined the action of these antidepressants on cloned rat P2×7 receptors that were stably expressed in human embryonic kidney (HEK) 293 cells by using the whole-cell patch-clamp technique, and found that paroxetine at a dose of 10µM could significantly reduce the inward currents evoked by the P2×7 receptors agonist BzATP by pre-incubation for 6-12 but not by acute application (10µM) or pre-incubation for 2-6h at a dose of 1µM, 3µM or 10µM paroxetine. Neither fluoxetine nor desipramine had significant effects on currents evoked by BzATP either applied acutely or by pre-incubation at various concentrations. These results suggest that the sensitivity of rat P2×7 receptors to antidepressants is different, which may represent an unknown mechanism by which these drugs exert their therapeutic effects and side effects.

  19. Comparison of ANOVA, McSweeney, Bradley, Harwell-Serlin, and Blair-Sawilowsky Tests in the Balanced 2x2x2 Layout. (United States)

    Kelley, D. Lynn; And Others

    The Type I error and power properties of the 2x2x2 analysis of variance (ANOVA) and tests developed by McSweeney (1967), Bradley (1979), Harwell-Serlin (1989; Harwell, 1991), and Blair-Sawilowsky (1990) were compared using Monte Carlo methods. The ANOVA was superior under the Gaussian and uniform distributions. The Blair-Sawilowsky test was…

  20. P2X3, but not P2X1, receptors mediate ATP-activated current in neurons innervating tooth-pulp. (United States)

    Liu, Yu-wei; Chen, Xiao-qing; Tian, Xiang; Chen, Lin; Wu, Yu-xiang; Huang, Dan; Yi, Hui-ling; Yi, Chu-li; Li, Chao-ying


    We developed a method that allows us to label nociceptive neurons innervating tooth-pulp in rat trigeminal ganglion neurons using a retrograde fluorescence-tracing method, to record ATP-activated current in freshly isolated fluorescence-labeled neurons and to conduct single cell immunohistochemical staining for P2X1 and P2X3 subunits in the same neuron. Three types of ATP-activated current in these neurons (F, I and S) were recorded. The cells exhibiting the type F current mainly showed positive staining for P2X3, but negative staining for P2X1. The results provide direct and convincing evidence at the level of single native nociceptive neurons for correlation of the characteristics of ATP-activated currents with their composition of P2X1 and P2X3 subunits and cell size. The results also suggest that the P2X3, but not P2X1, is the main subunit that mediates the fast ATP-activated current in nociceptive neurons.

  1. X1X1X2X2/X1X2Y sex chromosome systems in the Neotropical Gymnotiformes electric fish of the genus Brachyhypopomus

    Directory of Open Access Journals (Sweden)

    Adauto Lima Cardoso


    Full Text Available Several types of sex chromosome systems have been recorded among Gymnotiformes, including male and female heterogamety, simple and multiple sex chromosomes, and different mechanisms of origin and evolution. The X1X1X2X2/X1X2Y systems identified in three species of this order are considered homoplasic for the group. In the genus Brachyhypopomus, only B. gauderio presented this type of system. Herein we describe the karyotypes of Brachyhypopomus pinnicaudatus and B. n. sp. FLAV, which have an X1X1X2X2/X1X2Y sex chromosome system that evolved via fusion between an autosome and the Y chromosome. The morphology of the chromosomes and the meiotic pairing suggest that the sex chromosomes of B. gauderio and B. pinnicaudatus have a common origin, whereas in B . n. sp. FLAV the sex chromosome system evolved independently. However, we cannot discard the possibility of common origin followed by distinct processes of differentiation. The identification of two new karyotypes with an X1X1X2X2/X1X2Y sex chromosome system in Gymnotiformes makes it the most common among the karyotyped species of the group. Comparisons of these karyotypes and the evolutionary history of the taxa indicate independent origins for their sex chromosomes systems. The recurrent emergence of the X1X1X2X2/X1X2Y system may represent sex chromosomes turnover events in Gymnotiformes.

  2. Ionotropic P2X ATP Receptor Channels Mediate Purinergic Signaling in Mouse Odontoblasts (United States)

    Shiozaki, Yuta; Sato, Masaki; Kimura, Maki; Sato, Toru; Tazaki, Masakazu; Shibukawa, Yoshiyuki


    ATP modulates various functions in the dental pulp cells, such as intercellular communication and neurotransmission between odontoblasts and neurons, proliferation of dental pulp cells, and odontoblast differentiation. However, functional expression patterns and their biophysical properties of ionotropic ATP (P2X) receptors (P2X1–P2X7) in odontoblasts were still unclear. We examined these properties of P2X receptors in mouse odontoblasts by patch-clamp recordings. K+-ATP, nonselective P2X receptor agonist, induced inward currents in odontoblasts in a concentration-dependent manner. K+-ATP-induced currents were inhibited by P2X4 and P2X7 selective inhibitors (5-BDBD and KN62, respectively), while P2X1 and P2X3 inhibitors had no effects. P2X7 selective agonist (BzATP) induced inward currents dose-dependently. We could not observe P2X1, 2/3, 3 selective agonist (αβ-MeATP) induced currents. Amplitudes of K+-ATP-induced current were increased in solution without extracellular Ca2+, but decreased in Na+-free extracellular solution. In the absence of both of extracellular Na+ and Ca2+, K+-ATP-induced currents were completely abolished. K+-ATP-induced Na+ currents were inhibited by P2X7 inhibitor, while the Ca2+ currents were sensitive to P2X4 inhibitor. These results indicated that odontoblasts functionally expressed P2X4 and P2X7 receptors, which might play an important role in detecting extracellular ATP following local dental pulp injury. PMID:28163685

  3. P2X7受体与神经系统疾病%P2X7 receptor and neurological disorders

    Institute of Scientific and Technical Information of China (English)

    曾雯; 童煜; 毛萌


    As a subtype of P2X receptors, the ATP-gated ion channels, P2X7 receptor has important and unique physiological functions. P2X7 receptor mediates the influx of Ca2+ and Na+ as well as the release of proinflammatory cytokines. P2X7 receptor may be involved in the pathophysiology of neurological disorders, such as neurodegeneration, chronic inflammation, pain and depression, through their abilities to regulate the release of neurotransmitters, the activation of glia cells, inflammation reaction and the neuronal cell death. This review is focused on the role of P2X7 receptor in neurological disorders.%P2X受体是配体门控离子通道型受体,其亚型P2X7受体具有独特且重要的生理功能.P2X7受体(purinergic recepter p2x,ligand-gated ion channel,7)的活化可引起钠离子和钙离子内流、促炎细胞因子释放、胶质细胞活化、炎症反应以及参与调控神经递质释放、神经细胞存活等.P2X7受体与多种神经系统病变密切相关,如神经退行性变,慢性炎症,疼痛,抑郁症等.本文就P2X7受体与神经系统疾病做一综述.

  4. CAY10593 inhibits the human P2X7 receptor independently of phospholipase D1 stimulation


    Pupovac, A.; Stokes, L; Sluyter, R.


    The P2X7 receptor is a trimeric ATP-gated cation channel important in health and disease. We have observed that the specific phospholipase D (PLD)1 antagonist, CAY10593 impairs P2X7-induced shedding of the ‘low affinity’ IgE receptor, CD23. The current study investigated the mode of action of this compound on P2X7 activation. Measurements of ATP-induced ethidium+ uptake revealed that CAY10593 impaired P2X7-induced pore formation in human RPMI 8226 B cells, P2X7-transfected HEK-293 cells and p...

  5. The role of P2X7 receptors in a rodent PCP-induced schizophrenia model


    Bence Koványi; Cecilia Csölle; Stefano Calovi; Adrienn Hanuska; Erzsébet Kató; László Köles; Anindya Bhattacharya; József Haller; Beáta Sperlágh


    P2X7 receptors (P2X7Rs) are ligand-gated ion channels sensitive to extracellular ATP. Here we examined for the first time the role of P2X7R in an animal model of schizophrenia. Using the PCP induced schizophrenia model we show that both genetic deletion and pharmacological inhibition of P2X7Rs alleviate schizophrenia-like behavioral alterations. In P2rx7+/+ mice, PCP induced hyperlocomotion, stereotype behavior, ataxia and social withdrawal. In P2X7 receptor deficient mice (P2rx7−/−), the soc...

  6. Involvement of the P2X7-NLRP3 axis in leukemic cell proliferation and death


    Erica Salaro; Alessia Rambaldi; Simonetta Falzoni; Francesca Saveria Amoroso; Alessia Franceschini; Alba Clara Sarti; Massimo Bonora; Francesco Cavazzini; Gian Matteo Rigolin; Maria Ciccone; Valentina Audrito; Silvia Deaglio; Pablo Pelegrin; Paolo Pinton; Antonio Cuneo


    Lymphocyte growth and differentiation are modulated by extracellular nucleotides and P2 receptors. We previously showed that the P2X7 receptor (P2X7R or P2RX7) is overexpressed in circulating lymphocytes from chronic lymphocytic leukemia (CLL) patients. In the present study we investigated the P2X7R/NLRP3 inflammasome axis in lymphocytes from a cohort of 23 CLL patients. P2X7R, ASC and NLRP3 were investigated by Western blot, PCR and transfection techniques. P2X7R was overexpressed and correl...

  7. Macrophage activation and polarization modify P2X7 receptor secretome influencing the inflammatory process


    Carlos de Torre-Minguela; Maria Barberà-Cremades; Gómez, Ana I.; Fátima Martín-Sánchez; Pablo Pelegrín


    The activation of P2X7 receptor (P2X7R) on M1 polarized macrophages induces the assembly of the NLRP3 inflammasome leading to the release of pro-inflammatory cytokines and the establishment of the inflammatory response. However, P2X7R signaling to the NLRP3 inflammasome is uncoupled on M2 macrophages without changes on receptor activation. In this study, we analyzed P2X7R secretome in wild-type and P2X7R-deficient macrophages polarized either to M1 or M2 and proved that proteins released afte...

  8. Genetic Background Strongly Influences the Bone Phenotype of P2X7 Receptor Knockout Mice

    DEFF Research Database (Denmark)

    Syberg, Susanne; Petersen, Solveig; Beck Jensen, Jens-Erik;


    The purinergic P2X7 receptor is expressed by bone cells and has been shown to be important in both bone formation and bone resorption. In this study we investigated the importance of the genetic background of the mouse strains on which the P2X7 knock-out models were based by comparing bone status...... littermates. In conclusion, we have shown that the genetic background of P2X7(-/-) mice strongly influences the bone phenotype of the P2X7(-/-) mice and that P2X7 has a more significant regulatory role in bone remodeling than found in previous studies....

  9. Na+ Modulates Anion Permeation and Blockade of P2X7 Receptors from Mouse Parotid Glands


    Reyes, Juan Pablo; Pérez-Cornejo, Patricia; Hernández-Carballo, Carmen Y.; Srivastava, Alaka; Romanenko, Victor G.; Gonzalez, Mireya; Melvin, James E.; Arreola, Jorge


    We previously reported that mouse parotid acinar cells display an anion conductance (IATPCl) when stimulated by external ATP in Na+-free extracellular solutions. It has been suggested that the P2X7 receptor channel (P2X7R) might underlie IATPCl. In this work we show that IATPCl can be activated by ATP, ADP, AMP-PNP, ATPγS and CTP. This is consistent with the nucleotide sensitivity of P2X7R. Accordingly, acinar cells isolated from P2X7R−/− mice lacked IATPCl. Experiments with P2X7R heterologou...

  10. The role of P2X7 receptors in tissue fibrosis: a brief review. (United States)

    Gentile, Daniela; Natale, Mariarita; Lazzerini, Pietro Enea; Capecchi, Pier Leopoldo; Laghi-Pasini, Franco


    Many previous studies have demonstrated that P2X(7) receptors (P2X(7)Rs) have a pleiotropic function in different pathological conditions and could represent a novel target for the treatment of a range of diseases. In particular, recent studies have explored the role of P2X(7)R in fibrosis, the pathological outcome of most chronic inflammatory diseases. The aim of this review is to discuss the biological features of P2X(7)R and summarize the current knowledge about the putative role of the P2X(7)R in triggering fibrosis in a wide spectrum of organs such as the lung, kidney, liver, pancreas, and heart.

  11. P2 X7 receptor and renal diseases%P2 X7受体和肾脏疾病

    Institute of Scientific and Technical Information of China (English)

    刘辉; 纪旭


    P2 X7 receptor is a member of ATP-gated non-selective cation channels;and is one subtype family of the P2X purinergic receptor.Signaling pathways of P2X7 receptor couple with several key inflammatory molecules including IL-1β;IL-6 and COX-2;which suggests that P2 X7 receptor plays a key role in the development of dis-eases via increased inflammation;indicating its potential as a novel therapeutic target.Recent studies show that P2 X7 receptor has a relationship with renal diseases.This article reviews the effect of P2 X7 receptor on renal diseases and its mechanism.P2 X7 receptor may be a new drug target;and its selectivity antagonist may be a new therapeutic agent for the treatment of renal diseases.%P2X7受体是三磷酸腺苷(ATP)门控阳离子通道受体,是嘌呤受体P2X家族受体亚型之一。 P2X7受体信号通路与IL-1β、IL-6、COX-2等多种炎症因子的生成和释放相关,在多种疾病的发病过程中起到了至关重要的作用。目前以此受体为治疗靶点的P2 X7受体拮抗剂已进入临床试验阶段,表现出良好的安全性和疗效。最新研究表明P2 X7受体与多种肾脏疾病有关,P2X7受体拮抗剂具有潜在的肾脏疾病治疗作用。本文综述P2X7受体在肾脏疾病中的作用及其可能的作用机制,以期为肾脏疾病治疗的新靶点和新策略提供理论依据。

  12. Sensitization by extracellular Ca(2+) of rat P2X(5) receptor and its pharmacological properties compared with rat P2X(1). (United States)

    Wildman, Scott S; Brown, Sean G; Rahman, Mary; Noel, Carole A; Churchill, Linda; Burnstock, Geoffrey; Unwin, Robert J; King, Brian F


    The recombinant rat P2X(5) (rP2X(5)) receptor, a poorly understood ATP-gated ion channel, was studied under voltage-clamp conditions and compared with the better understood homomeric rP2X(1) receptor with which it may coexist in vivo. Expressed in defolliculated Xenopus laevis oocytes, rP2X(5) responded to ATP with slowly desensitizing inward currents that, for successive responses, ran down in the presence of extracellular Ca(2+) (1.8 mM). Replacement of Ca(2+) with either Ba(2+) or Mg(2+) prevented rundown, although agonist responses were very small, whereas reintroduction of Ca(2+) for short periods of time ( 2',3'-O-(2,4,6-trinitrophenyl)ATP (TNP-ATP) > suramin > reactive blue 2 (RB-2) > diinosine pentaphosphate (Ip(5)I). In contrast, the potency order at rP2X(1) was TNP-ATP = Ip(5)I > PPADS > suramin = RB-2. Thus, the Ca(2+)-sensitized homomeric rP2X(5) receptor is similar in agonist profile to homomeric rP2X(1)-although it can be distinguished from the latter by GTP agonism, antagonist profile, and the modulatory effects of H(+) and Zn(2+) ions.

  13. Atmospheric chemistry of perfluorinated aldehyde hydrates (n-C(x)F(2x+1)CH(OH)2, x = 1, 3, 4)

    DEFF Research Database (Denmark)

    Andersen, Mads Peter Sulbæk; Toft, A.; Nielsen, O.J.


    Smog chamber/Fourier transform infrared (FTIR) techniques were used to measure k(Cl+C(x)F(2x+1)CH(OH)(2)) (x = 1, 3, 4) = (5.84 +/- 0.92) x 10(-13) and k(OH+C(x)F(2x+1)CH(OH)(2)) = (1.22 +/- 0.26) x 10(-13) cm(3) molecule(-1) s(-1) in 700 Torr of N(2) or air at 296 +/- 2 K. The Cl initiated...

  14. Post-translational regulation of P2X receptor channels: modulation by phospholipids

    Directory of Open Access Journals (Sweden)

    Louis-Philippe eBernier


    Full Text Available P2X receptor channels mediate fast excitatory signaling by ATP and play major roles in sensory transduction, neuro-immune communication and inflammatory response. P2X receptors constitute a gene family of calcium-permeable ATP-gated cation channels therefore the regulation of P2X signaling is critical for both membrane potential and intracellular calcium homeostasis. Phosphoinositides (PIPn are anionic signaling phospholipids that act as functional regulators of many types of ion channels. Direct PIPn binding was demonstrated for several ligand- or voltage-gated ion channels, however no generic motif emerged to accurately predict lipid-protein binding sites. This review presents what is currently known about the modulation of the different P2X subtypes by phospholipids and about critical determinants underlying their sensitivity to PIPn levels in the plasma membrane.All functional mammalian P2X subtypes tested, with the notable exception of P2X5, have been shown to be positively modulated by PIPn, i.e. homomeric P2X1, P2X2, P2X3, P2X4, and P2X7, as well as heteromeric P2X1/5 and P2X2/3 receptors. Based on various results reported on the aforementioned subtypes including mutagenesis of the prototypical PIPn-sensitive P2X4 and PIPn-insensitive P2X5 receptor subtypes, an increasing amount of functional, biochemical and structural evidence converges on the modulatory role of a short polybasic domain located in the proximal C-terminus of P2X subunits. This linear motif, semi-conserved in the P2X family, seems necessary and sufficient for encoding direct modulation of ATP-gated channels by PIPn. Furthermore, the physiological impact of the regulation of ionotropic purinergic responses by phospholipids on pain pathways was recently revealed in the context of native crosstalks between phospholipase C-linked metabotropic receptors and P2X receptor channels in DRG sensory neurons and microglia.

  15. Concept of an enhanced V2X pedestrian collision avoidance system with a cost function-based pedestrian model. (United States)

    Kotte, Jens; Schmeichel, Carsten; Zlocki, Adrian; Gathmann, Hauke; Eckstein, Lutz


    Objective State-of-the-art collision avoidance and collision mitigation systems predict the behavior of pedestrians based on trivial models that assume a constant acceleration or velocity. New sources of sensor information, for example smart devices (smartphones, tablets, smartwatches, …), can support enhanced pedestrian behavior models. The objective of this paper is the development and implementation of a V2X pedestrian collision avoidance system that uses new information sources. Methods A literature review of existing state-of-the-art pedestrian collision avoidance systems, pedestrian behavior models in Advanced Driver Assistance Systems (ADAS), and traffic simulations is conducted together with an analysis of existing studies on typical pedestrian patterns in traffic. Based on this analysis, possible parameters for predicting pedestrian behavior were investigated. The results led to new requirements from which a concept was developed and implemented. Results The analysis of typical pedestrian behavior patterns in traffic situations showed the complexity of predicting pedestrian behavior. Requirements for an improved behavior prediction were derived. A concept for a V2X collision avoidance system, based on a cost function that predicts pedestrian near future presence, and its implementation, is presented. The concept presented considers several challenges such as information privacy, inaccuracies of the localization, and inaccuracies of the prediction. Conclusion A concept for an enhanced V2X pedestrian collision avoidance system was developed and introduced. The concept uses new information sources such as smart devices to improve the prediction of the pedestrian's presence in the near future and considers challenges that come along with the usage of these information sources.

  16. Selective cation exchange in the core region of Cu2-xSe/Cu2-xS core/shell nanocrystals. (United States)

    Miszta, Karol; Gariano, Graziella; Brescia, Rosaria; Marras, Sergio; De Donato, Francesco; Ghosh, Sandeep; De Trizio, Luca; Manna, Liberato


    We studied cation exchange (CE) in core/shell Cu2-xSe/Cu2-xS nanorods with two cations, Ag(+) and Hg(2+), which are known to induce rapid exchange within metal chalcogenide nanocrystals (NCs) at room temperature. At the initial stage of the reaction, the guest ions diffused through the Cu2-xS shell and reached the Cu2-xSe core, replacing first Cu(+) ions within the latter region. These experiments prove that CE in copper chalcogenide NCs is facilitated by the high diffusivity of guest cations in the lattice, such that they can probe the whole host structure and identify the preferred regions where to initiate the exchange. For both guest ions, CE is thermodynamically driven as it aims for the formation of the chalcogen phase characterized by the lower solubility under the specific reaction conditions.

  17. Role of purinergic P2X4 receptors in regulating striatal dopamine homeostasis and dependent behaviors. (United States)

    Khoja, Sheraz; Shah, Vivek; Garcia, Damaris; Asatryan, Liana; Jakowec, Michael W; Davies, Daryl L


    Purinergic P2X4 receptors (P2X4Rs) belong to the P2X superfamily of ion channels regulated by ATP. We recently demonstrated that P2X4R knockout (KO) mice exhibited deficits in sensorimotor gating, social interaction, and ethanol drinking behavior. Dopamine (DA) dysfunction may underlie these behavioral changes, but there is no direct evidence for P2X4Rs' role in DA neurotransmission. To test this hypothesis, we measured markers of DA function and dependent behaviors in P2X4R KO mice. P2X4R KO mice exhibited altered density of pre-synaptic markers including tyrosine hydroxylase, dopamine transporter; post-synaptic markers including dopamine receptors and phosphorylation of downstream targets including dopamine and cyclic-AMP regulated phosphoprotein of 32 kDa and cyclic-AMP-response element binding protein in different parts of the striatum. Ivermectin, an allosteric modulator of P2X4Rs, significantly affected dopamine and cyclic AMP regulated phosphoprotein of 32 kDa and extracellular regulated kinase1/2 phosphorylation in the striatum. Sensorimotor gating deficits in P2X4R KO mice were rescued by DA antagonists. Using the 6-hydroxydopamine model of DA depletion, P2X4R KO mice exhibited an attenuated levodopa (L-DOPA)-induced motor behavior, whereas ivermectin enhanced this behavior. Collectively, these findings identified an important role for P2X4Rs in maintaining DA homeostasis and illustrate how this association is important for CNS functions including motor control and sensorimotor gating. We propose that P2X4 receptors (P2X4Rs) regulate dopamine (DA) homeostasis and associated behaviors. Pre-synaptic and post-synaptic DA markers were significantly altered in the dorsal and ventral striatum of P2X4R KO mice, implicating altered DA neurotransmission. Sensorimotor gating deficits in P2X4R KO mice were rescued by DA antagonists. Ivermectin (IVM), a positive modulator of P2X4Rs, enhanced levodopa (L-DOPA)-induced motor behavior. These studies highlight potential

  18. P2X7 receptor and diabetic retinopathy%P2X7受体与糖尿病视网膜病变

    Institute of Scientific and Technical Information of China (English)

    刘琦; 周赛君; 孟振兴; 于珮


    P2X7 receptor,an important apoptosis regulatory receptor,is a member of the purinergic receptor family and a regulator of the ligand gated ion channel activated by ATP.P2X7 plays an important role in meditating excitatory neurotransmitter in the central and peripheral nervous system.The expression of P2X7 receptor has been demonstrated in most types of cells in the retina.Studies have shown that excessive activation of P2X7 receptor involves in the occurrence and development of diabetic retinopathy.In one hand,purinergic vasotoxicity caused by excessive activation of P2X7 receptor can lead to the reduction of retinal blood flow and vascular dysfunction.On the other hand,P2X7 receptor activation may result in the production of a large number of inflammatory cytokines,causing local inflammatory cell infiltration and the formation of vascular inflammatory microenvironment,which constitute the pathophysiological basis for the development of diabetic retinopathy.%P2X7受体是一种重要的凋亡调控受体,是嘌呤受体家族中的一员,也是ATP活化的配体门控离子通道的调节者.它在中枢和外周神经系统中对介导兴奋性神经递质起重要作用.P2X7受体广泛表达于视网膜多种细胞表面.研究显示,P2X7受体在糖尿病视网膜病变中过度激活,参与糖尿病视网膜病变的发生及发展.一方面,P2X7受体过度激活所致的嘌呤血管毒性,可导致视网膜血流减少和血管功能的紊乱;另一方面,P2X7受体活化可导致大量炎性因子的产生,引起局部炎性细胞浸润,形成血管炎性微环境,构成糖尿病视网膜病变发生、发展的病理生理基础.

  19. Comparison of P2X receptors in rat mesenteric, basilar and septal (coronary) arteries. (United States)

    Lewis, C J; Evans, R J


    alpha beta meATP-evoked concentration-dependent, PPADS-sensitive, desensitising, P2X receptor-mediated, constrictions of mesenteric, basilar and septal artery rings with EC(50) values of 1, 1 and 30 microM, respectively. In patch clamp studies on acutely dissociated artery smooth cells alpha beta meATP-evoked transient inward currents (tau approximately 100 ms) with mean current densities of approximately 340, 175 and 120 pA/pF, respectively. P2X(1) receptor immunoreactivity was expressed in mesenteric and basilar arteries and this receptor subunit appears to dominate the P2X receptor phenotype in these vessels. In contrast P2X(1) receptor immunoreactivity was not detected in septal arteries and the alpha beta meATP sensitivity of constriction was not consistent with the involvement of P2X(1) receptors. These results suggest that not all arteries share a common P2X receptor phenotype.

  20. Stable monolayer honeycomb-like structures of RuX2 (X =S,Se) (United States)

    Ersan, Fatih; Cahangirov, Seymur; Gökoǧlu, Gökhan; Rubio, Angel; Aktürk, Ethem


    Recent studies show that several metal oxides and dichalcogenides (M X2) , which exist in nature, can be stable in two-dimensional (2D) form and each year several new M X2 structures are explored. The unstable structures in H (hexagonal) or T (octahedral) forms can be stabilized through Peierls distortion. In this paper, we propose new 2D forms of RuS2 and RuSe2 materials. We investigate in detail the stability, electronic, magnetic, optical, and thermodynamic properties of 2D Ru X2 (X =S,Se) structures from first principles. While their H and T structures are unstable, the distorted T structures (T'-Ru X2) are stable and have a nonmagnetic semiconducting ground state. The molecular dynamic simulations also confirm that T'-Ru X2 systems are stable even at 500 K without any structural deformation. T'-RuS2 and T'-RuSe2 have indirect band gaps with 0.745 eV (1.694 eV with HSE) and 0.798 eV (1.675 eV with HSE) gap values, respectively. We also examine their bilayer and trilayer forms and find direct and smaller band gaps. We find that AA stacking is more favorable than the AB configuration. The new 2D materials obtained can be good candidates with striking properties for applications in semiconductor electronic, optoelectronic devices, and sensor technology.

  1. Tsdc and Neutron-Scattering Measurements on Ba1-Xlaxf2+X and Ba1-Xuxf2+2x Solid-Solutions

    DEFF Research Database (Denmark)

    Ouwerkerk, M; Veldkamp, F. F.; Andersen, Niels Hessel


    the TSDC spectra showed four reorientation peaks to be present in Ba1−xLaxF2+x, and six in Ba1−xUxF2+2x, along with the relaxation of the macroscopic space charge. The position of a space charge peak shifted to lower temperatures with increasing solute content. The dipolar realaxations were concentration......A study was made of the dynamical behaviour of bound interstitial fluoride ions in disordered Ba1−xLaxF2+x and Ba1−xUxF2+2x solid solutions with Thermally Stimulated Depolarisation Current measurements and neutron scattering measurements, and a combination of both techniques. From 10 K to 400 K...... invariant. In Ba1−xLaxF2+x neutral associates, L-shaped- and (222)- clusters occur. The present study reveals (212)-clusters to be present in Ba1−xUxF2+2x. The relations between ion dynamics and defect structures are discussed....

  2. Quantum spin liquid and electric quadrupolar states of single crystal Tb2+xTi2-xO7+y (United States)

    Wakita, M.; Taniguchi, T.; Edamoto, H.; Takatsu, H.; Kadowaki, H.


    The ground states of the frustrated pyrochlore oxide Tb2+xTi2-xO7+y, sensitively depending on the small off-stoichiometry parameter x, have been studied by specific heat measurements using well characterized samples. Single crystal Tb2+xTi2-xO7+y boules grown by the standard floating zone technique are shown to exhibit concentration (x) gradient. This off-stoichiometry parameter is determined by precisely measuring the lattice constant of small samples cut from a crystal boule. Specific heat shows that the phase boundary of the electric quadrupolar state has a dome structure in the x-T phase diagram with the highest Tc ≃ 0.5 K at about x = 0.01. This phase diagram suggests that the putative U(1) quantum spin-liquid state of Tb2+xTi2-xO7+y exists in the range x xc ≃ -0.0025, which is separated from the quadrupolar state via a first-order phase-transition line x = xc.

  3. P2x7受体在癫痫中的作用%Protective role of P2x7 receptor in epilepsy

    Institute of Scientific and Technical Information of China (English)



    P2x7 receptor is structurally and functionally unique and has important effect in immune response and inflammatory response. In the development of epilepsy, P2x7 receptor is rapidly up-regulated and engages in diverse signal cascades, including initiation and rapid release ofTNF-α and IL-1β. This article summarizes the effect of P2x7 receptor through TNF-a and IL-1β induction on the occurrence and development of epilepsy.%P2x7受体结构和功能独特,在炎性反应与免疫反应中对机体具有重要作用.在癫痫的发生发展过程中,P2x7受体表达迅速上调并介导多种信号级联反应(包括TNF-α和IL-1β的启动和快速释放).本文将就P2x7受体通过调控TNF-α、IL-1β影响癫痫发生发展的机制进行综述.

  4. Immunolocalization of the P2X4 receptor on neurons and glia in the mammalian retina. (United States)

    Ho, T; Vessey, K A; Fletcher, E L


    Extracellular adenosine 5'-triphosphate (eATP) acts as a neurotransmitter within the retina and brain, activating a range of ionotropic P2X and metabotropic P2Y receptors. In this study, the specific localization of the P2X4 receptor (P2X4-R) subunit was evaluated in the retina using fluorescence immunohistochemistry and pre-embedding immuno-electron microscopy. Punctate P2X4-R labeling was largely localized to the inner and outer plexiform layers of mouse, rat and cat retinae. In the mouse outer retina, double-labeling of P2X4-R with the horizontal cell marker, calbindin, revealed P2X4-R immunoreactivity (P2X4-R-IR) on horizontal cell somata and processes. In the inner retina, P2X4-R expression was found closely associated with rod and cone bipolar cell terminals, and the punctate labeling was observed on calretinin-positive amacrine cells. Using immuno-electron microscopy, P2X4-Rs were observed on processes post-synaptic to photoreceptor and bipolar cell terminals, likely representing horizontal, amacrine and ganglion cells, respectively. Furthermore, P2X4-R expression was also observed on Müller cells, astrocytes and microglia. These data suggest a role for P2X4-Rs in the lateral inhibitory pathways of the retina, modulating neuronal function of photoreceptors and bipolar cells. The expression on macro- and microglial cells implicates a role for P2X4-Rs in glial signaling, tissue homeostasis and immunosurveillance within the mammalian retina.

  5. Sociocommunicative and Sensorimotor Impairments in Male P2X4-Deficient Mice (United States)

    Wyatt, Letisha R; Godar, Sean C; Khoja, Sheraz; Jakowec, Michael W; Alkana, Ronald L; Bortolato, Marco; Davies, Daryl L


    Purinergic P2X receptors are a family of ligand-gated ion channels gated by extracellular adenosine 5′-triphosphate (ATP). Of the seven P2X subtypes, P2X4 receptors (P2X4Rs) are richly expressed in the brain, yet their role in behavioral organization remains poorly understood. In this study, we examined the behavioral responses of P2X4R heterozygous (HZ) and knockout (KO) mice in a variety of testing paradigms designed to assess complementary aspects of sensory functions, emotional reactivity, and cognitive organization. P2X4R deficiency did not induce significant alterations of locomotor activity and anxiety-related indices in the novel open field and elevated plus-maze tests. Conversely, P2X4R KO mice displayed marked deficits in acoustic startle reflex amplitude, as well as significant sensorimotor gating impairments, as assessed by the prepulse inhibition of the startle. In addition, P2X4R KO mice displayed enhanced tactile sensitivity, as signified by a lower latency in the sticky-tape removal test. Moreover, both P2X4R HZ and KO mice showed significant reductions in social interaction and maternal separation-induced ultrasonic vocalizations in pups. Notably, brain regions of P2X4R KO mice exhibited significant brain-regional alterations in the subunit composition of glutamate ionotropic receptors. These results collectively document that P2X4-deficient mice exhibit a spectrum of phenotypic abnormalities partially akin to those observed in other murine models of autism-spectrum disorder. In conclusion, our findings highlight a putative role of P2X4Rs in the regulation of perceptual and sociocommunicative functions and point to these receptors as putative targets for disturbances associated with neurodevelopmental disorders. PMID:23604007

  6. Novel Protective Role of Endogenous Cardiac Myocyte P2X4 Receptors in Heart Failure (United States)

    Yang, Tiehong; Shen, Jian-bing; Yang, Ronghua; Redden, John; Dodge-Kafka, Kimberly; Grady, James; Jacobson, Kenneth A.; Liang, Bruce T.


    Background Heart failure (HF), despite continuing progress, remains a leading cause of mortality and morbidity. P2X4 receptors (P2X4R) have emerged as potentially important molecules in regulating cardiac function and as potential targets for HF therapy. Transgenic P2X4R overexpression can protect against HF, but this does not explain the role of native cardiac P2X4R. Our goal is to define the physiological role of endogenous cardiac myocyte P2X4R under basal conditions and during HF induced by myocardial infarction or pressure overload. Methods and Results Mice established with conditional cardiac-specific P2X4R knockout were subjected to left anterior descending coronary artery ligation–induced postinfarct or transverse aorta constriction–induced pressure overload HF. Knockout cardiac myocytes did not show P2X4R by immunoblotting or by any response to the P2X4R-specific allosteric enhancer ivermectin. Knockout hearts showed normal basal cardiac function but depressed contractile performance in postinfarct and pressure overload models of HF by in vivo echocardiography and ex vivo isolated working heart parameters. P2X4R coimmunoprecipitated and colocalized with nitric oxide synthase 3 (eNOS) in wild-type cardiac myocytes. Mice with cardiac-specific P2X4R overexpression had increased S-nitrosylation, cyclic GMP, NO formation, and were protected from postinfarct and pressure overload HF. Inhibitor of eNOS, L-N5-(1-iminoethyl)ornithine hydrochloride, blocked the salutary effect of cardiac P2X4R overexpression in postinfarct and pressure overload HF as did eNOS knockout. Conclusions This study establishes a new protective role for endogenous cardiac myocyte P2X4R in HF and is the first to demonstrate a physical interaction between the myocyte receptor and eNOS, a mediator of HF protection. PMID:24622244

  7. P2X7 receptor in epilepsy; role in pathophysiology and potential targeting for seizure control.


    Engel, Tobias; Jimenez-Pacheco, Alba; Miras-Portugal, Maria Teresa; Diaz-Hernandez, Miguel; Henshall, David C.


    The P2X7 receptor is an ATP-gated non-selective cation-permeable ionotropic receptor selectively expressed in neurons and glia in the brain. Activation of the P2X7 receptor has been found to modulate neuronal excitability in the hippocampus and it has also been linked to microglia activation and neuroinflammatory responses. Accordingly, interest developed on the P2X7 receptor in disorders of the nervous system, including epilepsy. Studies show that expression of the P2X7 receptor is elevated ...

  8. P2X7 on Mouse T Cells: One Channel, Many Functions


    Rissiek, Björn; Haag, Friedrich; Boyer, Olivier; Koch-Nolte, Friedrich; Adriouch, Sahil


    The P2X7 receptor is an adenosine triphosphate (ATP)-gated cation channel that is expressed by several cells of the immune system. P2X7 is best known for its proinflammatory role in promoting inflammasome formation and release of mature interleukin (IL)-1β by innate immune cells. Mounting evidence indicates that P2X7 is also an important regulatory receptor of murine and human T cell functions. Murine T cells express a sensitive splice variant of P2X7 that can be activated either by non-coval...

  9. Optical control of trimeric P2X receptors and acid-sensing ion channels. (United States)

    Browne, Liam E; Nunes, João P M; Sim, Joan A; Chudasama, Vijay; Bragg, Laricia; Caddick, Stephen; North, R Alan


    P2X receptors are trimeric membrane proteins that function as ion channels gated by extracellular ATP. We have engineered a P2X2 receptor that opens within milliseconds by irradiation at 440 nm, and rapidly closes at 360 nm. This requires bridging receptor subunits via covalent attachment of 4,4'-bis(maleimido)azobenzene to a cysteine residue (P329C) introduced into each second transmembrane domain. The cis-trans isomerization of the azobenzene pushes apart the outer ends of the transmembrane helices and opens the channel in a light-dependent manner. Light-activated channels exhibited similar unitary currents, rectification, calcium permeability, and dye uptake as P2X2 receptors activated by ATP. P2X3 receptors with an equivalent mutation (P320C) were also light sensitive after chemical modification. They showed typical rapid desensitization, and they could coassemble with native P2X2 subunits in pheochromocytoma cells to form light-activated heteromeric P2X2/3 receptors. A similar approach was used to open and close human acid-sensing ion channels (ASICs), which are also trimers but are unrelated in sequence to P2X receptors. The experiments indicate that the opening of the permeation pathway requires similar and substantial movements of the transmembrane helices in both P2X receptors and ASICs, and the method will allow precise optical control of P2X receptors or ASICs in intact tissues.

  10. Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor

    Directory of Open Access Journals (Sweden)

    Elias Leiva-Salcedo


    Full Text Available The purinergic P2X7 receptor (P2X7R plays an important role during the immune response, participating in several events such as cytokine release, apoptosis, and necrosis. The bacterial endotoxin lipopolysaccharide (LPS is one of the strongest stimuli of the immune response, and it has been shown that P2X7R activation can modulate LPS-induced responses. Moreover, a C-terminal binding site for LPS has been proposed. In order to evaluate if LPS can directly modulate the activity of the P2X7R, we tested several signaling pathways associated with P2X7R activation in HEK293 cells that do not express the TLR-4 receptor. We found that LPS alone was unable to induce any P2X7R-related activity, suggesting that the P2X7R is not directly activated by the endotoxin. On the other hand, preapplication of LPS inhibited ATP-induced currents, intracellular calcium increase, and ethidium bromide uptake and had no effect on ERK activation in HEK293 cells. In splenocytes-derived T-regulatory cells, in which ATP-induced apoptosis is driven by the P2X7R, LPS inhibited ATP-induced apoptosis. Altogether, these results demonstrate that LPS modulates the activity of the P2X7R and suggest that this effect could be of physiological relevance.

  11. Lipopolysaccharide Inhibits the Channel Activity of the P2X7 Receptor (United States)

    Leiva-Salcedo, Elias; Coddou, Claudio; Rodríguez, Felipe E.; Penna, Antonello; Lopez, Ximena; Neira, Tanya; Fernández, Ricardo; Imarai, Mónica; Rios, Miguel; Escobar, Jorge; Montoya, Margarita; Huidobro-Toro, J. Pablo; Escobar, Alejandro; Acuña-Castillo, Claudio


    The purinergic P2X7 receptor (P2X7R) plays an important role during the immune response, participating in several events such as cytokine release, apoptosis, and necrosis. The bacterial endotoxin lipopolysaccharide (LPS) is one of the strongest stimuli of the immune response, and it has been shown that P2X7R activation can modulate LPS-induced responses. Moreover, a C-terminal binding site for LPS has been proposed. In order to evaluate if LPS can directly modulate the activity of the P2X7R, we tested several signaling pathways associated with P2X7R activation in HEK293 cells that do not express the TLR-4 receptor. We found that LPS alone was unable to induce any P2X7R-related activity, suggesting that the P2X7R is not directly activated by the endotoxin. On the other hand, preapplication of LPS inhibited ATP-induced currents, intracellular calcium increase, and ethidium bromide uptake and had no effect on ERK activation in HEK293 cells. In splenocytes-derived T-regulatory cells, in which ATP-induced apoptosis is driven by the P2X7R, LPS inhibited ATP-induced apoptosis. Altogether, these results demonstrate that LPS modulates the activity of the P2X7R and suggest that this effect could be of physiological relevance. PMID:21941410

  12. Clemastine Potentiates the Human P2X7 Receptor by Sensitizing It to Lower ATP Concentrations*


    Nörenberg, Wolfgang; Hempel, Christoph; Urban, Nicole; Sobottka, Helga; Illes, Peter; Schaefer, Michael


    P2X7 receptors have emerged as potential drug targets for the treatment of medical conditions such as e.g. rheumatoid arthritis and neuropathic pain. To assess the impact of pharmaceuticals on P2X7, we screened a compound library comprising approved or clinically tested drugs and identified several compounds that augment the ATP-triggered P2X7 activity in a stably transfected HEK293 cell line. Of these, clemastine markedly sensitized Ca2+ entry through P2X7 to lower ATP concentrations. Extrac...

  13. Localization of P2X7 Receptor Immunoreactivity in the Dorsal Root Ganglia of Guinea Pig

    Institute of Scientific and Technical Information of China (English)

    BAI Xuegong; JIANG Ling; XIANG Zhenghua


    The P2X7 receptor mRNA and proteins in guinea-pig dorsal root ganglia (DRG) were studied by using RT-PCR and immunohistochemistry. The co-localization of P2X7 receptor with four cytochemical markers, the neurofilament protein NF200, S100, substance P and isolectin B4 (IB4) binding glyco-conjugates, were also examined. It was found that P2X7 receptor immunoreactivity (P2X7R-IR) was present mostly in large- and medium-sized DRG neurons (62 %±9 % and 36 %±6 % respectively in all P2X7R-IR neurons). All the P2X7R-IR neurons were also NF200 and S100 immunopositive. However, in a small number of NF200 or S100 immunopositive neurons no P2X7R-IR was detectable. All the IB4-positive or substance P-immunopositive neurons had no P2X7R-IR. These results demonstrate that P2X7 receptors are expressed in a large subpopulation of DRG neurons and they may play a role in the transduction of specific peripheral sensory signals.

  14. P2X7 receptors: role in bone cell formation and function. (United States)

    Agrawal, Ankita; Gartland, Alison


    The role of the P2X7 receptor (P2X7R) is being explored with intensive interest in the context of normal bone physiology, bone-related diseases and, to an extent, bone cancer. In this review, we cover the current understanding of P2X7R regulation of bone cell formation, function and survival. We will discuss how the P2X7R drives lineage commitment of undifferentiated bone cell progenitors, the vital role of P2X7R activation in bone mineralisation and its relatively unexplored role in osteocyte function. We also review how P2X7R activation is imperative for osteoclast formation and its role in bone resorption via orchestrating osteoclast apoptosis. Variations in the gene for the P2X7R (P2RX7) have implications for P2X7R-mediated processes and we review the relevance of these genetic variations in bone physiology. Finally, we highlight how targeting P2X7R may have therapeutic potential in bone disease and cancer.

  15. Accelerated tumor progression in mice lacking the ATP receptor P2X7. (United States)

    Adinolfi, Elena; Capece, Marina; Franceschini, Alessia; Falzoni, Simonetta; Giuliani, Anna L; Rotondo, Alessandra; Sarti, Alba C; Bonora, Massimo; Syberg, Susanne; Corigliano, Domenica; Pinton, Paolo; Jorgensen, Niklas R; Abelli, Luigi; Emionite, Laura; Raffaghello, Lizzia; Pistoia, Vito; Di Virgilio, Francesco


    The ATP receptor P2X7 (P2X7R or P2RX7) has a key role in inflammation and immunity, but its possible roles in cancer are not firmly established. In the present study, we investigated the effect of host genetic deletion of P2X7R in the mouse on the growth of B16 melanoma or CT26 colon carcinoma cells. Tumor size and metastatic dissemination were assessed by in vivo calliper and luciferase luminescence emission measurements along with postmortem examination. In P2X7R-deficient mice, tumor growth and metastatic spreading were accelerated strongly, compared with wild-type (wt) mice. Intratumoral IL-1β and VEGF release were drastically reduced, and inflammatory cell infiltration was abrogated nearly completely. Similarly, tumor growth was also greatly accelerated in wt chimeric mice implanted with P2X7R-deficient bone marrow cells, defining hematopoietic cells as a sufficient site of P2X7R action. Finally, dendritic cells from P2X7R-deficient mice were unresponsive to stimulation with tumor cells, and chemotaxis of P2X7R-less cells was impaired. Overall, our results showed that host P2X7R expression was critical to support an antitumor immune response, and to restrict tumor growth and metastatic diffusion.

  16. P2X4 receptors (P2X4Rs represent a novel target for the development of drugs to prevent and/or treat alcohol use disorders

    Directory of Open Access Journals (Sweden)

    Kelle M. Franklin


    Full Text Available Alcohol use disorders (AUDs have a staggering socioeconomic impact. Few therapeutic options are available, and they are largely inadequate. These shortcomings highlight the urgent need to develop effective medications to prevent and/or treat AUDs. A critical barrier is the lack of information regarding the molecular target(s by which ethanol (EtOH exerts its pharmacological activity. This review highlights findings implicating P2X4 receptors (P2X4Rs as a target for the development of therapeutics to treat AUDs and discusses the use of ivermectin (IVM as a potential clinical tool for treatment of AUDs. P2XRs are a family of ligand-gated ion channels activated by extracellular ATP. Of the P2XR subtypes, P2X4Rs are expressed the most abundantly in the CNS. Converging evidence suggests that P2X4Rs are involved in the development and progression of AUDs. First, in vitro studies report that pharmacologically relevant EtOH concentrations can negatively modulate ATP-activated currents. Second, P2X4Rs in the mesocorticolimbic dopamine system are thought to play a role in synaptic plasticity and are located ideally to modulate brain reward systems. Third, alcohol-preferring (P rats have lower functional expression of the p2rx4 gene than alcohol-non-preferring (NP rats suggesting an inverse relationship between alcohol intake and P2X4R expression. Similarly, whole brain p2rx4 expression has been shown to relate inversely to innate 24 hr alcohol preference across 28 strains of rats. Fourth, mice lacking the p2rx4 gene drink more EtOH than wildtype controls. Fifth, IVM, a positive modulator of P2X4Rs, antagonizes EtOH-mediated inhibition of P2X4Rs in vitro and reduces EtOH intake and preference in vivo. These findings suggest that P2X4Rs contribute to EtOH intake. The present review summarizes recent findings focusing on the P2X4R as a molecular target of EtOH action, its role in EtOH drinking behavior and modulation of its activity by IVM as a potential

  17. Comparison of the Giemsa C-banded karyotypes of the three subspecies of Psathyrostachys fragilis, subspp. villosus (2x), secaliformis (2x, 4x), and fragilis (2x) (Poaceae), with notes on chromosome pairing

    DEFF Research Database (Denmark)

    Linde-Laursen, I.; Baden, C.


    The karyotypes of diploid P. fragilis subsp. villosus (2n = 2x = 14) and tetraploid subsp. secaliformis (2n = 4x = 28) were studied by Giemsa C- and N-banding, and AgNO3 staining and compared with the karyotype of subsp. fragilis (2x). The complements of subsp. villosus and subsp. fragilis were...... in chromosome morphology and C-banding patterns identified homology of all chromosomes of subsp. villosus, but for 12 pairs only in subsp. secaliformis. Between plants, reliable identification of homology and homoeology (subsp. secaliformis) was possible only for the SAT-chromosomes and the shortest...

  18. Identification and characterization of a selective allosteric antagonist of human P2X4 receptor channels. (United States)

    Ase, Ariel R; Honson, Nicolette S; Zaghdane, Helmi; Pfeifer, Tom A; Séguéla, Philippe


    P2X4 is an ATP-gated nonselective cation channel highly permeable to calcium. There is increasing evidence that this homomeric purinoceptor, which is expressed in several neuronal and immune cell types, is involved in chronic pain and inflammation. The current paucity of unambiguous pharmacological tools available to interrogate or modulate P2X4 function led us to pursue the search for selective antagonists. In the high-throughput screen of a compound library, we identified the phenylurea BX430 (1-(2,6-dibromo-4-isopropyl-phenyl)-3-(3-pyridyl)urea, molecular weight = 413), with antagonist properties on human P2X4-mediated calcium uptake. Patch-clamp electrophysiology confirmed direct inhibition of P2X4 currents by extracellular BX430, with submicromolar potency (IC50 = 0.54 µM). BX430 is highly selective, having virtually no functional impact on all other P2X subtypes, namely, P2X1-P2X3, P2X5, and P2X7, at 10-100 times its IC50. Unexpected species differences were noticed, as BX430 is a potent antagonist of zebrafish P2X4 but has no effect on rat and mouse P2X4 orthologs. The concentration-response curve for ATP on human P2X4 in the presence of BX430 shows an insurmountable blockade, indicating a noncompetitive allosteric mechanism of action. Using a fluorescent dye uptake assay, we observed that BX430 also effectively suppresses ATP-evoked and ivermectin-potentiated membrane permeabilization induced by P2X4 pore dilation. Finally, in single-cell calcium imaging, we validated its selective inhibitory effects on native P2X4 channels at the surface of human THP-1 cells that were differentiated into macrophages. In summary, this ligand provides a novel molecular probe to assess the specific role of P2X4 in inflammatory and neuropathic conditions, where ATP signaling has been shown to be dysfunctional.

  19. The effect of anions on the human P2X7 receptor. (United States)

    Kubick, Christoph; Schmalzing, Günther; Markwardt, Fritz


    P2X7 receptors (P2X7Rs) are nonselective cation channels that are opened by the binding of extracellular ATP and are involved in the modulation of epithelial secretion, inflammation and nociception. Here, we investigated the effect of extracellular anions on channel gating and permeation of human P2X7Rs (hP2X7Rs) expressed in Xenopus laevis oocytes. Two-microelectrode voltage-clamp recordings showed that ATP-induced hP2X7R-mediated currents increased when extracellular chloride was substituted by the organic anions glutamate or aspartate and decreased when chloride was replaced by the inorganic anions nitrate, sulfate or iodide. ATP concentration-response comparisons revealed that substitution of chloride by glutamate decreased agonist efficacy, while substitution by iodide increased agonist efficacy at high ATP concentrations. Meanwhile, the ATP potency remained unchanged. Activation of the hP2X7R at low ATP concentrations via the high-affinity ATP effector site was not affected by the replacement of chloride by glutamate or iodide. To analyze the anion effect on the hP2X7R at the single-molecule level, we performed single-channel current measurements using the patch-clamp technique in the outside-out configuration. Chloride substitution did not affect the single-channel conductance, but the probability that the P2X7R channel was open increased when chloride was replaced by glutamate and decreased when chloride was replaced by iodide. This effect was due to an influence of the anions on the mean closed times of the hP2X7R channel. We conclude that hP2X7R channels are not anion-permeable in physiological Na+-based media and that external anions allosterically affect ion channel opening in the fully ATP4-liganded P2X7R through an extracellular anion binding site.

  20. Targeting of the P2X7 receptor in pancreatic cancer and stellate cells. (United States)

    Giannuzzo, Andrea; Saccomano, Mara; Napp, Joanna; Ellegaard, Maria; Alves, Frauke; Novak, Ivana


    The ATP-gated receptor P2X7 (P2X7R) is involved in regulation of cell survival and has been of interest in cancer field. Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer and new markers and therapeutic targets are needed. PDAC is characterized by a complex tumour microenvironment, which includes cancer and pancreatic stellate cells (PSCs), and potentially high nucleotide/side turnover. Our aim was to determine P2X7R expression and function in human pancreatic cancer cells in vitro as well as to perform in vivo efficacy study applying P2X7R inhibitor in an orthotopic xenograft mouse model of PDAC. In the in vitro studies we show that human PDAC cells with luciferase gene (PancTu-1 Luc cells) express high levels of P2X7R protein. Allosteric P2X7R antagonist AZ10606120 inhibited cell proliferation in basal conditions, indicating that P2X7R was tonically active. Extracellular ATP and BzATP, to which the P2X7R is more sensitive, further affected cell survival and confirmed complex functionality of P2X7R. PancTu-1 Luc migration and invasion was reduced by AZ10606120, and it was stimulated by PSCs, but not by PSCs from P2X7(-/-) animals. PancTu-1 Luc cells were orthotopically transplanted into nude mice and tumour growth was followed noninvasively by bioluminescence imaging. AZ10606120-treated mice showed reduced bioluminescence compared to saline-treated mice. Immunohistochemical analysis confirmed P2X7R expression in cancer and PSC cells, and in metaplastic/neoplastic acinar and duct structures. PSCs number/activity and collagen deposition was reduced in AZ10606120-treated tumours.

  1. Charge Distribution and Local Structure and Speciation in the UO2+x and PuO2+x Binary Oxides for x <= 0.25

    Energy Technology Data Exchange (ETDEWEB)

    Conradson, Steven D.; Begg, Bruce D.; Clark, David L.; Den Auwer, Christophe J.; Ding, Mei; Dorhout, Peter K.; Espinosa-Faller, Francisco J.; Gordon, Pamela L.; Haire, Richard G.; Hess, Nancy J.; Hess, Ryan F.; Keogh, D. Webster; Lander, Gerard H.; Manara, Dario; Morales, Luis A.; Neu, Mary P.; Paviet-Hartmann, Patricia; Rebizant, Jean; Rondinella, Vincenzo V.; Runde, Wolfgang; Tait, C DREW.; Veirs, D. Kirk; Villella, Phillip M.; Wastin, Franck


    The local structure and chemical speciation of the mixed valence, fluorite-based oxides UO2+x (0.00pxp0.20) and PuO2+x/PuO2+x*y(OH)2y * zH2O have been determined by U/Pu LIII XAFS spectroscopy. The U spectra indicate (1) that the O atoms are incorporated as oxo groups at short (1.75A ? ) U?O distances consistent with U(VI) concomitant with a large range of U displacements that reduce the apparent number of U neighbors and (2) that the UO2 fraction remains intact implying that these O defects interact to form clusters and give the heterogeneous structure consistent with the diffraction patterns. The PuO2+x system, which does not show a separate phase at its x ? 0:25 endpoint, also displays (1) oxo groups at longer 1.9A ? distances consistent with Pu(V+d), (2) a multisite Pu?O distribution even when x is close to zero indicative of the formation of stable species with H2O and its hydrolysis products with O2*, and (3) a highly disordered, spectroscopically invisible Pu?Pu component. The structure and bonding in AnO2+x are therefore more complicated than have previously been assumed and show both similarities but also distinct differences among the different elements.

  2. The infinite order point on Y~2=X~3-p~3

    Institute of Scientific and Technical Information of China (English)



    The parameterization of the elliptic curve Y2=X2+1 is given by using the modular forms of X(12) Then using class field theory over imaginary quadratic field and Shimura reciprocity, an infinite order point on the curve y2- = x3-p3 is constructed, for prime p=7 (mod 24).

  3. Mobility Patterns Informing V2X Research Projects: Eco-Routing and Electrified Roadway Project Examples

    Energy Technology Data Exchange (ETDEWEB)

    Gonder, Jeff; Brooker, Aaron; Burton, Evan; Wang, Lijuan; Wood, Eric


    Presentation given at an 'Expert Workshop on V2X Enabled Electric Vehicles' hosted at NREL on behalf of the International Energy Agency (IEA) Hybrid and Electric Vehicle Implementing Agreement for Task 28: Home Grids and V2X Technologies.

  4. P2X7 receptor-deficient mice are susceptible to bone cancer pain

    DEFF Research Database (Denmark)

    Hansen, RR; Nielsen, CK; Nasser, A;


    The purinergic P2X7 receptor is implicated in both neuropathic and inflammatory pain, and has been suggested as a possible target in pain treatment. However, the specific role of the P2X7 receptor in bone cancer pain is unknown. We demonstrated that BALB/cJ P2X7 receptor knockout (P2X7R KO) mice...... were susceptible to bone cancer pain and moreover had an earlier onset of pain-related behaviours compared with cancer-bearing, wild-type mice. Furthermore, acute treatment with the selective P2X7 receptor antagonist, A-438079, failed to alleviate pain-related behaviours in models of bone cancer pain...... of the P2X7R KO mouse. Further experiments are needed to elucidate the exact role of the P2X7 receptors in bone cancer pain. Pain-related behaviours had an earlier onset in bone cancer-bearing, P2X7 receptor-deficient mice, and treatment with A-438079 failed to alleviate pain-related behaviours....

  5. P2X7 on mouse T cells: one channel, many functions

    Directory of Open Access Journals (Sweden)

    Björn eRissiek


    Full Text Available The P2X7 receptor is an adenosine triphosphate (ATP-gated cation channel that is expressed by several cells of the immune system. P2X7 is best known for its proinflammatory role in promoting inflammasome formation and release of mature IL-1β by innate immune cells. Mounting evidence indicates that P2X7 is also an important regulatory receptor of murine and human T cell functions. Murine T cells express a sensitive splice variant of P2X7 that can be activated either by non-covalent binding of ATP or, in the presence of nicotinamide adenine dinucleotide (NAD+, by its covalent ADP-ribosylation catalyzed by the ecto-ADP-ribosyltransferase ARTC2.2. Prolonged activation of P2X7 by either one of these pathways triggers the induction of T cell death. Conversely, lower concentrations of ATP can activate P2X7 to enhance T cell proliferation and production of IL-2. In this review we will highlight the molecular and cellular consequences of P2X7 activation on mouse T cells and its versatile role in T cell homeostasis and activation. Further, we will discuss important differences in the function of P2X7 on human and murine T cells.

  6. Nociceptive transmission and modulation via P2X receptors in central pain syndrome. (United States)

    Kuan, Yung-Hui; Shyu, Bai-Chuang


    Painful sensations are some of the most frequent complaints of patients who are admitted to local medical clinics. Persistent pain varies according to its causes, often resulting from local tissue damage or inflammation. Central somatosensory pathway lesions that are not adequately relieved can consequently cause central pain syndrome or central neuropathic pain. Research on the molecular mechanisms that underlie this pathogenesis is important for treating such pain. To date, evidence suggests the involvement of ion channels, including adenosine triphosphate (ATP)-gated cation channel P2X receptors, in central nervous system pain transmission and persistent modulation upon and following the occurrence of neuropathic pain. Several P2X receptor subtypes, including P2X2, P2X3, P2X4, and P2X7, have been shown to play diverse roles in the pathogenesis of central pain including the mediation of fast transmission in the peripheral nervous system and modulation of neuronal activity in the central nervous system. This review article highlights the role of the P2X family of ATP receptors in the pathogenesis of central neuropathic pain and pain transmission. We discuss basic research that may be translated to clinical application, suggesting that P2X receptors may be treatment targets for central pain syndrome.

  7. The P2X7 Receptor Supports Both Life and Death in Fibrogenic Pancreatic Stellate Cells

    DEFF Research Database (Denmark)

    Haanes, Kristian; Schwab, Albrecht; Novak, Ivana


    receptor and elucidate how it regulates PSC viability. The number of PSCs isolated from wild type (WT) mice was 50% higher than those from the Pfizer P2X7 receptor knock out (KO) mice. The P2X7 receptor protein and mRNA of all known isoforms were expressed in WT PSCs, while KO PSCs only expressed truncated...

  8. P2X7 receptors regulate engulfing activity of non-stimulated resting astrocytes. (United States)

    Yamamoto, Mina; Kamatsuka, Yosuke; Ohishi, Akihiro; Nishida, Kentaro; Nagasawa, Kazuki


    We previously demonstrated that P2X7 receptors (P2X7Rs) expressed by cultured mouse astrocytes were activated without any exogenous stimuli, but its roles in non-stimulated resting astrocytes remained unknown. It has been reported that astrocytes exhibit engulfing activity, and that the basal activity of P2X7Rs regulates the phagocytic activity of macrophages. In this study, therefore, we investigated whether P2X7Rs regulate the engulfing activity of mouse astrocytes. Uptake of non-opsonized beads by resting astrocytes derived from ddY-mouse cortex time-dependently increased, and the uptaken beads were detected in the intracellular space. The bead uptake was inhibited by cytochalasin D (CytD), an F-actin polymerization inhibitor, and agonists and antagonists of P2X7Rs apparently decreased the uptake. Spontaneous YO-PRO-1 uptake by ddY-mouse astrocytes was reduced by the agonists and antagonists of P2X7Rs, but not by CytD. Down-regulation of P2X7Rs using siRNA decreased the bead uptake by ddY-mouse astrocytes. In addition, compared to in the case of ddY-mouse astrocytes, SJL-mouse astrocytes exhibited higher YO-PRO-1 uptake activity, and their bead uptake was significantly greater. These findings suggest that resting astrocytes exhibit engulfing activity and that the activity is regulated, at least in part, by their P2X7Rs.

  9. Mechanism of microglia neuroprotection: Involvement of P2X7, TNFα, and valproic acid. (United States)

    Masuch, Annette; Shieh, Chu-Hsin; van Rooijen, Nico; van Calker, Dietrich; Biber, Knut


    Recently, we have demonstrated that ramified microglia are neuroprotective in N-methyl-D-aspartate (NMDA)-induced excitotoxicity in organotypic hippocampal slice cultures (OHSCs). The present study aimed to elucidate the underlying neuron-glia communication mechanism. It is shown here that pretreatment of OHSC with high concentrations of adenosine 5'-triphosphate (ATP) reduced NMDA-induced neuronal death only in presence of microglia. Specific agonists and antagonists identified the P2X7 receptor as neuroprotective receptor which was confirmed by absence of ATP-dependent neuroprotection in P2X7-deficient OHSC. Microglia replenished chimeric OHSC consisting of wild-type tissue replenished with P2X7-deficient microglia confirmed the involvement of microglial P2X7 receptor in neuroprotection. Stimulation of P2X7 in primary microglia induced tumor necrosis factor α (TNFα) release and blocking TNFα by a neutralizing antibody in OHSC abolished neuroprotection by ATP. OHSC from TNFα-deficient mice show increased exicitoxicity and activation of P2X7 did not rescue neuronal survival in the absence of TNFα. The neuroprotective effect of valproic acid (VPA) was strictly dependent on the presence of microglia and was mediated by upregulation of P2X7 in the cells. The present study demonstrates that microglia-mediated neuroprotection depends on ATP-activated purine receptor P2X7 and induction of TNFα release. This neuroprotective pathway was strengthened by VPA elucidating a novel mechanism for the neuroprotective function of VPA.

  10. P2X7 receptors enhance glutamate release in hippocampal hilar neurons. (United States)

    Cho, Jin-Hwa; Choi, In-Sun; Jang, Il-Sung


    We examined the effect of 2'-3'-O-(4-benzoylbenzoyl)-adenosine-5'-triphosphate (Bz-ATP), a P2X7 receptor agonist, on action potential-independent glutamate release from nerve terminals attached to mechanically isolated immature hilar neurons. Bz-ATP increased spontaneous excitatory postsynaptic current (sEPSC) frequency, and this effect was blocked by Brilliant blue G, a P2X7 receptor antagonist, suggesting that P2X7 receptors mediate the facilitatory action of Bz-ATP on sEPSCs. In most of hilar neurons tested, the Bz-ATP-induced increase in sEPSC frequency was blocked by tetrodotoxin or Cd, suggesting that the activation of P2X7 receptors leads to a presynaptic depolarization. The P2X7 receptor-mediated facilitation of glutamate release would modulate the excitability of hilar neurons, and eventually have a broad impact on the pathophysiological functions mediated by the hippocampus.

  11. P2X purinoceptors as a link between hyperexcitability and neuroinflammation in status epilepticus. (United States)

    Henshall, David C; Engel, Tobias


    There remains a need for more efficacious treatments for status epilepticus. Prolonged seizures result in the release of ATP from cells which activates the P2 class of ionotropic and metabotropic purinoceptors. The P2X receptors gate depolarizing sodium and calcium entry and are expressed by both neurons and glia throughout the brain, and a number of subtypes are upregulated after status epilepticus. Recent studies have explored the in vivo effects of targeting ATP-gated P2X receptors in preclinical models of status epilepticus, with particular focus on the P2X7 receptor (P2X7R). The P2X7R mediates microglial activation and the release of the proepileptogenic inflammatory cytokine interleukin 1β. The receptor may also directly modulate neurotransmission and gliotransmission and promote the recruitment of immune cells into brain parenchyma. Data from our group and collaborators show that status epilepticus produced by intraamygdala microinjection of kainic acid increases P2X7R expression in the hippocampus and neocortex of mice. Antagonism of the P2X7R in the model reduced seizure severity, microglial activation and interleukin 1β release, and neuronal injury. Coadministration of a P2X7R antagonist with a benzodiazepine also provided seizure suppression in a model of drug-refractory status epilepticus when either treatment alone was minimally effective. More recently, we showed that status epilepticus in immature rats is also reduced by P2X7R antagonism. Together, these findings suggest that P2X receptors may be novel targets for seizure control and interruption of neuroinflammation after status epilepticus. This article is part of a Special Issue entitled "Status Epilepticus".

  12. Expression of the apoptotic calcium channel P2X7 in the glandular epithelium. (United States)

    Slater, Michael; Danieletto, Suzanne; Barden, Julian A


    In the current study, expression of the apoptotic calcium channel receptor P2X(7) and prostate-specific antigen (PSA) levels were studied in biopsy cores from 174 patients as well as 20 radical prostatectomy cases. In clinical biopsies, we have previously demonstrated that P2X(1 )and P2X(2) calcium channel receptors are absent from normal prostate epithelium that does not progress to prostate cancer within 5 years. In cases that did progress to prostate cancer however, P2X(1 )and P2X(2) labeling was observed in a stage-specific manner first in the nucleus, then the cytoplasm and finally on the apical epithelium, as prostate cancer developed. These markers were present up to 5 years before cancer was detectable by the usual morphological criteria (Gleason grading) as determined by H and E staining. In the current study, the apoptotic calcium channel receptor P2X(7) yielded similar results to that of P2X(1) and P2X(2). Using radical prostatectomy tissue sections as well as biopsies, these changes in calcium channel metabolism were noted throughout the prostate, indicating a field effect. This finding suggests that the presence of a prostate tumor could be detected without the need for direct sampling of tumor tissue, leading to detection of false negative cases missed by H or E stain. The reliability of PSA levels as a prognostic indicator has been questioned in recent years. In the current study, PSA levels were correlated with the P2X(7) labeling results. All patients who exhibited no P2X(7) labeling had a prostatic serum antigen (PSA) level of 2. This finding suggests that increasing PSA may be an accurate indicator of cancer development.

  13. Purinergic signaling mediated by P2X7 receptors controls myelination in sciatic nerves. (United States)

    Faroni, A; Smith, R J P; Procacci, P; Castelnovo, L F; Puccianti, E; Reid, A J; Magnaghi, V; Verkhratsky, A


    Adenosine-5'-triphosphate, the physiological ligand of P2X receptors, is an important factor in peripheral nerve development. P2X7 receptor is expressed in Schwann cells (SCs), but the specific effects of P2X7 purinergic signaling on peripheral nerve development, myelination, and function are largely unknown. In this study, sciatic nerves from P2X7 knockout mice were analyzed for altered expression of myelin-associated proteins and for alterations in nerve morphology. Immunohistochemical analyses revealed that, in the wild-type peripheral nerves, the P2X7 receptor was localized mainly in myelinating SCs, with only a few immunopositive nonmyelinating SCs. Complete absence of P2X7 receptor protein was confirmed in the sciatic nerves of the knockout mice by Western blot and immunohistochemistry. Western blot analysis revealed that expression levels of the myelin proteins protein zero and myelin-associated glycoprotein are reduced in P2X7 knockout nerves. In accordance with the molecular results, transmission electron microscopy analyses revealed that P2X7 knockout nerves possess significantly more unmyelinated axons, contained in a higher number of Remak bundles. The myelinating/nonmyelinating SC ratio was also decreased in knockout mice, and we found a significantly increased number of irregular fibers compared with control nerves. Nevertheless, the myelin thickness in the knockout was unaltered, suggesting a stronger role for P2X7 in determining SC maturation than in myelin formation. In conclusion, we present morphological and molecular evidence of the importance of P2X7 signaling in peripheral nerve maturation and in determining SC commitment to a myelinating phenotype.

  14. P2X receptors as targets for the treatment of status epilepticus

    Directory of Open Access Journals (Sweden)

    David C Henshall


    Full Text Available Prolonged seizures are amongst the most common neurological emergencies. Status epilepticus is a state of continuous seizures that is life-threatening and prompt termination of status epilepticus is critical to protect the brain from permanent damage. Frontline treatment comprises parenteral administration of anticonvulsants such as lorazepam that facilitate γ-amino butyric acid (GABA transmission. Because status epilepticus can become refractory to anticonvulsants in a significant proportion of patients, drugs which act on different neurotransmitter systems may represent potential adjunctive treatments. P2X receptors are a class of ligand-gated ion channel activated by ATP that contributes to neuro- and glio-transmission. P2X receptors are expressed by both neurons and glia in various brain regions, including the hippocampus. Electrophysiology, pharmacology and genetic studies suggest certain P2X receptors are activated during pathologic brain activity. Expression of several members of the family including P2X2, P2X4 and P2X7 receptors has been reported to be altered in the hippocampus following status epilepticus. Recent studies have shown that ligands of the P2X7 receptor can have potent effects on seizure severity during status epilepticus and mice lacking this receptor display altered seizures in response to chemoconvulsants. Antagonists of the P2X7 receptor also modulate neuronal death, microglial responses and neuroinflammatory signaling. Recent work also found altered neuronal injury and inflammation after status epilepticus in mice lacking the P2X4 receptor. In summary, members of the P2X receptor family may serve important roles in the pathophysiology of status epilepticus and represent novel targets for seizure control and neuroprotection.

  15. Spin-Stripe Density Varies Linearly With the Hole Content in Single-Layer Bi2+xSr2-xCuO6+y Cuprate Superconductors (United States)

    Enoki, M.; Fujita, M.; Nishizaki, T.; Iikubo, S.; Singh, D. K.; Chang, S.; Tranquada, J. M.; Yamada, K.


    We have performed inelastic neutron scattering measurements on the single-layer cuprate Bi2+xSr2-xCuO6+y (Bi2201) with x=0.2, 0.3, 0.4, and 0.5, a doping range that spans the spin-glass to superconducting phase boundary. The doping evolution of low energy spin fluctuations (≲11meV) was found to be characterized by a change in the incommensurate modulation wave vector from the tetragonal [110] to [100]/[010] directions, while maintaining a linear relation between the incommensurability and the hole concentration, δ≈p. In the superconducting regime, the spectral weight is strongly suppressed below ˜4meV. Similarities and differences in the spin correlations between Bi2201 and the prototypical single-layer system La2-xSrxCuO4 are discussed.

  16. Frequency and temperature dependence of dielectric and electric properties of Ba2-xSm4+2x/3Ti8O24 with structural analysis


    Narang Sukhleen Bindra; Kaur Dalveer; Pubby Kunal


    Dielectric ceramics samples of barium titanium oxide doped with samarium, having a complex structural formula of Ba2-xSm4+2x/3Ti8O24 (referred to as BST), were fabricated by a high temperature solid-state reaction technique with varying x (0.0, 0.2, 0.4, 0.6). X-ray diffraction technique was used to check the formation of particular phases. Scanning electron microscope technique was used to study the surface morphology of the samples. The samples were studied in a temperature range of 298 K t...

  17. A note on the PT-invariant periodic potential V(x)=4 cos^2 x + 4 i V_0 sin 2x

    CERN Document Server

    Midya, Bikashkali; Roychoudhury, Rajkumar


    It is shown that the PT symmetric Hamiltonian with the periodic potential V(x) = 4 cos^2 x + 4 i V_0 sin 2x can be mapped into a Hermitian Hamiltonian for $V_0<0.5$, by a similarity transformation. It is also shown that there exist a second critical point of the potential V(x), apart from the known critical point $V_0=0.5$, for $V_0^c ~ .888437$ after which no part of the eigenvalues and the band structure remains real. Relevant physical consequence of this finding has been pointed out.

  18. P2X7受体与骨代谢研究进展%Relationship between P2X7 receptor and bone metabolism: recent progress

    Institute of Scientific and Technical Information of China (English)

    李喆; 马蓓; 陈爱民



  19. P2x7 deficiency suppresses development of experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Lin Shao X


    Full Text Available Abstract Background The purinergic receptor P2x7 is expressed on myeloid cells as well as on CNS glial cells, and P2x7 activation has been shown to increase both glial and T-cell activation. These properties suggest a role in the development of autoimmune disease including multiple sclerosis. Methods The animal model of MS, experimental autoimmune encephalomyelitis (EAE using myelin oligodendrocyte glycoprotein (MOG peptide residues 35–55 was induced in wildtype C57BL6 mice and in P2x7 deficient mice ('P2x7 mice' that were backcrossed to C57BL6 mice. Disease progression was monitored by appearance of clinical signs, immunocytochemical staining to assess brain inflammation and neuronal damage, and by measurement of Tcell cytokine production. Results The incidence of EAE disease in P2x7 mice was reduced 4-fold compared to the wildtype mice; however the P2x7 mice that became ill had similar days of onset and clinical scores as the wildtype mice. Splenic T-cells isolated from P2x7 null mice produced greater IFNγ and IL-17 (from 3 to 12 fold greater levels than wildtype cells, however cytokine production from P2x7 derived cells was not increased by a selective P2x7 agonist as was cytokine production from wildtype cells. Although infiltrating cells were detected in brains of both the P2x7 and wildtype mice, astroglial activation and axonal damage was reduced versus wildtype mice, and the distribution of astroglial activation was markedly distinct in the two strains. In contrast, microglial activation was similar in the two strains. Conclusion P2x7 deficiency resulted in compensatory changes leading to increased T-cell cytokine production, and activated T-cells were detected in the brains of P2x7 null mice with no clinical signs. However, the greatly reduced incidence of disease suggests that an initiating event is absent in these mice, and points to a role for astroglial P2x7 in development of EAE disease.

  20. Modulating P2X7 Receptor Signaling during Rheumatoid Arthritis: New Therapeutic Approaches for Bisphosphonates

    Directory of Open Access Journals (Sweden)

    Alberto Baroja-Mazo


    Full Text Available P2X7 receptor-mediated purinergic signaling is a well-known mechanism involved in bone remodeling. The P2X7 receptor has been implicated in the pathophysiology of various bone and cartilage diseases, including rheumatoid arthritis (RA, a widespread and complex chronic inflammatory disorder. The P2X7 receptor induces the release into the synovial fluid of the proinflammatory factors (e.g., interleukin-1β, prostaglandins, and proteases responsible for the clinical symptoms of RA. Thus, the P2X7 receptor is emerging as a novel anti-inflammatory therapeutic target, and various selective P2X7 receptor antagonists are under clinical trials. Extracellular ATP signaling acting through the P2X7 receptor is a complex and dynamic scenario, which varies over the course of inflammation. This signaling is partially modulated by the activity of ectonucleotidases, which degrade extracellular ATP to generate other active molecules such as adenosine or pyrophosphates. Recent evidence suggests differential extracellular metabolism of ATP during the resolution of inflammation to generate pyrophosphates. Extracellular pyrophosphate dampens proinflammatory signaling by promoting alternative macrophage activation. Our paper shows that bisphosphonates are metabolically stable pyrophosphate analogues that are able to mimic the anti-inflammatory function of pyrophosphates. Bisphosphonates are arising per se as promising anti-inflammatory drugs to treat RA, and this therapy could be improved when administrated in combination with P2X7 receptor antagonists.

  1. Accelerated tumor progression in mice lacking the ATP receptor P2X7

    DEFF Research Database (Denmark)

    Adinolfi, Elena; Capece, Marina; Franceschini, Alessia


    action. Finally, dendritic cells from P2X7R-deficient mice were unresponsive to stimulation with tumor cells, and chemotaxis of P2X7R-less cells was impaired. Overall, our results showed that host P2X7R expression was critical to support an antitumor immune response, and to restrict tumor growth......The ATP receptor P2X7 (P2X7R or P2RX7) has a key role in inflammation and immunity, but its possible roles in cancer are not firmly established. In the present study, we investigated the effect of host genetic deletion of P2X7R in the mouse on the growth of B16 melanoma or CT26 colon carcinoma...... cells. Tumor size and metastatic dissemination were assessed by in vivo calliper and luciferase luminescence emission measurements along with postmortem examination. In P2X7R-deficient mice, tumor growth and metastatic spreading were accelerated strongly, compared with wild-type (wt) mice. Intratumoral...

  2. Targeting of the P2X7 receptor in pancreatic cancer and stellate cells

    DEFF Research Database (Denmark)

    Giannuzzo, Andrea; Saccomano, Mara; Napp, Joanna;


    The ATP-gated receptor P2X7 (P2X7R) is involved in regulation of cell survival and has been of interest in cancer field. Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer and new markers and therapeutic targets are needed. PDAC is characterized by a complex tumour microenvironment, which...... includes cancer and pancreatic stellate cells (PSCs), and potentially high nucleotide/side turnover. Our aim was to determine P2X7R expression and function in human pancreatic cancer cells in vitro as well as to perform in vivo efficacy study applying P2X7R inhibitor in an orthotopic xenograft mouse model...... of PDAC. In the in vitro studies we show that human PDAC cells with luciferase gene (PancTu-1 Luc cells) express high levels of P2X7R protein. Allosteric P2X7R antagonist AZ10606120 inhibited cell proliferation in basal conditions, indicating that P2X7R was tonically active. Extracellular ATP and Bz...

  3. P2X receptors mediate ATP-induced primary nociceptive neurone activation. (United States)

    Bland-Ward, P A; Humphrey, P P


    ATP-gated P2X ion-channel receptors are localised throughout the mammalian nervous system and have been identified on neurones which participate in conduction of nociceptive information from the periphery to, and within, the CNS. This article briefly reviews recently published research describing the role that ATP and P2X receptors may play in pain perception, highlighting the importance of the P2X(3) receptor in this process. The P2X(3) receptor subunit is almost exclusively expressed on a subset of small and medium diameter sensory neurones innervating cutaneous and visceral tissue. Activation of P2X receptors present on the peripheral terminals of primary afferents results in neuronal depolarisation and, in conscious animals, leads to the manifestation of acute nociceptive behaviour. Recent animal studies have also shown that P2X(3) receptor expression is increased in sensory ganglia following acute neuronal injury, hinting that similar plasticity in the expression of this receptor subtype could underlie the mechanisms involved in a range of conditions characterised by sensory hypersensitivity in man. It is apparent from the evidence available that functional antagonists at specific P2X receptor subtypes could represent an important class of novel analgesic agents.

  4. Involvement of P2X7 receptor in neuronal degeneration triggered by traumatic injury (United States)

    Nadal-Nicolás, Francisco M.; Galindo-Romero, Caridad; Valiente-Soriano, Francisco J.; Barberà-Cremades, María; deTorre-Minguela, Carlos; Salinas-Navarro, Manuel; Pelegrín, Pablo; Agudo-Barriuso, Marta


    Axonal injury is a common feature of central nervous system insults that culminates with the death of the affected neurons, and an irreversible loss of function. Inflammation is an important component of the neurodegenerative process, where the microglia plays an important role by releasing proinflammatory factors as well as clearing the death neurons by phagocytosis. Here we have identified the purinergic signaling through the P2X7 receptor as an important component for the neuronal death in a model of optic nerve axotomy. We have found that in P2X7 receptor deficient mice there is a delayed loss of retinal ganglion cells and a decrease of phagocytic microglia at early times points after axotomy. In contralateral to the axotomy retinas, P2X7 receptor controlled the numbers of phagocytic microglia, suggesting that extracellular ATP could act as a danger signal activating the P2X7 receptor in mediating the loss of neurons in contralateral retinas. Finally, we show that intravitreal administration of the selective P2X7 receptor antagonist A438079 also delays axotomy-induced retinal ganglion cell death in retinas from wild type mice. Thus, our work demonstrates that P2X7 receptor signaling is involved in neuronal cell death after axonal injury, being P2X7 receptor antagonism a potential therapeutic strategy. PMID:27929040

  5. Blockade of P2X7 receptors or pannexin-1 channels similarly attenuates postischemic damage. (United States)

    Cisneros-Mejorado, Abraham; Gottlieb, Miroslav; Cavaliere, Fabio; Magnus, Tim; Koch-Nolte, Friederich; Scemes, Eliana; Pérez-Samartín, Alberto; Matute, Carlos


    The role of P2X7 receptors and pannexin-1 channels in ischemic damage remains controversial. Here, we analyzed their contribution to postanoxic depolarization after ischemia in cultured neurons and in brain slices. We observed that pharmacological blockade of P2X7 receptors or pannexin-1 channels delayed the onset of postanoxic currents and reduced their slope, and that simultaneous inhibition did not further enhance the effects of blocking either one. These results were confirmed in acute cortical slices from P2X7 and pannexin-1 knockout mice. Oxygen-glucose deprivation in cortical organotypic cultures caused neuronal death that was reduced with P2X7 and pannexin-1 blockers as well as in organotypic cultures derived from mice lacking P2X7 and pannexin 1. Subsequently, we used transient middle cerebral artery occlusion to monitor the neuroprotective effect of those drugs in vivo. We found that P2X7 and pannexin-1 antagonists, and their ablation in knockout mice, substantially attenuated the motor symptoms and reduced the infarct volume to ~50% of that in vehicle-treated or wild-type animals. These results show that P2X7 receptors and pannexin-1 channels are major mediators of postanoxic depolarization in neurons and of brain damage after ischemia, and that they operate in the same deleterious signaling cascade leading to neuronal and tissue demise.

  6. P2X7 Receptor Mediated Growth-Inhibitory Effect in KG1 a Cell Line

    Institute of Scientific and Technical Information of China (English)

    Xiujun Zhang; Lijun Meng


    This study was conducted to investigate ATP-induced growth inhibition in human leukemic cells KGla.METHoDS ATP inhibited cell growth was analyzed by MTSassay.Extemalization of phosphatidylserine could be detected byAnnexin-V-FITC apoptosis staining after activation of the P2X7 re-ceptor.P2X7 mediated pore formation was detected in KGla cellsby Yo-Pro-1 uptake assay.RESUlTS ATP inhibited cell growth in a dose-dependent man-ner.The cytotoxic effect could be blocked by P2X7 antagonists,oxidized ATP(OATP)and KN62.Externalization of phosphatidyl-serine could be detected in a time-dependent manner.P2X7 medi-ated pore forigation could be detected in KGla cells.These effectscould not be observed in P2X7 null Ramos cells.CONCLUSIoN The results and our previously reports thatmRNA,protein expression and calcium response of the P2X7receptor in KGla cells,suggested that extracellular ATP effectivelyinduces growth inhibition through apoptosis in KGla cells byactivation of P2X7 receptor,and that may be mediated by extracel-lular Ca2+ineux and pore formation.

  7. Saffron reduces ATP-induced retinal cytotoxicity by targeting P2X7 receptors. (United States)

    Corso, Lucia; Cavallero, Anna; Baroni, Debora; Garbati, Patrizia; Prestipino, Gianfranco; Bisti, Silvia; Nobile, Mario; Picco, Cristiana


    P2X7-type purinergic receptors are distributed throughout the nervous system where they contribute to physiological and pathological functions. In the retina, this receptor is found in both inner and outer cells including microglia modulating signaling and health of retinal cells. It is involved in retinal neurodegenerative disorders such as retinitis pigmentosa and age-related macular degeneration (AMD). Experimental studies demonstrated that saffron protects photoreceptors from light-induced damage preserving both retinal morphology and visual function and improves retinal flicker sensitivity in AMD patients. To evaluate a possible interaction between saffron and P2X7 receptors (P2X7Rs), different cellular models and experimental approaches were used. We found that saffron positively influences the viability of mouse primary retinal cells and photoreceptor-derived 661W cells exposed to ATP, and reduced the ATP-induced intracellular calcium increase in 661W cells. Similar results were obtained on HEK cells transfected with recombinant rat P2X7R but not on cells transfected with rat P2X2R. Finally, patch-clamp experiments showed that saffron inhibited cationic currents in HEK-P2X7R cells. These results point out a novel mechanism through which saffron may exert its protective role in neurodegeneration and support the idea that P2X7-mediated calcium signaling may be a crucial therapeutic target in the treatment of neurodegenerative diseases.

  8. P2X7 receptors trigger ATP exocytosis and modify secretory vesicle dynamics in neuroblastoma cells. (United States)

    Gutiérrez-Martín, Yolanda; Bustillo, Diego; Gómez-Villafuertes, Rosa; Sánchez-Nogueiro, Jesús; Torregrosa-Hetland, Cristina; Binz, Thomas; Gutiérrez, Luis Miguel; Miras-Portugal, María Teresa; Artalejo, Antonio R


    Previously, we reported that purinergic ionotropic P2X7 receptors negatively regulate neurite formation in Neuro-2a (N2a) mouse neuroblastoma cells through a Ca(2+)/calmodulin-dependent kinase II-related mechanism. In the present study we used this cell line to investigate a parallel though faster P2X7 receptor-mediated signaling pathway, namely Ca(2+)-regulated exocytosis. Selective activation of P2X7 receptors evoked exocytosis as assayed by high resolution membrane capacitance measurements. Using dual-wavelength total internal reflection microscopy, we have observed both the increase in near-membrane Ca(2+) concentration and the exocytosis of fluorescently labeled vesicles in response to P2X7 receptor stimulation. Moreover, activation of P2X7 receptors also affects vesicle motion in the vertical and horizontal directions, thus, involving this receptor type in the control of early steps (docking and priming) of the secretory pathway. Immunocytochemical and RT-PCR experiments evidenced that N2a cells express the three neuronal SNAREs as well as vesicular nucleotide and monoamine (VMAT-1 and VMAT-2) transporters. Biochemical measurements indicated that ionomycin induced a significant release of ATP from N2a cells. Finally, P2X7 receptor stimulation and ionomycin increased the incidence of small transient inward currents, reminiscent of postsynaptic quantal events observed at synapses. Small transient inward currents were dependent on extracellular Ca(2+) and were abolished by Brilliant Blue G, suggesting they were mediated by P2X7 receptors. Altogether, these results suggest the existence of a positive feedback mechanism mediated by P2X7 receptor-stimulated exocytotic release of ATP that would act on P2X7 receptors on the same or neighbor cells to further stimulate its own release and negatively control N2a cell differentiation.

  9. Programmable direct current power supply (charger) GBE 2 x 38/4. mod II. Programmierbare Gleichstromversorgung (Ladegeraet) GBE 2 x 38/4. mod II

    Energy Technology Data Exchange (ETDEWEB)

    Obstfelder, I. (Benning (Theo) GmbH und Co. KG, Bocholt (Germany))


    The configuration and technical data of the microcontroller-controlled 'GBE 2x38/4 mod. II' battery charger is disclosed. Furthermore, the sequence of the charging program, i.e. the procedure for charging a closed battery each, is described. (MM).

  10. Targeting of the P2X7 receptor in pancreatic cancer and stellate cells.


    Giannuzzo, Andrea; Saccomano, Mara; Napp, Joanna; Ellegaard, Maria; Alves, Frauke; Novak, Ivana


    The ATP-gated receptor P2X7 (P2X7R) is involved in regulation of cell survival and has been of interest in cancer field. Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer and new markers and therapeutic targets are needed. PDAC is characterized by a complex tumour microenvironment, which includes cancer and pancreatic stellate cells (PSCs), and potentially high nucleotide/side turnover. Our aim was to determine P2X7R expression and function in human pancreatic cancer cells in vitro a...

  11. Atmospheric chemistry of n-CxF2x+1CHO (x = 1, 2, 3, 4)

    DEFF Research Database (Denmark)

    Hurley, M. D.; Ball, J. C.; Wallington, T. J.;


    Smog chamber/FTIR techniques were used to study the atmospheric fate of n-C(x)F(2)(x)(+1)C(O) (x = 1, 2, 3, 4) radicals in 700 Torr O(2)/N(2) diluent at 298 +/- 3 K. A competition is observed between reaction with O(2) to form n-C(x)()F(2)(x)()(+1)C(O)O(2) radicals and decomposition to form n-C(x...... to the atmospheric chemistry of n-C(x)F(2)(x)(+1)C(O) radicals and their possible role in contributing to the formation of perfluorocarboxylic acids in the environment....

  12. Topological phase diagrams of bulk and monolayer TiS2-x Tex. (United States)

    Zhu, Zhiyong; Cheng, Yingchun; Schwingenschlögl, Udo


    With the use of ab initio calculations, the topological phase diagrams of bulk and monolayer TiS(2-x) Te(x) are established. Whereas bulk TiS(2-x) Te(x) shows two strong topological phases [1;(000)] and [1;(001)] for 0.442-x) Te(x) is a unique system for studying topological phases in three and two dimensions simultaneously.

  13. Association between P2X7 Receptor Polymorphisms and Bone Status in Mice

    DEFF Research Database (Denmark)

    Syberg, Susanne; Schwarz, Peter; Petersen, Solveig;


    Macrophages from mouse strains with the naturally occurring mutation P451L in the purinergic receptor P2X7 have impaired responses to agonists (1). Because P2X7 receptors are expressed in bone cells and are implicated in bone physiology, we asked whether strains with the P451L mutation have...... a different bone phenotype. By sequencing the most common strains of inbred mice, we found that only a few strains (BALB, NOD, NZW, and 129) were harboring the wild allelic version of the mutation (P451) in the gene for the purinergic receptor P2X7. The strains were compared by means of dual energy X...

  14. Building layered NixCo2x(OH)6x nanosheets decorated three-dimensional Ni frameworks for electrochemical applications (United States)

    Liu, Zhao-Qing; Chen, Gao-Feng; Zhou, Pei-Lin; Li, Nan; Su, Yu-Zhi


    To achieve high electrochemical performance in energy storage and conversion devices, transition metal hydroxides electrode materials need enhancing their intrinsic poor conductivity and fully utilizing their unexploited active sites. Accordingly, a simple and effective strategy is developed to synthesize layered NixCo2x(OH)6x nanosheets using dual three-dimensional Ni as structural and conductive support system. Owing to highly electrical conductivity, rich of interconnected ion/electron transport pathways, and robust structure stability, NixCo2x(OH)6x@Ni electrode exhibits remarkably high specific capacitance, excellent rate capability, and superior cycle stability. Moreover, the asymmetric supercapacitor assembled by NixCo2x(OH)6x@Ni and activated carbon/carbon nanotube achieves a large working voltage window of 1.5 V, a high energy density (≈44.2 Wh kg-1 at a power density of 750 W kg-1) and outstanding long-term cycle ability (remaining 100% of the initial Csp after 5000 cycles). Furthermore, the NixCo2x(OH)6x@Ni as an oxygen evolution reaction electrocatalyst shows small onset overpotential (263 mV), low Tafel slope (78 mV dec-1), large anodic current density of 30 mA cm-2 at a low overpotential of 336 mV and prominent electrochemical durability.

  15. Two P2X1 receptor transcripts able to form functional channels are present in most human monocytes. (United States)

    López-López, Cintya; Jaramillo-Polanco, Josue; Portales-Pérez, Diana P; Gómez-Coronado, Karen S; Rodríguez-Meléndez, Jessica G; Cortés-García, Juan D; Espinosa-Luna, Rosa; Montaño, Luis M; Barajas-López, Carlos


    To characterize the presence and general properties of P2X1 receptors in single human monocytes we used RT-PCR, flow cytometry, and the patch-clamp and the two-electrode voltage-clamp techniques. Most human monocytes expressed the canonical P2X1 (90%) and its splicing variant P2X1del (88%) mRNAs. P2X1 receptor immunoreactivity was also observed in 70% of these cells. Currents mediated by P2X1 (EC50=1.9±0.8µm) and P2X1del (EC50 >1000µm) channels, expressed in Xenopus leavis oocytes, have different ATP sensitivity and kinetics. Both currents mediated by P2X1 and P2X1del channels kept increasing during the continuous presence of high ATP concentrations. Currents mediated by the native P2X1 receptors in human monocytes showed an EC50=6.3±0.2µm. Currents have kinetics that resemble those observed for P2X1 and P2X1del receptors in oocytes. Our study is the first to demonstrate the expression of P2X1 transcript and its splicing variant P2X1del in most human monocytes. We also, for the first time, described functional homomeric P2X1del channels and demonstrated that currents mediated by P2X1 or P2X1del receptors, during heterologous expression, increased in amplitude when activated with high ATP concentrations in a similar fashion to those channels that increase their conductance under similar conditions, such as P2X7, P2X2, and P2X4 channels.

  16. Insertion devices

    CERN Document Server

    Bahrdt, J


    The interaction of an insertion device with the electron beam in a storage ring is discussed. The radiation property including brightness, ux and polarization of an ideal and real planar and helical / elliptical device is described. The magnet design of planar, helical, quasiperiodic devices and of devices with a reduced on axis power density are resumed.

  17. Using Decision Trees to Detect and Isolate Leaks in the J-2X (United States)

    National Aeronautics and Space Administration — Full title: Using Decision Trees to Detect and Isolate Simulated Leaks in the J-2X Rocket Engine Mark Schwabacher, NASA Ames Research Center Robert Aguilar, Pratt...

  18. Data of evolutionary structure change: 1CPDA-2VO2X [Confc[Archive

    Lifescience Database Archive (English)


  19. Corneal epithelium expresses a variant of P2X(7 receptor in health and disease.

    Directory of Open Access Journals (Sweden)

    Courtney Mankus

    Full Text Available Improper wound repair of the corneal epithelium can alter refraction of light resulting in impaired vision. We have shown that ATP is released after injury, activates purinergic receptor signaling pathways and plays a major role in wound closure. In many cells or tissues, ATP activates P2X(7 receptors leading to cation fluxes and cytotoxicity. The corneal epithelium is an excellent model to study the expression of both the full-length P2X(7 form (defined as the canonical receptor and its truncated forms. When Ca(2+ mobilization is induced by BzATP, a P2X(7 agonist, it is attenuated in the presence of extracellular Mg(2+ or Zn(2+, negligible in the absence of extracellular Ca(2+, and inhibited by the competitive P2X7 receptor inhibitor, A438079. BzATP enhanced phosphorylation of ERK. Together these responses indicate the presence of a canonical or full-length P2X(7 receptor. In addition BzATP enhanced epithelial cell migration, and transfection with siRNA to the P2X(7 receptor reduced cell migration. Furthermore, sustained activation did not induce dye uptake indicating the presence of truncated or variant forms that lack the ability to form large pores. Reverse transcription-polymerase chain reaction and Northern blot analysis revealed a P2X(7 splice variant. Western blots identified a full-length and truncated form, and the expression pattern changed as cultures progressed from monolayer to stratified. Cross-linking gels demonstrated the presence of homo- and heterotrimers. We examined epithelium from age matched diabetic and non-diabetic corneas patients and detected a 4-fold increase in P2X(7 mRNA from diabetic corneal epithelium compared to non-diabetic controls and an increased trend in expression of P2X(7variant mRNA. Taken together, these data indicate that corneal epithelial cells express full-length and truncated forms of P2X(7, which ultimately allows P2X(7 to function as a multifaceted receptor that can mediate cell proliferation and

  20. The P2X7 receptor and intracellular pathogens: a continuing struggle


    Coutinho-Silva, Robson; Corrêa, Gladys; Sater, Ali Abdul; Ojcius, David M.


    The purinergic receptor, P2X7, has recently emerged as an important component of the innate immune response against microbial infections. Ligation of P2X7 by ATP can stimulate inflammasome activation and secretion of proinflammatory cytokines, but it can also lead directly to killing of intracellular pathogens in infected macrophages and epithelial cells. Thus, while some intracellular pathogens evade host defense responses by modulating with membrane trafficking or cell signaling in the infe...

  1. Porphyromonas gingivalis fimbriae dampen P2X7-dependent IL-1β secretion (United States)

    Morandini, Ana Carolina; Ramos-Junior, Erivan S.; Potempa, Jan; Nguyen, Ky-Anh; Oliveira, Ana Carolina; Bellio, Maria; Ojcius, David M.; Scharfstein, Julio; Coutinho-Silva, Robson


    Porphyromonas gingivalis is a major contributor to the pathogenesis of periodontitis, an infection-driven inflammatory disease that leads to bone destruction. This pathogen stimulates pro-IL-1β synthesis but not mature IL-1β secretion, unless the P2X7 receptor is activated by extracellular ATP. Here, we investigated the role of Pg fimbriae in eATP-induced IL-1β release. Bone marrow derived macrophages (BMDMs) from wild type (WT) or P2X7-deficient mice were infected with Pg (strain 381) or isogenic fimbriae deficient (strain DPG3) with or without subsequent eATP stimulation. DPG3 induced higher IL-1β secretion after eATP stimulation compared to 381 in WT BMDMs, but not in P2X7-deficient cells. This mechanism was dependent of K+ efflux and Ca2+-iPLA2 activity. Accordingly, non-fimbriated Pg failed to inhibit apoptosis via eATP/P2X7-pathway. Furthermore, Pg-driven stimulation of IL-1β was TLR2- and MyD88-dependent, and irrespective of fimbriae expression. Fimbriae-dependent down-modulation of IL-1β was selective, as levels of other cytokines remained unaffected by P2X7 deficiency. Confocal microscopy demonstrated the presence of discrete P2X7 expression in the absence of Pg stimulation which was enhanced by 381-stimulated cells. Notably, DPG3-infected macrophages revealed a distinct pattern of P2X7 receptor expression with a markedly foci formation. Collectively, these data demonstrate that eATP-induced IL-1β secretion is impaired by Pg fimbriae in a P2X7-dependent manner. PMID:24925032

  2. Fully reconfigurable 2x2 optical cross-connect using tunable wavelength switching modules

    DEFF Research Database (Denmark)

    Liu, Fenghai; Zheng, Xueyan; Pedersen, Rune Johan Skullerud;


    A modular tunable wavelength switching module is proposed and used to construct 2x2 fully reconfigurable optical cross-connects. Large size optical switch is avoided in the OXC and it is easy to upgrade to more wavelength channels.......A modular tunable wavelength switching module is proposed and used to construct 2x2 fully reconfigurable optical cross-connects. Large size optical switch is avoided in the OXC and it is easy to upgrade to more wavelength channels....

  3. Radiosensitizing Effect of P2X7 Receptor Antagonist on Melanoma in vitro and in vivo. (United States)

    Tanamachi, Keisuke; Nishino, Keisuke; Mori, Natsuki; Suzuki, Toshihiro; Tanuma, Sei-Ichi; Abe, Ryo; Tsukimoto, Mitsutoshi


    Melanoma is highly malignant, and generally exhibits radioresistance, responding poorly to radiation therapy. We previously reported that activation of P2X7, P2Y6, and P2Y12 receptors is involved in the DNA damage response after γ-irradiation of human lung adenocarcinoma A549 cells. However, it is not clear whether these receptors are also involved in the case of melanoma cells, although P2X7 receptor is highly expressed in various cancers, including melanoma. Here, we show that P2X7 receptor antagonist enhances radiation-induced cytotoxicity in B16 melanoma cells in vitro and in vivo. We confirmed that these cells express P2X7 receptor mRNA and exhibit P2X7 receptor-mediated activities, such as ATP-induced pore formation and cytotoxicity. We further examined the radiosensitizing effect of P2X7 receptor antagonist Brilliant Blue G (BBG) in vitro by colony formation assay of B16 cells. γ-Irradiation dose-dependently reduced cell survival, and pretreatment with BBG enhanced the radiation-induced cytotoxicity. BBG pretreatment also decreased the number of DNA repair foci in nuclei, supporting involvement of P2X7 receptor in the DNA damage response. Finally, we investigated the radiosensitizing effect of BBG on B16 melanoma cells inoculated into the hind footpad of C57BL/6 mice. Neither 1 Gy γ-irradiation alone nor BBG alone suppressed the increase of tumor volume, but the combination of irradiation and BBG significantly suppressed tumor growth. Our results suggest that P2X7 receptor antagonist BBG has a radiosensitizing effect in melanoma in vitro and in vivo. BBG, which is used as a food coloring agent, appears to be a promising candidate as a radiosensitizer.

  4. Potent and long-lasting inhibition of human P2X2 receptors by copper (United States)

    Punthambaker, Sukanya; Hume, Richard I.


    P2X receptors are ion channels gated by ATP. In rodents these channels are modulated by zinc and copper. Zinc is co-released with neurotransmitter at some synapses and can modulate neuronal activity, but the role of copper in the brain is unclear. Rat P2X2 receptors show potentiation by 2–100 µM zinc or copper in the presence of a submaximal concentration of ATP but are inhibited by zinc or copper at concentrations above 100 µM. In contrast, human P2X2 (hP2X2) receptors show no potentiation and are strongly inhibited by zinc over the range of 2–100 µM. The effect of copper on hP2X2 is of interest because there are human brain disorders in which copper concentration is altered. We found that hP2X2 receptors are potently inhibited by copper (IC50 = 40 nM). ATP responsiveness recovered extremely slowly after copper washout, with full recovery requiring over 1 h. ATP binding facilitated copper binding but not unbinding from this inhibitory site. A mutant receptor in which the first six extracellular cysteines were deleted, C(1–6)S, showed normal copper inhibition, however reducing agents dramatically accelerated recovery from copper inhibition in wild type hP2X2 and the C(1–6)S mutant, indicating that the final two disulfide bonds are required to maintain the high affinity copper binding site. Three histidine residues required for normal zinc inhibition were also required for normal copper inhibition. Humans with untreated Wilson’s disease have excess amounts of copper in the brain. The high copper sensitivity of hP2X2 receptors suggests that they are non-functional in these patients. PMID:24067922

  5. Critical Evaluation of P2X7 Receptor Antagonists in Selected Seizure Models (United States)

    Fischer, Wolfgang; Franke, Heike; Krügel, Ute; Müller, Heiko; Dinkel, Klaus; Lord, Brian; Letavic, Michael A.; Henshall, David C.; Engel, Tobias


    The ATP-gated P2X7 receptor (P2X7R) is a non-selective cation channel which senses high extracellular ATP concentrations and has been suggested as a target for the treatment of neuroinflammation and neurodegenerative diseases. The use of P2X7R antagonists may therefore be a viable approach for treating CNS pathologies, including epileptic disorders. Recent studies showed anticonvulsant potential of P2X7R antagonists in certain animal models. To extend this work, we tested three CNS-permeable P2X7R blocker (Brilliant Blue G, AFC-5128, JNJ-47965567) and a natural compound derivative (tanshinone IIA sulfonate) in four well-characterized animal seizure models. In the maximal electroshock seizure threshold test and the pentylenetetrazol (PTZ) seizure threshold test in mice, none of the four compounds demonstrated anticonvulsant effects when given alone. Notably, in combination with carbamazepine, both AFC-5128 and JNJ-47965567 increased the threshold in the maximal electroshock seizure test. In the PTZ-kindling model in rats, useful for testing antiepileptogenic activities, Brilliant Blue G and tanshinone exhibited a moderate retarding effect, whereas the potent P2X7R blocker AFC-5128 and JNJ-47965567 showed a significant and long-lasting delay in kindling development. In fully kindled rats, the investigated compounds revealed modest effects to reduce the mean seizure stage. Furthermore, AFC-5128- and JNJ-47965567-treated animals displayed strongly reduced Iba 1 and GFAP immunoreactivity in the hippocampal CA3 region. In summary, our results show that P2X7R antagonists possess no remarkable anticonvulsant effects in the used acute screening tests, but can attenuate chemically-induced kindling. Further studies would be of interest to support the concept that P2X7R signalling plays a crucial role in the pathogenesis of epileptic disorders. PMID:27281030

  6. Anthraquinone emodin inhibits human cancer cell invasiveness by antagonizing P2X7 receptors. (United States)

    Jelassi, Bilel; Anchelin, Monique; Chamouton, Julie; Cayuela, María Luisa; Clarysse, Lucie; Li, Junying; Goré, Jacques; Jiang, Lin-Hua; Roger, Sébastien


    The adenosine 5'-triphosphate (ATP)-gated Ca(2+)-permeable channel P2X7 receptor (P2X7R) is strongly upregulated in many tumors and cancer cells, and has an important role in cancer cell invasion associated with metastases. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an anthraquinone derivative originally isolated from Rheum officinale Baill known for decades to possess anticancer properties. In this study, we examined the effects of emodin on P2X7R-dependent Ca(2+) signaling, extracellular matrix degradation, and in vitro and in vivo cancer cell invasiveness using highly aggressive human cancer cells. Inclusion of emodin at doses ≤10 µM in cell culture had no or very mild effect on the cell viability. ATP elicited increases in intracellular Ca(2+) concentration were reduced by 35 and 60% by 1 and 10 µM emodin, respectively. Emodin specifically inhibited P2X7R-mediated currents with an IC50 of 3 µM and did not inhibit the currents mediated by the other human P2X receptors heterologously expressed in human embryonic kidney (HEK293T) cells. ATP-induced increase in gelatinolytic activity, in cancer cell invasiveness in vitro and in cell morphology changes were prevented by 1 µM emodin. Furthermore, such ATP-evoked effects and inhibition by emodin were almost completely ablated in cancer cells transfected with P2X7R-specific small interfering RNA (siRNA) but not with scrambled siRNA. Finally, the in vivo invasiveness of the P2X7R-positive MDA-MB-435s breast cancer cells, assessed using a zebrafish model of micrometastases, was suppressed by 40 and 50% by 1 and 10 µM emodin. Taken together, these results provide consistent evidence to indicate that emodin inhibits human cancer cell invasiveness by specifically antagonizing the P2X7R.

  7. P2X7 receptors mediate resistance to toxin-induced cell lysis. (United States)

    Schoenauer, Roman; Atanassoff, Alexander P; Wolfmeier, Heidi; Pelegrin, Pablo; Babiychuk, Eduard B; Draeger, Annette


    In the majority of cells, the integrity of the plasmalemma is recurrently compromised by mechanical or chemical stress. Serum complement or bacterial pore-forming toxins can perforate the plasma membrane provoking uncontrolled Ca(2+) influx, loss of cytoplasmic constituents and cell lysis. Plasmalemmal blebbing has previously been shown to protect cells against bacterial pore-forming toxins. The activation of the P2X7 receptor (P2X7R), an ATP-gated trimeric membrane cation channel, triggers Ca(2+) influx and induces blebbing. We have investigated the role of the P2X7R as a regulator of plasmalemmal protection after toxin-induced membrane perforation caused by bacterial streptolysin O (SLO). Our results show that the expression and activation of the P2X7R furnishes cells with an increased chance of surviving attacks by SLO. This protective effect can be demonstrated not only in human embryonic kidney 293 (HEK) cells transfected with the P2X7R, but also in human mast cells (HMC-1), which express the receptor endogenously. In addition, this effect is abolished by treatment with blebbistatin or A-438079, a selective P2X7R antagonist. Thus blebbing, which is elicited by the ATP-mediated, paracrine activation of the P2X7R, is part of a cellular non-immune defense mechanism. It pre-empts plasmalemmal damage and promotes cellular survival. This mechanism is of considerable importance for cells of the immune system which carry the P2X7R and which are specifically exposed to toxin attacks.

  8. Selective P2X7 receptor antagonists for chronic inflammation and pain


    Carroll, William A; Donnelly-Roberts, Diana; Jarvis, Michael F.


    ATP, acting on P2X7 receptors, stimulates changes in intracellular calcium concentrations, maturation, and release of interleukin-1β (IL-1β), and following prolonged agonist exposure, cell death. The functional effects of P2X7 receptor activation facilitate several proinflammatory processes associated with arthritis. Within the nervous system, these proinflammatory processes may also contribute to the development and maintenance of chronic pain. Emerging data from genetic knockout studies hav...

  9. P2X7 receptors mediate innate phagocytosis by human neural precursor cells and neuroblasts. (United States)

    Lovelace, Michael D; Gu, Ben J; Eamegdool, Steven S; Weible, Michael W; Wiley, James S; Allen, David G; Chan-Ling, Tailoi


    During early human neurogenesis there is overproduction of neuroblasts and neurons accompanied by widespread programmed cell death (PCD). While it is understood that CD68(+) microglia and astrocytes mediate phagocytosis during target-dependent PCD, little is known of the cell identity or the scavenger molecules used to remove apoptotic corpses during the earliest stages of human neurogenesis. Using a combination of multiple-marker immunohistochemical staining, functional blocking antibodies and antagonists, we showed that human neural precursor cells (hNPCs) and neuroblasts express functional P2X7 receptors. Furthermore, using live-cell imaging, flow cytometry, phagocytic assays, and siRNA knockdown, we showed that in a serum-free environment, doublecortin(+) (DCX) neuroblasts and hNPCs can clear apoptotic cells by innate phagocytosis mediated via P2X7. We found that both P2X7(high) DCX(low) hNPCs and P2X7(high) DCX(high) neuroblasts, derived from primary cultures of human fetal telencephalon, phagocytosed targets including latex beads, apoptotic ReNcells, and apoptotic hNPC/neuroblasts. Pretreatment of neuroblasts and hNPCs with 1 mM adenosine triphosphate (ATP), 100 µM OxATP (P2X7 antagonist), or siRNA knockdown of P2X7 inhibited phagocytosis of these targets. Our results show that P2X7 functions as a scavenger receptor under serum-free conditions resembling those in early neurogenesis. This is the first demonstration that hNPCs and neuroblasts may participate in clearance of apoptotic corpses during pre target-dependent neurogenesis and mediate phagocytosis using P2X7 as a scavenger receptor.

  10. UV Written 2x8 Optical Power Splitter for FTTH Applications

    DEFF Research Database (Denmark)

    Olivero, Massimo; Svalgaard, Mikael


    Silica based integrated optical 2x8 power splitters are reported for the first time using UV-writing waveguide fabrication technology. High performance, compactness and low production costs make these components well suited for deployment in FTTH networks.......Silica based integrated optical 2x8 power splitters are reported for the first time using UV-writing waveguide fabrication technology. High performance, compactness and low production costs make these components well suited for deployment in FTTH networks....

  11. Allosteric modulation of ATP-gated P2X receptor channels (United States)

    Coddou, Claudio; Stojilkovic, Stanko S.; Huidobro-Toro, J. Pablo


    Seven mammalian purinergic receptor subunits, denoted P2X1 to P2X7, and several spliced forms of these subunits have been cloned. When heterologously expressed, these cDNAs encode ATP-gated non-selective cation channels organized as trimers. All activated receptors produce cell depolarization and promote Ca2+ influx through their pores and indirectly by activating voltage-gated calcium channels. However, the biophysical and pharmacological properties of these receptors differ considerably, and the majority of these subunits are also capable of forming heterotrimers with other members of the P2X receptor family, which confers further different properties. These channels have three ATP binding domains, presumably located between neighboring subunits, and occupancy of at least two binding sites is needed for their activation. In addition to the orthosteric binding sites for ATP, these receptors have additional allosteric sites that modulate the agonist action at receptors, including sites for trace metals, protons, neurosteroids, reactive oxygen species and phosphoinositides. The allosteric regulation of P2X receptors is frequently receptor-specific and could be a useful tool to identify P2X members in native tissues and their roles in signaling. The focus of this review is on common and receptor-specific allosteric modulation of P2X receptors and the molecular base accounting for allosteric binding sites. PMID:21639805

  12. P2X7 receptor-mediated analgesia in cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; D. Schwab, Samantha; Frøsig-Jørgensen, Majbrit


    for cancer-induced bone pain. The P2X7 receptor (P2X7R) is involved in a variety of cellular functions and has been linked to both inflammatory and neuropathic pain. Here we study the analgesic potential of P2X7 receptor antagonism in a rat model of cancer-induced bone pain. In cancer-bearing animals, the P2......Pain is a common and debilitating complication for cancer patients significantly compromising their quality of life. Cancer-induced bone pain involves a complex interplay of molecular events, including mechanisms observed in inflammatory and neuropathic pain states, but also changes unique....... The results suggest that the P2X7R is involved in the mechanisms of cancer-induced bone pain, and that P2X7R antagonism might be a useful analgesic target. No effect was observed in sham or naïve animals, indicating that the P2X7R-mediated effect is state-dependent, and might therefore be an advantageous...

  13. Molecular and functional properties of P2X receptors--recent progress and persisting challenges. (United States)

    Kaczmarek-Hájek, Karina; Lörinczi, Eva; Hausmann, Ralf; Nicke, Annette


    ATP-gated P2X receptors are trimeric ion channels that assemble as homo- or heteromers from seven cloned subunits. Transcripts and/or proteins of P2X subunits have been found in most, if not all, mammalian tissues and are being discovered in an increasing number of non-vertebrates. Both the first crystal structure of a P2X receptor and the generation of knockout (KO) mice for five of the seven cloned subtypes greatly advanced our understanding of their molecular and physiological function and their validation as drug targets. This review summarizes the current understanding of the structure and function of P2X receptors and gives an update on recent developments in the search for P2X subtype-selective ligands. It also provides an overview about the current knowledge of the regulation and modulation of P2X receptors on the cellular level and finally on their physiological roles as inferred from studies on KO mice.

  14. Role of P2X7 receptors in the development of diabetic retinopathy. (United States)

    Sugiyama, Tetsuya


    The P2X7 receptor is one of the members of the family of purinoceptors which are ligand-gated membrane ion channels activated by extracellular adenosine 5'-triphosphate. A unique feature of the P2X7 receptor is that its activation can result in the formation of large plasma membrane pores that allow not only the flux of ions but also of hydrophilic molecules of up to 900 Da. Recent studies indicate that P2X7-mediated signaling can trigger apoptotic cell death after ischemia and during the course of certain neurodegenerative disorders. Expression of the P2X7 receptor has been demonstrated in most types of cells in the retina. This purinoceptor mediates the contraction of pericytes and regulates the spatial and temporal dynamics of the vasomotor response through cell-to-cell electrotonic transmission within the microvascular networks. Of potential clinical significance, investigators have found that diabetes markedly boosts the vulnerability of retinal microvessels to the lethal effect of P2X7 receptor activation. This purinergic vasotoxicity may result in reduced retinal blood flow and disrupted vascular function in the diabetic retina. With recent reports indicating an association between P2X7 receptor activation and inflammatory cytokine expression in the retina, this receptor may also exacerbate the development of diabetic retinopathy by a mechanism involving inflammation.

  15. P2X7 receptors induce degranulation in human mast cells. (United States)

    Wareham, Kathryn J; Seward, Elizabeth P


    Mast cells play important roles in host defence against pathogens, as well as being a key effector cell in diseases with an allergic basis such as asthma and an increasing list of other chronic inflammatory conditions. Mast cells initiate immune responses through the release of newly synthesised eicosanoids and the secretion of pre-formed mediators such as histamine which they store in specialised granules. Calcium plays a key role in regulating both the synthesis and secretion of mast-cell-derived mediators, with influx across the membrane, in particular, being necessary for degranulation. This raises the possibility that calcium influx through P2X receptors may lead to antigen-independent secretion of histamine and other granule-derived mediators from human mast cells. Here we show that activation of P2X7 receptors with both ATP and BzATP induces robust calcium rises in human mast cells and triggers their degranulation; both effects are blocked by the P2X7 antagonist AZ11645373, or the removal of calcium from the extracellular medium. Activation of P2X1 receptors with αβmeATP also induces calcium influx in human mast cells, which is significantly reduced by both PPADS and NF 449. P2X1 receptor activation, however, does not trigger degranulation. The results indicate that P2X7 receptors may play a significant role in contributing to the unwanted activation of mast cells in chronic inflammatory conditions where extracellular ATP levels are elevated.

  16. Activation of P2X7 receptors decreases the proliferation of murine luteal cells. (United States)

    Wang, Jing; Liu, Shuangmei; Nie, Yijun; Wu, Bing; Wu, Qin; Song, Miaomiao; Tang, Min; Xiao, Li; Xu, Ping; Tan, Ximin; Zhang, Luyin; Li, Gang; Liang, Shangdong; Zhang, Chunping


    Extracellular ATP regulates cellular function in an autocrine or paracrine manner through activating purinergic signalling. Studies have shown that purinergic receptors were expressed in mammalian ovaries and they have been proposed as an intra-ovarian regulatory mechanism. P2X7 was expressed in porcine ovarian theca cells and murine and human ovarian surface epithelium and is involved in ATP-induced apoptotic cell death. However, the role of P2X7 in corpus luteum is still unclear. The aim of this study was to investigate the role of ATP signalling in murine luteal cells and the possible mechanism(s) involved. We found that P2X7 was highly expressed in murine small luteal cells. The agonists of P2X7, ATP and BzATP, inhibited the proliferation of luteal cells. P2X7 antagonist BBG reversed the inhibition induced by ATP and BzATP. Further studies showed that ATP and BzATP inhibited the expression of cell cycle regulators cyclinD2 and cyclinE2. ATP and BzATP also inhibited the p38-mitogen-activated protein kinase (MAPK) signalling pathway. These results reveal that P2X7 receptor activation is involved in corpus luteum formation and function.

  17. 矿物钠快离子导体Na1+3x+yAlxNdyTi2-x-ySi2xP3-2xO12合成与表征%Synthesis and characterization of Na1+3x+yAlxNdyTi2-x-ySi2xP3-2xO12 mineral sodium fast ionic conductors

    Institute of Scientific and Technical Information of China (English)

    曾飞; 蔡增良; 王文继



  18. The comparison of visible-light photocatalytic activity for the degradation of propylene between Ag TiO2-x Nx and TiO2-x Nx%Ag/TiO2-x Nx 与 TiO2-x Nx 可见光催化降解丙烯的活性对比

    Institute of Scientific and Technical Information of China (English)

    张郴艳; 朱兆田; 彭琳珊; 马清晨; 王曼丽; 庞钰华; 何建英; 冯彩霞


    利用纳米管钛酸(NTA)和氨水的水热反应制得 TiO 2-x Nx 系列催化剂,并进一步通过热分解-机械研磨的方法在 TiO 2-x Nx 表面附着上银颗粒,制得 Ag/TiO 2-x Nx 系列催化剂。采用 X 射线衍射(XRD)、紫外-可见漫反射(DRS)、X 射线光电子能谱(XPS)等技术对催化剂进行了表征和分析。光催化氧化丙烯的实验对比了TiO 2-x Nx 与 Ag/TiO 2-x Nx 两个系列催化剂的可见光催化活性,考察了氧空位、晶型结构、氮含量和银颗粒对催化剂可见光催化活性的影响。结果表明,催化剂锐钛矿的晶型越好,氧空位含量越高,催化剂的可见光催化活性越好;贵金属银的电子捕获能力使得 Ag/TiO 2-x Nx 的可见光催化活性远高于 TiO 2-x Nx 催化剂。%TiO 2 -x Nx series of catalysts were prepared by hydrothermal reaction method using nanotubed titanic acid (denoted as NTA)and ammonia as raw materials.Furthermore,silver nanoparticles were loaded on the surface of TiO 2 -x Nx by thermal decomposition-mechanical grinding method to produce Ag/TiO 2 -x Nx photocatalysts,TiO 2 -x Nx catalysts were character-ized by X-ray diffraction (XRD),UV-Vis diffuse reflectance spectroscopy (DRS)and X-ray photoelectron spectroscopy (XPS).The visible-light activity of two series of photocatalysts, TiO 2 -x Nx and Ag/TiO 2 -x Nx ,were compared by the degradation of propylene.Some effects of oxygen vacancy,crystal structure,contents of doped nitrogen and loaded silver on the visible-light activity were also studied.Results show that the better anatase structure and the higher content of oxygen vacancy are the higher visible-light activity will be.In addition,the visible-light activity of Ag/TiO 2 -x Nx is much higher than that of TiO 2 -x Nx due to the strong trapping electron ability of noble metal silver.

  19. A solid solution series of atacamite type Ni{sub 2x}Mg{sub 2−2x}Cl(OH){sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Bette, Sebastian [TU Bergakademie Freiberg, Institute of Inorganic Chemistry, Leipziger Strasse 29, Freiberg 09596 (Germany); Dinnebier, Robert E. [Max Planck Institute for Solid State Research, Heisenbergstrasse 1, Stuttgart 70569 (Germany); Röder, Christian [TU Bergakademie Freiberg, Institute of Theoretical Physics, Leipziger Strasse 23, Freiberg 09596 (Germany); Freyer, Daniela, E-mail: [TU Bergakademie Freiberg, Institute of Inorganic Chemistry, Leipziger Strasse 29, Freiberg 09596 (Germany)


    For the first time a complete solid solution series Ni{sub 2x}Mg{sub 2−2x}Cl(OH){sub 3} of an atacamite type alkaline main group metal chloride, Mg{sub 2}Cl(OH){sub 3}, and a transition group metal chloride, Ni{sub 2}Cl(OH){sub 3}, was prepared and characterized by chemical and thermal analysis as well as by Raman and IR spectroscopy, and high resolution laboratory X-ray powder diffraction. All members of the solid solution series crystallize in space group Pnam (62). The main building units of these crystal structures are distorted, edge-linked Ni/MgO{sub 4}Cl{sub 2} and Ni/MgO{sub 5}Cl octahedra. The distribution of Ni{sup 2+}- and Mg{sup 2+}-ions among these two metal-sites within the solid solution series is discussed in detail. The crystallization of the solid solution phases occurs via an intermediate solid solution series, (Ni/Mg)Cl{sub 2x}(OH){sub 2−2x}, with variable Cl: OH ratio up to the 1:3 ratio according to the formula Ni{sub 2x}Mg{sub 2−2x} Cl(OH){sub 3}. For one isolated intermediate solid solution member, Ni{sub 0.70}Mg{sub 0.30}Cl{sub 0.58}(OH){sub 1.42}, the formation and crystal structure is presented as well. - Graphical abstract: For the first time a complete solid solution series, Ni{sub 2x}Mg{sub 2−2x} Cl(OH){sub 3}, was synthesized and characterized. Structure solution by revealed that Ni{sup 2+} prefers to occupy the Jahn–Teller-like distorted hole, out of two available cation sites. Substitution of Ni{sup 2+} by Mg{sup 2+} in atacamite type Ni{sub 2}Cl(OH){sub 3} results in systematic band shifts in Raman and IR spectra as well as in systematic changes in thermal properties. The α-polymorphs M{sub 2}Cl(OH){sub 3} with M=Mg{sup 2+}, Ni{sup 2+} and other divalent transition metal ions, as described in literature, were identified as separate compounds. - Highlights: • First synthesis of solid solution series between main and transition metal chloride. • Ni{sup 2+} prefers to occupy Jahn–Teller-like distorted octahedral holes

  20. Recovery of citrus triploid hybrids by embryo rescue and flow cytometry from 2x x 2x sexual hybridisation and its application to extensive breeding programs. (United States)

    Aleza, P; Juárez, J; Cuenca, J; Ollitrault, P; Navarro, Luis


    Seedlessness is one of the most important characteristics for mandarins for the fresh-fruit market and mandarin triploid hybrids have this trait. Citrus triploid plants can be recovered by 2x x 2x sexual hybridisations as a consequence of the formation of unreduced gametes at low frequency. Triploid embryos are found in small seeds that do not germinate under greenhouse conditions. Extensive breeding programs based on this type of hybridisation require very effective methodologies for embryo rescue and ploidy evaluation. In this work, we describe an effective methodology to recover triploid hybrids from 2x x 2x hybridisations based on in vitro embryo rescue and ploidy level determination by means of flow cytometry. The influence of parents and environmental conditions on obtaining triploid hybrids has been analysed. The strongest effect was associated with the genotype of the female parent while a strong interaction was found between the male parent genotype and environmental conditions. The effect of the female parent genotype on the length of the juvenile phase was also demonstrated by observing a large number of progenies over the last 10 years. The methodology described here has enabled us to obtain over 4,000 triploid hybrids so far, of which 13 have been protected in the European Union and two are being extensively planted by citrus growers to establish new commercial plots. These triploid hybrids have been analysed with simple sequence repeats markers to differentiate all the new triploid varieties and their parents, and thus molecular identification will help defend plant breeders' rights.

  1. Electronic structure and thermoelectric properties of (Mg2X)2 / (Mg2Y)2 (X, Y = Si, Ge, Sn) superlattices from first-principle calculations (United States)

    Guo, San-Dong


    To identify thermoelectric materials containing abundant, low-cost and non-toxic elements, we have studied the electronic structures and thermoelectric properties of (Mg2X)2/ (Mg2Y)2 (X, Y = Si, Ge, Sn) superlattices with state-of-the-art first-principles calculations using a modified Becke and Johnson (mBJ) exchange potential. Our results show that (Mg2Ge)2/ (Mg2Sn)2 and (Mg2Si)2/ (Mg2Sn)2 are semi-metals using mBJ plus spin-orbit coupling (mBJ + SOC), while (Mg2Si)2/ (Mg2Ge)2 is predicted to be a direct-gap semiconductor with a mBJ gap value of 0.46 eV and mBJ + SOC gap value of 0.44 eV. Thermoelectric properties are predicted by through solving the Boltzmann transport equations within the constant scattering time approximation. It is found that (Mg2Si)2/ (Mg2Ge)2 has a larger Seebeck coefficient and power factor than (Mg2Ge)2/ (Mg2Sn)2 and (Mg2Si)2/ (Mg2Sn)2 for both p-type and n-type doping. The detrimental influence of SOC on the power factor of p-type (Mg2X)2/ (Mg2Y)2 (X, Y = Si, Ge, Sn) is analyzed as a function of the carrier concentration, but there is a negligible SOC effect for n-type. These results can be explained by the influence of SOC on their valence and conduction bands near the Fermi level.

  2. Crystal structure, phase transition and conductivity study of two new organic - inorganic hybrids: [(CH2)7(NH3)2]X2, X = Cl/Br (United States)

    Mostafa, Mohga Farid; El-khiyami, Shimaa Said; Abd-Elal, Seham Kamal


    Two hybrids 1,7-heptanediammonium di-halide, [(C7H20N2]X2,X = Cl/Br crystallize in monoclinic P21/c, Z = 4. [(C7H20N2]Cl2: a = 4.7838 (2) Å, b = 16.9879 (8) Å, c = 13.9476 (8) Å, β = 97.773 (2)°, V = 1203.58(10) Å3, D = 1.137 g/cm3, λ = 0.71073 Å, R = 0.052 for 1055 reflections with I > 2σ(I), T = 298(2) K. [(C7H20N2]Br2: a = 4.7952 (10) Å, b = 16.9740 (5) Å, c = 13.9281 (5) Å, β = 97.793 (2)°, V = 1203.83(6) Å3, D = 1.612 g/cm3, λ = 0.71073 Å, R = 0.03 for 1959 reflections with I > 2σ(I) T = 298(2) K. Asymmetric unit cell of [(C7H20N2]X2,X = Cl/Br, each consist of one heptane-1,7-diammonium cation and two halide anions. The organic hydrocarbon layers pack in a stacked herring-bone manner, hydrogen bonded to the halide ions. Lattice potential energy is 1568.59 kJ/mol and 1560.78 kJ/mol, and cation molar volumes are 0.295 nm3 and 0.300 nm3 for chloride and bromide respectively. DTA confirmed chain melting transitions for both hybrids below T ∼ 340 K. Dielectric and ac conductivity measurements (290 340 K. Cross over from Jonscher's universal dielectric response at low temperatures T 340 K is observed. At high temperatures halide ion hopping in accordance with the jump relaxation model prevails.

  3. Study of ferrite Co1 + x Ti x Fe2-2 x O4 (0.2 < x < 0.5) nanoparticles for magnetic hyperthermia (United States)

    Kamzin, A. S.; Ichiyanagi, Y.


    Magnetic nanoparticles (MNPs) of Co1 + x Ti x Fe2-2 x O4 (0.2 MNP released heat as a function of the applied external alternating magnetic field (EAMF) strength and frequency, the particle heating mechanisms are studied. The imaginary part of the magnetic susceptibility χ″ identical to the MNP heat release is analyzed at room temperature in an EAMF of strength 1 Oe and a frequency of 100 Hz. The χ″ maximum temperature decreases with increasing Ti content in CoTi spinel. An increase in the temperature by 10 K was observed in an EAMF of frequency 10 kHz and a strength of 300 Oe. The temperature increase rate ΔT/ dt was measured in the range from 0.001 to 0.008 K/s depending on the EAMF frequency and sample composition. It is found that Co1 + x Ti x Fe2-2 x O4 MNPs synthesized at 0.2 < x < 0.5 satisfy the requirements imposed on materials used as heat sources during magnetic hyperthermia. Based on measurements of the magnetic susceptibility in an EAMF and Mössbauer studies, it is shown that CoTi ferrite MNPs with a titanium ion content x = 0.3, i.e., Co1.3Ti0.3Fe1.4O4, are most efficient for magnetic hyperthermia.

  4. The planarian P2X homolog in the regulation of asexual reproduction. (United States)

    Sakurai, Toshihide; Lee, Hayoung; Kashima, Makoto; Saito, Yumi; Hayashi, Tetsutaro; Kudome-Takamatsu, Tomomi; Nishimura, Osamu; Agata, Kiyokazu; Shibata, Norito


    The growth in size of freshwater planarians in response to nutrient intake is limited by the eventual separation of tail and body fragments in a process called fission. The resulting tail fragment regenerates the entire body as an artificially amputated tail fragment would do, and the body fragment regenerates a tail, resulting in two whole planarians. This regenerative ability is supported by pluripotent somatic stem cells, called neoblasts, which are distributed throughout almost the entire body of the planarian. Neoblasts are the only planarian cells with the ability to continuously proliferate and give rise to all types of cells during regeneration, asexual reproduction, homeostasis, and growth. In order to investigate the molecular characteristics of neoblasts, we conducted an extensive search for neoblast-specific genes using the High Coverage Expression Profiling (HiCEP) method, and tested the function of the resulting candidates by RNAi. Disruption of the expression of one candidate gene, DjP2X-A (Dugesia japonica membrane protein P2X homologue), resulted in a unique phenotype. DjP2X-A RNAi leads to an increase of fission events upon feeding. We confirmed by immunohistochemistry that DjP2X-A is a membrane protein, and elucidated its role in regulating neoblast proliferation, thereby explaining its unique phenotype. We found that DjP2X-A decreases the burst of neoblast proliferation that normally occurs after feeding. We also found that DjP2X-A is required for normal proliferation in starved animals. We propose that DjP2X-A modulates stem cell proliferation in response to the nutritional condition.

  5. P2X receptor-mediated ATP purinergic signaling in health and disease

    Directory of Open Access Journals (Sweden)

    Jiang LH


    Full Text Available Lin-Hua JiangSchool of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomAbstract: Purinergic P2X receptors are plasma membrane proteins present in a wide range of mammalian cells where they act as a cellular sensor, enabling cells to detect and respond to extracellular adenosine triphosphate (ATP, an important signaling molecule. P2X receptors function as ligand-gated Ca2+-permeable cationic channels that open upon ATP binding to elevate intracellular Ca2+ concentrations and cause membrane depolarization. In response to sustained activation, P2X receptors induce formation of a pore permeable to large molecules. P2X receptors also interact with distinct functional proteins and membrane lipids to form specialized signaling complexes. Studies have provided compelling evidence to show that such P2X receptor-mediated ATP-signaling mechanisms determine and regulate a growing number and diversity of important physiological processes, including neurotransmission, muscle contraction, and cytokine release. There is accumulating evidence to support strong causative relationships of altered receptor expression and function with chronic pain, inflammatory diseases, cancers, and other pathologies or diseases. Numerous high throughput screening drug discovery programs and preclinical studies have thus far demonstrated the proof of concepts that the P2X receptors are druggable targets and selective receptor antagonism is a promising therapeutics approach. This review will discuss the recent progress in understanding the mammalian P2X receptors with respect to the ATP-signaling mechanisms, physiological and pathophysiological roles, and development and preclinical studies of receptor antagonists.Keywords: extracellular ATP, ion channel, large pore, signaling complex, chronic pain, inflammatory diseases

  6. Expression and function of the purinergic receptor P2X7 in patients with pulmonary tuberculosis. (United States)

    Franco-Martínez, S; Niño-Moreno, P; Bernal-Silva, S; Baranda, L; Rocha-Meza, M; Portales-Cervantes, L; Layseca-Espinosa, E; González-Amaro, R; Portales-Pérez, D


    P2X(7) is a channel receptor gated by adenosine triphosphate (ATP) that is involved in the killing of intracellular mycobacteria. To explore further the role of P2X(7) in immunity against Mycobacterium tuberculosis, we studied its expression and function in 19 patients with pulmonary tuberculosis (TB) and 19 healthy contacts. Flow cytometry analysis showed a similar and variable expression of P2X(7) in TB patients and healthy subjects. In contrast, P2X(7) mARN levels were significantly higher in TB patients. When the function of the P2X(7) receptor in peripheral blood mononuclear cells (PBMC) was assessed by the effect of exogenous ATP on apoptosis, the uptake of the fluorescent marker Lucifer yellow or extracellular signal regulated kinase (ERK) phosphorylation, no significant differences were detected in patients and controls. However, mRNA macroarray analysis showed that upon stimulation with ATP, the PBMC from TB patients showed a significant induction of a higher number of cytokine genes (27 of 96), and a lower number of apoptosis genes (20 of 96) compared to healthy controls (17 and 76 genes, respectively). These results suggest that although the PBMC from TB patients do not show apparent abnormalities in the expression of P2X(7), and the intracellular signals generated through it, the pattern of gene expression induced by ATP in these cells is different from that found in healthy contacts. This phenomenon suggests a defective function of P2X(7) in the immune cells from TB patients, a condition that may contribute to the inability of these patients to eliminate the mycobacteria.

  7. Structural, electronic and optical properties of AgXY{sub 2}(X = Al, Ga, In and Y = S, Se, Te)

    Energy Technology Data Exchange (ETDEWEB)

    Ullah, Saeed; Din, Haleem Ud [Materials Modeling Lab, Department of Physics, Islamia College University, Peshawar (Pakistan); Murtaza, G., E-mail: [Materials Modeling Lab, Department of Physics, Islamia College University, Peshawar (Pakistan); Ouahrani, T. [Laboratoire de Physique Théorique, B.P. 119, Université de Tlemcen, Tlemcen 13000 (Algeria); Khenata, R., E-mail: [Laboratoire de Physique Quantique et de Modélisation Mathématique, Université de Mascara, Mascara 29000 (Algeria); Naeemullah [Department of Physics, G.D.C. Darra Adam Khel, F.R. Kohat, KPK (Pakistan); Bin Omran, S. [Department of Physics and Astronomy, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia)


    Highlights: • The compounds are studied by FP-LAPW method within mBJ approximation. • All of the studied materials show isotropic behavior. • All the compounds show direct band gap nature. • Bonding nature is mostly covalent among the studied compounds. • High absorption peaks and reflectivity ensures there utility in optoelectronic devices. - Abstract: The structural, electronic and optical properties of the ternary semiconducting compounds AgXY{sub 2} (X = Al, Ga, In and Y = S, Se, Te) in Heusler and chalcopyrite crystal phases have been investigated using the density functional theory (DFT) based on the full potential linear augmented plane wave (FP-LAPW) method. The calculated lattice constant and band gap values for AgXY{sub 2} in chalcopyrite phase are in good agreement with the available experimental data. Band structure calculations are performed using modified Becke–Johnson (mBJ) method which match closely with experimental data and yield better band gaps rather than those obtained by using generalized gradient approximation (GGA) and Engel–Vosko generalized gradient approximation (EV–GGA). Decrease in band gap is observed by changing cations X and Y from the top to bottom of periodic table. Chemical bonding trends are predicted through charge density plots and quantified by Bader’s analysis. Optical properties reveal that these compounds are suitable candidates for optoelectronic devices in the visible and ultraviolet (UV) regions.

  8. Detection of P2z/P2x7 Receptors%P2z/P2x7受体检测的研究

    Institute of Scientific and Technical Information of China (English)

    彭黎明; 杨寒朔; 张芹


    目的检测白血病细胞的P2z/P2x7受体.方法将T淋巴细胞白血病细胞株(CEM)、急性单核细胞白血病细胞株(THP-1)、M2型白血病细胞株(HL-60)、M3型白血病细胞株(NB4)、巨核细胞病细胞株(Dami/Dam)和伯基特淋巴瘤细胞株(Raji)共六株白血病细胞株制成2×107/ml的细胞悬液,分别加入P2z/P2x7受体的激动剂ATP和/或特异性抑制剂KN-62,测定加入前后细胞内荧光强度变化,同时以P2z/P2x7受体多克隆抗体免疫组化ABC法鉴定P2z/P2x7受体.结果① 0.4 mmol/L的ATP对于THP-1、NB4和HL-60细胞株钙离子通透性有较强的激活作用,其激活率分别为54.91%、39.45%和30.46%;ATP对CEM、Dam和Raji细胞株的激活作用很弱,激活率分别为10.435%、13.215%和2.67%; KN-62对THP-1有很强的抑制作用(抑制率达88.74%),而对NB4和HL-60的抑制作用很弱(抑制率仅为15.81%和12.50%),对Raji细胞株没有抑制作用;②免疫组化ABC法显示各对照细胞株均成阴性,而白血病细胞株均成阳性.结论 THP-1细胞含P2z/P2x7受体,NB4和HL-60含P2受体其它亚型的细胞株,CEM、Raji和Dam细胞株不含P2z/P2x7受体;免疫组化ABC法使用的多克隆抗体与其它蛋白有交叉反应,其结果不具P2z/P2x7受体特异性.

  9. In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization. (United States)

    Ford, Anthony P


    Treating pain by inhibiting ATP activation of P2X3-containing receptors heralds an exciting new approach to pain management, and Afferent's program marks the vanguard in a new class of drugs poised to explore this approach to meet the significant unmet needs in pain management. P2X3 receptor subunits are expressed predominately and selectively in so-called C- and Aδ-fiber primary afferent neurons in most tissues and organ systems, including skin, joints, and hollow organs, suggesting a high degree of specificity to the pain sensing system in the human body. P2X3 antagonists block the activation of these fibers by ATP and stand to offer an alternative approach to the management of pain and discomfort. In addition, P2X3 is expressed pre-synaptically at central terminals of C-fiber afferent neurons, where ATP further sensitizes transmission of painful signals. As a result of the selectivity of the expression of P2X3, there is a lower likelihood of adverse effects in the brain, gastrointestinal, or cardiovascular tissues, effects which remain limiting factors for many existing pain therapeutics. In the periphery, ATP (the factor that triggers P2X3 receptor activation) can be released from various cells as a result of tissue inflammation, injury or stress, as well as visceral organ distension, and stimulate these local nociceptors. The P2X3 receptor rationale has aroused a formidable level of investigation producing many reports that clarify the potential role of ATP as a pain mediator, in chronic sensitized states in particular, and has piqued the interest of pharmaceutical companies. P2X receptor-mediated afferent activation has been implicated in inflammatory, visceral, and neuropathic pain states, as well as in airways hyperreactivity, migraine, itch, and cancer pain. It is well appreciated that oftentimes new mechanisms translate poorly from models into clinical efficacy and effectiveness; however, the breadth of activity seen from P2X3 inhibition in models offers

  10. Purinergic P2X7 receptors mediate cell death in mouse cerebellar astrocytes in culture. (United States)

    Salas, Elvira; Carrasquero, Luz María G; Olivos-Oré, Luis A; Bustillo, Diego; Artalejo, Antonio R; Miras-Portugal, Maria Teresa; Delicado, Esmerilda G


    The brain distribution and functional role of glial P2X7 receptors are broader and more complex than initially anticipated. We characterized P2X7 receptors from cerebellar astrocytes at the molecular, immunocytochemical, biophysical, and cell physiologic levels. Mouse cerebellar astrocytes in culture express mRNA coding for P2X7 receptors, which is translated into P2X7 receptor protein as proven by Western blot analysis and immunocytochemistry. Fura-2 imaging showed cytosolic calcium responses to ATP and the synthetic analog 3'-O-(4-benzoyl)benzoyl-ATP (BzATP) exhibited two components, namely an initial transient and metabotropic component followed by a sustained one that depended on extracellular calcium. This latter component, which was absent in astrocytes from P2X7 receptor knockout mice (P2X7 KO), was modulated by extracellular Mg(2+), and was sensitive to Brilliant Blue G (BBG) and 3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methyl pyridine (A438079) antagonism. BzATP also elicited inwardly directed nondesensitizing whole-cell ionic currents that were reduced by extracellular Mg(2+) and P2X7 antagonists (BBG and calmidazolium). In contrast to that previously reported in rat cerebellar astrocytes, sustained BzATP application induced a gradual increase in membrane permeability to large cations, such as N-methyl-d-glucamine and 4-[3-methyl-2(3H)-benzoxazolylidene)-methyl]-1-[3-(triethylammonio)propyl]diiodide, which ultimately led to the death of mouse astrocytes. Cerebellar astrocyte cell death was prevented by BBG but not by calmidazolium, removal of extracellular calcium, or treatment with the caspase-3 inhibitor, benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone, thus suggesting a necrotic-type mechanism of cell death. Since this cellular response was not observed in astrocytes from P2X7 KO mice, this study suggests that stimulation of P2X7 receptor may convey a cell death signal to cerebellar astrocytes in a species-specific manner.

  11. Photovoltaic device

    Energy Technology Data Exchange (ETDEWEB)

    Reese, Jason A; Keenihan, James R; Gaston, Ryan S; Kauffmann, Keith L; Langmaid, Joseph A; Lopez, Leonardo; Maak, Kevin D; Mills, Michael E; Ramesh, Narayan; Teli, Samar R


    The present invention is premised upon an improved photovoltaic device ("PV device"), more particularly to an improved photovoltaic device with a multilayered photovoltaic cell assembly and a body portion joined at an interface region and including an intermediate layer, at least one interconnecting structural member, relieving feature, unique component geometry, or any combination thereof.

  12. Photovoltaic device (United States)

    Reese, Jason A.; Keenihan, James R.; Gaston, Ryan S.; Kauffmann, Keith L.; Langmaid, Joseph A.; Lopez, Leonardo C.; Maak, Kevin D.; Mills, Michael E.; Ramesh, Narayan; Teli, Samar R.


    The present invention is premised upon an improved photovoltaic device ("PV device"), more particularly to an improved photovoltaic device with a multilayered photovoltaic cell assembly and a body portion joined at an interface region and including an intermediate layer, at least one interconnecting structural member, relieving feature, unique component geometry, or any combination thereof.

  13. Photovoltaic device (United States)

    Reese, Jason A.; Keenihan, James R.; Gaston, Ryan S.; Kauffmann, Keith L.; Langmaid, Joseph A.; Lopez, Leonardo C.; Maak, Kevin D.; Mills, Michael E.; Ramesh, Narayan; Teli, Samar R.


    The present invention is premised upon an improved photovoltaic device ("PV device"), more particularly to an improved photovoltaic device (10) with a multilayered photovoltaic cell assembly (100) and a body portion (200) joined at an interface region (410) and including an intermediate layer (500), at least one interconnecting structural member (1500), relieving feature (2500), unique component geometry, or any combination thereof.

  14. Lack of run-down of smooth muscle P2X receptor currents recorded with the amphotericin permeabilized patch technique, physiological and pharmacological characterization of the properties of mesenteric artery P2X receptor ion channels. (United States)

    Lewis, C J; Evans, R J


    Immunoreactivity for P2X(1), P2X(4) and P2X(5) receptor subtypes was detected in the smooth muscle cell layer of second and third order rat mesenteric arteries immunoreactivity, for P2X(2), P2X(3), P2X(6) and P2X(7) receptors was below the level of detection in the smooth muscle layer. P2X receptor-mediated currents were recorded in patch clamp studies on acutely dissociated mesenteric artery smooth muscle cells. Purinergic agonists evoked transient inward currents that decayed rapidly in the continued presence of agonist (tau approximately 200 ms). Standard whole cell responses to repeated applications of agonist at 5 min intervals ran down. Run-down was unaffected by changes in extracellular calcium concentration, intracellular calcium buffering or the inclusion of ATP and GTP in the pipette solution. Run-down was overcome and reproducible responses to purinergic agonists were recorded using the amphotericin permeabilized patch recording configuration. The rank order of potency at the P2X receptor was ATP=2 methylthio ATP>alpha, beta-methylene ATP>CTP=l-beta,gamma-methylene ATP. Only ATP and 2meSATP were full agonists. The P2 receptor antagonists suramin and PPADS inhibited P2X receptor-mediated currents with IC(50)s of 4 microM and 70 nM respectively. These results provide further characterization of artery P2X receptors and demonstrate that the properties are dominated by a P2X(1)-like receptor phenotype. No evidence could be found for a phenotype corresponding to homomeric P2X(4) or P2X(5) receptors or to heteromeric P2X(1/5) receptors and the functional role of these receptors in arteries remains unclear.

  15. Theoretical investigation of superconductivity in MgB2-xCx alloys (United States)

    Sharma, Gargee; Sharma, Smita


    In this paper we investigated the superconducting properties of MgB2-xCx alloys where x is the concentration (0.0, 0.03, 0.11 and 0.20). The superconducting state parameters, namely, the electron-phonon coupling strength (λ), Coulomb pseudopotential (μ*), transition temperature (Tc), isotope effect exponent (α) and interaction strength (NoV) of MgB2-xCx alloys have been investigated in the BCS-Eliashberg-McMillan framework, as modified for MgB2-xCx alloys. Pseudo ions with average properties have been considered to replace different types of ions in the system. It is observed that all the superconducting parameters go on decreasing as the concentration of C is increased. The magnitudes of λ and Tc indicate that MgB2-xCx is strong-to-intermediate coupling superconductor. It is also observed that Tc is composition dependent. Present computations yield almost linear variation of Tc with concentration x of C in the MgB2-xCx system, which is in agreement with the experimental data. A linear Tc equation is proposed by fitting the present results.

  16. Functional polymorphisms in the P2X7 receptor gene are associated with osteoporosis

    DEFF Research Database (Denmark)

    Husted, L B; Harsløf, T; Stenkjær, L;


    -rays. RESULTS: The rare allele of a splice site polymorphism, 151 + 1: G-T, was associated with increased fracture risk and reduced BMD in women. Two other loss-of-function polymorphisms, Glu496Ala and Gly150Arg, were also associated with BMD. The Glu496Ala variant allele was associated with decreased lumbar......UNLABELLED: The P2X(7) receptor is an ATP-gated cation channel. We investigated the effect of both loss-of-function and gain-of-function polymorphisms in the P2X(7) receptor gene on BMD and risk of vertebral fractures and found that five polymorphisms and haplotypes containing three...... of these polymorphisms were associated with BMD and fracture risk. INTRODUCTION: The P2X(7) receptor is an ATP-gated cation channel. P2X(7) receptor knockout mice have reduced total bone mineral content, and because several functional polymorphisms have been identified in the human P2X(7) receptor gene, we wanted...

  17. Purinergic signaling in the cerebellum: Bergmann glial cells express functional ionotropic P2X7 receptors. (United States)

    Habbas, Samia; Ango, Fabrice; Daniel, Hervé; Galante, Micaela


    Astrocytes constitute active networks of intercommunicating cells that support the metabolism and the development of neurons and affect synaptic functions via multiple pathways. ATP is one of the major neurotransmitters mediating signaling between neurons and astrocytes. Potentially acting through both purinergic metabotropic P2Y receptors (P2YRs) and ionotropic P2X receptors (P2XRs), up until now ATP has only been shown to activate P2YRs in Bergmann cells, the radial glia of the cerebellar cortex that envelopes Purkinje cell afferent synapses. In this study, using multiple experimental approaches in acute cerebellar slices we demonstrate the existence of functional P2XRs on Bergmann cells. In particular, we show here that Bergmann cells express uniquely P2X7R subtypes: (i) immunohistochemical analysis revealed the presence of P2X7Rs on Bergmann cell processes, (ii) in whole cell recordings P2XR pharmacological agonists induced depolarizing currents that were blocked by specific antagonists of P2X7Rs, and could not be elicited in slices from P2X₇R-deficient mice and finally, (iii) calcium imaging experiments revealed two distinct calcium signals triggered by application of exogenous ATP: a transient signal deriving from release of calcium from intracellular stores, and a persistent one following activation of P2X7Rs. Our data thus reveal a new pathway by which extracellular ATP may affect glial cell function, thus broadening our knowledge on purinergic signaling in the cerebellum.

  18. Quantifying Ca2+ current and permeability in ATP-gated P2X7 receptors. (United States)

    Liang, Xin; Samways, Damien S K; Wolf, Kyle; Bowles, Elizabeth A; Richards, Jennifer P; Bruno, Jonathan; Dutertre, Sébastien; DiPaolo, Richard J; Egan, Terrance M


    ATP-gated P2X7 receptors are prominently expressed in inflammatory cells and play a key role in the immune response. A major consequence of receptor activation is the regulated influx of Ca(2+) through the self-contained cation non-selective channel. Although the physiological importance of the resulting rise in intracellular Ca(2+) is universally acknowledged, the biophysics of the Ca(2+) flux responsible for the effects are poorly understood, largely because traditional methods of measuring Ca(2+) permeability are difficult to apply to P2X7 receptors. Here we use an alternative approach, called dye-overload patch-clamp photometry, to quantify the agonist-gated Ca(2+) flux of recombinant P2X7 receptors of dog, guinea pig, human, monkey, mouse, rat, and zebrafish. We find that the magnitude of the Ca(2+) component of the ATP-gated current depends on the species of origin, the splice variant, and the concentration of the purinergic agonist. We also measured a significant contribution of Ca(2+) to the agonist-gated current of the native P2X7Rs of mouse and human immune cells. Our results provide cross-species quantitative measures of the Ca(2+) current of the P2X7 receptor for the first time, and suggest that the cytoplasmic N terminus plays a meaningful role in regulating the flow of Ca(2+) through the channel.

  19. P2X7 receptor activation regulates rapid unconventional export of transglutaminase-2. (United States)

    Adamczyk, Magdalena; Griffiths, Rhiannon; Dewitt, Sharon; Knäuper, Vera; Aeschlimann, Daniel


    Transglutaminases (denoted TG or TGM) are externalized from cells via an unknown unconventional secretory pathway. Here, we show for the first time that purinergic signaling regulates active secretion of TG2 (also known as TGM2), an enzyme with a pivotal role in stabilizing extracellular matrices and modulating cell-matrix interactions in tissue repair. Extracellular ATP promotes TG2 secretion by macrophages, and this can be blocked by a selective antagonist against the purinergic receptor P2X7 (P2X7R, also known as P2RX7). Introduction of functional P2X7R into HEK293 cells is sufficient to confer rapid, regulated TG2 export. By employing pharmacological agents, TG2 release could be separated from P2X7R-mediated microvesicle shedding. Neither Ca(2+) signaling alone nor membrane depolarization triggered TG2 secretion, which occurred only upon receptor membrane pore formation and without pannexin channel involvement. A gain-of-function mutation in P2X7R associated with autoimmune disease caused enhanced TG2 externalization from cells, and this correlated with increased pore activity. These results provide a mechanistic explanation for a link between active TG2 secretion and inflammatory responses, and aberrant enhanced TG2 activity in certain autoimmune conditions.

  20. The Purinergic P2X7 Receptor Is Not Required for Control of Pulmonary Mycobacterium tuberculosis Infection


    Myers, Amy J.; Eilertson, Brandon; Fulton, Scott A; JoAnne L Flynn; Canaday, David H.


    The importance in vivo of P2X7 receptors in control of virulent Mycobacterium tuberculosis was examined in a low-dose aerosol infection mouse model. P2X7−/− mice controlled infection in lungs as well as wild-type mice, suggesting that the P2X7 receptor is not required for control of pulmonary M. tuberculosis infection.

  1. P2X7Rs are involved in cell death, growth and cellular signaling in primary human osteoblasts

    DEFF Research Database (Denmark)

    Agrawal, Ankita; Henriksen, Zanne; Syberg, Susanne;


    The ionotropic ATP-gated P2X7 receptor (P2X7R) is involved in the regulation of many physiological functions including bone metabolism. Several studies on osteoblasts from rodents and human osteoblast-like cell lines have addressed the expression and function of P2X7R on these bone-forming cells...

  2. The crystal structure and magnetic properties of Ba2-xSrxCo2Fe12O22 (United States)

    Cho, Kwang Lae; Rhee, Chan Hyuk; Kim, Chul Sung


    We have synthesized the Ba2-xSrxCo2Fe12O22 samples (x = 0.1, 0.2, 0.3, 0.4, 0.5) by the solid-state reaction method and investigated their crystalline and magnetic properties by X-ray diffractometer (XRD), Mössbauer spectrometer, vibrating sample magnetometer, and network analyzer. XRD patterns show that all samples are rhombohedral with space group R-3m. The lattice constants a0 and c0 decrease with Sr substitution due to smaller ion radius of Sr2+ (1.27 Å) than that of Ba2+ (1.43 Å). The Mössbauer spectroscopy measurements show that the relative area ratios of Fe ion were maintained constant regardless of the Sr concentration. However, average magnetic hyperfine field slightly increased with the Sr concentration. This observation agrees with the fact that the saturation magnetization (Ms) linearly increases due to the increasing super-exchange interaction, originated from the difference in the ionic radius between Ba2+ and Sr2+. To investigate its properties at high frequency range, all samples were sintered at 1100 °C, and complex permeability and permittivity were measured by network analyzer between 100 MHz and 4 GHz. For x below 0.3, the initial permeability at 100 MHz increases, at higher values of x, its value decreases. Our study shows that magnetic properties of Sr2+ substitution for Ba2+ in Y-type hexaferrite as well as low magnetic loss less than 0.1 in 1 GHz band, indicating the potential application of Ba2-xSrxCo2Fe12O22 samples for RF and antenna devices in ultra high frequency band.

  3. Preparation of Bi2-xSbxTe3 thermoelectric films by electrodeposition

    Institute of Scientific and Technical Information of China (English)


    Bi2-xSbxTe3 thermoelectric films were electrochemically deposited from the solution containing Bi3+, HTeO2+and SbO+.ESEM (environmental scanning electron microscope) investigations indicated that the crystalline state of Bi2-xSbxTe3 films transformed from equiaxed crystal to dendritic crystal with the negative shift of deposition potential. XRD and EDS were used to characterize the structure and composition of the electrodeposited films. The Seebeck coefficient and the temperature dependence of the resistance of Bi2-xSbxTe3 films were measured. The results showed that the composition of the film electrodeposited at -0.5 V is Bi0.5Sb1.5Te3 with the largest Seebeck coefficient of 213 μV·K-1.

  4. Electroacupuncture at He-Mu points reduces P2X 4 receptor expression in visceral hypersensitivity***

    Institute of Scientific and Technical Information of China (English)

    Xinxin Guo; Jianqiao Fang; Jifei Chen; Yuan Lu; Luyi Wu; Zhijun Weng; Ling Yang; Yuhu Xin; Xianming Lin; Yi Liang


    Electroacupuncture at Shangjuxu (ST37) and Tianshu (ST25) was reported to improve visceral hypersensitivity in rats. Colorectal distension was utilized to generate a rat model of chronic visceral hypersensitivity in irritable bowel syndrome. Results showed that abdominal withdrawal reflex scores noticeably increased after model establishment. Simultaneously, P2X 4 receptor immu-reactivity significantly increased in the colon and spinal cord. Electroacupuncture and pinaverium bromide therapy both markedly decreased abdominal withdrawal reflex scores in rats with visceral hypersensitivity, and significantly decreased P2X 4 receptor immunoreactivity in the colon and spinal cord. These data suggest that electroacupuncture treatment can improve visceral hypersensitivity in rats with irritable bowel syndrome by diminishing P2X 4 receptor immunoreactivity in the colon and spinal cord.

  5. Emerging role of P2X7 receptors in CNS health and disease. (United States)

    Tewari, Manju; Seth, Pankaj


    Purinergic signalling in the brain is becoming an important focus in the study of CNS health and disease. Various purinergic receptors are found to be present in different brain cells in varying extent, which get activated upon binding of ATP or its analogues. Conventionally, ATP was considered only as a major metabolic fuel of the cell but its recognition as a neurotransmitter in early 1970s, brought meaningful insights in neuron glia crosstalk, participating in various physiological functions in the brain. P2X7R, a member of ligand gated purinergic receptor (P2X) family, is gaining attention in the field of neuroscience because of its emerging role in broad spectrum of ageing and age related neurological disorders. The aim of this review is to provide an overview about the structure and function of P2X7R highlighting its unique features which distinguish it from the other members of its family. This review critically analyzes the literature mentioning the details about the agonist and antagonist of the P2X7R. It also emphasizes the advancements in understanding the dual role of P2X7R in brain development and disorders inviting meaningful insights about its involvement in Alzheimer's disease, Huntington's disease, Multiple Sclerosis, Neuropathic pain, Spinal Cord Injury and NeuroAIDS. Exploring the roles of P2X7R in detail is critical to identify its therapeutic potential in the treatment of acute and chronic neurodegenerative diseases. Moreover, this review also helps to raise more interest in the neurobiology of the purinergic receptors and thus providing new avenues for future research.

  6. The P2X7 receptor supports both life and death in fibrogenic pancreatic stellate cells.

    Directory of Open Access Journals (Sweden)

    Kristian A Haanes

    Full Text Available The pancreatic stellate cells (PSCs have complex roles in pancreas, including tissue repair and fibrosis. PSCs surround ATP releasing exocrine cells, but little is known about purinergic receptors and their function in PSCs. Our aim was to resolve whether PSCs express the multifunctional P2X7 receptor and elucidate how it regulates PSC viability. The number of PSCs isolated from wild type (WT mice was 50% higher than those from the Pfizer P2X7 receptor knock out (KO mice. The P2X7 receptor protein and mRNA of all known isoforms were expressed in WT PSCs, while KO PSCs only expressed truncated versions of the receptor. In culture, the proliferation rate of the KO PSCs was significantly lower. Inclusion of apyrase reduced the proliferation rate in both WT and KO PSCs, indicating importance of endogenous ATP. Exogenous ATP had a two-sided effect. Proliferation of both WT and KO cells was stimulated with ATP in a concentration-dependent manner with a maximum effect at 100 µM. At high ATP concentration (5 mM, WT PSCs, but not the KO PSCs died. The intracellular Ca(2+ signals and proliferation rate induced by micromolar ATP concentrations were inhibited by the allosteric P2X7 receptor inhibitor az10606120. The P2X7 receptor-pore inhibitor A438079 partially prevented cell death induced by millimolar ATP concentrations. This study shows that ATP and P2X7 receptors are important regulators of PSC proliferation and death, and therefore might be potential targets for treatments of pancreatic fibrosis and cancer.

  7. Effect of Electroacupuncture at Hegu (LI 4) on P2X2 and P2X3 Receptors in Trigeminal Ganglion in Pulpalgia Rats%电针合谷穴对实验性牙髓痛大鼠三叉神经节P2X2、P2X3受体的影响

    Institute of Scientific and Technical Information of China (English)

    陈莉; 张英; 严琴; 乐凯


    目的:探讨电针合谷穴对实验性牙髓痛大鼠三叉神经节P2X2、P2X3受体表达的影响。方法将42只成年雄性SD大鼠随机分为正常组(N组)、对照组(C组)、牙髓痛组(M组)、拮抗剂组(A组)、电针组(E组)和拮抗剂+电针组(AE组),每组7只。N组不做任何处理;C组在钻好的牙髓腔内注入与M组等量的生理盐水,浸润5~6 min后用牙科填料将牙洞封闭;M组用小型电钻或手钻(钻头直径约1 mm)在上颌一侧第一和第二磨牙上钻孔,深入牙髓腔并暴露牙髓,用微量注射器注入浓度为5μg/μL的大肠杆菌内毒素(LPS)溶液(每孔注入1~3μL),浸润5~6 min后用牙科填料将牙洞封闭;A组造模方法同M组,在注射器注入LPS溶液时,将A-317491(0.5 mg/kg)同时注射进牙髓;E组电针双侧合谷穴,留针30 min,每日1次,共治疗3次;AE组按A组造模后按E组方法治疗。每日治疗后观察大鼠的行为学变化及体重变化30 min。第4天处死所有大鼠,运用RT-PCR方法检测大鼠三叉神经节P2X2、P2X3受体及β-actin的基因(mRNA)表达,比较各组P2X2、P2X3受体mRNA相对表达量。结果 M组、A组、E组和AE组行为学变化均显著高于C组和N组(P<0.01);A组、E组和AE组行为学变化均显著低于M组(P<0.01)。C组体重显著低于N组(P<0.01);M组、A组、E组和AE组体重均显著低于C组和N组(P<0.01);E组、AE组体重均显著高于M组和A组(P<0.01,P<0.05);A组体重稍高于M组(P<0.05);AE组体重显著高于E组(P<0.01)。M组、A组、E组和AE组P2X2受体mRNA表达量均显著高于N组和C组(P<0.01);A组、E组和AE组P2X2受体mRNA表达量低于M组(P<0.05);A组P2X2受体mRNA表达量低于E组(P<0.05);E组P2X2受体mRNA表达量高于AE组(P<0.05)。M组、A组和E组P2X3受体mRNA表达量均高于C组(P<0.05),且显著高于N组(P<0.01);A组、E组和AE组P2X3受体mRNA表达量显著低于M组(P<0.01);AE组P2X3受体m

  8. Truncated Moments of Nonsinglet Parton Distributions in the double logarithmic $ln^2x$ approximation

    CERN Document Server

    Kotlorz, D


    The method of truncated Mellin moments in a solving QCD evolution equations of the nonsinglet structure functions $F_2^{NS}(x,Q^2)$ and $g_1^{NS}(x,Q^2)$ is presented. All calculations are performed within double logarithmic $ln^2x$ approximation. An equation for truncated moments which incorporates $ln^2x$ effects is formulated and solved for the unintegrated structure function $f^{NS}(x,Q^2)$. The contribution to the Bjorken sum rule coming from the region of very small $x$ is quantified. Further possible improvement of this approach is also discussed.

  9. Planning for Plume Diagnostics for Ground Testing of J-2X Engines at the SSC (United States)

    SaintCyr, William W.; Tejwani, Gopal D.; McVay, Gregory P.; Langford, Lester A.; SaintCyr, William W.


    John C. Stennis Space Center (SSC) is the premier test facility for liquid rocket engine development and certification for the National Aeronautics and Space Administration (NASA). Therefore, it is no surprise that the SSC will play the most prominent role in the engine development testing and certification for the J-2X engine. The Pratt & Whitney Rocketdyne J-2X engine has been selected by the Constellation Program to power the Ares I Upper Stage Element and the Ares V Earth Departure Stage in NASA s strategy of risk mitigation for hardware development by building on the Apollo program and other lessons learned to deliver a human-rated engine that is on an aggressive development schedule, with first demonstration flight in 2010 and human test flights in 2012. Accordingly, J-2X engine design, development, test, and evaluation is to build upon heritage hardware and apply valuable experience gained from past development and testing efforts. In order to leverage SSC s successful and innovative expertise in the plume diagnostics for the space shuttle main engine (SSME) health monitoring,1-10 this paper will present a blueprint for plume diagnostics for various proposed ground testing activities for J-2X at SSC. Complete description of the SSC s test facilities, supporting infrastructure, and test facilities is available in Ref. 11. The A-1 Test Stand is currently being prepared for testing the J-2X engine at sea level conditions. The A-2 Test Stand is currently being used for testing the SSME and may also be used for testing the J-2X engine at sea level conditions in the future. Very recently, ground-breaking ceremony for the new A-3 rocket engine test stand took place at SSC on August 23, 2007. A-3 is the first large - scale test stand to be built at the SSC since the A and B stands were constructed in the 1960s. The A-3 Test Stand will be used for testing J-2X engines under vacuum conditions simulating high altitude operation at approximately 30,480 m (100,000 ft

  10. LDPC decoder architecture for DVB-S2 and DVB-S2X standards


    Marchand, Cédric; Boutillon, Emmanuel


    International audience; A particular type of conflict due to multiple-diagonal sub-matrices in the DVB-S2 parity-check matrices is known to complicate the implementation of the layered decoder architecture. The new matrices proposed in DVB-S2X no longer use such sub-matrices. For implementing a decoder compliant both with DVB-S2 and DVB-S2X, we propose an elegant solution which overcomes this conflicts relying on an efficient write disable of the memories, allowing a straightforward implement...

  11. Impaired P2X1 Receptor-Mediated Adhesion in Eosinophils from Asthmatic Patients. (United States)

    Wright, Adam; Mahaut-Smith, Martyn; Symon, Fiona; Sylvius, Nicolas; Ran, Shaun; Bafadhel, Mona; Muessel, Michelle; Bradding, Peter; Wardlaw, Andrew; Vial, Catherine


    Eosinophils play an important role in the pathogenesis of asthma and can be activated by extracellular nucleotides released following cell damage or inflammation. For example, increased ATP concentrations were reported in bronchoalveolar lavage fluids of asthmatic patients. Although eosinophils are known to express several subtypes of P2 receptors for extracellular nucleotides, their function and contribution to asthma remain unclear. In this article, we show that transcripts for P2X1, P2X4, and P2X5 receptors were expressed in healthy and asthmatic eosinophils. The P2X receptor agonist α,β-methylene ATP (α,β-meATP; 10 μM) evoked rapidly activating and desensitizing inward currents (peak 18 ± 3 pA/pF at -60 mV) in healthy eosinophils, typical of P2X1 homomeric receptors, which were abolished by the selective P2X1 antagonist NF449 (1 μM) (3 ± 2 pA/pF). α,β-meATP-evoked currents were smaller in eosinophils from asthmatic patients (8 ± 2 versus 27 ± 5 pA/pF for healthy) but were enhanced following treatment with a high concentration of the nucleotidase apyrase (17 ± 5 pA/pF for 10 IU/ml and 11 ± 3 pA/pF for 0.32 IU/ml), indicating that the channels are partially desensitized by extracellular nucleotides. α,β-meATP (10 μM) increased the expression of CD11b activated form in eosinophils from healthy, but not asthmatic, donors (143 ± 21% and 108 ± 11% of control response, respectively). Furthermore, α,β-meATP increased healthy (18 ± 2% compared with control 10 ± 1%) but not asthmatic (13 ± 1% versus 10 ± 0% for control) eosinophil adhesion. Healthy human eosinophils express functional P2X1 receptors whose activation leads to eosinophil αMβ2 integrin-dependent adhesion. P2X1 responses are constitutively reduced in asthmatic compared with healthy eosinophils, probably as the result of an increase in extracellular nucleotide concentration.

  12. Synthesis and spectroscopic characterization of Yb3+ in Ca1-XYbXF2+X crystals (United States)

    Ito, M.; Goutaudier, C.; Guyot, Y.; Lebbou, K.; Fukuda, T.; Boulon, G.


    Ca1-XYbXF2+X crystals were grown by two different methods: simple melting under CF{4} atmosphere and laser heated pedestal growth (LHPG) method under Ar atmosphere. Spectroscopic characterization has been carried out to separate different crystallographic site in Ca1-XYbXF2+X crystals and to identify Stark's levels of Yb3+ transitions. Experimental decay time dependence of Yb3+ concentration was analyzed by using concentration gradient fiber in order to understand concentration quenching mechanisms. Energy transfer to unexpected rare earth impurities observed by up-conversion emission spectra in visible region under IR Yb3+ ion pumping seems to be an efficient process.

  13. Gluon contribution to the structure function $g_{2}(x,Q^{2})$

    CERN Document Server

    Braun, V M; Manashov, A N


    We calculate the one-loop twist-3 gluon contribution to the flavor-singlet structure function g_2(x,Q^2) in polarized deep-inelastic scattering and find that it is dominated by the contribution of the three-gluon operator with the lowest anomalous dimension (for each moment N). The similar property was observed earlier for the nonsinglet distributions, although the reason is in our case different. The result is encouraging and suggests a simple evolution pattern of g_2(x,Q^2) in analogy with the conventional description of twist-2 parton distributions.

  14. P2X7 receptors at adult neural progenitor cells of the mouse subventricular zone. (United States)

    Messemer, Nanette; Kunert, Christin; Grohmann, Marcus; Sobottka, Helga; Nieber, Karen; Zimmermann, Herbert; Franke, Heike; Nörenberg, Wolfgang; Straub, Isabelle; Schaefer, Michael; Riedel, Thomas; Illes, Peter; Rubini, Patrizia


    Neurogenesis requires the balance between the proliferation of newly formed progenitor cells and subsequent death of surplus cells. RT-PCR and immunocytochemistry demonstrated the presence of P2X7 receptor mRNA and immunoreactivity in cultured neural progenitor cells (NPCs) prepared from the adult mouse subventricular zone (SVZ). Whole-cell patch-clamp recordings showed a marked potentiation of the inward current responses both to ATP and the prototypic P2X7 receptor agonist dibenzoyl-ATP (Bz-ATP) at low Ca(2+) and zero Mg(2+) concentrations in the bath medium. The Bz-ATP-induced currents reversed their polarity near 0 mV; in NPCs prepared from P2X7(-/-) mice, Bz-ATP failed to elicit membrane currents. The general P2X/P2Y receptor antagonist PPADS and the P2X7 selective antagonists Brilliant Blue G and A-438079 strongly depressed the effect of Bz-ATP. Long-lasting application of Bz-ATP induced an initial current, which slowly increased to a steady-state response. In combination with the determination of YO-PRO uptake, these experiments suggest the dilation of a receptor-channel and/or the recruitment of a dye-uptake pathway. Ca(2+)-imaging by means of Fura-2 revealed that in a Mg(2+)-deficient bath medium Bz-ATP causes [Ca(2+)](i) transients fully depending on the presence of external Ca(2+). The MTT test indicated a concentration-dependent decrease in cell viability by Bz-ATP treatment. Correspondingly, Bz-ATP led to an increase in active caspase 3 immunoreactivity, indicating a P2X7-controlled apoptosis. In acute SVZ brain slices of transgenic Tg(nestin/EGFP) mice, patch-clamp recordings identified P2X7 receptors at NPCs with pharmacological properties identical to those of their cultured counterparts. We suggest that the apoptotic/necrotic P2X7 receptors at NPCs may be of particular relevance during pathological conditions which lead to increased ATP release and thus could counterbalance the ensuing excessive cell proliferation.

  15. P2X7R activation drives distinct IL-1 responses in dendritic cells compared to macrophages


    Englezou, Pavlos C.; Rothwell, Simon W.; Ainscough, Joseph S.; Brough, David; Landsiedel, Robert; Verkhratsky, Alexei; Kimber, Ian; Dearman, Rebecca J


    The P2X7R is a functionally distinct member of the P2X family of non-selective cation channels associated with rapid activation of the inflammasome complex and signalling interleukin (IL)-1β release in macrophages. The main focus of this investigation was to compare P2X7R-driven IL-1 production by primary murine bone marrow derived dendritic cells (BMDC) and macrophages (BMM). P2X7R expression in murine BMDC and BMM at both transcriptional (P2X7A variant) and protein levels was demonstrated....

  16. The P2X7 receptor–pannexin-1 complex decreases muscarinic acetylcholine receptor–mediated seizure susceptibility in mice


    Kim, Ji-Eun; Kang, Tae-Cheon


    Pannexin-1 (Panx1) plays a role in the release of ATP and glutamate in neurons and astrocytes. Panx1 can be opened at the resting membrane potential by extracellular ATP via the P2X7 receptor (P2X7R). Panx1 opening has been shown to induce neuronal death and aberrant firing, but its role in neuronal activity has not been established. Here, we report the role of the P2X7R-Panx1 complex in regulating muscarinic acetylcholine 1 (M1) receptor function. P2X7R knockout (P2X7–/–) mice showed greater...

  17. 关于Diophantine方程2yny-x=(b+2)x-bx%On the Diophantine equation 2y ny-x =(b + 2) x-bx

    Institute of Scientific and Technical Information of China (English)

    关文吉; 车顺



  18. Inhibition of P2X7 Receptor by Extracts of Chinese Medicine

    Institute of Scientific and Technical Information of China (English)

    Andreas Spielmann; 顾全保; 马春辉; 黄成钢; 宣利江; Wolfgang Schwarz


    目的:探讨中草药石菖蒲粗提物SCP01及其纯化物SCP02(α-细辛脑)和迷迭香抽提物X0728对人肥大细胞的作用.方法:用膜片钳技术全细胞记录人肥大细胞膜ATP激活的P2X7受体的电流.结果:40μg/mL SCP01抑制P2X7电流(27.6±2.0)%,而同样浓度的SCP02抑制(29.5±2.2)%(-100 mV电位下),笔者还比较了商业用α-细辛脑的效厘,42 μg/mL可抑制P2X7电流(52.2±2.0)%.相反,40 μg/mL X0728激活P2X7电流(28.6±2.8)%,所有这些作用都是电压依赖性的.结论:α-细辛脑对P2X7的抑制将阻滞胞内钙的增加,从而可以解释抑制神经元死亡的原因.而X0728刺激P2X7的药理学效应尚需进一步研究.%Objective: To investigate the influence of Acorus gramineus (Soland), a crude extract, SCP01, and a purified component, SCP02, and of Rosmarinus officinalis L., X0728 on human mast cells (HMC-1 Cell Line). Methods: Current-voltage of P2X7 receptors on human mast cell membrane activated by ATP was recorded by the whole-cell patch clamp technique. Results: The current at-100 mV mediated by P2X7was inhibited by (27.6±2.0) % in the presence of 40 μg/mL SCP01 and by (29.5±2.2) % in the presence of 40 μg/mL SCP02, which was identified as α-asarone. 42 μg/mL of the commercially available α-asarone inhibited the P2X7-mediated current by (52.2±2.0) %. In contrast to SCP01 and SCP02, 40μg/mL X0728 provoked stimulation of the current by (28.6±2.8) %. All effects were voltage-independent. Conclusion: The inhibition of P2X7by α-asarone will inhibit intracellular calcium increase and this may account for the inhibition of reported excitotoxic cell death. The pharmacological function of P2X7stimulation by X0728 needs further investigation.

  19. P2X7R activation drives distinct IL-1 responses in dendritic cells compared to macrophages. (United States)

    Englezou, Pavlos C; Rothwell, Simon W; Ainscough, Joseph S; Brough, David; Landsiedel, Robert; Verkhratsky, Alexei; Kimber, Ian; Dearman, Rebecca J


    The P2X(7)R is a functionally distinct member of the P2X family of non-selective cation channels associated with rapid activation of the inflammasome complex and signalling interleukin (IL)-1β release in macrophages. The main focus of this investigation was to compare P2X(7)R-driven IL-1 production by primary murine bone marrow derived dendritic cells (BMDC) and macrophages (BMM). P2X(7)R expression in murine BMDC and BMM at both transcriptional (P2X(7)A variant) and protein levels was demonstrated. Priming with lipopolysaccharide (LPS) and receptor activation with adenosine triphosphate (ATP) resulted in markedly enhanced IL-1 (α and β) secretion in BMDC compared with BMM. In both cell types IL-1 production was profoundly inhibited with a P2X(7)R-specific inhibitor (A-740003) demonstrating that this release is predominantly a P2X(7)R-dependent process. These data also suggest that P2X(7)R and caspase-1 activation drive IL-1α release from BMDC. Both cell types expressed constitutively the gain-of-function P2X(7)K as well as the full P2X(7)A variant at equivalent levels. LPS priming reduced significantly levels of P2X(7)A but not P2X(7)K transcripts in both BMDC and BMM. P2X(7)R-induced pore formation, assessed by YO-PRO-1 dye uptake, was greater in BMDC, and these cells were protected from cell death. These data demonstrate that DC and macrophages display distinct patterns of cytokine regulation, particularly with respect to IL-1, as a consequence of cell-type specific differences in the physicochemical properties of the P2X(7)R. Understanding the cell-specific regulation of these cytokines is essential for manipulating such responses in health and disease.

  20. P2X7 receptors contribute to the currents induced by ATP in guinea pig intestinal myenteric neurons. (United States)

    Valdez-Morales, Eduardo; Guerrero-Alba, Raquel; Liñán-Rico, Andrómeda; Espinosa-Luna, Rosa; Zarazua-Guzman, Sergio; Miranda-Morales, Marcela; Montaño, Luis M; Barajas-López, Carlos


    The whole-cell configuration, several pharmacological tools, and single-cell RT-PCR were used to investigate the contribution of P2X7 subunits to the ATP-induced currents (I(ATP)) in guinea pig myenteric neurons. I(ATP) was recorded in the great majority of tested neurons. ATP concentration-response curve (0.01-10mM) showed two phases, the first mediated by high-sensitive P2X receptors (hsP2X receptors), observed between 0.01-0.3mM and the second mediated by low-sensitive P2X receptors (lsP2X receptors). The calculated EC(50) values of these phases were 38 and 1759 μM, respectively. 2'-3'-O-(4-benzoylbenzoyl)-ATP (BzATP) concentration-response curve was monophasic (0.01-1mM), and less potent (EC(50) 142 μM) than ATP to activate hsP2X receptors. A strong inward rectification was noticed when hsP2X receptors were activated with ATP (0.1mM) and for BzATP-induced currents (0.1mM; I(BzATP)) but a significant lower rectification was noticed when lsP2X receptors were activated (5mM). Brilliant blue G (BBG) at a concentration of 0.3 μM (known to inhibit only P2X7 receptors) reduced I(ATP) when lsP2X receptors contributed to it but neither affect hsP2X receptors nor I(BzATP). However, hsP2X receptors and I(BzATP) were both inhibited by concentrations ≥ 1 μM of this antagonist. BzATP inhibited hsP2X receptors and therefore, it behaves as partial agonist on these receptors. Using the single-cell RT-PCR technique P2X7 mRNA was detectable in 7 out of 13 myenteric neurons exhibiting P2X2 mRNA. Altogether, our results show that low-sensitive P2X receptors are likely P2X7, whereas, the high-sensitive P2X channels are probably constituted, at least in part, by P2X2 subunits.

  1. Microfluidic Device (United States)

    Tai, Yu-Chong (Inventor); Zheng, Siyang (Inventor); Lin, Jeffrey Chun-Hui (Inventor); Kasdan, Harvey L. (Inventor)


    Described herein are particular embodiments relating to a microfluidic device that may be utilized for cell sensing, counting, and/or sorting. Particular aspects relate to a microfabricated device that is capable of differentiating single cell types from dense cell populations. One particular embodiment relates a device and methods of using the same for sensing, counting, and/or sorting leukocytes from whole, undiluted blood samples.

  2. Synthesis and Characterization of Li1+2x+3yAlxScyZnyTi2-x-2ySixP3-xO12

    Institute of Scientific and Technical Information of China (English)

    李荣华; 许泽润; 王文继


    Rare earth mineral fast ion conductors of Li1+2x+3yAlxScyZnyTi2-x-2ySixP3-xO12 system based on LiTi2(PO4)3 were prepared by solid phase reaction at high temperature (1000~1300 ℃) for about 30 h using refined natural kaolinite and Sc2O3. The X-ray diffraction analysis shows that a Nasicon-like structure with R3c space group can be found in the composition range of x=0.1, 0.2, y≤0.2. The maximum lithium ion conductivity is 1.19×10-4 S*cm-1 for the composition with x=0.1, y=0.08 at room temperature, and its activation energy is 30.6 kJ*mol-1 in the temperature range of 150~300 ℃. The systems with these compositions have high conductivity of about 10-2 S*cm-1 at 300 ℃.

  3. Frequency and temperature dependence of dielectric and electric properties of Ba2-xSm4+2x/3Ti8O24 with structural analysis

    Directory of Open Access Journals (Sweden)

    Narang Sukhleen Bindra


    Full Text Available Dielectric ceramics samples of barium titanium oxide doped with samarium, having a complex structural formula of Ba2-xSm4+2x/3Ti8O24 (referred to as BST, were fabricated by a high temperature solid-state reaction technique with varying x (0.0, 0.2, 0.4, 0.6. X-ray diffraction technique was used to check the formation of particular phases. Scanning electron microscope technique was used to study the surface morphology of the samples. The samples were studied in a temperature range of 298 K to 623 K and frequency range of 10 KHz to 1 MHz. The dielectric constant (εr, loss tangent (tan δ, and AC conductivity (σAC were measured on sintered disks of BST samples. The DC resistivity of different compositions was measured at room temperature. Detailed studies of dielectric and electrical properties showed that these properties are strongly dependent on composition, frequency and temperature. The compounds showed stable behavior in lower temperature range (up to 523 K, therefore, they can be used in practical applications in this temperature range.

  4. Structural determination of new solid solutions [Y2-x Mx ][Sn2-x Mx ]O7-3x/2 (M = Mg or Zn by Rietveld method

    Directory of Open Access Journals (Sweden)

    Mohamed Douma


    Full Text Available New [Y2-x Mx][Sn2-x Mx]O7-3x/2 (0 ≤x≤ 0.30 for M = Mg and 0 ≤x≤ 0.36 for M = Zn solid solutions with the pyrochlore structure were synthesized via high-temperature solid-state reaction method. Powder X-ray diffraction (PXRD patterns and Fourier transform infrared (FT-IR spectra showed that these materials are new non-stoichiometric solid solutions with the pyrochlore type structure. The structural parameters for the solids obtained were successfully determined by Rietveld refinement based on the analysis of the PXRD diagrams. Lattice parameter (a of these solid solutions decreases when x increases in both series. All samples obtained have the pyrochlore structure Fd-3m, no. 227 (origin at center -3m with M2+ (M = Mg2+ or Zn2+ cations in Y3+ and Sn4+ sites, thus creating vacancies in the anionic sublattice.

  5. Structure cristalline du composé Hg3-xSbx(S+Se2+xI2-x (x ≃ 0.1

    Directory of Open Access Journals (Sweden)

    Mohammed Kars


    Full Text Available Single crystals of the mercury chalcohalide Hg3-xSbx(S+Se2+xI2-x (x ≃ 0.1 (mercury antimony sulfide selenide iodide, were grown by a chemical transport reaction. The structure contains three independent A (Hg/Sb atoms; each atom is strongly covalently bonded with two X (Se/S atoms to form approximately linear X–A–X units. The X–A–X units link to form A4X4 rings, which are combined into infinite crankshaft-type bands running along the [100] direction. Four equatorial E (I/X = Se,S atoms at relatively long distances complete the distorted octahedral coordination of A (Hg/Sb. The crystal under investigation was twinned by non-merohedry with a refined twin domain fraction of 0.814 (6:0.186 (6. The structure is isotypic with Hg3Se2I2 [Beck & Hedderich (2000. J. Solid State Chem. 151, 73–76], but the current determination reveals a coupled substitution, with partial replacement of Hg+2 by Sb+3, balanced by the equivalent substitution of I−1 by S−2 and Se−2. Bond-valence calculations are consistent with this relative substitution model.

  6. Uncommon potential hysteresis in the Li/Li{sub 2x}VO(H{sub 2-x}PO{sub 4}){sub 2} (0 {<=} x {<=} 2) system

    Energy Technology Data Exchange (ETDEWEB)

    Dubarry, M. [Institut des Materiaux Jean Rouxel, 2 rue de la Houssiniere, BP32229, 44322 Nantes Cedex 3 (France); Gaubicher, J. [Institut des Materiaux Jean Rouxel, 2 rue de la Houssiniere, BP32229, 44322 Nantes Cedex 3 (France)], E-mail:; Guyomard, D. [Institut des Materiaux Jean Rouxel, 2 rue de la Houssiniere, BP32229, 44322 Nantes Cedex 3 (France); Wallez, G.; Quarton, M. [Laboratoire de Cristallochimie du Solide, Universite Pierre et Marie Curie-Paris VI, 4 place Jussieu, 75252 Paris Cedex 05 (France); Baehtz, C. [Deutsches Elektronen Synchrotron HASYLAB, Notkestr. 85, 22607 Hamburg (Germany)


    Physical and electrochemical investigations of vanadium phosphates, Li{sub 2x}VO(H{sub 2-x}PO{sub 4}){sub 2} (0 < x < 2), have been undertaken. H{sup +}/Li{sup +} ionic exchange from VO(H{sub 2}PO{sub 4}){sub 2} to Li{sub 2}VO(HPO{sub 4}){sub 2} leads to grain decrepitation. Further ionic exchange toward formation of Li{sub 4}VO(PO{sub 4}){sub 2} lowers the symmetry. As inferred from potentiodynamic cycling correlated to ex situ and in situ X-ray diffraction (XRD), the system Li/Li{sub 4}VO(PO{sub 4}){sub 2} shows several phase transformations that are associated with thermodynamical potential hysteresis that span from roughly 15 mV to more than 1.8 V. Small hysteresis are associated with topotactic reactions and with V{sup V}/V{sup IV} and V{sup III}/V{sup II} redox couples. Large potential hysteresis values (>1 V) were observed when oxidation of V{sup III} to V{sup IV} is involved.

  7. [Effect of Zhuangyao Jianshen Wan (ZYJCW) on P2X1 and P2X3 mRNA expressions in rats with diuresis caused by kidney deficiency]. (United States)

    Chen, Jia-yi; Jiang, Wei-wen; He, Feng-lei; Mo, Guo-qiang; Guo, Zhong-hui; Wang, Xiao-dan; Wu, Qing-he; Cao, Hong-yin


    To investigate the urination-reducing effect and mechanism of Zhuangyao Jianshen Wan (ZYJCW). In this study, SI rats were subcutaneously injected with 150 mg · kg(-1) dose of D-galactose to prepare the sub-acute aging model and randomly divided into the model group, the Suoquan Wan group (1.17 g · kg(-1) · d(-1)), and ZYJCW high, medium and low dose groups (2.39, 1.20, 0.60 g · kg(-1) · d(-1)) , with normal rats in the blank group. They were continuously administered with drugs for eight weeks. The metabolic cage method was adopted to measure the 24 h urine volume and 5 h water load urine volume in rats. The automatic biochemistry analyzer was adopted to detect urine concentrations of Na+, Cl-, K+. The ELISA method was used to determine serum aldosterone (ALD) and antidiuretic hormone (ADH). The changes in P2X1 and P2X3 mRNA expressions in bladder tissues of rats were detected by RT-PCR. According to the results, both ZYJCW high and medium dose groups showed significant down-regulations in 24 h urine volume and 5 h water load urine volume in (P diuresis caused by kidney deficiency.

  8. Magnetic structure of NdMn{sub 2-x}Fe{sub x}Ge{sub 2} (x=0.1 and 0.15) compounds

    Energy Technology Data Exchange (ETDEWEB)

    Szytula, A.; Duraj, R.; Hernandez-Velasco, J.; Penc, B.; Venturini, G.; Wawrzynska, E


    Magnetic properties of NdMn{sub 2-x}Fe{sub x}Ge{sub 2} (x=0.1 and 0.15) are investigated by ac magnetic measurements and neutron diffraction in the temperature range 1.5-400 K. At 1.5 K a complex magnetic structure is observed in both compounds, with a noncollinear magnetic structure in the Mn-sublattice and a ferromagnetic one for the Nd-sublattice. The magnetic ordering in the Nd-sublattice disappears near 50 K, while in the Mn-sublattice at 194 K for x=0.1 and 185 K for x=0.15 a reorientation of the ferromagnetic axis direction from the a- to the c-axis in the Mn-sublattice is detected. An additional phase transition at 320 K for x=0.1 and at 304 K for x=0.15 is connected with the change of the magnetic structure to the antiferromagnetic phase.

  9. Regulation of neurogenesis and gliogenesis of retinoic acid-induced P19 embryonal carcinoma cells by P2X2 and P2X7 receptors studied by RNA interference. (United States)

    Yuahasi, Katia K; Demasi, Marcos A; Tamajusuku, Alessandra S K; Lenz, Guido; Sogayar, Mari C; Fornazari, Maynara; Lameu, Claudiana; Nascimento, Isis C; Glaser, Talita; Schwindt, Telma T; Negraes, Priscilla D; Ulrich, Henning


    Embryonic carcinoma cells are widely used models for studying the mechanisms of proliferation and differentiation occurring during early embryogenesis. We have now investigated how down-regulation of P2X2 and P2X7 receptor expression by RNA interference (RNAi) affects neural differentiation and phenotype specification of P19 embryonal carcinoma cells. Wild-type P19 embryonal carcinoma cells or cells stably expressing shRNAs targeting P2X2 or P2X7 receptor expression were induced to differentiate into neurons and glial cells in the presence of retinoic acid. Silencing of P2X2 receptor expression along differentiation promoted cell proliferation and an increase in the percentage of cells expressing glial-specific GFAP, while the presence of beta-3 tubulin-positive cells diminished at the same time. Proliferation induction in the presence of stable anti-P2X2 receptor RNAi points at a mechanism where glial proliferation is favored over growth arrest of progenitor cells which would allow neuronal maturation. Differently from the P2X2 receptor, inhibition of P2X7 receptor expression during neural differentiation of P19 cells resulted in a decrease in cell proliferation and GFAP expression, suggesting the need of functional P2X7 receptors for the progress of gliogenesis. The results obtained in this study indicate the importance of purinergic signaling for cell fate determination during neural differentiation, with P2X2 and P2X7 receptors promoting neurogenesis and gliogenesis, respectively. The shRNAs down-regulating P2X2 or P2X7 receptor gene expression, developed during this work, present useful tools for studying mechanisms of neural differentiation in other stem cell models.

  10. Direct observation of dynamic charge stripes in La2-xSrxNiO4 (United States)

    Anissimova, S.; Parshall, D.; Gu, G. D.; Marty, K.; Lumsden, M. D.; Chi, Songxue; Fernandez-Baca, J. A.; Abernathy, D. L.; Lamago, D.; Tranquada, J. M.; Reznik, D.


    The insulator-to-metal transition continues to be a challenging subject, especially when electronic correlations are strong. In layered compounds, such as La2-xSrxNiO4 and La2-xBaxCuO4, the doped charge carriers can segregate into periodically spaced charge stripes separating narrow domains of antiferromagnetic order. Although there have been theoretical proposals of dynamically fluctuating stripes, direct spectroscopic evidence of charge-stripe fluctuations has been lacking. Here we report the detection of critical lattice fluctuations, driven by charge-stripe correlations, in La2-xSrxNiO4 using inelastic neutron scattering. This scattering is detected at large momentum transfers where the magnetic form factor suppresses the spin fluctuation signal. The lattice fluctuations associated with the dynamic charge stripes are narrow in q and broad in energy. They are strongest near the charge-stripe melting temperature. Our results open the way towards the quantitative theory of dynamic stripes and for directly detecting dynamical charge stripes in other strongly correlated systems, including high-temperature superconductors such as La2-xSrxCuO4.

  11. Direct observation of dynamic charge stripes in La2 xSrxNiO4

    Energy Technology Data Exchange (ETDEWEB)

    Anissimova, S. [University of Colorado, Boulder; Parshall, D [University of Colorado, Boulder; Gu, Genda [Brookhaven National Laboratory (BNL); Marty, K. [Oak Ridge National Laboratory (ORNL); Lumsden, Mark D [ORNL; Chi, Songxue [ORNL; Fernandez-Baca, Jaime A [ORNL; Abernathy, D. [Oak Ridge National Laboratory (ORNL); Lamago, D. [Laboratoire Leon Brillouin, France; Tranquada, John M. [Brookhaven National Laboratory (BNL); Reznik, Dmitry [University of Colorado, Boulder


    The insulator-to-metal transition continues to be a challenging subject, especially when electronic correlations are strong. In layered compounds, such as La2 xSrxNiO4 and La2 xBaxCuO4, the doped charge carriers can segregate into periodically spaced charge stripes separating narrow domains of antiferromagnetic order. Although there have been theoretical proposals of dynamically fluctuating stripes, direct spectroscopic evidence of charge-stripe fluctuations has been lacking. Here we report the detection of critical lattice fluctuations, driven by charge-stripe correlations, in La2 xSrxNiO4 using inelastic neutron scattering. This scattering is detected at large momentum transfers where the magnetic form factor suppresses the spin fluctuation signal. The lattice fluctuations associated with the dynamic charge stripes are narrow in q and broad in energy. They are strongest near the charge-stripe melting temperature. Our results open the way towards the quantitative theory of dynamic stripes and for directly detecting dynamical charge stripes in other strongly correlated systems, including high-temperature superconductors such as La2 xSrxCuO4.

  12. Targeting of the P2X7 receptor in pancreatic cancer and stellate cells

    DEFF Research Database (Denmark)

    Giannuzzo, Andrea; Saccomano, Mara; Napp, Joanna


    into nude mice and tumour growth was followed noninvasively by bioluminescence imaging. AZ10606120-treated mice showed reduced bioluminescence compared to saline-treated mice. Immunohistochemical analysis confirmed P2X7R expression in cancer and PSC cells, and in metaplastic/neoplastic acinar and duct...

  13. X-ray structures define human P2X3 receptor gating cycle and antagonist action

    NARCIS (Netherlands)

    Mansoor, Steven E.; Lü, Wei; Oosterheert, W.; Shekhar, Mrinal; Tajkhorshid, Emad; Gouaux, Eric


    P2X receptors are trimeric, non-selective cation channels activated by ATP that have important roles in the cardiovascular, neuronal and immune systems. Despite their central function in human physiology and although they are potential targets of therapeutic agents, there are no structures of human

  14. Sequential shrinkage and swelling underlie P2X7-stimulated lymphocyte phosphatidylserine exposure and death. (United States)

    Taylor, Simon R J; Gonzalez-Begne, Mireya; Dewhurst, Stephen; Chimini, Giovanna; Higgins, Christopher F; Melvin, James E; Elliott, James I


    Patterns of change in cell volume and plasma membrane phospholipid distribution during cell death are regarded as diagnostic means of distinguishing apoptosis from necrosis, the former being associated with cell shrinkage and early phosphatidylserine (PS) exposure, whereas necrosis is associated with cell swelling and consequent lysis. We demonstrate that cell volume regulation during lymphocyte death stimulated via the purinergic receptor P2X7 is distinct from both. Within seconds of stimulation, murine lymphocytes undergo rapid shrinkage concomitant with, but also required for, PS exposure. However, within 2 min shrinkage is reversed and swelling ensues ending in cell rupture. P2X7-induced shrinkage and PS translocation depend upon K+ efflux via KCa3.1, but use a pathway of Cl- efflux distinct from that previously implicated in apoptosis. Thus, P2X7 stimulation activates a novel pathway of cell death that does not conform to those conventionally associated with apoptosis and necrosis. The mixed apoptotic/necrotic phenotype of P2X7-stimulated cells is consistent with a potential role for this death pathway in lupus disease.

  15. The 2 x 2 Model of Perfectionism: A Comparison across Asian Canadians and European Canadians (United States)

    Franche, Veronique; Gaudreau, Patrick; Miranda, Dave


    The 2 x 2 model of perfectionism posits that the 4 within-person combinations of self-oriented and socially prescribed perfectionism (i.e., pure SOP, mixed perfectionism, pure SPP, and nonperfectionism) can be distinctively associated with psychological adjustment. This study examined whether the relationship between the 4 subtypes of…

  16. Growth and Electronic Properties of Ag Nanoparticles on Reduced CeO2-x(111) Films

    Institute of Scientific and Technical Information of China (English)

    Dan-dan Kong; Yong-he Pan; Guo-dong Wang; Hai-bin Pan; Jun-fa Zhu


    Ag nanoparticles grown on reduced CeO2-x thin films have been studied by X-ray photoelectron spectroscopy and resonant photoelectron spectroscopy of the valence band to understand the effect of oxygen vacancies in the CeO2-x thin films on the growth and interfacial electronic properties of Ag.Ag grows as three-dimensional particles on the CeO2-x(111) surface at 300 K.Compared to the fully oxidized ceria substrate surface,Ag favors the growth of smaller particles with a larger particle density on the reduced ceria substrate surface,which can be attributed to the nucleation of Ag on oxygen vacancies.The binding energy of Ag3d increases when the Ag particle size decreases,which is mainly attributed to the final-state screening.The interfacial interaction between Ag and CeO2-x(111) is weak.The resonant enhancement of the 4f level of Ce3+ species in RPES indicates a partial Ce4+→Ce3+ reduction after Ag deposited on reduced ceria surface.The sintering temperature of Ag on CeO 1.85 (111) surface during annealing is a little higher than that of Ag on CeO2 (111) surface,indicating that Ag nanoparticles are more stable on the reduced ceria surface.

  17. Structural basis for subtype-specific inhibition of the P2X7 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Karasawa, Akira; Kawate, Toshimitsu


    The P2X7 receptor is a non-selective cation channel activated by extracellular adenosine triphosphate (ATP). Chronic activation of P2X7 underlies many health problems such as pathologic pain, yet we lack effective antagonists due to poorly understood mechanisms of inhibition. Here we present crystal structures of a mammalian P2X7 receptor complexed with five structurally-unrelated antagonists. Unexpectedly, these drugs all bind to an allosteric site distinct from the ATP-binding pocket in a groove formed between two neighboring subunits. This novel drug-binding pocket accommodates a diversity of small molecules mainly through hydrophobic interactions. Functional assays propose that these compounds allosterically prevent narrowing of the drug-binding pocket and the turret-like architecture during channel opening, which is consistent with a site of action distal to the ATP-binding pocket. These novel mechanistic insights will facilitate the development of P2X7-specific drugs for treating human diseases.

  18. The P2X7 Receptor Supports Both Life and Death in Fibrogenic Pancreatic Stellate Cells

    DEFF Research Database (Denmark)

    Haanes, Kristian; Schwab, Albrecht; Novak, Ivana


    The pancreatic stellate cells (PSCs) have complex roles in pancreas, including tissue repair and fibrosis. PSCs surround ATP releasing exocrine cells, but little is known about purinergic receptors and their function in PSCs. Our aim was to resolve whether PSCs express the multifunctional P2X7...... receptor and elucidate how it regulates PSC viability. The number of PSCs isolated from wild type (WT) mice was 50% higher than those from the Pfizer P2X7 receptor knock out (KO) mice. The P2X7 receptor protein and mRNA of all known isoforms were expressed in WT PSCs, while KO PSCs only expressed truncated...... was stimulated with ATP in a concentration-dependent manner with a maximum effect at 100 µM. At high ATP concentration (5 mM), WT PSCs, but not the KO PSCs died. The intracellular Ca(2+) signals and proliferation rate induced by micromolar ATP concentrations were inhibited by the allosteric P2X7 receptor...

  19. Unbalanced 2 x 2 factorial designs and the interaction effect : A troublesome combination

    NARCIS (Netherlands)

    Landsheer, Johannes A.; Van Wittenboer, Godfried Den


    In this power study, ANOVAs of unbalanced and balanced 2 x 2 datasets are compared (N = 120). Datasets are created under the assumption that H1 of the effects is true. The effects are constructed in two ways, assuming: 1. contributions to the effects solely in the treatment groups; 2. contrasting co


    Directory of Open Access Journals (Sweden)



    Full Text Available Eight new SbF3, SbCl5 and HgX2 (X = Cl, Br amine adducts have been synthesized and their infrared study carried out. Discrete structures have been suggested on the basis of elemental analysis and infrared data, the coordination number of antimony varying from five to nine, while the environment around Hg is tetrahedral.

  1. Sensing arterial CO(2) levels: a role for medullary P2X receptors. (United States)

    Spyer, K M; Thomas, T


    ATP has been shown to act as an excitatory neurotransmitter in the central nervous system. In this review, evidence is presented to indicate that when ATP is micro-injected into the ventrolateral medulla (VLM) of the rat, changes in respiratory activity are elicited. These effects, and accompanying changes in heart rate and blood pressure are mediated by P2X purinoreceptors. Immunocytochemistry indicates a prevalence of P2X(2) and P2X(6) purinoreceptors in this region of the medulla. The P2 purinoceptor antagonists, suramin and PPADS blunt the respiratory responses to changes in arterial CO(2) levels when micro-injected into the VLM. This effect is shown electrophysiologically to be mediated by purinoreceptors located primarily on respiratory neurones of the VLM including the Bötzinger complex. As the effects of agonist activation of P2X(2) purinoceptors expressed in HEK293 cells and Xenopus oocytes are potentiated by lowering pH, these data imply that the central respiratory response to CO(2) depends in part on the pH sensitivity of purinoreceptors located on inspiratory neurones. The implications for respiratory activity and control are discussed.

  2. Molecular mechanism of ATP binding and ion channel activation in P2X receptors

    Energy Technology Data Exchange (ETDEWEB)

    Hattori, Motoyuki; Gouaux, Eric (Oregon HSU)


    P2X receptors are trimeric ATP-activated ion channels permeable to Na{sup +}, K{sup +} and Ca{sup 2+}. The seven P2X receptor subtypes are implicated in physiological processes that include modulation of synaptic transmission, contraction of smooth muscle, secretion of chemical transmitters and regulation of immune responses. Despite the importance of P2X receptors in cellular physiology, the three-dimensional composition of the ATP-binding site, the structural mechanism of ATP-dependent ion channel gating and the architecture of the open ion channel pore are unknown. Here we report the crystal structure of the zebrafish P2X4 receptor in complex with ATP and a new structure of the apo receptor. The agonist-bound structure reveals a previously unseen ATP-binding motif and an open ion channel pore. ATP binding induces cleft closure of the nucleotide-binding pocket, flexing of the lower body {beta}-sheet and a radial expansion of the extracellular vestibule. The structural widening of the extracellular vestibule is directly coupled to the opening of the ion channel pore by way of an iris-like expansion of the transmembrane helices. The structural delineation of the ATP-binding site and the ion channel pore, together with the conformational changes associated with ion channel gating, will stimulate development of new pharmacological agents.

  3. Structural insights into the nucleotide base specificity of P2X receptors (United States)

    Kasuya, Go; Fujiwara, Yuichiro; Tsukamoto, Hisao; Morinaga, Satoshi; Ryu, Satoshi; Touhara, Kazushige; Ishitani, Ryuichiro; Furutani, Yuji; Hattori, Motoyuki; Nureki, Osamu


    P2X receptors are trimeric ATP-gated cation channels involved in diverse physiological processes, ranging from muscle contraction to nociception. Despite the recent structure determination of the ATP-bound P2X receptors, the molecular mechanism of the nucleotide base specificity has remained elusive. Here, we present the crystal structure of zebrafish P2X4 in complex with a weak affinity agonist, CTP, together with structure-based electrophysiological and spectroscopic analyses. The CTP-bound structure revealed a hydrogen bond, between the cytosine base and the side chain of the basic residue in the agonist binding site, which mediates the weak but significant affinity for CTP. The cytosine base is further recognized by two main chain atoms, as in the ATP-bound structure, but their bond lengths seem to be extended in the CTP-bound structure, also possibly contributing to the weaker affinity for CTP over ATP. This work provides the structural insights for the nucleotide base specificity of P2X receptors. PMID:28332633

  4. Lack of a Functioning P2X7 Receptor Leads to Increased Susceptibility to Toxoplasmic Ileitis.

    Directory of Open Access Journals (Sweden)

    Catherine M Miller

    Full Text Available Oral infection of C57BL/6J mice with the protozoan parasite Toxoplasma gondii leads to a lethal inflammatory ileitis.Mice lacking the purinergic receptor P2X7R are acutely susceptible to toxoplasmic ileitis, losing significantly more weight than C57BL/6J mice and exhibiting much greater intestinal inflammatory pathology in response to infection with only 10 cysts of T. gondii. This susceptibility is not dependent on the ability of P2X7R-deficient mice to control the parasite, which they accomplish just as efficiently as C57BL/6J mice. Rather, susceptibility is associated with elevated ileal concentrations of pro-inflammatory cytokines, reactive nitrogen intermediates and altered regulation of elements of NFκB activation in P2X7R-deficient mice.Our data support the thesis that P2X7R, a well-documented activator of pro-inflammatory cytokine production, also plays an important role in the regulation of intestinal inflammation.

  5. X-ray structures define human P2X3 receptor gating cycle and antagonist action (United States)

    Mansoor, Steven E.; Lü, Wei; Oosterheert, Wout; Shekhar, Mrinal; Tajkhorshid, Emad; Gouaux, Eric


    P2X receptors are trimeric, non-selective cation channels activated by ATP that have important roles in the cardiovascular, neuronal and immune systems. Despite their central function in human physiology and although they are potential targets of therapeutic agents, there are no structures of human P2X receptors. The mechanisms of receptor desensitization and ion permeation, principles of antagonism, and complete structures of the pore-forming transmembrane domains of these receptors remain unclear. Here we report X-ray crystal structures of the human P2X3 receptor in apo/resting, agonist-bound/open-pore, agonist-bound/closed-pore/desensitized and antagonist-bound/closed states. The open state structure harbours an intracellular motif we term the ‘cytoplasmic cap’, which stabilizes the open state of the ion channel pore and creates lateral, phospholipid-lined cytoplasmic fenestrations for water and ion egress. The competitive antagonists TNP-ATP and A-317491 stabilize the apo/resting state and reveal the interactions responsible for competitive inhibition. These structures illuminate the conformational rearrangements that underlie P2X receptor gating and provide a foundation for the development of new pharmacological agents.

  6. Electronic decal: a security function based on V2X communication

    NARCIS (Netherlands)

    Knapik, Peter; Schoch, Elmar; Kargl, Frank


    New technologies such as vehicle-to-X (V2X) communication and advanced driver assistance systems (ADAS) are on the rise. They are mainly used to increase road safety as well as traffic efficiency and to provide customers with infotainment features. However, these new technologies also provide the op

  7. Color-Space-Based Visual-MIMO for V2X Communication. (United States)

    Kim, Jai-Eun; Kim, Ji-Won; Park, Youngil; Kim, Ki-Doo


    In this paper, we analyze the applicability of color-space-based, color-independent visual-MIMO for V2X. We aim to achieve a visual-MIMO scheme that can maintain the original color and brightness while performing seamless communication. We consider two scenarios of GCM based visual-MIMO for V2X. One is a multipath transmission using visual-MIMO networking and the other is multi-node V2X communication. In the scenario of multipath transmission, we analyze the channel capacity numerically and we illustrate the significance of networking information such as distance, reference color (symbol), and multiplexing-diversity mode transitions. In addition, in the V2X scenario of multiple access, we may achieve the simultaneous multiple access communication without node interferences by dividing the communication area using image processing. Finally, through numerical simulation, we show the superior SER performance of the visual-MIMO scheme compared with LED-PD communication and show the numerical result of the GCM based visual-MIMO channel capacity versus distance.

  8. P2X7 receptor-deficient mice are susceptible to bone cancer pain

    DEFF Research Database (Denmark)

    Hansen, Rikke Rie; Nielsen, Christian K.; Nasser, Arafat;


    with and without astrocyte activation (BALB/cJ or C3H mice inoculated with 4T1 mammary cancer cells or NCTC 2472 osteosarcoma cells, respectively), suggesting that astrocytic P2X7 receptors play a negligible role in bone cancer pain. The results support the hypothesis that bone cancer pain is a separate pain state...

  9. New magnetic coherence effect in superconducting La2-xSrxCuO4

    DEFF Research Database (Denmark)

    Mason, T.E.; Schröder, A.; Aeppli, G.


    We have used inelastic neutron scattering to examine the magnetic fluctuations at intermediate frequencies in the simplest high temperature superconductor, La2-xSrxCuO4. The suppression of the low energy magnetic response in the superconducting state is accompanied by an increase in the response...

  10. Dispersive excitations in the high-temperature superconductor La2-xSrxCuO4

    DEFF Research Database (Denmark)

    Christensen, N.B.; McMorrow, D.F.; Rønnow, H.M.


    High-resolution neutron scattering experiments on optimally doped La(2-x)Sr(x)CuO(4) (x=0.16) reveal that the magnetic excitations are dispersive. The dispersion is the same as in YBa(2)Cu(3)O(6.85), and is quantitatively related to that observed with charge sensitive probes. The associated veloc...

  11. Structural Insights into Divalent Cation Modulations of ATP-Gated P2X Receptor Channels

    Directory of Open Access Journals (Sweden)

    Go Kasuya


    Full Text Available P2X receptors are trimeric ATP-gated cation channels involved in physiological processes ranging widely from neurotransmission to pain and taste signal transduction. The modulation of the channel gating, including that by divalent cations, contributes to these diverse physiological functions of P2X receptors. Here, we report the crystal structure of an invertebrate P2X receptor from the Gulf Coast tick Amblyomma maculatum in the presence of ATP and Zn2+ ion, together with electrophysiological and computational analyses. The structure revealed two distinct metal binding sites, M1 and M2, in the extracellular region. The M1 site, located at the trimer interface, is responsible for Zn2+ potentiation by facilitating the structural change of the extracellular domain for pore opening. In contrast, the M2 site, coupled with the ATP binding site, might contribute to regulation by Mg2+. Overall, our work provides structural insights into the divalent cation modulations of P2X receptors.

  12. Testing of the J-2X Augmented Spark Igniter (ASI) and Its Electronics (United States)

    Osborne, Robin


    Reliable operation of the spark ignition system electronics in the J-2X Augmented Spark Igniter (ASI) is imperative in assuring ASI ignition and subsequent Main Combustion Chamber (MCC) ignition events are reliable in the J-2X Engine. Similar to the man-rated J-2 and RS-25 engines, the J-2X ignition system electronics are equipped with spark monitor outputs intended to indicate that the spark igniters are properly energized and sparking. To better understand anomalous spark monitor data collected on the J-2X development engines at NASA Stennis Space Center (SSC), a comprehensive subsystem study of the engine's low- and high-tension spark ignition system electronics was conducted at NASA Marshall Space Flight Center (MSFC). Spark monitor output data were compared to more detailed spark diagnostics to determine if the spark monitor was an accurate indication of actual sparking events. In addition, ignition system electronics data were closely scrutinized for any indication of an electrical discharge in some location other than the firing tip of the spark igniter - a problem not uncommon in the development of high voltage ignition systems.

  13. (TMTSF)2X materials and structural implications for low-dimensional polymeric and disordered molecular semiconductors

    DEFF Research Database (Denmark)

    Bechgaard, Klaus; Nielsen, Martin Meedom; Krebs, Frederik C


    The structural characteristics and the relation to the electronic properties of three types of molecular materials are discussed. In TMTSF2X salts a triclinic unit cell it suggested to be important in avoiding a 2k(F) Peierls distortion. In polythiophenes appropriate ordering of microcrystallites...

  14. P2X7 receptors and Fyn kinase mediate ATP-induced oligodendrocyte progenitor cell migration. (United States)

    Feng, Ji-Feng; Gao, Xiao-Fei; Pu, Ying-Yan; Burnstock, Geoffrey; Xiang, Zhenghua; He, Cheng


    Recruitment of oligodendrocyte precursor cells (OPCs) to the lesions is the most important event for remyelination after central nervous system (CNS) injury or in demyelinating diseases. However, the underlying molecular mechanism is not fully understood. In the present study, we found high concentrations of ATP could increase the number of migrating OPCs in vitro, while after pretreatment with oxidized ATP (a P2X7 receptor antagonist), the promotive effect was attenuated. The promotive effect of 2'(3')-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP) (a P2X7 receptor agonist) was more potent than ATP. After incubation with BzATP, the activity of Fyn, one member of the Src family of kinases, was enhanced. Moreover, the interaction between P2X7 and Fyn was identified by co-immunoprecipitation. After blocking the activity of Fyn or down-regulating the expression of Fyn, the migration of OPCs induced by BzATP was inhibited. These data indicate that P2X7 receptors/Fyn may mediate ATP-induced OPC migration under pathological conditions.

  15. Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice. (United States)

    Beaucage, Kim L; Xiao, Andrew; Pollmann, Steven I; Grol, Matthew W; Beach, Ryan J; Holdsworth, David W; Sims, Stephen M; Darling, Mark R; Dixon, S Jeffrey


    The P2X7 receptor is an ATP-gated cation channel expressed by a number of cell types. We have shown previously that disruption of P2X7 receptor function results in downregulation of osteogenic markers and upregulation of adipogenic markers in calvarial cell cultures. In the present study, we assessed whether loss of P2X7 receptor function results in changes to adipocyte distribution and lipid accumulation in vivo. Male P2X7 loss-of-function (KO) mice exhibited significantly greater body weight and epididymal fat pad mass than wild-type (WT) mice at 9 months of age. Fat pad adipocytes did not differ in size, consistent with adipocyte hyperplasia rather than hypertrophy. Histological examination revealed ectopic lipid accumulation in the form of adipocytes and/or lipid droplets in several non-adipose tissues of older male KO mice (9-12 months of age). Ectopic lipid was observed in kidney, extraorbital lacrimal gland and pancreas, but not in liver, heart or skeletal muscle. Specifically, lacrimal gland and pancreas from 12-month-old male KO mice had greater numbers of adipocytes in perivascular, periductal and acinar regions. As well, lipid droplets accumulated in the renal tubular epithelium and lacrimal acinar cells. Blood plasma analyses revealed diminished total cholesterol levels in 9- and 12-month-old male KO mice compared with WT controls. Interestingly, no differences were observed in female mice. Moreover, there were no significant differences in food consumption between male KO and WT mice. Taken together, these data establish novel in vivo roles for the P2X7 receptor in regulating adipogenesis and lipid metabolism in an age- and sex-dependent manner.

  16. Critical role of P2X7 receptors in the neuroinflammation and cognitive dysfunction after surgery. (United States)

    Zheng, Bin; Lai, Renchun; Li, Jun; Zuo, Zhiyi


    Postoperative cognitive dysfunction worsens patient outcome after surgery. Neuroinflammation is a critical neuropathological process for it. We determined the role of P2X7 receptors, proteins that participate in inflammatory response, in the neuroinflammation induction after surgery, and whether the choice of volatile anesthetics affects its occurrence. Eight-week old C57BL/6J or P2X7 receptor knockout male mice were subjected to right carotid arterial exposure under anesthesia with 1.8% isoflurane, 2.5% sevoflurane or 10% desflurane. They were tested by Barnes maze and fear conditioning from 2weeks after the surgery. Hippocampus was harvested 6h, 24h and 7days after the surgery for immunohistochemical staining and Western blotting. Mice with surgery under anesthesia with isoflurane, sevoflurane or desflurane took longer than control mice to identify the target box 1 or 8days after the training sessions in Barnes maze. Mice anesthetized by isoflurane or sevoflurane, but not by desflurane, had less freezing behavior than control mice in fear conditioning test. Mice with surgery and anesthesia had increased ionized calcium binding adapter molecule 1 and interleukin 1β in the hippocampus but this increase was smaller in mice anesthetized with desflurane than mice anesthetized with isoflurane. Mice with surgery had increased P2X7 receptors and its downstream molecule caspase 1. Inhibition or knockout of P2X7 receptors attenuated surgery and anesthesia-induced neuroinflammation and cognitive impairment. We conclude that surgery under desflurane anesthesia may have reduced neuroinflammation and cognitive impairment compared with surgery under isoflurane anesthesia. P2X7 receptors may mediate the neuroinflammation and cognitive impairment after surgery.

  17. Synthesis, characterization, and photocatalytic activity of TiO(2-x)N(x) nanocatalyst. (United States)

    Wang, Y Q; Yu, X J; Sun, D Z


    Nitrogen-doped titanium dioxide powders were prepared by wet method, that is, the hydrolysis of acidic tetra-butyl titanate using aqueous ammonia solution, followed by calcination at temperatures about 350 degrees C. The catalysts exhibited photocatalytic activity in the visible light region owing to N-doping. The light absorption onset of TiO(2-x)N(x) was shifted to the visible region at 459 nm compared to 330 nm of pure TiO(2). An obvious decrease in the band gap was observed by the optical absorption spectroscopy, which resulted from N2p localized states above the valence band of TiO(2-x)N(x) (compared to TiO(2)). The TiO(2-x)N(x) catalyst was characterized to be anatase with oxygen-deficient stoichiometry by X-ray diffraction (XRD), surface photovoltage spectroscopy (SPS) and X-ray photoelectron spectroscopy (XPS). The binding energy of N1s measured by XPS characterization was 396.6 eV (TiN bonds, beta-N) and 400.9 eV (NN bonds, gamma-N(2)), respectively. The photocatalytic activity of TiO(2-x)N(x) under visible light was induced by the formation of beta-N in the structure. Photocatalytic decomposition of benzoic acid solutions was carried out in the ultraviolet and visible (UV-vis) light region, and the TiO(2-x)N(x) catalyst showed higher activity than pure TiO(2).

  18. Association between P2X7 Receptor Polymorphisms and Bone Status in Mice

    Directory of Open Access Journals (Sweden)

    Susanne Syberg


    Full Text Available Macrophages from mouse strains with the naturally occurring mutation P451L in the purinergic receptor P2X7 have impaired responses to agonists (1. Because P2X7 receptors are expressed in bone cells and are implicated in bone physiology, we asked whether strains with the P451L mutation have a different bone phenotype. By sequencing the most common strains of inbred mice, we found that only a few strains (BALB, NOD, NZW, and 129 were harboring the wild allelic version of the mutation (P451 in the gene for the purinergic receptor P2X7. The strains were compared by means of dual energy X-ray absorptiometry (DXA, bone markers, and three-point bending. Cultured osteoclasts were used in the ATP-induced pore formation assay. We found that strains with the P451 allele (BALB/cJ and 129X1/SvJ had stronger femurs and higher levels of the bone resorption marker C-telopeptide collagen (CTX compared to C57Bl/6 (B6 and DBA/2J mice. In strains with the 451L allele, pore-formation activity in osteoclasts in vitro was lower after application of ATP. In conclusion, two strains with the 451L allele of the naturally occurring mutation P451L, have weaker bones and lower levels of CTX, suggesting lower resorption levels in these animals, which could be related to the decreased ATP-induced pore formation observed in vitro. The importance of these findings for the interpretation of the earlier reported effects of P2X7 in mice is discussed, along with strategies in developing a murine model for testing the therapeutic effects of P2X7 agonists and antagonists upon postmenopausal osteoporosis.

  19. Functional expression of purinergic P2X7 receptors in pregnant rat myometrium. (United States)

    Miyoshi, Hiroshi; Yamaoka, Kaoru; Urabe, Satoshi; Kodama, Miho; Kudo, Yoshiki


    ATP has been reported to enhance the membrane conductance of myometrial cells and uterine contractility. Purinergic P2 receptor expression has been reported in the myometrium, using molecular biology, but the functional identity of the receptor subtype has not been determined. In this study, ATP-induced currents were recorded and characterized in single myometrial cells from pregnant rats using whole cell patch clamping. Extracellular ATP was applied in the range of 10 muM-1 mM and induced currents with an EC(50) of 74 muM, with no desensitization, time dependency, or voltage dependency. The currents induced carried multiple monovalent cations, with conductances ranked as K(+) > Cs(+) > Li(+) > Na(+). They were activated by P2X receptor agonists, with their effectiveness ranked as 2',3'-O-(4-benzoylbenzoyl)-ATP > ATP > alphabeta-methylene-ATP > 2-methylthio ATP > or = UTP > or = GTP > ADP. These currents were blocked by the selective P2X7 receptor antagonist 3-[5-(2,3-dichlorophenyl)-1 H-tetrazol-1-yl]methyl pyridine (A-438079). We therefore concluded that ATP-induced currents in rat myometrial cells crossed cell membranes via P2X7 receptors. We further showed that the ATP-induced currents were blocked by extracellular Mg(2+) (IC(50) = 0.26 mM). Clinically, administering extracellular Mg(2+) is known to inhibit uterine contraction. It therefore seems likely that uterine contraction may be induced by raised extracellular ATP and suppressed via Mg(2+) inhibiting P2X7 receptors. Further research is needed into the P2X7 receptor as a therapeutic target in abnormal uterine contraction, as a possible treatment for premature labor.

  20. Association between P2X7 Receptor Polymorphisms and Bone Status in Mice. (United States)

    Syberg, Susanne; Schwarz, Peter; Petersen, Solveig; Steinberg, Thomas H; Jensen, Jens-Erik Beck; Teilmann, Jenni; Jørgensen, Niklas Rye


    Macrophages from mouse strains with the naturally occurring mutation P451L in the purinergic receptor P2X7 have impaired responses to agonists (1). Because P2X7 receptors are expressed in bone cells and are implicated in bone physiology, we asked whether strains with the P451L mutation have a different bone phenotype. By sequencing the most common strains of inbred mice, we found that only a few strains (BALB, NOD, NZW, and 129) were harboring the wild allelic version of the mutation (P451) in the gene for the purinergic receptor P2X7. The strains were compared by means of dual energy X-ray absorptiometry (DXA), bone markers, and three-point bending. Cultured osteoclasts were used in the ATP-induced pore formation assay. We found that strains with the P451 allele (BALB/cJ and 129X1/SvJ) had stronger femurs and higher levels of the bone resorption marker C-telopeptide collagen (CTX) compared to C57Bl/6 (B6) and DBA/2J mice. In strains with the 451L allele, pore-formation activity in osteoclasts in vitro was lower after application of ATP. In conclusion, two strains with the 451L allele of the naturally occurring mutation P451L, have weaker bones and lower levels of CTX, suggesting lower resorption levels in these animals, which could be related to the decreased ATP-induced pore formation observed in vitro. The importance of these findings for the interpretation of the earlier reported effects of P2X7 in mice is discussed, along with strategies in developing a murine model for testing the therapeutic effects of P2X7 agonists and antagonists upon postmenopausal osteoporosis.

  1. P2X receptors regulate adenosine diphosphate release from hepatic cells. (United States)

    Chatterjee, Cynthia; Sparks, Daniel L


    Extracellular nucleotides act as paracrine regulators of cellular signaling and metabolic pathways. Adenosine polyphosphate (adenosine triphosphate (ATP) and adenosine diphosphate (ADP)) release and metabolism by human hepatic carcinoma cells was therefore evaluated. Hepatic cells maintain static nanomolar concentrations of extracellular ATP and ADP levels until stress or nutrient deprivation stimulates a rapid burst of nucleotide release. Reducing the levels of media serum or glucose has no effect on ATP levels, but stimulates ADP release by up to 10-fold. Extracellular ADP is then metabolized or degraded and media ADP levels fall to basal levels within 2-4 h. Nucleotide release from hepatic cells is stimulated by the Ca(2+) ionophore, ionomycin, and by the P2 receptor agonist, 2'3'-O-(4-benzoyl-benzoyl)-adenosine 5'-triphosphate (BzATP). Ionomycin (10 μM) has a minimal effect on ATP release, but doubles media ADP levels at 5 min. In contrast, BzATP (10-100 μM) increases both ATP and ADP levels by over 100-fold at 5 min. Ion channel purinergic receptor P2X7 and P2X4 gene silencing with small interference RNA (siRNA) and treatment with the P2X inhibitor, A438079 (100 μM), decrease ADP release from hepatic cells, but have no effect on ATP. P2X inhibitors and siRNA have no effect on BzATP-stimulated nucleotide release. ADP release from human hepatic carcinoma cells is therefore regulated by P2X receptors and intracellular Ca(2+) levels. Extracellular ADP levels increase as a consequence of a cellular stress response resulting from serum or glucose deprivation.

  2. Establishment of P2X7 stable expressed cell strain in Caski cells and the activity detection%P2X7受体在Caski细胞膜上的表达及功能检测

    Institute of Scientific and Technical Information of China (English)

    孙丽; 韩莉; 刘朝奇; 石慧; 赵琳; 神谢静; 谭超


    目的:用重组质粒pcDNA6/His-V5-P2X7建立细胞膜稳定表达P2X7受体的人宫颈癌Caski细胞株.方法:采用脂质体转染法将重组质粒pcDNA6/His-V5-P2X7转染入Caski细胞后,应用RT-PCR、Western blotting及细胞免疫荧光法筛选高表达P2X7的Caski细胞株;MTT法检测细胞增殖;P2X7的天然配体ATP处理高表达细胞后,MTF检测细胞生存率,FCM检测细胞凋亡率.结果:成功获得高表达P2X7受体的Caski细胞株;与对照细胞相比,高表达P2X7受体可抑制Caski细胞生长;不同浓度ATP作用细胞株后可抑制细胞增殖,并导致细胞凋亡率增加.结论:高表达P2X7可抑制Caski细胞生长,并且在其配体ATP作用下诱导细胞凋亡.%Objective:To study the effects of high expression P2X7 receptor on the growth of human cervical canc-er Caski cell. Methods;The recombinant plasmid pcDNA6/V5 - His - P2X7 was transfected into Caski cell with Li-pofectamine2000 reagents. The positive clone with P2X7 receptor overexpression was identified by reverse transcrip-tion PCR,Western blotting and immunofluorescence . The effects of P2X7 overexpression on the cell proliferation was detected by MTT assay. After treatment by the natural ligand ATP on the P2X7 overexpression cells using MTT assay detected cell survival and FCM detection of apoptosis. Results;The Caski clone cell with P2X7 receptor overexpres-sion was obtained successfully comparing with the control cell, high expression of P2X7 receptor resulted in cell growth inhibition and increased cell apoptosis. Conclusion:stable expression of P2X7 Caski inhibit cell proliferation, while under the effect of ATP via P2X7 receptor pathway leading to apoptosis.

  3. Co-Expression of Wild-Type P2X7R with Gln460Arg Variant Alters Receptor Function.

    Directory of Open Access Journals (Sweden)

    Fernando Aprile-Garcia

    Full Text Available The P2X7 receptor is a member of the P2X family of ligand-gated ion channels. A single-nucleotide polymorphism leading to a glutamine (Gln by arginine (Arg substitution at codon 460 of the purinergic P2X7 receptor (P2X7R has been associated with mood disorders. No change in function (loss or gain has been described for this SNP so far. Here we show that although the P2X7R-Gln460Arg variant per se is not compromised in its function, co-expression of wild-type P2X7R with P2X7R-Gln460Arg impairs receptor function with respect to calcium influx, channel currents and intracellular signaling in vitro. Moreover, co-immunoprecipitation and FRET studies show that the P2X7R-Gln460Arg variant physically interacts with P2X7R-WT. Specific silencing of either the normal or polymorphic variant rescues the heterozygous loss of function phenotype and restores normal function. The described loss of function due to co-expression, unique for mutations in the P2RX7 gene so far, explains the mechanism by which the P2X7R-Gln460Arg variant affects the normal function of the channel and may represent a mechanism of action for other mutations.

  4. Rod and cone pathway signalling is altered in the P2X7 receptor knock out mouse.

    Directory of Open Access Journals (Sweden)

    Kirstan A Vessey

    Full Text Available The P2X7 receptor (P2X7-R is expressed in the retina and brain and has been implicated in neurodegenerative diseases. However, whether it is expressed by neurons and plays a role as a neurotransmitter receptor has been the subject of controversy. In this study, we first show that the novel vesicular transporter for ATP, VNUT, is expressed in the retina, verifying the presence of the molecular machinery for ATP to act as neurotransmitter at P2X7-Rs. Secondly we show the presence of P2X7-R mRNA and protein in the retina and cortex and absence of the full length variant 1 of the receptor in the P2X7-R knock out (P2X7-KO mouse. The role of the P2X7-R in neuronal function of the retina was assessed by comparing the electroretinogram response of P2X7-KO with WT mice. The rod photoreceptor response was found to be similar, while both rod and cone pathway post-photoreceptor responses were significantly larger in P2X7-KO mice. This suggests that activation of P2X7-Rs modulates output of second order retinal neurons. In line with this finding, P2X7-Rs were found in the outer plexiform layer and on inner retinal cell classes, including horizontal, amacrine and ganglion cells. The receptor co-localized with conventional synapses in the IPL and was expressed on amacrine cells post-synaptic to rod bipolar ribbon synapses. In view of the changes in visual function in the P2X7-KO mouse and the immunocytochemical location of the receptor in the normal retina, it is likely the P2X7-R provides excitatory input to photoreceptor terminals or to inhibitory cells that shape both the rod and cone pathway response.

  5. Gd3Al2-xGax系合金磁热效应的研究%Study on Magnetocaloric Effect of Gd3Al2-xGax

    Institute of Scientific and Technical Information of China (English)

    生利英; 曹朝霞; 黄焦宏; 齐勇田; 宋博宇


    The organization structure and the magnetocaloric effect of Gd3 Al2-x Gax (0.1 x =0,0.2,0.3) series alloy prepared by smelting in a a high-frequency floating furnace and annealing treatment at 900 ℃ for 30 h were investigated.The results show that Gd3Al2-xGax series alloy keeps simple tetragonal crystal structure of Gd3Al2.The content of base phase Gd3Al2 increases after heat treatment.The Curie temperature of Gd3 Al2-xGaxseries alloy changes between 1 K ~ 2 K along with the increase of the content of Ga.The half peak width of △Sm-T curve is almost the same.The maximum magnetic entropy changes of Gd3Al1.8Ga0.2 alloy is the largest under magnetic field changes of 1.5 T,which exceeds 30% of Gd3Al2 alloy.A small amount of Ga to replace Al can improve the magnetocaloric effect of Gd3Al2 alloy.%对经真空高频磁悬浮炉熔炼、900℃30 h热处理的Gd3 Al2-XGax(x=0,0.1,0.2,0.3)系列合金的组织结构和磁热效应进行了研究.研究发现,Gd3Al2-XGax系列合金保持了Gd3Al2的简单正方晶体结构,热处理后基相Gd3Al2的含量增加,随着Ga含量的增加,Gd3Al2-XGax合金的居里温度变化在1K~2K之间,在1.5T的外加磁场下,△Sm-T曲线半峰宽几乎不变,Gd3Al1.8Ga0.2合金的最大磁熵变最大,超过Gd3Al2的最大磁熵变30%.少量Ga替代Al可以提高Gd3Al2合金的磁热效应.

  6. Research progress of P2X7 receptor mediates breast cancer of JNK/SAPK signaling pathway%P2X7受体激活乳腺癌JNK/SAPK信号通路的研究进展

    Institute of Scientific and Technical Information of China (English)

    谭超; 韩莉


    P2X7受体是ATP门控的离子通道,对二价阳离子有较强的选择性,属于嘌呤受体P2X家族.P2X7受体参与细胞信号转导、细胞因子的分泌等多种生理功能.近年研究发现P2X7受体通过增加氧化磷酸化及细胞内ATP的储备,介导细胞的存活与生长.在乳腺癌中P2X7受体表达异常,并能激活JNK/SAPK途径,诱导乳腺癌细胞凋亡.本文综述了P2X7受体与乳腺癌发生发展分子机制的相关研究.%P2X7 receptor is an ATP - gated cation channel, which can choose the bivalent cation freely, and belongs to purine receptors P2X family. P2X7 receptors joins in cell signal to the report, the discharge of physical features. In recent years, researchers have discovered P2X7 receptors by increasing oxidation phosphoric acid and cells within the ATP reserves, a report that the cells to live and grow. P2X7 receptor is expresssed abnormally in breast cancer , and the P2X7 receptor can activate the JNK / SAPK pathway, inducting the apoptosis in breast cancer cells. This article reviews the development of molecular mechanisms of the P2X7 receptor and breast cancer.

  7. Physical and electrical properties of band-engineered SiO2/(TiO2) x (SiO2)1- x stacks for nonvolatile memory applications (United States)

    Oh, Jinho; Na, Heedo; Mok, In-Su; Kim, Jonggi; Lee, Kyumin; Sohn, Hyunchul


    In our study, the physical properties of (TiO2) x (SiO2)1- x , including band-gap, band-offset, and thermal stability and the electrical properties of band-engineered SiO2/(TiO2) x (SiO2)1- x tunnel barrier stacks, including the tunneling current and charge-trapping characteristics for applications to nonvolatile memory devices were investigated. It was observed that the band-gap and band-offset of (TiO2) x (SiO2)1- x can be controlled by adjustment in the composition of the (TiO2) x (SiO2)1- x films. Ti-silicate film with TiO2:SiO2 cycle ratio of 1:5 was maintained in an amorphous phase, even after annealing at 950 °C. The tunneling current of the band-engineered SiO2/(TiO2) x (SiO2)1- x stacked tunnel barrier was larger than that of a single SiO2 barrier under a higher external bias, while the tunneling current of a SiO2/(TiO2) x (SiO2)1- x stacked tunnel barrier under a lower external bias was smaller. Charge-trapping tests showed that the voltage shift for SiO2/(TiO2) x (SiO2)1- x is slightly larger than that for single SiO2.

  8. Computational study on the characteristics of the interaction in naphthalene...(H2X)n=1,2 (X = O,S) clusters. (United States)

    Cabaleiro-Lago, Enrique M; Rodríguez-Otero, Jesús; Peña-Gallego, Angeles


    The characteristics of the interaction between the pi cloud of naphthalene and up to two H2O or H2S molecules were studied. Calculations show that clusters formed by naphthalene and one H2O or H2S molecule have similar geometric features, and also present similar interaction energies. Our best estimates for the interaction energy amount to -2.95 and -2.92 kcal/mol for H2O and H2S, respectively, as obtained with the CCSD(T) method. Calculations at the MP2 level employing large basis sets should be avoided because they produce highly overestimated interaction energies, especially for hydrogen sulfide complexes. The MPWB1K functional, however, provides values pretty similar to those obtained with the CCSD(T) method. Although the magnitude of the interaction is similar with both H2X molecules, its nature is somewhat different: the H2O complex presents electrostatic and dispersion contributions of similar magnitude, whereas for H2S the interaction is dominated by dispersion. In clusters containing two H2X molecules several minima were characterized. In water clusters, the total interaction energy is dominated by the presence of a O-H...O hydrogen bond and, as a consequence, structures where this contact is present are the most stable. However, clusters containing H2S show structures with no interaction between H2S moieties which are as stable as the hydrogen bonded ones, because they allow an optimal H2S...naphthalene interaction, which is stronger than the S-H...S contact. Therefore it is possible that in larger polycycles hydrogen sulfide molecules will be spread onto the surface maximizing S-H...pi interactions rather than aggregated, forming H2S clusters.

  9. Contribution of the spinal P2X7 receptors to bee venom-induced nociception and inflammation in conscious rats. (United States)

    Zhou, Zhong-He; Wang, Jian-Xiu; Liu, Bao-Jun; Li, Man; Lu, Yao; Chen, Hui-Sheng


    Recently, P2X7 receptor (P2X7R) has been found to contribute to the development of inflammatory pain, however, the role of spinal P2X7R is not clear. The present study was designed to determine the roles of spinal P2X7R in the bee venom (BV) model, characterized by multiple pain-related behaviors and obvious inflammatory edema. We determined the effects of P2X7R antagonist A438790 on BV-induced PSN, mechanical allodynia and inflammatory swelling. Pre-treatment with intrathecal administration of A438079 significantly inhibited BV-induced PSN and mechanical allodynia in a dose-dependent manner, but had no effect on BV-induced inflammatory swelling. These data suggest that the activation of spinal P2X7Rs may play a key role in BV-induced nociception, but not inflammation.

  10. Alteration of P2X3 expression in dorsal root ganglia after sciatic nerve ligation

    Institute of Scientific and Technical Information of China (English)

    Guoxing Zhou; Lesi Xie; Qiben Wang; Qingping Yu; Xiaofu Liu; Qiumei Liu; Wei Peng; Zhicheng Zeng


    BACKGROUND: The expressions of P2X3 receptor in dorsal root ganglia (DRG) after different peripheral nerve injuries are diverse. It indicates the different roles of P2X3 in different models-caused neuropathologic pains.OBJECTIVE: To observe the expressions of P2X3 in corresponding DRG after sciatic nerve ligation in rats.DESIGN: Controlled observation experiment.SETTING: Department of Morphology, Hunan Traditional Chinese Medical College; Department of Human Anatomy and Neurobiology, Xiangya Medical College, Central South University.MATERIALS: Thirty-five healthy adult SD rats of clean grade an d either gender, weighing (200±20) g,were involved. According to the random digits table, the involved rats were randomized into 3 groups:normal group (n =5), sham-operated group (n =5) and experimental group (n =25). The experimental group were subdivided into 3, 7, 14, 21, 28 days groups according to different surviving time after operation, 5 rats at each time point. Polyclonal rabbit anti-P2X3 antibody (ABCAM company); biotinylated goat anti-rabbit IgG (Zhongshanjingqiao Biotechnical Co., Ltd., Beijing); Motic fluorescence microscope (Motic, Germany).METHODS: The experiments were carried out in the Department of Human Anatomy and Neurobiology,Xiangya Medical College, Central South University from June to December 2006. ① Rats of experimental group were created into models by ligation of right sciatic nerve according to the method of Seltzer et al. Left sciatic nerve was used as self-control. As for rats in the sham-operated group, ligation of sciatic nerve was omitted, but other procedures were the same as those in the experimental group. Rats of normal group were untouched. ② Rats of the normal group and sham-operated group survived for 14 days separately, and those of experimental group survived for corresponding time. After being deeply anesthetized by intraperitoneal injection of over-dose sodium pentobarbital, the rats of experimental group were transcardially

  11. Stripe order in La2-xBaxCuO4 in high magnetic fields (United States)

    Huecker, M.; von Zimmermann, M.; Xu, Z. J.; Wen, J. S.; Gu, G. D.; Zaliznyak, I. A.; Chung, J.-H.; Choi, E. S.; Tranquada, J. M.


    The observation of enhanced spin stripe order in the vortex cores of La2-xSrxCuO4 has been a landmark experiment that revealed the intimate connection between superconductivity and incommensurate antiferromagnetism. Only recently we have observed a corresponding field dependence of the spin and, more importantly, of the charge stripe order in La2-xBaxCuO4. Here we present our recent results from neutron diffraction, x-ray diffraction, and torque measurements in high magnetic fields. These helped us to establish the field versus temperature and doping phase diagrams for spin and charge order, and to further corroborate the stripe model as the more appropriate description than for example spiral and vortex states.

  12. Broken bond symmetry assists stripe pinning in superconducting La2-xSrxCuO4 (United States)

    Tranquada, John; Jacobsen, H.; Zaliznyak, I. A.; Huecker, M.; Gu, G. D.; Savici, A. T.; Winn, B.; Chang, S.

    There has been evidence for quite some time for some degree of charge and spin stripe order in La2-xSrxCuO4 (LSCO). This has been a bit surprising as the crystal structure is supposed to lack the anisotropic Cu-O bonds that lead to robust stripe pinning in La2-xBaxCuO4. Using neutron scattering measurements on the HYSPEC instrument at the Spallation Neutron Source, we have discovered evidence for broken bond symmetry and strong associated lattice fluctuations in an LSCO crystal with x = 0 . 07. The broken bond symmetry occurs within the orthorhombic phase. We also observe quasielastic incommensurate spin excitations that coexist with the bulk superconductivity, suggesting some degree of pair-density-wave order in the superconducting state. Work at BNL supported by Office of Basic Energy Sciences, US DOE, under Contract No. DE-SC00112704.

  13. Dynamical optical properties of La2-xSrxCuO4 cuprates (United States)

    Schneider, M. L.; Rast, S.; Onellion, M.; Ren, Y.; Zhang, X.; Luepke, G.; Perakis, I.; Abrecht, M.; Ariosa, D.; Pavuna, D.; Zeng, X. H.; Weidong, Si; Xi, X. X.


    We present pump-probe optical reflectivity measurements on underdoped, optimally doped and overdoped La2-xSrxCuO4 thin films grown on SrTiO3.[1] We find qualitative changes of the reflectivity with temperature, in particular below and above the superconducting transition temperature. We have measured YBa2Cu3O7-x and NdBa2Cu3O7-y thin films for comparison and present these comparative results. The La2-xSrxCuO4 data indicate the existence of two subsystems within the material. The two subsystems are electronic (or optically active), interact, and they transfer energy between them. We discuss our reasoning on these points. 1. M.L. Schneider, submitted

  14. Prediction of intrinsic motivation and sports performance using 2 x 2 achievement goal framework. (United States)

    Li, Chiung-Huang; Chi, Likang; Yeh, Suh-Ruu; Guo, Kwei-Bin; Ou, Cheng-Tsung; Kao, Chun-Chieh


    The purpose of this study was to examine the influence of 2 x 2 achievement goals on intrinsic motivation and performance in handball. Participants were 164 high school athletes. All completed the 2 x 2 Achievement Goals Questionnaire for Sport and the Intrinsic Motivation subscale of the Sport Motivation Scale; the coach for each team rated his athletes' overall sports performance. Using simultaneous-regression analyses, mastery-approach goals positively predicted both intrinsic motivation and performance in sports, whereas performance-avoidance goals negatively predicted sports performance. These results suggest that athletes who pursue task mastery and improvement of their competence perform well and enjoy their participation. In contrast, those who focus on avoiding normative incompetence perform poorly.

  15. Hydrogen sensitive gas sensor based on porous silicon/TiO{sub 2-x} structure

    Energy Technology Data Exchange (ETDEWEB)

    Arakelyan, V.M.; Galstyan, V.E.; Martirosyan, Kh.S.; Shahnazaryan, G.E.; Aroutiounian, V.M. [Yerevan State Univ, Dept Phys Semicond and Microelect, Yerevan 0025, (Armenia); Soukiassian, P.G. [CEA, DSM, DRECAM, SPCSI, Lab SIMA, F-91191 Gif Sur Yvette, (France); Soukiassian, P.G. [Univ Paris 11, Dept Phys, F-91405 Orsay, (France)


    Porous silicon (PS) layer was formed by electrochemical anodization on a p-type Si surface. Thereafter, n-type TiO{sub 2-x} thin film was deposited onto the PS surface by electron-beam evaporation. Pt catalytic layer and Au electrical contacts for further measurements were deposited onto the PS/TiO{sub 2-x} structure by ion-beam sputtering. Current-voltage characteristic, sensitivity to different concentration of hydrogen and resistance change of obtained structures versus time were examined. Results of measurements have shown that the current-voltage characteristics of structures are similar to that of diode. High sensitivity to hydrogen of obtained structures was also detected. Note that all measurements were carried out at room temperature. (authors)

  16. Complex spin glass behavior in Ga2-xFexO3 (United States)

    Mahana, Sudipta; Topwal, D.


    We report the results of the dc magnetization and ac susceptibility measurements on solid solutions of Ga2-xFexO3 (with x = 0.75, 1.0, and 1.25). Magnetic behavior in this series of compounds could broadly be explained by the molecular-field-approximation of a three-sublattice ferrimagnetic model considering three inequivalent octahedral sites. Analysis of frequency dispersion of ac susceptibility reveals a transition from the cluster-glass-like phase to the spin-glass-like phase with decreasing temperature for the x = 0.75 composition. Mentioned glassy behavior is found to gradually evolve with the composition (x) from the Ising type character to Heisenberg type behavior to unconventional glassy behavior for the x = 1.25 composition. Ga2-xFexO3 can hence serve as an ideal system for modeling complex spin glasses.

  17. Investigation on the electrochemical behaviours of Mg2-xCrxNi negative electrode

    Institute of Scientific and Technical Information of China (English)


    A series of Mg2-xCrxNi alloy powder has been produced by combination of solid-state diffusion with mechanicalgrinding (MG). X-ray diffraction patterns show that the alloy powders have an amorphous structure and great increase in thespecific surface. Electrochemical detection results indicate that the partial substitution of Mg by Cr in Mg2Ni alloy improvesthe cycle life of this alloy greatly, which gets up to 100 cycles at 200 mA/g mass discharge current, keeping its mass dis-charge capacity over 200 mA@h/g. In the meanwhile, partial replacement of Mg by Cr also increases the mass discharge ca-pacity compared with Mg2Ni alloy. With the increasing of mass discharge current and content of Cr in Mg2-xCrxNi, the cyclelife of the alloys are increased and the decay of mass discharge capacity slows down.

  18. Magnetocaloric effect in a cluster-glass system Ho5Pd2-xNix (United States)

    Toyoizumi, Saori; Kitazawa, Hideaki; Morita, Kengo; Tamaki, Akira


    In order to investigate the effect of chemical pressure on the large magnetocaloric effect in Ho5 Pd2, we conducted X-ray diffraction, magnetization, and specific heat measurements on Ho5Pd2-xNix(0≤ x ≤ 1.0) rare-earth intermetallic compounds. The linear x dependence of the lattice constant a suggests that Ni is replaced with Pd in the case of Ho5Pd2-xNix (0 ≤ x ≤ 0.5). The spin-glass transition temperature Tg and paramagnetic Curie temperature θP indicate a weak oscillatory x dependence. However, the magnetic entropy change —ΔSm and the relative cooling power (RCP) are rapidly suppressed with increasing x. These large reductions in —ΔSm and RCP cannot be explained only in terms of normal Ruderman-Kittel- Kasuya-Yoshida (RKKY)-type indirect exchange interactions.

  19. Functional characterization of P2X7 receptors in the rat pineal gland


    Luis Henrique de Souza Teodoro


    A sinalização purinérgica tem sido demonstrada como um um importante modulador dediversos processos fisiológicos e fisiopatológicos. Dentre os receptores purinérgicos, o receptor P2X7 distingui-se por requerir altas concentrações de ATP em sua ativação. As demonstrações prévias de que a glândula pineal responde a diferentes estímulos purinérgicose a altas concentrações de ATP sugere um papel para os receptores P2X7 nesta glândula, embora sua expressão e função não estivesse estabelecida. O ob...

  20. Chemisorption of aromatic molecules on Si(100)-2x1. An HREELS study

    CERN Document Server

    Alkunshalie, T


    HREELS has been used to investigate the growth of ultra-thin organic film on Si(100)-2x1 by reactive coupling of polyimide precursors. 1,4- phenylenediamine and pyromelltic dianhydride were sequentially dosed on clean Si(100)-2x1 under ultra high vacuum conditions. The interfacial imidisation was initiated by thermal curing at 200 deg C. To simplify the analysis of the vibrational data, model compounds benzoic acid, aniline and phthalic anhydride were characterised first. HREEL spectra show that the model compounds absorb through dissociation of the functional group. The spectra also show that an oligimide chain has been formed which stands upright on the surface. The oligomer chain bonds to the silicon surface via a Si-(NH)-C linkage.

  1. Thermal expansion properties of Lu2-x FexMo3O12

    Institute of Scientific and Technical Information of China (English)

    Wu Mei-Mei; Peng Jie; Zu Yong; Liu Rong-Deng; Hu Zhong-Bo; Liu Yun-Tao; Chen Dong-Feng


    The structures and thermal expansion properties of Lu2-xFex Mo3O12 have been investigated by X-ray diffraction (XRD).XRD patterns at room temperature indicate that componnds Lu2 xFexMo3O12 with x ≤ 1.3 exhibit an orthorhombic structure with space group Pnca;compounds with x =1.5 and 1.7 have a monoclinic structure with space group P21/a.Studies on thermal expansion properties show that the linear thermal expansion coefficients of orthorhombic phase vary from negative to positive with increasing Fe content.Attempts to make zero thermal expansion materials indicate that zero thermal expansion can be observed in Lu1.3Feo.7Mo3O12 in the temperature range of 200-400°C.

  2. Haemolysis induced by α-toxin from Staphylococcus aureus requires P2X receptor activation

    DEFF Research Database (Denmark)

    Skals, Marianne Gerberg; Leipziger, Jens Georg; Prætorius, Helle


    -forming bacterial toxins. In this context, it is essential to know whether this is specific to HlyA-induced cell damage or if other bacterial pore-forming toxins involve purinergic signals to orchestrate haemolysis. Here, we investigate if the haemolysis produced by α-toxin from Staphylococcus aureus involves P2...... receptor activation. We observed that α-toxin-induced haemolysis is completely blocked by the unselective P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid. Moreover, several selective blockers of P2X1 and P2X7 ionotropic receptors abolished haemolysis in murine and equine...... erythrocytes. Inhibitors of pannexin channels partially reduced the α-toxin induced lysis. Thus, we conclude that α-toxin, similar to HlyA from E. coli produces cell damage by specific activation of a purinergic signalling cascade. These data indicate that pore-forming toxins in general require purinergic...

  3. X-ray-scattering determination of the Cu(110)-(2x3)N structure

    DEFF Research Database (Denmark)

    Baddorf, A.P.; Zehner, D.M.; Helgesen, G.;


    corrugation amplitude (50%, of the bulk interlayer spacing) in the outermost layer. These values can be understood by considering a hard-sphere model of the surface structure. The corrugation results in two raised and two lowered rows of copper atoms in the outermost layer and extends to several layers......The structure of Cu(110)-(2X3)N has been investigated with x-ray reflectivity measurements of nine independent surface rods. Observed reflectivities ranging over five orders of magnitude were compared with calculations based on structural models. A pseudo-(100) reconstruction consisting of four......, and form a nearly (square-root 2 X square-root 2) R 45-degrees structure with respect to the reconstructed copper. This model is shown to be consistent with most previous experimental observations....

  4. Evolution equation for the structure function g_2(x,Q^2)

    CERN Document Server

    Braun, V M; Manashov, A N


    We perform an extensive study of the scale dependence of flavor-singlet contributions to the structure function g_2(x,Q^2) in polarized deep-inelastic scattering. We find that the mixing between quark-antiquark-gluon and three-gluon twist-3 operators only involves the three-gluon operator with the lowest anomalous dimension and is weak in other cases. This means, effectively, that only those three-gluon operators with the lowest anomalous dimension for each moment are important, and allows to formulate a simple two-component parton-like description of g_2(x,Q^2) in analogy with the conventional description of twist-2 parton distributions. The similar simplification was observed earlier for the nonsinglet distributions, although the reason is in our case different.

  5. Characterization of M2X formed during 5 MeV Fe2+ irradiation (United States)

    Getto, E.; Sun, K.; Was, G. S.


    The growth of M2X phase in HT9 irradiated to high dpa was explored using self-ion irradiation. HT9 was pre-implanted with 10 appm He and irradiated with a raster-scanned Fe2+ beam with a damage rate of ∼1 × 10-3 dpa/s at 460 °C. The precipitation of M2X was observed and a combination of high resolution transmission electron microscopy (HRTEM), energy filtered transmission electron microscopy (EFTEM) and diffraction analysis was used to characterize the Cr-rich carbide observed at 250 dpa and above. Cr2C was determined to be semi-coherent with the matrix such that [ 100 ] Cr2 C / /[100]α and [ 001 ] Cr2 C / /[ 10 1 bar ] α .with a = 2.71 Å and c = 2.82 Å.

  6. A P2X receptor from the tardigrade species Hypsibius dujardini with fast kinetics and sensitivity to zinc and copper

    Directory of Open Access Journals (Sweden)

    Blaxter Mark L


    Full Text Available Abstract Background Orthologs of the vertebrate ATP gated P2X channels have been identified in Dictyostelium and green algae, demonstrating that the emergence of ionotropic purinergic signalling was an early event in eukaryotic evolution. However, the genomes of a number of animals including Drosophila melanogaster and Caenorhabditis elegans, both members of the Ecdysozoa superphylum, lack P2X-like proteins, whilst other species such as the flatworm Schistosoma mansoni have P2X proteins making it unclear as to what stages in evolution P2X receptors were lost. Here we describe the functional characterisation of a P2X receptor (HdP2X from the tardigrade Hypsibius dujardini demonstrating that purinergic signalling is preserved in some ecdysozoa. Results ATP (EC50 ~44.5 μM evoked transient inward currents in HdP2X with millisecond rates of activation and desensitisation. HdP2X is antagonised by pyridoxal-phosphate-6-azophenyl-2',4' disulfonic acid (IC50 15.0 μM and suramin (IC50 22.6 μM and zinc and copper inhibit ATP-evoked currents with IC50 values of 62.8 μM and 19.9 μM respectively. Site-directed mutagenesis showed that unlike vertebrate P2X receptors, extracellular histidines do not play a major role in coordinating metal binding in HdP2X. However, H306 was identified as playing a minor role in the actions of copper but not zinc. Ivermectin potentiated responses to ATP with no effect on the rates of current activation or decay. Conclusion The presence of a P2X receptor in a tardigrade species suggests that both nematodes and arthropods lost their P2X genes independently, as both traditional and molecular phylogenies place the divergence between Nematoda and Arthropoda before their divergence from Tardigrada. The phylogenetic analysis performed in our study also clearly demonstrates that the emergence of the family of seven P2X channels in human and other mammalian species was a relatively recent evolutionary event that occurred subsequent

  7. Stable, synthetic analogs of diadenosine tetraphosphate inhibit rat and human P2X3 receptors and inflammatory pain (United States)

    Viatchenko-Karpinski, Viacheslav; Novosolova, Natalia; Ishchenko, Yevheniia; Azhar, M Ameruddin; Wright, Michael; Tsintsadze, Vera; Kamal, Ahmed; Burnashev, Nail; Voitenko, Nana; Giniatullin, Rashid; Lozovaya, Natalia


    Background A growing body of evidence suggests that ATP-gated P2X3 receptors (P2X3Rs) are implicated in chronic pain. We address the possibility that stable, synthetic analogs of diadenosine tetraphosphate (Ap4A) might induce antinociceptive effects by inhibiting P2X3Rs in peripheral sensory neurons. Results The effects of two stable, synthetic Ap4A analogs (AppNHppA and AppCH2ppA) are studied firstly in vitro on HEK293 cells expressing recombinant rat P2XRs (P2X2Rs, P2X3Rs, P2X4Rs, and P2X7Rs) and then using native rat brain cells (cultured trigeminal, nodose, or dorsal root ganglion neurons). Thereafter, the action of these stable, synthetic Ap4A analogs on inflammatory pain and thermal hyperalgesia is studied through the measurement of antinociceptive effects in formalin and Hargreaves plantar tests in rats in vivo. In vitro inhibition of rat P2X3Rs (not P2X2Rs, P2X4Rs nor P2X7Rs) is shown to take place mediated by high-affinity desensitization (at low concentrations; IC50 values 100–250 nM) giving way to only weak partial agonism at much higher concentrations (EC50 values ≥ 10 µM). Similar inhibitory activity is observed with human recombinant P2X3Rs. The inhibitory effects of AppNHppA on nodose, dorsal root, and trigeminal neuron whole cell currents suggest that stable, synthetic Ap4A analogs inhibit homomeric P2X3Rs in preference to heteromeric P2X2/3Rs. Both Ap4A analogs mediate clear inhibition of pain responses in both in vivo inflammation models. Conclusions Stable, synthetic Ap4A analogs (AppNHppA and AppCH2ppA) being weak partial agonist provoke potent high-affinity desensitization-mediated inhibition of homomeric P2X3Rs at low concentrations. Therefore, both analogs demonstrate clear potential as potent analgesic agents for use in the management of chronic pain associated with heightened P2X3R activation. PMID:27030723

  8. P2X7 Receptor Activation Impairs Exogenous MHC Class I Oligopeptides Presentation in Antigen Presenting Cells


    Alberto Baroja-Mazo; Maria Barberà-Cremades; Pablo Pelegrín


    Major histocompatibility complex class I (MHC I) on antigen presenting cells (APCs) is a potent molecule to activate CD8(+) T cells and initiate immunity. P2X7 receptors (P2X7Rs) are present on the plasma membrane of APCs to sense the extracellular danger signal adenosine-5'-triphosphate (ATP). P2X7R activates the inflammasome and the release of IL-1β in macrophages and other immune cells to initiate the inflammatory response. Here we show that P2X7R stimulation by ATP in APCs decreased the a...

  9. Dynamic micro-organization of P2X7 receptors revealed by PALM based single particle tracking


    Shrivastava, Amulya N.; Rodriguez, Pamela C.; Triller, Antoine; Renner, Marianne


    Adenosine triphosphate (ATP)-gated P2X7 receptors (P2X7Rs) are members of the purinergic receptor family that are expressed in several cell types including neurons. A high concentration of ATP is required for the channel opening of P2X7Rs compared to other members of this receptor family. Recent work suggests that ATP binding to members of the P2X receptor family determines the diffusion and localization of these receptors on the plasma membrane of neurons. Here, we employed single particle t...

  10. Valence Fluctuations in La2-xSrxCuO4

    NARCIS (Netherlands)

    Groot, R.A. de; Gutfreund, H.; Weger, M.


    Ab-initio electronic band structure calculations are presented for the perovskite La2CuO4 and for this material doped with Sr for a supercell of composition La3SrCu2O8. This material is close to the high Tc superconductor La2-xSrxCuO4 discovered recently. The Sr doping gives rise to strong valence f

  11. Blow up for a 2x2 strictly hyperbolic system arising from chemical engineering

    CERN Document Server

    Bourdarias, Christian; Junca, Stéphane


    We consider a 2x2 hyperbolic system of conservation laws modeling heat less adsorption of a gaseous mixture with two species and infinite exchange kinetics, close to the system of Chromatography. In this model the velocity is not constant because the sorption effect is taken in account. Our aim is to construct a solution with a velocity which blows up at the characteristic boundary. This phenomenon only occurs in particular but physically relevant cases.

  12. Phonons in the ordered c(2 x 2) phases of Na and Li on Al(001)

    Energy Technology Data Exchange (ETDEWEB)

    Rusina, G G [Institute of Strength Physics and Materials Science SB RAS, 634021, Tomsk (Russian Federation); Eremeev, S V [Institute of Strength Physics and Materials Science SB RAS, 634021, Tomsk (Russian Federation); Borisova, S D [Institute of Strength Physics and Materials Science SB RAS, 634021, Tomsk (Russian Federation); Sklyadneva, I Yu [Institute of Strength Physics and Materials Science SB RAS, 634021, Tomsk (Russian Federation); Echenique, P M [Donostia International Physics Center (DIPC), 20018 San Sebastian/Donostia, Basque Country (Spain); Chulkov, E V [Donostia International Physics Center (DIPC), 20018 San Sebastian/Donostia, Basque Country (Spain)


    The vibrational properties of the Al(001)-c(2 x 2)-Na (Li) ordered phases formed by alkali atoms (Na and Li) on the Al(001) surface at low and room temperatures are presented. The equilibrium structural characteristics, phonon dispersions and polarization of vibrational modes as well as the local density of phonon states are calculated using the embedded-atom method. The obtained structural parameters are in close agreement with experimental data.

  13. Sustained calcium entry through P2X nucleotide receptor channels in human airway epithelial cells. (United States)

    Zsembery, Akos; Boyce, Amanda T; Liang, Lihua; Peti-Peterdi, János; Bell, P Darwin; Schwiebert, Erik M


    Purinergic receptor stimulation has potential therapeutic effects for cystic fibrosis (CF). Thus, we explored roles for P2Y and P2X receptors in stably increasing [Ca(2+)](i) in human CF (IB3-1) and non-CF (16HBE14o(-)) airway epithelial cells. Cytosolic Ca(2+) was measured by fluorospectrometry using the fluorescent dye Fura-2/AM. Expression of P2X receptor (P2XR) subtypes was assessed by immunoblotting and biotinylation. In IB3-1 cells, ATP and other P2Y agonists caused only a transient increase in [Ca(2+)](i) derived from intracellular stores in a Na(+)-rich environment. In contrast, ATP induced an increase in [Ca(2+)](i) that had transient and sustained components in a Na(+)-free medium; the sustained plateau was potentiated by zinc or increasing extracellular pH. Benzoyl-benzoyl-ATP, a P2XR-selective agonist, increased [Ca(2+)](i) only in Na(+)-free medium, suggesting competition between Na(+) and Ca(2+) through P2XRs. Biochemical evidence showed that the P2X(4) receptor is the major subtype shared by these airway epithelial cells. A role for store-operated Ca(2+) channels, voltage-dependent Ca(2+) channels, or Na(+)/Ca(2+) exchanger in the ATP-induced sustained Ca(2+) signal was ruled out. In conclusion, these data show that epithelial P2X(4) receptors serve as ATP-gated calcium entry channels that induce a sustained increase in [Ca(2+)](i). In airway epithelia, a P2XR-mediated Ca(2+) signal may have therapeutic benefit for CF.

  14. Structural and Controllable Thermal Expansion Properties of Sc2-xAlxMo3O12

    Institute of Scientific and Technical Information of China (English)

    WU; Mei-mei; CHEN; Dong-feng


    Materials with controllable thermal expansion are the subject of fundamental studies because of the important applications in high-precision optical mirrors,fiber optic systems,and electronic materials.Samples Sc2-xAlxMo3O12(x=0.0,0.3,0.7,1.0,1.3,1.7,and 2.0)were prepared by the solid-state reaction,

  15. Functional P2X7 receptors at cultured hippocampal astrocytes but not neurons. (United States)

    Rubini, Patrizia; Pagel, Gregor; Mehri, Soghra; Marquardt, Peter; Riedel, Thomas; Illes, Peter


    P2X7 receptors have been suggested to be located both on neurons and astrocytes of the central and peripheral nervous systems. In the present Ca(2+)-imaging and patch-clamp study, we reinvestigated these findings on mixed neuronal-astrocytic cell cultures prepared from embryonic or newborn rat hippocampi. We found in a Mg(2+)-free bath medium that the prototypic P2X7 receptor agonist dibenzoyl-adenosine triphosphate (Bz-ATP) increased the intracellular Ca(2+) concentration ([Ca(2+)]i) both in the neuronal cell bodies and in their axo-dendritic processes only to a very minor extent. However, Bz-ATP produced marked [Ca(2+)]i transients in the neuronal processes, when they grew above a glial carpet, which was uniformly sensitive to Bz-ATP. These glial signals might be misinterpreted as neuronal responses because of the poor focal discrimination by a fluorescent microscope. Most astrocytes had a polygonal shape without clearly circumscribable boundaries, but a subgroup of them had neuron-like appearance. The cellular processes of this astrocytic subgroup, just as their cell somata and their polygonal counterparts, appeared to possess a high density of functional P2X7 receptors. In contrast to astrocytes, in a low Ca(2+)/no Mg(2+)-containing bath medium, hippocampal neurons failed to respond to Bz-ATP with membrane currents. In addition, neither the amplitude nor the frequency of spontaneous excitatory postsynaptic currents, representing the quantal release of glutamate, was modified by Bz-ATP. We conclude that cultured hippocampal neurons, in contrast to astrocytes, possess P2X7 receptors, if at all, only at a low density.

  16. The P2X7 receptor is an important regulator of extracellular ATP levels

    Directory of Open Access Journals (Sweden)

    Andrea eBrandao-Burch


    Full Text Available Controlled ATP release has been demonstrated from many neuronal and non-neuronal cell types. Once released, extracellular ATP acts on cells in a paracrine manner via purinergic receptors. Considerable evidence now suggests that extracellular nucleotides, signalling via P2 receptors, play important roles in bone homeostasis modulating both osteoblast and osteoclast function. In this study, we demonstrate that mouse osteoclasts and their precursors constitutively release ATP into their extracellular environment. Levels were highest at day 2 (precursor cells, possibly reflecting the high number of red blood cells and accessory cells present. Mature osteoclasts constitutively released ATP in the range 0.05-0.5pmol/ml/cell. Both osteoclasts and osteoblasts express mRNA and protein for the P2X7 receptor. We found that in osteoclasts, expression levels are 4-fold higher in mature cells relative to precursors, whilst in osteoblasts expression remains relatively constant during differentiation. Selective antagonists (0.1-100µM AZ10606120, A438079 and KN-62 were used to determine whether this release was mediated via P2X7 receptors. AZ10606120, A438079 and KN-62, at 0.1-10µM, decreased ATP release by mature osteoclasts by up to 70%, 60% and 80%, respectively. No differences in cell viability were observed. ATP release also occurs via vesicular exocytosis; inhibitors of this process (1-100µM NEM or brefeldin A had no effect on ATP release from osteoclasts. P2X7 receptor antagonists (0.1-10µM also decreased ATP release from primary rat osteoblasts by up to 80%. These data show that ATP release via the P2X7 receptor contributes to extracellular ATP levels in osteoclast and osteoblast cultures, suggesting an important additional role for this receptor in autocrine/paracrine purinergic signalling in bone.

  17. Hyperfine specific heats of PrX 2 ( X = Ir, Pt, Rh, Ru) laves phase compounds (United States)

    Greidanus, F. J. A. M.; de Jongh, L. J.; Huiskamp, W. J.; Buschow, K. H. J.


    Specific heat data below 1 K for the C-15 compounds PrX 2 (X = Ir, Pt, Rh, Ru) reveal Schottky-type anomalies, ascribed to hyperfine interactions. Apparently the 4f-moments are magnetically ordered. The values deduced for these moments are only ≈ 70% of that for J = 4, indicating that the Pr 3+ moment is partially quenched by the crystal field.

  18. Characterization of spin dynamics in stripe-ordered La2-xSrxNiO4 (United States)

    Woo, H.; Tranquada, J. M.; Boothroyd, A. T.; Nakajima, K.; Perring, T. G.; Frost, C.; Freeman, P. G.; Prabhakaran, D.; Yamada, K.


    Inelastic neutron scattering experiments at a spallation source have enabled us to measure the full momentum- and energy- dependent spectra of magnetic fluctuations in the charge- and spin-stripe ordered systems La_2-xSr_xNiO4 ( x=1/3 and x=0.275). Peaks in the dynamic magnetic response at incommensurate wavevectors and over a wide frequency range are commonly observed in the high-Tc superconductors YBa_2Cu_3O_6+x and La_2-xA_xCuO_4(A=Sr,Ba) , as well as in the static charge- and spin-striped system nickelates La_2-xSr_xNiO_4. High energy transfer up to 90meV with broad reciprocal spaces was observed. In addition to intrastripe and interstripe exchange interactions between neighboring Ni spins [1], exchange interactions between diagonal Ni spins (not through oxygen) are also considered. We will present a detailed measurement and analysis in the NiO2 plane. We acknowledge U.S.-DOE for financial support: contract # DE-AC02-98CH1088. [1] Boothroyd et al. Phys. Rev. B 67, 100407(R) (2003).

  19. Magnetic behavior of RMn2+xAl10-x (R=La,Gd) crystals (United States)

    Sefat, Athena S.; Li, Bin; Bud'Ko, Sergey L.; Canfield, Paul C.


    The crystallographic and magnetic properties of the solution grown RMn2+xAl10-x ( R=Gd and La) crystals with tetragonal (P4/nmm) structure are investigated. For these, single-crystal x-ray diffraction results have shown the preferential occupation of excess manganese on the aluminum 8i crystallographic site. Due to excess Mn, there is evidence of local-moment magnetism in LaMn2+xAl10-x and their random distribution is thought to be responsible for the magnetic correlations below ˜50K and the spin-glass behavior below ˜3K . For GdMn2+xAl10-x , the extra manganese influences temperature below which the sample enters into a state with a net ferromagnetic component: TC≈16K for GdMn2.21(4)Al9.79(4) and 25.5K for GdMn2.39(2)Al9.61(2) . Assuming a linear dependence between TC and excess Mn concentration, the fully stoichiometric and ordered GdMn2Al10 should have TC≈5K .

  20. Low-x contribution to the Bjorken sum rule within double logarithmic $ln^2x$ approximation

    CERN Document Server

    Kotlorz, D; Kotlorz, Dorota; Kotlorz, Andrzej


    The small-$x$ contributions to the Bjorken sum rule within double logarithmic $ln^2x$ approximation for different input parametrisations $g_1^{NS}(x,Q_0^2)$ are presented. Analytical solutions of the evolution equations for full and truncated moments of the unintegrated structure function $f^{NS}(x,Q^2)$ are used. Theoretical predictions for $\\int_{0}^{0.003} g_1^{NS}(x,Q^2=10) dx$ are compared with the SMC small-$x$ data. Rough estimation of the slope $\\lambda$, controlling the small-$x$ behaviour of $g_1^{NS}\\sim x^{-\\lambda}$ from the SMC data is performed. Double logarithmic terms $\\sim (\\alpha_s ln^2x)^n$ become leading when $x\\to 0$ and imply the singular behaviour of $g_1^{NS}\\sim x^{-0.4}$. This seems to be confirmed by recent experimental SMC and HERMES data. Advantages of the unified $ln^2x$+LO DGLAP approach and the crucial role of the running coupling $\\alpha_s=\\alpha_s(Q^2/z)$ at low-$x$ are also discussed.

  1. The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X4 Receptors (United States)

    Lorca, Ramón A.; Varela-Nallar, Lorena; Inestrosa, Nibaldo C.; Huidobro-Toro, J. Pablo


    Although the physiological function of the cellular prion protein (PrPC) remains unknown, several evidences support the notion of its role in copper homeostasis. PrPC binds Cu2+ through a domain composed by four to five repeats of eight amino acids. Previously, we have shown that the perfusion of this domain prevents and reverses the inhibition by Cu2+ of the adenosine triphosphate (ATP)-evoked currents in the P2X4 receptor subtype, highlighting a modulatory role for PrPC in synaptic transmission through regulation of Cu2+ levels. Here, we study the effect of full-length PrPC in Cu2+ inhibition of P2X4 receptor when both are coexpressed. PrPC expression does not significantly change the ATP concentration-response curve in oocytes expressing P2X4 receptors. However, the presence of PrPC reduces the inhibition by Cu2+ of the ATP-elicited currents in these oocytes, confirming our previous observations with the Cu2+ binding domain. Thus, our observations suggest a role for PrPC in modulating synaptic activity through binding of extracellular Cu2+. PMID:22114745

  2. The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X4 Receptors

    Directory of Open Access Journals (Sweden)

    Ramón A. Lorca


    Full Text Available Although the physiological function of the cellular prion protein (PrPC remains unknown, several evidences support the notion of its role in copper homeostasis. PrPC binds Cu2+ through a domain composed by four to five repeats of eight amino acids. Previously, we have shown that the perfusion of this domain prevents and reverses the inhibition by Cu2+ of the adenosine triphosphate (ATP-evoked currents in the P2X4 receptor subtype, highlighting a modulatory role for PrPC in synaptic transmission through regulation of Cu2+ levels. Here, we study the effect of full-length PrPC in Cu2+ inhibition of P2X4 receptor when both are coexpressed. PrPC expression does not significantly change the ATP concentration-response curve in oocytes expressing P2X4 receptors. However, the presence of PrPC reduces the inhibition by Cu2+ of the ATP-elicited currents in these oocytes, confirming our previous observations with the Cu2+ binding domain. Thus, our observations suggest a role for PrPC in modulating synaptic activity through binding of extracellular Cu2+.

  3. Cleavage sites in the polypeptide precursors of poliovirus protein P2-X

    Energy Technology Data Exchange (ETDEWEB)

    Selmer, B.L. (State Univ. of New York, Stony Brook); Hanecak, R.; Anderson, C.W.; Wimmer, E.


    Partial amino-terminal sequence analysis has been performed on the three major polypeptide products (P2-3b, P2-5b, and P2-X) from the central region (P2) of the poliovirus polyprotein, and this analysis precisely locates the amino termini of these products with respect to the nucleotide sequence of the poliovirus RNA genome. Like most of the products of the replicase region (P3), the amino termini of P2-5b and P2-X are generated by cleavage between glutamine and glycine residues. Thus, P2-5b and P2-X are probably both produced by the action of a singly (virus-encoded.) proteinase. The amino terminus of P2-3b, on the other hand, is produced by a cleavage between the carboxy-terminal tyrosine of VP1 and the glycine encoded by nucleotides 3381-3383. This result may suggest that more than one proteolytic activity is required for the complete processing of the poliovirus polyprotein.

  4. The Grid Density Dependence of the Unsteady Pressures of the J-2X Turbines (United States)

    Schmauch, Preston B.


    The J-2X engine was originally designed for the upper stage of the cancelled Crew Launch Vehicle. Although the Crew Launch Vehicle was cancelled the J-2X engine, which is currently undergoing hot-fire testing, may be used on future programs. The J-2X engine is a direct descendent of the J-2 engine which powered the upper stage during the Apollo program. Many changes including a thrust increase from 230K to 294K lbf have been implemented in this engine. As part of the design requirements, the turbine blades must meet minimum high cycle fatigue factors of safety for various vibrational modes that have resonant frequencies in the engine's operating range. The unsteady blade loading is calculated directly from CFD simulations. A grid density study was performed to understand the sensitivity of the spatial loading and the magnitude of the on blade loading due to changes in grid density. Given that the unsteady blade loading has a first order effect on the high cycle fatigue factors of safety, it is important to understand the level of convergence when applying the unsteady loads. The convergence of the unsteady pressures of several grid densities will be presented for various frequencies in the engine's operating range.

  5. Water adsorption on O(2x2)/Ru(0001) from STM experiments andfirst-principles calculations

    Energy Technology Data Exchange (ETDEWEB)

    Cabrera-Sanfelix, P.; Sanchez-Portal, D.; Mugarza, A.; Shimizu,T.K.; Salmeron, M.; Arnau, A.


    We present a combined theoretical and experimental study of water adsorption on Ru(0001) pre-covered with 0.25 monolayers (ML) of oxygen forming a (2 x 2) structure. Several structures were analyzed by means of Density Functional Theory calculations for which STM simulations were performed and compared with experimental data. Up to 0.25 monolayers the molecules bind to the exposed Ru atoms of the 2 x 2 unit cell via the lone pair orbitals. The molecular plane is almost parallel to the surface with its H atoms pointing towards the chemisorbed O atoms of the 2 x 2 unit cell forming hydrogen bonds. The existence of these additional hydrogen bonds increases the adsorption energy of the water molecule to approximately 616 meV, which is {approx}220 meV more stable than on the clean Ru(0001) surface with a similar configuration. The binding energy shows only a weak dependence on water coverage, with a shallow minimum for a row structure at 0.125 ML. This is consistent with the STM experiments that show a tendency of the molecules to form linear rows at intermediate coverage. Our calculations also suggest the possible formation of water dimers near 0.25 ML.

  6. Synthesis and Characterization of LiCoxMn2-xO4 Cathode Materials

    Institute of Scientific and Technical Information of China (English)

    YAO Yaochun; DAI Yongnian; YANG Bin; MA Wenhui; Takayuki Watanabe


    LiCoxMn2-xO4 cathode materials for lithium ion batteries were synthesized by mechanical activation-solid state reaction at 750℃ for 24 h in air atmosphere, and their crystal structure, morphology, element composition and electrochemical performance were characterized with XRD, SEM, ICP-AES and charge-discharge test. The experimental results show that all samples have a single spinel structure, well formed crystal shape and uniformly particle size distribution. The lattice parameters of LiCoxMa2-xO4 decrease and the average oxidation states of manganese ions increase with an increase in Co content. Compared with pure LiMn2O4, the LiCoxMn2-xO4(x=0.03-0.12) samples show a lower special capacity, but their cycling life are improved. The capacity loss of LiCo0.09Mn1.91O4 and LiCo0.12Mn1.88O4 is only 0.95% ,respectively, after the 20th cycle. The improvement of the cycle performance is attributed to the substitution of Co at the Mn sites in the spinel structure, which suppresses the Jahn-Teller distortion and improves the structural stability.

  7. Maximizing Entropy of Pickard Random Fields for 2x2 Binary Constraints

    DEFF Research Database (Denmark)

    Søgaard, Jacob; Forchhammer, Søren


    This paper considers the problem of maximizing the entropy of two-dimensional (2D) Pickard Random Fields (PRF) subject to constraints. We consider binary Pickard Random Fields, which provides a 2D causal finite context model and use it to define stationary probabilities for 2x2 squares, thus allo...... of the maximum PRF entropy. As examples, we consider the well known hard square constraint along with a few other constraints.......This paper considers the problem of maximizing the entropy of two-dimensional (2D) Pickard Random Fields (PRF) subject to constraints. We consider binary Pickard Random Fields, which provides a 2D causal finite context model and use it to define stationary probabilities for 2x2 squares, thus...... allowing us to calculate the entropy of the field. All possible binary 2x2 constraints are considered and all constraints are categorized into groups according to their properties. For constraints which can be modeled by a PRF approach and with positive entropy, we characterize and provide statistics...

  8. Emerging key roles for P2X receptors in the kidney

    Directory of Open Access Journals (Sweden)

    Scott S Wildman


    Full Text Available P2X ionotropic non-selective cation channels are expressed throughout the kidney and are activated in a paracrine or autocrine manner following the binding of extracellular ATP and related extracellular nucleotides. Whilst there is a wealth of literature describing a regulatory role of P2 receptors (P2R in the kidney, there are significantly less data on the regulatory role of P2X receptors (P2XR compared with that described for metabotropic P2Y. Much of the historical literature describing a role for P2XR in the kidney has focused heavily on the role of P2X1R in the autoregulation of renal blood flow. More recently however, there has been a plethora of manuscripts providing compelling evidence for additional roles for P2XR in both kidney health and disease. This review summarizes the current evidence for the involvement of P2XR in the regulation of renal tubular and vascular function, and highlights the novel data describing their putative roles in regulating physiological and pathophysiological processes in the kidney.

  9. Ferroelectric devices

    CERN Document Server

    Uchino, Kenji


    Updating its bestselling predecessor, Ferroelectric Devices, Second Edition assesses the last decade of developments-and setbacks-in the commercialization of ferroelectricity. Field pioneer and esteemed author Uchino provides insight into why this relatively nascent and interdisciplinary process has failed so far without a systematic accumulation of fundamental knowledge regarding materials and device development.Filling the informational void, this collection of information reviews state-of-the-art research and development trends reflecting nano and optical technologies, environmental regulat

  10. Morphological changes mediated by P2X7 receptor and its expression in microglial cells%P2X7介导的小胶质细胞形态和受体表达的变化

    Institute of Scientific and Technical Information of China (English)

    陈翀; 吕军; 向正华; 蒋平; 陈鸣; 焦炳华



  11. Modulation of Mouse Embryonic Stem Cell Proliferation and Neural Differentiation by the P2X7 Receptor (United States)

    Glaser, Talita; de Oliveira, Sophia La Banca; Cheffer, Arquimedes; Beco, Renata; Martins, Patrícia; Fornazari, Maynara; Lameu, Claudiana; Junior, Helio Miranda Costa; Coutinho-Silva, Robson; Ulrich, Henning


    Background Novel developmental functions have been attributed to the P2X7 receptor (P2X7R) including proliferation stimulation and neural differentiation. Mouse embryonic stem cells (ESC), induced with retinoic acid to neural differentiation, closely assemble processes occurring during neuroectodermal development of the early embryo. Principal Findings P2X7R expression together with the pluripotency marker Oct-4 was highest in undifferentiated ESC. In undifferentiated cells, the P2X7R agonist Bz-ATP accelerated cell cycle entry, which was blocked by the specific P2X7R inhibitor KN-62. ESC induced to neural differentiation with retinoic acid, reduced Oct-4 and P2X7R expression. P2X7R receptor-promoted intracellular calcium fluxes were obtained at lower Bz-ATP ligand concentrations in undifferentiated and in neural-differentiated cells compared to other studies. The presence of KN-62 led to increased number of cells expressing SSEA-1, Dcx and β3-tubulin, as well as the number of SSEA-1 and β3-tubulin-double-positive cells confirming that onset of neuroectodermal differentiation and neuronal fate determination depends on suppression of P2X7R activity. Moreover, an increase in the number of Ki-67 positive cells in conditions of P2X7R inhibition indicates rescue of progenitors into the cell cycle, augmenting the number of neuroblasts and consequently neurogenesis. Conclusions In embryonic cells, P2X7R expression and activity is upregulated, maintaining proliferation, while upon induction to neural differentiation P2X7 receptor expression and activity needs to be suppressed. PMID:24798220

  12. Modulation of mouse embryonic stem cell proliferation and neural differentiation by the P2X7 receptor.

    Directory of Open Access Journals (Sweden)

    Talita Glaser

    Full Text Available BACKGROUND: Novel developmental functions have been attributed to the P2X7 receptor (P2X7R including proliferation stimulation and neural differentiation. Mouse embryonic stem cells (ESC, induced with retinoic acid to neural differentiation, closely assemble processes occurring during neuroectodermal development of the early embryo. PRINCIPAL FINDINGS: P2X7R expression together with the pluripotency marker Oct-4 was highest in undifferentiated ESC. In undifferentiated cells, the P2X7R agonist Bz-ATP accelerated cell cycle entry, which was blocked by the specific P2X7R inhibitor KN-62. ESC induced to neural differentiation with retinoic acid, reduced Oct-4 and P2X7R expression. P2X7R receptor-promoted intracellular calcium fluxes were obtained at lower Bz-ATP ligand concentrations in undifferentiated and in neural-differentiated cells compared to other studies. The presence of KN-62 led to increased number of cells expressing SSEA-1, Dcx and β3-tubulin, as well as the number of SSEA-1 and β3-tubulin-double-positive cells confirming that onset of neuroectodermal differentiation and neuronal fate determination depends on suppression of P2X7R activity. Moreover, an increase in the number of Ki-67 positive cells in conditions of P2X7R inhibition indicates rescue of progenitors into the cell cycle, augmenting the number of neuroblasts and consequently neurogenesis. CONCLUSIONS: In embryonic cells, P2X7R expression and activity is upregulated, maintaining proliferation, while upon induction to neural differentiation P2X7 receptor expression and activity needs to be suppressed.

  13. Bradykinin Contributes to Sympathetic and Pressor Responses Evoked by Activation of Skeletal Muscle Afferents P2X in Heart Failure

    Directory of Open Access Journals (Sweden)

    Jihong Xing


    Full Text Available Background/Aims: Published data suggest that purinergic P2X receptors of muscle afferent nerves contribute to the enhanced sympathetic nervous activity (SNA and blood pressure (BP responses during static exercise in heart failure (HF. In this study, we examined engagement of bradykinin (BK in regulating responses of SNA and BP evoked by P2X stimulation in rats with HF. We further examined cellular mechanisms responsible for BK. We hypothesized that BK potentiates P2X currents of muscle dorsal root ganglion (DRG neurons, and this effect is greater in HF due to upregulation of BK kinin B2 and P2X3 receptor. As a result, BK amplifies muscle afferents P2X-mediated SNA and BP responses. Methods: Renal SNA and BP responses were recorded in control rats and rats with HF. Western Blot analysis and patch-clamp methods were employed to examine the receptor expression and function of DRG neurons involved in the effects of BK. Results: BK injected into the arterial blood supply of the hindlimb muscles heightened the reflex SNA and BP responses induced by P2X activation with α,β-methylene ATP to a greater degree in HF rats. In addition, HF upregulated the protein expression of kinin B2 and P2X3 in DRG and the prior application of BK increased the magnitude of α,β-methylene ATP-induced currents in muscle DRG neurons from HF rats. Conclusion: BK plays a facilitating role in modulating muscle afferent P2X-engaged reflex sympathetic and pressor responses. In HF, P2X responsivness is augmented due to increases in expression of kinin B2 and P2X3 receptors and P2X current activity.


    Directory of Open Access Journals (Sweden)

    Regina Sesilia Noy


    Full Text Available VO2 max is very important in everyday life, so as to facilitate any physicalactivity, specially for athletes in order to achieve maximum performance. In aneffort to increase VO2 max training should be carried out regularly, measured andplanned. This study aims to determine the increase in VO2 max through circuittraining run and run continuously. The sample is taekwondoin son Manggarai-NTTwith an average age of 15 years. This study is an experimental study with the studydesign used was Randomized Pre and Post Test Group desigen. With a totalsample of 7 people in each group. Samples were randomly selected. Treatmentgroup 1 (KP1 given training run circuit 2 x 10 minute and Treatment Group 2(KP2 are given continuous training run 2 x 10 minute. Training carried out for 6weeks with a frequency of four times a week starting at 17:00 to 18:00 pm locatedat Frans Sales Lega Airport Manggarai-NTT. The analysis showed an increase inVO2 max was significantly (p <0.05 against both groups fled. In both groups thecircuit run by Pulse Oxymeter and Norma Cooper an increase in VO2 max with p<0.05, as well as a continuous run either by Pulse Oxymeter and Norma Cooperwith an increase in VO2 max value of p <0.05. The results of this analysis meansthat either the training or circuit training run run continuously to improve VO2max. Based on a comparison of test data by an independent test after training inboth groups either by Pulse Oxymeter and Norma Cooper in get p values > 0.05, orthere is no significant difference. Based on these results it can be concluded thatthe run circuit training and continuous training run together can increase VO2 maxand there was no significant difference. The results of this study are expected toincrease the knowledge of coaches, teachers and taekwondoin to perform trainingon a regular basis and are also expected to do similar research that examines VO2max with different training.

  15. P2X2阳性感觉神经末梢在小鼠食管的分布%The Distribution of P2X2 Immunoreactive Afferent Nerve Endings in the Mouse Esophagus

    Institute of Scientific and Technical Information of China (English)

    庞传武; 安淑红; 王昭金


    The distribution of P2X2 immunoreactive afferent endings and the relationship with calcitonin gene-related peptide (CGRP) immunoreactive fibers in the mouse esophagus was studied using double immunofluorescence method combined confocal laser scanning microscope technique. P2X2 immunoreactive endings were seen in sections from all levels of the mouse esophagus. The distribution of P2X2 immunoreactive structures concentrated in the area between outer and inner muscular layers, covered myenteric ganglia totally or partly. The dense clusters of fine varicose P2X2 immunoreactive terminals protruded into myenteric ganglia forming complexes of profuse laminar structures for intraganglionic laminar endings (IGLEs). Double immunofluorescence for P2X2 and CGRP revealed that numerous varicose fibers immunoreactive for CGRP closely surrounded P2X2 immunopositive IGLEs. However, P2X2 immunoreactive terminals never expressed CGRP immunoreactivity. In nodose ganglion, numerous neuronal cell bodies in small- and middle-sized displayed P2X2 immunoreactivity. P2X2/CGRP double-labeling neurons were rare. However, many P2X2 positive neurons in dorsal root ganglion contained CGRP immunoreactivity. These results demonstrated that some afferent endings in mouse esophagus expressed nociceptor P2X2, and formed IGLEs structures.%本文采用免疫荧光组织化学双标方法结合激光共聚焦显微镜技术研究了伤害性受体P2X2阳性感觉纤维末梢在小鼠食管内的分布及与降钙素基因相关肽(CGRP)阳性纤维的关系。结果表明:在食管各水平均可见到P2X2阳性感觉纤维末梢。P2X2阳性纤维集中分布于食管的内、外肌层之间,部分或全部的覆盖在肌间神经节的表面。一些串珠样的纤维深入到肌间神经节内,相互缠绕在一起形成许多结构复杂、形状各异的神经节内板状末稍(IGLEs)。荧光双标显示许多CGRP阳性纤维围绕在P2X2阳性IGLEs周围,没有见到P2X2和CGRP

  16. 配体门控性离子通道P2X7受体在肿瘤中的意义%The Significance of Ligand-gated Ion Channel P2X7 Receptor in Tumor

    Institute of Scientific and Technical Information of China (English)



    Nucleotides such as ATP are players in intercellular communication and regulate cell function through the interaction with purinergic receptors on cell membrane, which are classified into P2Y and P2X families according to their structures.P2X7 receptor is a member of the P2X ATP-gated ion channels purinergic receptors with a wide distribution in a variety of tissues.P2X7 function is regulated at multiple levels by different mechanisms.P2X7 receptor abnormal expression and function are related to various tumors, especially hematological malignancy.The better understanding of P2X7 receptors functional mechanism in tumor formation and development has both theoretical significance and potential application possibility.%ATP等核苷酸类物质作为细胞间通讯的载体可结合细胞膜上的嘌呤受体调节细胞的功能.嘌呤受体根据结构不同分为P2Y和P2X.P2X7受体是P2X家族配体门控离子通道型嘌呤受体的一员,广泛表达于多种组织,生理功能呈多样性,可受多种因素调控.P2X7受体表达及功能异常与多种肿瘤尤其是血液肿瘤相关,进一步阐明P2X7受体在肿瘤发生、发展中的作用机制具有重要的理论意义和潜在的应用前景.

  17. Analysis of the functional expression of P2X7 receptor in leukemia patients%白血病患者P2X7受体的功能性表达分析

    Institute of Scientific and Technical Information of China (English)

    郑国光; 张秀军; 林永敏; 吴克复


    目的研究P2X7受体在白血病患者中的功能性表达及与白血病治疗的关系.方法采用半定量RT-PCR、流式细胞术和细胞内钙离子测定的方法,从核酸、蛋白和功能水平研究白血病患者骨髓单个核细胞(BMMC)P2X7受体的表达和功能.结果白血病患者和正常人标本中可检出P2X7受体的表达,核酸、蛋白和功能水平结果一致.AML、ALL、CML患者P2X7受体表达阳性率高于正常人;但AML各亚型中P2X7受体阳性强度存在差异,M2组低于正常人,M5,M6组高于正常人;按照P2X7受体阳性强度分组,P2X7受体高表达患者诱导治疗后的完全缓解率显著低于P2X7受体阴性和P2X7受体低表达患者.结论 P2X7受体在白血病患者BMMC中有功能性表达,其高表达与患者治疗不敏感相关.

  18. P2X7受体与炎性细胞因子%P2X7 receptor and inflammation cytokine

    Institute of Scientific and Technical Information of China (English)

    习德娥; 韩莉; 卢建明



  19. P2X7 receptor-mediated PARP1 activity regulates astroglial death in the rat hippocampus following status epilepticus

    Directory of Open Access Journals (Sweden)

    Ji Yang eKim


    Full Text Available Poly(ADP-ribose polymerase-1 (PARP1 plays a regulatory role in apoptosis, necrosis, and other cellular processes after injury. Recently, we revealed that PARP1 regulates the differential neuronal/astroglial responses to pilocarpine-induced status epilepticus (SE in the distinct brain regions. In addition, P2X7 receptor (P2X7R, an ATP-gated ion channel, activation accelerates astroglial apoptosis, while it attenuates clasmatodendrosis (lysosome-derived autophagic astroglial death. Therefore, we investigated whether P2X7R regulates regional specific astroglial PARP1 expression/activation in response to SE. In the present study, P2X7R activation exacerbates SE-induced astroglial apoptosis, while P2X7R inhibition attenuates it accompanied by increasing PARP1 activity in the molecular layer of the dentate gyrus following SE. In the CA1 region, however, P2X7R inhibition deteriorates SE-induced clasmatodendrosis via PARP1 activation following SE. Taken together, our findings suggest that P2X7R function may affect SE-induced astroglial death by regulating PARP1 activation/expression in regional-specific manner. Therefore, the selective modulation of P2X7R-mediated PARP1 functions may be a considerable strategy for controls in various types of cell deaths.

  20. P2X(7) receptor activation enhances SK3 channels- and cystein cathepsin-dependent cancer cells invasiveness. (United States)

    Jelassi, B; Chantôme, A; Alcaraz-Pérez, F; Baroja-Mazo, A; Cayuela, M L; Pelegrin, P; Surprenant, A; Roger, S


    ATP-gated P2X(7) receptors (P2X(7)R) are unusual plasma membrane ion channels that have been extensively studied in immune cells. More recently, P2X(7)R have been described as potential cancer cell biomarkers. However, mechanistic links between P2X(7)R and cancer cell processes are unknown. Here, we show, in the highly aggressive human breast cancer cell line MDA-MB-435s, that P2X(7) receptor is highly expressed and fully functional. Its activation is responsible for the extension of neurite-like cellular prolongations, of the increase in cell migration by 35% and in cell invasion through extracellular matrix by 150%. The change in cancer cell morphology and the increased migration appeared to be due to the activation of Ca(2+)-activated SK3 potassium channels. The enhanced invasion through the extracellular matrix was related to the increase of mature forms of cysteine cathepsins in the extracellular medium, which was independent of SK3 channel activity and not associated with cell death. Pharmacological targeting of P2X(7)R in vivo was crucial for cell invasiveness in a zebrafish model of metastases. Our results demonstrate a novel mechanistic link between P2X(7)R functionality in cancer cells and invasiveness, a key parameter in tumour growth and in the development of metastases. They also suggest a potential therapeutic role for the newly developed P2X(7)R antagonists.

  1. Gas phase UV and IR absorption spectra of CxF2x+1CHO (x=1-4)

    DEFF Research Database (Denmark)

    Hashikawa, Y; Kawasaki, M; Waterland, RL;


    The UV and IR spectra of CxF2x+1 CHO (x = 1-4) were investigated using computational and experimental techniques. CxF2x+1CHO (x = 1-4) have broad UV absorption features centered at 300-310 nm. The maximum absorption cross-section increases significantly and shifts slightly to the red with increas...

  2. Effect of P2X(7) receptor knockout on exocrine secretion of pancreas, salivary glands and lacrimal glands

    DEFF Research Database (Denmark)

    Novak, Ivana; Jans, Ida M; Wohlfahrt, Louise


    the P2X(7) receptors affect fluid secretion in pancreas, salivary glands and tear glands. We monitored gland secretions in in vivo preparations of wild-type and P2X(7)(-/-) (Pfizer) mice stimulated with pilocarpine. In cell preparations from pancreas, parotid and lacrimal glands we measured ATP release...

  3. Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1β secretion in response to ATP. (United States)

    Karmakar, Mausita; Katsnelson, Michael A; Dubyak, George R; Pearlman, Eric


    Although extracellular ATP is abundant at sites of inflammation, its role in activating inflammasome signalling in neutrophils is not well characterized. In the current study, we demonstrate that human and murine neutrophils express functional cell-surface P2X7R, which leads to ATP-induced loss of intracellular K(+), NLRP3 inflammasome activation and IL-1β secretion. ATP-induced P2X7R activation caused a sustained increase in intracellular [Ca(2+)], which is indicative of P2X7R channel opening. Although there are multiple polymorphic variants of P2X7R, we found that neutrophils from multiple donors express P2X7R, but with differential efficacies in ATP-induced increase in cytosolic [Ca(2+)]. Neutrophils were also the predominant P2X7R-expressing cells during Streptococcus pneumoniae corneal infection, and P2X7R was required for bacterial clearance. Given the ubiquitous presence of neutrophils and extracellular ATP in multiple inflammatory conditions, ATP-induced P2X7R activation and IL-1β secretion by neutrophils likely has a significant, wide ranging clinical impact.

  4. Electrophysiological studies of upregulated P2X7 receptors in rat superior cervical ganglia after myocardial ischemic injury. (United States)

    Kong, Fanjun; Liu, Shuangmei; Xu, Changshui; Liu, Jun; Li, Guodong; Li, Guilin; Gao, Yun; Lin, Hong; Tu, Guihua; Peng, Haiying; Qiu, Shuyi; Fan, Bo; Zhu, Qicheng; Yu, Shicheng; Zheng, Chaoran; Liang, Shangdong


    Myocardial ischemic injury activates cardiac sympathetic afferent fibers and elicits a sympathoexcitatory reflex by exciting sympathetic efferent action, with resultant augmentation of myocardial oxygen consumption, leading to a vicious cycle of exaggerating myocardial ischemia. P2X7 receptor participates in the neuronal functions and the neurological disorders. This study examined the role of P2X7 receptor of superior cervical ganglia (SCG) in sympathoexcitatory reflex. Our results showed that the expression of P2X7 receptor at both mRNA and protein in SCG was increased after myocardial ischemic injury. P2X7 receptor agonists at the same concentration activated much larger amplitudes of the currents in the SCG neurons of myocardial ischemic rats than those in control rats. P2X7 receptor antagonist (brilliant blue G, BBG) significantly inhibited P2X7 receptor agonist-activated currents in the SCG neurons. Excessive phosphorylation of MAPK ERK1/2 upon the activation of P2X7 receptor might be a mechanism mediating the signal transduction after myocardial ischemic injury. Therefore, the sensitized P2X7 receptor in SCG was involved in the nociceptive transmission of sympathoexcitatory reflex induced by myocardial ischemic injury.

  5. Purinoreceptor P2X7 Regulation of Ca(2+) Mobilization and Cytoskeletal Rearrangement Is Required for Corneal Reepithelialization after Injury. (United States)

    Minns, Martin S; Teicher, Gregory; Rich, Celeste B; Trinkaus-Randall, Vickery


    The process of wound healing involves a complex network of signaling pathways working to promote rapid cell migration and wound closure. Activation of purinergic receptors by secreted nucleotides plays a major role in calcium mobilization and the subsequent calcium-dependent signaling that is essential for proper healing. The role of the purinergic receptor P2X7 in wound healing is still relatively unknown. We demonstrate that P2X7 expression increases at the leading edge of corneal epithelium after injury in an organ culture model, and that this change occurs despite an overall decrease in P2X7 expression throughout the epithelium. Inhibition of P2X7 prevents this change in localization after injury and impairs wound healing. In cell culture, P2X7 inhibition attenuates the amplitude and duration of injury-induced calcium mobilization in cells at the leading edge. Immunofluorescence analysis of scratch-wounded cells reveals that P2X7 inhibition results in an overall decrease in the number of focal adhesions along with a concentration of focal adhesions at the wound margin. Live cell imaging of green fluorescent protein-labeled actin and talin shows that P2X7 inhibition alters actin cytoskeletal rearrangements and focal adhesion dynamics after injury. Together, these data demonstrate that P2X7 plays a critical role in mediating calcium signaling and coordinating cytoskeletal rearrangement at the leading edge, both of which processes are early signaling events necessary for proper epithelial wound healing.

  6. Blockage of P2X7 attenuates acute lung injury in mice by inhibiting NLRP3 inflammasome. (United States)

    Wang, Shuang; Zhao, Jijun; Wang, Hongyue; Liang, Yingjie; Yang, Niansheng; Huang, Yuefang


    NLRP3 inflammasome is engaged in the inflammatory response during acute lung injury (ALI). Purinergic receptor P2X7 has been reported to be upstream of NLRP3 activation. However, the therapeutic implication of P2X7 in ALI remains to be explored. The present study used lipopolysaccharide (LPS)-induced mouse model to investigate the therapeutic potential of P2X7 blockage in ALI. Our results showed that P2X7/NLRP3 inflammasome pathway was significantly upregulated in the lungs of ALI mice as compared with control mice. P2X7 antagonist A438079 suppressed NLRP3/ASC/caspase 1 activation, production of IL-1β, IL-17A and IFN-γ and neutrophil infiltration but not the production of IL-10, resulting in a significant amelioration of lung injury. Moreover, blockage of P2X7 significantly inhibited NLRP3 inflammasome activation and IL-1β production in bone marrow derived macrophages. Similar results were obtained using another P2X7 inhibitor brilliant blue G (BBG) in vivo. Thus, pharmacological blockage of P2X7/NLRP3 pathway can be considered as a potential therapeutic strategy in patients with ALI.

  7. Purinoreceptor P2X7 Regulation of Ca2+ Mobilization and Cytoskeletal Rearrangement Is Required for Corneal Reepithelialization after Injury (United States)

    Minns, Martin S.; Teicher, Gregory; Rich, Celeste B.; Trinkaus-Randall, Vickery


    The process of wound healing involves a complex network of signaling pathways working to promote rapid cell migration and wound closure. Activation of purinergic receptors by secreted nucleotides plays a major role in calcium mobilization and the subsequent calcium-dependent signaling that is essential for proper healing. The role of the purinergic receptor P2X7 in wound healing is still relatively unknown. We demonstrate that P2X7 expression increases at the leading edge of corneal epithelium after injury in an organ culture model, and that this change occurs despite an overall decrease in P2X7 expression throughout the epithelium. Inhibition of P2X7 prevents this change in localization after injury and impairs wound healing. In cell culture, P2X7 inhibition attenuates the amplitude and duration of injury-induced calcium mobilization in cells at the leading edge. Immunofluorescence analysis of scratch-wounded cells reveals that P2X7 inhibition results in an overall decrease in the number of focal adhesions along with a concentration of focal adhesions at the wound margin. Live cell imaging of green fluorescent protein–labeled actin and talin shows that P2X7 inhibition alters actin cytoskeletal rearrangements and focal adhesion dynamics after injury. Together, these data demonstrate that P2X7 plays a critical role in mediating calcium signaling and coordinating cytoskeletal rearrangement at the leading edge, both of which processes are early signaling events necessary for proper epithelial wound healing. PMID:26683661

  8. Effect of the purinergic receptor P2X7 on Chlamydia infection in cervical epithelial cells and vaginally infected mice. (United States)

    Darville, Toni; Welter-Stahl, Lynn; Cruz, Cristiane; Sater, Ali Abdul; Andrews, Charles W; Ojcius, David M


    Ligation of the purinergic receptor, P2X7R, with its agonist ATP has been previously shown to inhibit intracellular infection by chlamydiae and mycobacteria in macrophages. The effect of P2X7R on chlamydial infection had never been investigated in the preferred target cells of chlamydiae, cervical epithelial cells, nor in vaginally infected mice. In this study, we show that treatment of epithelial cells with P2X7R agonists inhibits partially Chlamydia infection in epithelial cells. Chelation of ATP with magnesium or pretreatment with a P2X7R antagonist blocks the inhibitory effects of ATP. Similarly to previous results obtained with macrophages, ATP-mediated inhibition of infection in epithelial cells requires activation of host-cell phospholipase D. Vaginal infection was also more efficient in P2X7R-deficient mice, which also displayed a higher level of acute inflammation in the endocervix, oviduct, and mesosalpingeal tissues than in infected wild-type mice. However, secretion of IL-1beta, which requires P2X7R ligation during infection by other pathogens, was decreased mildly and only at short times of infection. Taken together, these results suggest that P2X7R affects Chlamydia infection by directly inhibiting infection in epithelial cells, rather than through the ability of P2X7R to modulate IL-1beta secretion.

  9. Understanding RuO{sub 2}.xH{sub 2}O/carbon nanofibre composites as supercapacitor electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Pico, F.; Rojas, R.M.; Amarilla, J.M.; Rojo, J.M. [Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Cientificas (CSIC), Cantoblanco, Sor Juana Ines de la Cruz 3, E-28049 Madrid (Spain); Ibanez, J. [Centro Nacional de Investigaciones Metalurgicas, CSIC, Avda Gregorio del Amo 8, E-28040 Madrid (Spain); Lillo-Rodenas, M.A.; Linares-Solano, A. [MCMA, Departamento de Quimica Inorganica, Universidad de Alicante, P.O. Box 99, E-03080 Alicante (Spain)


    Composites made from RuO{sub 2}.xH{sub 2}O particles supported on carbon nanofibres (CNF) have been prepared for supercapacitor electrodes. CNF, produced by Grupo Antolin Ing. SA. using a floating catalyst procedure was treated either in HCl or in HNO{sub 3}. Then the composites were obtained by impregnation of CNF with an aqueous RuCl{sub 3}.0.5H{sub 2}O solution followed by filtering and alkali solution treatment. Heat treatment at 150 C for 2 h was done. Specific capacitance of the composites has been measured and discussed on the basis of their RuO{sub 2}.xH{sub 2}O content and RuO{sub 2}.xH{sub 2}O particle size. The composites having RuO{sub 2}.xH{sub 2}O contents below 11 wt% show RuO{sub 2}.xH{sub 2}O particles, which grow from 2 to 4 nm as the RuO{sub 2}.xH{sub 2}O content increases. The specific capacitance of supported RuO{sub 2}.xH{sub 2}O, which can be very high (up to 840 F g{sup -1}), decreases as the RuO{sub 2}.xH{sub 2}O content increases and RuO{sub 2}.xH{sub 2}O particles grow. The composites having RuO{sub 2}.xH{sub 2}O contents above 11 wt% show RuO{sub 2}.xH{sub 2}O particles of nearly constant size (4 nm); the effect of increasing the RuO{sub 2}.xH{sub 2}O content is to increase the amount of particles but not the size of the particles. In these composites the specific capacitance of supported RuO{sub 2}.xH{sub 2}O is nearly constant (440 F g{sup -1}) and close to bare RuO{sub 2}.xH{sub 2}O (460 F g{sup -1}). (author)

  10. Contribution of P2X4 receptors to ethanol intake in male C57BL/6 mice. (United States)

    Wyatt, Letisha R; Finn, Deborah A; Khoja, Sheraz; Yardley, Megan M; Asatryan, Liana; Alkana, Ronald L; Davies, Daryl L


    P2X receptors (P2XRs) are a family of cation-permeable ligand-gated ion channels activated by synaptically released extracellular adenosine 5'-triphosphate. The P2X4 subtype is abundantly expressed in the central nervous system and is sensitive to low intoxicating ethanol concentrations. Genetic meta-analyses identified the p2rx4 gene as a candidate gene for innate alcohol intake and/or preference. The current study used mice lacking the p2rx4 gene (knockout, KO) and wildtype (WT) C57BL/6 controls to test the hypothesis that P2X4Rs contribute to ethanol intake. The early acquisition and early maintenance phases of ethanol intake were measured with three different drinking procedures. Further, we tested the effects of ivermectin (IVM), a drug previously shown to reduce ethanol's effects on P2X4Rs and to reduce ethanol intake and preference, for its ability to differentially alter stable ethanol intake in KO and WT mice. Depending on the procedure and the concentration of the ethanol solution, ethanol intake was transiently increased in P2X4R KO versus WT mice during the acquisition of 24-h and limited access ethanol intake. IVM significantly reduced ethanol intake in P2X4R KO and WT mice, but the degree of reduction was 50 % less in the P2X4R KO mice. Western blot analysis identified significant changes in γ-aminobutyric acidA receptor α1 subunit expression in brain regions associated with the regulation of ethanol behaviors in P2X4R KO mice. These findings add to evidence that P2X4Rs contribute to ethanol intake and indicate that there is a complex interaction between P2X4Rs, ethanol, and other neurotransmitter receptor systems.

  11. P2X7 receptors in neurohypophysial terminals: evidence for their role in arginine-vasopressin secretion. (United States)

    Cuadra, Adolfo E; Custer, Edward E; Bosworth, Elizabeth L; Lemos, José R


    Arginine-vasopressin (AVP) plays a major role in maintaining cardiovascular function and related pathologies. The mechanism involved in its release into the circulation is complex and highly regulated. Recent work has implicated the purinergic receptor, P2X7R, in a role for catecholamine-enhanced AVP release in the rat hypothalamic-neurohypophysial (NH) system. However, the site of P2X7R action in this endocrine system, and whether or not it directly mediates release in secretory neurons have not been determined. We hypothesized that the P2X7R is expressed and mediates AVP release in NH terminals. P2X7R function was first examined by patch-clamp recordings in isolated NH terminals. Results revealed that subpopulations of isolated terminals displayed either high ATP-sensitivity or low ATP-sensitivity, the latter of which was characteristic of the rat P2X7R. Additional recordings showed that terminals showing sensitivity to the P2X7R-selective agonist, BzATP, were further inhibited by P2X7R selective antagonists, AZ10606120 and brilliant blue-G. In confocal micrographs from tissue sections and isolated terminals of the NH P2X7R-immunoreactivity was found to be localized in plasma membranes. Lastly, the role of P2X7R on AVP release was tested. Our results showed that BzATP evoked sustained AVP release in NH terminals, which was inhibited by AZ10606120. Taken together, our data lead us to conclude that the P2X7R is expressed in NH terminals and corroborates its role in AVP secretion.

  12. Dynamic micro-organization of P2X7 receptors revealed by PALM based single particle tracking

    Directory of Open Access Journals (Sweden)

    Amulya Nidhi Shrivastava


    Full Text Available Adenosine triphosphate (ATP-gated P2X7 receptors (P2X7Rs are members of the purinergic receptor family that are expressed in several cell types including neurons. A high concentration of ATP is required for the channel opening of P2X7Rs compared to other members of this receptor family. Recent work suggests that ATP binding to members of the P2X receptor family determines the diffusion and localization of these receptors on the plasma membrane of neurons. Here, we employed single particle tracking photoactivated localization microscopy (sptPALM to study the diffusion and ATP-dependence of rat P2X7Rs. Dendra2-tagged P2X7Rs were transfected in hippocampal neurons and imaged on proximal dendrites. Our results suggest the presence of two populations of P2X7Rs within the extra-synaptic membrane: a population composed of rapidly diffusing receptors and one stabilized within nanoclusters (~100 nm diameter. P2X7R trajectories were rarely observed at synaptic sites. P2X7R mutations in the ATP-binding site (K64A or the conserved phosphorylation site (K17A resulted in faster- and slower-diffusing receptors, respectively. Furthermore, ATP differentially accelerated wild type and K17A-mutant receptors but not K64A-mutant receptors. Our results indicate that receptor conformation plays a critical role in regulating ATP-mediated changes in P2X7R diffusion and micro-organization.

  13. Dynamic micro-organization of P2X7 receptors revealed by PALM based single particle tracking. (United States)

    Shrivastava, Amulya N; Rodriguez, Pamela C; Triller, Antoine; Renner, Marianne


    Adenosine triphosphate (ATP)-gated P2X7 receptors (P2X7Rs) are members of the purinergic receptor family that are expressed in several cell types including neurons. A high concentration of ATP is required for the channel opening of P2X7Rs compared to other members of this receptor family. Recent work suggests that ATP binding to members of the P2X receptor family determines the diffusion and localization of these receptors on the plasma membrane of neurons. Here, we employed single particle tracking photoactivated localization microscopy (sptPALM) to study the diffusion and ATP-dependence of rat P2X7Rs. Dendra2-tagged P2X7Rs were transfected in hippocampal neurons and imaged on proximal dendrites. Our results suggest the presence of two populations of P2X7Rs within the extra-synaptic membrane: a population composed of rapidly diffusing receptors and one stabilized within nanoclusters (~100 nm diameter). P2X7R trajectories were rarely observed at synaptic sites. P2X7R mutations in the ATP-binding site (K64A) or the conserved phosphorylation site (K17A) resulted in faster- and slower-diffusing receptors, respectively. Furthermore, ATP differentially accelerated wild type and K17A-mutant receptors but not K64A-mutant receptors. Our results indicate that receptor conformation plays a critical role in regulating ATP-mediated changes in P2X7R diffusion and micro-organization.

  14. Changes in expression of P2X7 receptors in NOD mouse pancreas during the development of diabetes. (United States)

    Coutinho-Silva, Robson; Robson, Tim; Beales, Philip E; Burnstock, Geoffrey


    This study examined the expression of P2X7 receptors in pancreatic islets of the non-obese diabetic (NOD) mouse model of human autoimmune insulin-dependent diabetes mellitus, to determine whether they are involved in islet cell destruction during early- and late-developing diabetes. Pancreatic cells containing glucagon (alpha-cells), insulin (beta-cells) and somatostatin (delta-cells) were co-localized with P2X7 receptors. We examined P2X7 receptor expression in normal and diabetic spleens using flow cytometry. In non-diabetic NOD controls, P2X7 receptors were expressed in glucagon-containing cells at the periphery of islets, being consistent with previous studies. In early NOD diabetes (12 weeks), there was migration of peripheral P2X7 receptor positive, glucagon-containing cells into the center of islets. In late NOD diabetes (34 weeks), P2X7 receptor- and glucagon-stained alpha-cells were gone from islets. Migration of macrophages and dendritic cells into islets took place, but they lacked P2X7 immunoreactivity. There was no significant difference in the percentage of splenic macrophages stained for P2X7 receptors from control and diabetic spleens. In conclusion, in the development of early to late diabetes, there is a down-regulation of P2X7 receptors on islet cells and a loss of alpha- and beta-cell populations. P2X7 receptor signalling might be involved in alpha-cell clearance from late diabetic islets.

  15. Functional expression of P2X7 receptors in non-neuronal cells of rat dorsal root ganglia. (United States)

    Zhang, Xu-Feng; Han, Ping; Faltynek, Connie R; Jarvis, Michael F; Shieh, Char-Chang


    The P2X7 receptor is an ATP-sensitive ligand-gated cation channel, expressed predominantly in cells with immune origin. Recent studies have demonstrated that P2X7 may play an important role in pain signaling. In the present study, the expression of P2X7 receptors in non-neuronal cells and neurons isolated from dorsal root ganglia was characterized using patch clamp, pharmacological and confocal microscopy approaches. In small diameter DRG neurons, 100 microM 2', 3'-O-(4-benzoylbenzoyl)-ATP (BzATP) evoked an inward current, which was inhibited completely by 1 microM A-317491, a potent and selective P2X3 receptor antagonist. In contrast, BzATP evoked concentration-dependent increases in inward currents in non-neuronal DRG cells with an EC50 value of 26 +/- 0.14 microM, which were resistant to the blockade by A-317491. The activity to evoke cationic currents by P2X receptor agonists in non-neuronal cells showed a rank order of BzATP > ATP > alpha,beta-meATP. Pyridoxal-phosphate-6-azophenyl-,2',4'-disulphonic acid (PPADS) and Mg2+ produced concentration-dependent inhibition of BzATP-evoked currents in non-neuronal cells. Confocal microscopy revealed positive immunoreactivity of anti-P2X7 receptor antibodies on non-neuronal cells. No anti-P2X7 immunoreactivity was observed on DRG neurons. Further electrophysiological studies showed that prolonged agonist activation of P2X7 receptors in non-neuronal cells did not lead to cytolytic pore formation. Taken together, the present study demonstrated functional expression of P2X7 receptors in non-neuronal but not in small diameter neurons from rat DRG. Modulation of P2X7 receptors in non-neuronal cells might have impact on peripheral sensory transduction under normal and pathological states.

  16. Feasibility study of B16 melanoma therapy using oxidized ATP to target purinergic receptor P2X7. (United States)

    Hattori, Fumie; Ohshima, Yasuhiro; Seki, Shizuka; Tsukimoto, Mitsutoshi; Sato, Mitsuru; Takenouchi, Takato; Suzuki, Akina; Takai, Erina; Kitani, Hiroshi; Harada, Hitoshi; Kojima, Shuji


    The P2X7 receptor is not only involved in cell proliferation, but also acts as an adenosine 5'-triphosphate (ATP)-gated non-selective channel, and its expression is increased in human melanoma. An irreversible antagonist of P2X7, such as oxidized ATP (oxATP), might block P2X7 receptor-mediated ATP release and proliferative signaling. Therefore, we carried out basic studies to test this idea and to examine the feasibility of using oxATP to treat B16 melanoma. We first found that low-pH conditions (mimicking the hypoxia and acidosis commonly seen in solid tumors) induced P2X7 receptor-mediated ATP release from B16 melanoma cells. Then, we compared the proliferation rates of B16 melanoma wild-type cells and B16 P2X7 receptor-knockdown clone (P2X7-KDC) cells in the presence of P2X7 agonists. The proliferation rate, as well as the ATP release, of agonist-treated P2X7-KDC cells was lower than that of agonist-treated wild-type cells. Next, the effect of P2X7 antagonist oxATP on B16 melanoma cell growth was examined in vitro and in vivo. oxATP significantly decreased B16 melanoma cell proliferation in vitro, and also significantly inhibited tumor growth in B16 melanoma-bearing mice. These data indicate that extracellularly released ATP may serve as an intercellular signaling molecule. We propose that the P2X7 receptor is a promising target for treatment of solid tumors.

  17. R270C polymorphism leads to loss of function of the canine P2X7 receptor. (United States)

    Spildrejorde, Mari; Bartlett, Rachael; Stokes, Leanne; Jalilian, Iman; Peranec, Michelle; Sluyter, Vanessa; Curtis, Belinda L; Skarratt, Kristen K; Skora, Amanda; Bakhsh, Tahani; Seavers, Aine; McArthur, Jason D; Dowton, Mark; Sluyter, Ronald


    The relative function of the P2X7 receptor, an ATP-gated ion channel, varies between humans due to polymorphisms in the P2RX7 gene. This study aimed to assess the functional impact of P2X7 variation in a random sample of the canine population. Blood and genomic DNA were obtained from 69 dogs selected as representatives of a cross section of different breeds. P2X7 function was determined by flow cytometric measurements of dye uptake and patch-clamp measurements of inward currents. P2X7 expression was determined by immunoblotting and immunocytochemistry. Sequencing was used to identify P2RX7 gene polymorphisms. P2X7 was cloned from an English springer spaniel, and point mutations were introduced into this receptor by site-directed mutagenesis. The relative function of P2X7 on monocytes varied between individual dogs. The canine P2RX7 gene encoded four missense polymorphisms: F103L and P452S, found in heterozygous and homozygous dosage, and R270C and R365Q, found only in heterozygous dosage. Moreover, R270C and R365Q were associated with the cocker spaniel and Labrador retriever, respectively. F103L, R270C, and R365Q but not P452S corresponded to decreased P2X7 function in monocytes but did not explain the majority of differences in P2X7 function between dogs, indicating that other factors contribute to this variability. Heterologous expression of site-directed mutants of P2X7 in human embryonic kidney-293 cells indicated that the R270C mutant was nonfunctional, the F103L and R365Q mutants had partly reduced function, and the P452S mutant functioned normally. Taken together, these data highlight that a R270C polymorphism has major functional impact on canine P2X7.

  18. Ventricular assist device (United States)

    VAD; RVAD; LVAD; BVAD; Right ventricular assist device; Left ventricular assist device; Biventricular assist device; Heart pump; Left ventricular assist system; LVAS; Implantable ventricular assist device

  19. Development of the Functional Flow Block Diagram for the J-2X Rocket Engine System (United States)

    White, Thomas; Stoller, Sandra L.; Greene, WIlliam D.; Christenson, Rick L.; Bowen, Barry C.


    The J-2X program calls for the upgrade of the Apollo-era Rocketdyne J-2 engine to higher power levels, using new materials and manufacturing techniques, and with more restrictive safety and reliability requirements than prior human-rated engines in NASA history. Such requirements demand a comprehensive systems engineering effort to ensure success. Pratt & Whitney Rocketdyne system engineers performed a functional analysis of the engine to establish the functional architecture. J-2X functions were captured in six major operational blocks. Each block was divided into sub-blocks or states. In each sub-block, functions necessary to perform each state were determined. A functional engine schematic consistent with the fidelity of the system model was defined for this analysis. The blocks, sub-blocks, and functions were sequentially numbered to differentiate the states in which the function were performed and to indicate the sequence of events. The Engine System was functionally partitioned, to provide separate and unique functional operators. Establishing unique functional operators as work output of the System Architecture process is novel in Liquid Propulsion Engine design. Each functional operator was described such that its unique functionality was identified. The decomposed functions were then allocated to the functional operators both of which were the inputs to the subsystem or component performance specifications. PWR also used a novel approach to identify and map the engine functional requirements to customer-specified functions. The final result was a comprehensive Functional Flow Block Diagram (FFBD) for the J-2X Engine System, decomposed to the component level and mapped to all functional requirements. This FFBD greatly facilitates component specification development, providing a well-defined trade space for functional trades at the subsystem and component level. It also provides a framework for function-based failure modes and effects analysis (FMEA), and a

  20. Reconsidering the magnetic structure in NiS2-xSex (United States)

    Yano, Shinichiro; Louca, Despina; Chatterjee, Utpal; Chung, Duck Young; Bugaris, Daniel E.; Kanatzidis, Mercouri; Neuefeind, Joerg C.; Feygenson, Mikhail


    The Mott metal-insulator transition (MIT) has been at the forefront of condensed matter research for decades. A Mott insulator is associated with antiferromagnetism (AFM) as well as an energy gap. The AFM order parameter can be directly traced by neutron scattering measurements. We focused on the study of MIT on the NiS2-2xSex system. With increase in x where x corresponds to the atomic volume of S that is replaced by Se, the system undergoes an AFM insulator to an AFM metalic transition at x = 0 . 43 at T = 0 . Although NiS2-2xSex has been previously studied, the magnetic structure is not well understood. We measured the powder neutron diffraction for 4 compositions, x = 0, 0.4, 0.6, and 0.8, as a function of temperature. At T = 2K, we observed a clear composition dependence of the magnetic structure. While NiS2 (x = 0) has two magnetic propagation vectors, M1 = (000) and M2 = (0.5 0.5 0.5), NiS1.6Se0.4 and NiS1.4Se0.6 have only one magnetic phase, M1. However, the M1 structure vanishes by NiS1.2Se0.8. While the two magnetic phases have been previously reported, we determined the magnetic structures by using representation analysis.the magnetic structure and physical properties of this system will be discussed.

  1. P2X7受体在炎症性疾病中的作用及其机制%Effect of P2X7 receptor on inflammatory diseases and its mechanism

    Institute of Scientific and Technical Information of China (English)

    徐宏; 梁尚栋



  2. The interaction between BeX2 (X = H, F, Cl molecules and ethylene/acetilene


    Fernández Villanueva, Estefanía


    En estudios recientes se ha mostrado la existencia de un nuevo tipo de ‘interacciones no covalentes’, llamadas ‘enlaces de Berilio’[1], cuyas propiedades químicas parecen indicar un futuro prometedor en áreas como la ciencia de materiales. Estos enlaces de Berilio se producen como aductos entre moléculas de berilio que actúan como ácidos de Lewis y otras moléculas que actúan como bases de Lewis. En este marco, el presente estudio analiza el enlace entre las pequeñas moléculas BeX2 (X = H, F, ...

  3. Disappearance of antiferromagnetic spin excitations in overdoped La2-xSrxCuO4. (United States)

    Wakimoto, S; Yamada, K; Tranquada, J M; Frost, C D; Birgeneau, R J; Zhang, H


    Magnetic excitations for energies up to approximately 100 meV are studied for overdoped La(2-x)Sr(x)CuO(4) with x=0.25 and 0.30, using time-of-flight neutron spectroscopy. Comparison of spectra integrated over the width of an antiferromagnetic Brillouin zone demonstrates that the magnetic scattering at intermediate energies, 20

  4. Experimental surface charge density of the Si (100)-2x1H surface

    DEFF Research Database (Denmark)

    Ciston, J.; Marks, L.D.; Feidenhans'l, R.;


    We report a three-dimensional charge density refinement from x-ray diffraction intensities of the Si (100) 2x1H surface. By paying careful attention to parameterizing the bulk Si bonding, we are able to locate the hydrogen atoms at the surface, which could not be done previously. In addition, we...... are able to partially refine the local charge density at the surface. We find experimentally an increased, slightly localized bond density of approximately 0.31 electrons between each Si atom pair at the surface. Both the atomic positions and the charge density are in remarkably good agreement with density...

  5. {sup 77}Se NMR study of nonmagnetic-magnetic transition in (TMTSF){sub 2}X

    Energy Technology Data Exchange (ETDEWEB)

    Mito, T., E-mail: [Graduate School of Material Science, University of Hyogo, Hyogo 678-1297 (Japan); Nishiyama, K.; Koyama, T.; Ueda, K.; Kohara, T.; Takeuchi, K.; Akutsu, H.; Yamada, J. [Graduate School of Material Science, University of Hyogo, Hyogo 678-1297 (Japan); Kornilov, A.; Pudalov, V.M. [P.N. Lebedev Physics Institute, Moscow 119991 (Russian Federation); Qualls, J.S. [Sonoma State University, Rohnert Park, CA 94928 (United States)


    {sup 77}Se NMR measurements have been carried out on (TMTSF){sub 2}X (X = PF{sub 6} and AsF{sub 6}) single crystals. For both compounds, NMR lines split into double-peaked spectra in the SDW state, which is explained with sinusoidal internal field at Se nucleus positions having the same incommensurate wave number with that of the SDW order. No change in the lineshape was observed at T{sub x} at which the spin-relaxation rate shows a kink, suggesting that this anomaly does not cause significant static changes in internal field at the Se-site.

  6. Magnetic properties and magnetocaloric effect in TbCo2-xFex compounds

    Institute of Scientific and Technical Information of China (English)

    Zou Jun-Ding; Shen Bao-Gen; Sun Ji-Rong


    Magnetic properties and magnetocaloric effect in TbCo2-xFex compounds are studied by DC magnetic measurement. With increasing content of Fe, the entropy changes decrease slightly, though the Curie temperature is tuned from 231 K (x = 0) to 303 K (x = 0.1). Magnetic entropies of TbCo2 compound are calculated by using mean field approximation (MFA). Results estimated by using Maxwell relation are consistent with that of MFA calculation. It si shown that the entropy changes are mainly derived from the magnetic entropy change. The lattice has almost no contribution to the entropy change in the vicinity of phase transition.

  7. Magnetic phase transitions in PrMn 2- xCr xGe 2 (United States)

    Dincer, I.; Elerman, Y.; Elmali, A.; Ehrenberg, H.; Fuess, H.; Duman, E.; Acet, M.


    The structural and magnetic properties of PrMn 2- xCr xGe 2 (0⩽ x⩽1.0) were studied by X-ray diffraction and magnetization measurements. The powder samples crystallize in the ThCr 2Si 2-type structure, and the lattice constants at room temperature show almost no variation as Cr substitutes Mn. The observed phase transitions are summarized in a proposed magnetic x- T phase diagram and compared with previous Moessbauer spectroscopy and neutron diffraction results for x=0.

  8. P2X7 receptors in the genesis and development of breast cancer%P2X7受体与乳腺癌的发生和发展

    Institute of Scientific and Technical Information of China (English)

    谭超; 韩莉


    P2X7 receptors,belonging to purinergic P2 receptor family,are ATP-gated cation channels,which can choose the bivalent cations freely.P2X7 receptors join in cell signal conduction and the excretion of the cytokines and other physical functions.In recent years,researchers have discovered P2X7 receptors mediate the cells to live and grow by increasing oxidation and phosphorylation and intracellular ATP reserve.In breast cancer,the P2X7 receptors express abnormally,and can activate the MAPK lied in cytoplasm.The phosphorylated MAPK enter the nucleus and activates a series of protein kinases,and then affects the genesis and development of breast cancer.%P2X7受体是腺甘三磷酸(ATP)门控的离子通道,对二价阳离子有较强的选择性,属于嘌呤能P2受体家族.P2X7受体参与细胞信号传导、细胞因子的分泌等多种生理功能.近几年研究发现P2X7受体通过增加氧化、磷酸化及细胞内ATP的储备,介导细胞的存活与生长.在乳腺癌中P2X7受体表达异常,活化的P2X7受体激活位于细胞质内的丝裂原活化蛋白激酶(MAPK),后者受到刺激后磷酸化进入核内,引起细胞内一系列蛋白激酶的活化,进而影响乳腺癌的发生发展.

  9. Electrochemical device (United States)

    Grimes, Patrick G.; Einstein, Harry; Bellows, Richard J.


    A tunnel protected electrochemical device features channels fluidically communicating between manifold, tunnels and cells. The channels are designed to provide the most efficient use of auxiliary power. The channels have a greater hydraulic pressure drop and electrical resistance than the manifold. This will provide a design with the optimum auxiliary energy requirements.

  10. Assistive Devices (United States)

    ... a number of assistive devices. These are tools, products or types of equipment that help you perform tasks and activities. They may help you move around, see, communicate, eat, or get dressed. Some are high-tech tools, such as computers. Others are much simpler, ...

  11. Printing Device

    NARCIS (Netherlands)

    Berg, van den M.J.; Markies, P.R.; Zuilhof, H.


    An ink jetprinting device includes a pressure chamber formed by a plurality of wall segments, a first aperture extending through a wall segment and communicating with an ink jet orifice and a second aperture extending through a wall segment and communicating with an ink supply duct. The pressure cha

  12. Detection device (United States)

    Smith, J.E.


    The present invention is directed to a detection device comprising: (1) an entrance chamber; (2) a central chamber; and (3) an exit chamber. The central chamber includes an ionizing gas, anode, and means for connecting the anode with an external power supply and pulse counter.

  13. Separating device

    NARCIS (Netherlands)

    De Jong, T.P.R.


    A sorting device (1) suitable for sorting wire from a waste stream, comprising a body (2) that moves when in use, and provided with spikes or similar projections. The body is embodied as a rotatable roll (2), which oscillates axially during its rotation. The roll is coupled to an oscillation engine

  14. Controllable conversion of plasmonic Cu2-xS nanoparticles to Au2S by cation exchange and electron beam induced transformation of Cu2-xS-Au2S core/shell nanostructures. (United States)

    Wang, Xianliang; Liu, Xin; Zhu, Dewei; Swihart, Mark T


    Self-doped Cu2-xS nanocrystals (NCs) were converted into monodisperse Cu2-xS-Au2S NCs of tunable composition, including pure Au2S, by cation exchange. The near-infrared (NIR) localized surface plasmon resonance (LSPR) was dampened and red-shifted with increasing Au content. Cation exchange was accompanied by elimination of cation vacancies and a change in crystal structure. Partially exchanged Cu2-xS-Au2S core/shell structures evolved to dumbbell-like structures under electron irradiation in the transmission electron microscope (TEM).

  15. 过表达P2x7受体引发小胶质细胞的炎症反应%Overexpressing P2x7 receptors in microglia induce inflamation

    Institute of Scientific and Technical Information of China (English)

    王珏; 唐亚梅; 周俊宜


    目的 研究嘌呤受体P2x7在小胶质细胞炎症反应中的作用.方法 通过分子克隆的方法构建pCDNA3.1-P2x7重组质粒,构建成功后经测序确认质粒序列无误,通过Lipo2000转染小胶质细胞株BV-2细胞,采用PCR方法测定BV-2细胞内P2x7的表达,Western blot法测定P2x7和Cox-2的蛋白表达.结果 细胞经重组质粒转染成功后,pCDNA3.1-P2x7组P2x7和Cox-2蛋白表达水平分别为(4.21±0.13)%和(2.60±0.05)%,高于pCDNA3.1组的(2.61±0.05)%和(1.62±0.04)%,差异均有统计学意义(P<0.05).结论 通过过表达P2x7受体,能引起小胶质细胞的激活,提示可进一步引发炎症反应.%Objective To observe the effects of the purine receptor P2x7 in the microglia inflamation. Methods The recombinant plasmid pCDNA3.1 was constructed and sequenced. Then the plasmid was transfected by Lipo2000 into the microglia cell line BV-2. The mRNA expressions and the protein expressions of the P2x7 and Cox-2 were detected by PCR and Western blot, respectively. Result After the plasmid was transfected, the mRNA expressions of P2x7 and the protein expressions of P2x7 and Cox-2 were significantly increased (P < 0.05). Conclusion After over-expression P2x7, the microglia is activated, and then induced inflamation.

  16. Water Induced Surface Reconstruction of the Oxygen (2x1) covered Ru(0001)

    Energy Technology Data Exchange (ETDEWEB)

    Maier, Sabine; Cabrera-Sanfelix, Pepa; Stass, Ingeborg; Sanchez-Portal, Daniel; Arnau, Andres; Salmeron, Miquel


    Low temperature scanning tunneling microscopy (STM) and density functional theory (DFT) were used to study the adsorption of water on a Ru(0001) surface covered with half monolayer of oxygen. The oxygen atoms occupy hcp sites in an ordered structure with (2x1) periodicity. DFT predicts that water is weakly bound to the unmodified surface, 86 meV compared to the ~;;200 meV water-water H-bond. Instead, we found that water adsorption causes a shift of half of the oxygen atoms from hcp sites to fcc sites, creating a honeycomb structure where water molecules bind strongly to the exposed Ru atoms. The energy cost of reconstructing the oxygen overlayer, around 230 meV per displaced oxygen atom, is more than compensated by the larger adsorption energy of water on the newly exposed Ru atoms. Water forms hydrogen bonds with the fcc O atoms in a (4x2) superstructure due to alternating orientations of the molecules. Heating to 185 K results in the complete desorption of the water layer, leaving behind the oxygen honeycomb structure, which is metastable relative to the original (2x1). This stable structure is not recovered until after heating to temperatures close to 260K.

  17. Ultrasonic attenuation anomalies of n-type superconductor Pr2-xCexCuO4 (United States)

    Chong, Tet Vui; Abd-Shukor, R.


    Pr2-xCexCuO4 (x = 0 and 0.15) samples were prepared via solid state reaction. Pr2CuO4 sample is insulating while Pr1.85Ce0.15CuO4 sample exhibited an onset critical temperature, Tc of 21 K. The temperature dependences of ultrasonic attenuation in these polycrystalline n-type superconductor Pr2-xCexCuO4 (x = 0 and 0.15) samples have been measured between 80 K and 300 K using longitudinal and shear waves by pulse-echo-overlap method with frequencies between 5 MHz and 10 MHz. For the longitudinal mode, a pronounced attenuation peak around 200 K was observed in Pr2CuO4, but it is not observed in the superconducting material Pr1.85Ce0.15CuO4. For the shear mode, no pronounced attenuation peaks were observed in the samples. It is suggested that the attenuation peak in the x = 0 sample at 200 K is due to the weak structural distortion induced by the magnetic transition.

  18. Anoxic depolarization of hippocampal astrocytes: possible modulation by P2X7 receptors. (United States)

    Leichsenring, Anna; Riedel, Thomas; Qin, Ying; Rubini, Patrizia; Illes, Peter


    Current responses from CA1 neurons and stratum oriens astrocytes were recorded from hippocampal brain slices by means of the whole-cell patch-clamp technique. Anoxic depolarization (AD) was induced by an oxygen/glucose-deprived (OGD) medium also containing sodium iodoacetate and antimycin, in order to block glycolysis and oxidative phosphorylation, respectively. Anoxic depolarization has been reported to be due to the sudden increase of the extracellular K(+) concentration and the accompanying explosive rise in glutamate concentration. We asked ourselves whether the release of ATP activating P2X7 receptors is also involved in the AD. Although, the AD was evoked in absolute synchrony in neurons and astrocytes, and the NMDA receptor antagonistic AP-5 depressed these responses, neither the non-selective P2 receptor antagonist PPADS, nor the highly selective P2X7 receptor antagonist A438079 interfered with the AD or its delay time in neurons/astrocytes after inducing chemical hypoxia. However, A438079, but not PPADS increased in astrocytes the slow inward current observed in a hypoxic medium. It is concluded that ATP co-released with glutamate by hypoxic stimulation has only a minor function in the present brain slice system.

  19. P2X7 receptor is critical in α-synuclein--mediated microglial NADPH oxidase activation. (United States)

    Jiang, Tianfang; Hoekstra, Jake; Heng, Xin; Kang, Wenyan; Ding, Jianqing; Liu, Jun; Chen, Shengdi; Zhang, Jing


    Activated microglia are commonly observed in individuals with neurodegenerative disorders, including Parkinson's disease (PD) and are believed to contribute to neuronal death. This process occurs at least due partially to nicotinamide adenine dinucleotide phosphate oxidase (PHOX) activation, which leads to the production of superoxide and oxidative stress. α-Synuclein (α-Syn), a key protein implicated in PD pathogenesis, can activate microglia, contributing to death of dopaminergic neurons. Here, microglial cells (BV2) and primary cultured microglia were used to study the role that the purinergic receptor P2X7 plays in recognizing α-Syn and promoting PHOX activation. We demonstrate that both wild type and A53T mutant α-Syn readily activate PHOX, with the A53T form producing more rapid and sustained effects,that is, oxidative stress and cellular injuries. Furthermore, this process involves the activation of phosphoinositide 3-kinase (PI3K)/AKT (protein kinase B) pathway. Thus, it is concluded that stimulation of the microglial P2X7 receptor by extracellular α-Syn, with PI3K/AKT activation and increased oxidative stress, could be an important mechanism and a potential therapeutic target for PD.

  20. Theoretical aspects of charge correlations in θ-(BEDT-TTF2X

    Directory of Open Access Journals (Sweden)

    Kazuhiko Kuroki


    Full Text Available A review is given on the theoretical studies of charge correlations in θ-(BEDT-TTF2X. Various studies show that within a purely electronic model on the θ-type lattice with on-site U and nearest neighbor Vp and Vc interactions, the diagonal stripe, c-axis three-fold, and the vertical stripe charge correlations are favored in the regime VpVc, respectively. In the realistic parameter regime of Vp~Vc, there is competition between the c-axis three fold state and diagonal stripe state. Since these are different from the experimentally observed a-axis three fold and the horizontal stripe charge correlations, additional effects have to be included in order to understand the experiments. The electron–lattice coupling, which tends to distort the lattice into the θd-type, is found to favor the horizontal stripe state, suggesting that the occurrence of this stripe ordering in the actual materials may not be of purely electronic origin. On the other hand, distant electron–electron interactions have to be considered in order to understand the a-axis three fold correlation, whose wave vector is close to the nesting vector of the Fermi surface. These studies seem to suggest that the minimal model to understand the charge correlation in θ-(BEDT-TTF2X may be more complicated than expected. Future problems regarding the competition between different types of charge correlations are discussed.

  1. P2X7 receptor-mediated calcium dynamics in HEK293 cells: experimental characterization and modelling approach (United States)

    Di Garbo, A.; Alloisio, S.; Nobile, M.


    The P2X7 receptor (P2X7R) induces ionotropic Ca2 + signalling in different cell types. It plays an important role in the immune response and in the nervous system. Here, the mechanisms underlying intracellular Ca2 + variations evoked by 3‧-O-(4-benzoyl)benzoyl-ATP (BzATP), a potent agonist of the P2X7R, in transfected HEK293 cells, are investigated both experimentally and theoretically. We propose a minimal model of P2X7R that is capable of reproducing, qualitatively and quantitatively, the experimental data. This approach was also adopted for the P2X7R variant, which lacks the entire C-terminus tail (trP2X7R). Then we introduce a biophysical model describing the Ca2 + dynamics in HEK293. Our model gives an account of the ionotropic Ca2 + influx evoked by BzATP on the basis of the kinetics model of P2X7R. To explain the complex Ca2 + responses evoked by BzATP, the model predicted that an impairment in Ca2 + extrusion flux through the plasma membrane is a key factor for Ca2 + homeostasis in HEK293 cells.

  2. HSP90 Regulation of P2X7 Receptor Function Requires an Intact Cytoplasmic C-Terminus. (United States)

    Migita, Keisuke; Ozaki, Taku; Shimoyama, Shuji; Yamada, Junko; Nikaido, Yoshikazu; Furukawa, Tomonori; Shiba, Yuko; Egan, Terrance M; Ueno, Shinya


    P2X7 receptors (P2X7Rs) are ATP-gated ion channels that display the unusual property of current facilitation during long applications of agonists. Here we show that facilitation disappears in chimeric P2X7Rs containing the C-terminus of the P2X2 receptor (P2X2R), and in a truncated P2X7R missing the cysteine-rich domain of the C-terminus. The chimeric and truncated receptors also show an apparent decreased permeability to N-methyl-d-glucamine(+) (NMDG(+)). The effects of genetic modification of the C-terminus on NMDG(+) permeability were mimicked by preapplication of the HSP90 antagonist geldanamycin to the wild-type receptor. Further, the geldanamycin decreased the shift in the reversal potential of the ATP-gated current measured under bi-ionic NMDG(+)/Na(+) condition without affecting the ability of the long application of agonist to facilitate current amplitude. Taken together, the results suggest that HSP90 may be essential for stabilization and function of P2X7Rs through an action on the cysteine-rich domain of the cytoplasmic the C-terminus.

  3. Effect of P2X7 receptor knockout on AQP-5 expression of type I alveolar epithelial cells.

    Directory of Open Access Journals (Sweden)

    Georg Ebeling

    Full Text Available P2X7 receptors, ATP-gated cation channels, are specifically expressed in alveolar epithelial cells. The pathophysiological function of this lung cell type, except a recently reported putative involvement in surfactant secretion, is unknown. In addition, P2X7 receptor-deficient mice show reduced inflammation and lung fibrosis after exposure with bleomycin. To elucidate the role of the P2X7 receptor in alveolar epithelial type I cells we characterized the pulmonary phenotype of P2X7 receptor knockout mice by using immunohistochemistry, western blot analysis and real-time RT PCR. No pathomorphological signs of fibrosis were found. Results revealed, however, a remarkable loss of aquaporin-5 protein and mRNA in young knockout animals. Additional in vitro experiments with bleomycin treated precision cut lung slices showed a greater sensitivity of the P2X7 receptor knockout mice in terms of aquaporin-5 reduction as wild type animals. Finally, P2X7 receptor function was examined by using the alveolar epithelial cell lines E10 and MLE-12 for stimulation experiments with bleomycin. The in vitro activation of P2X7 receptor was connected with an increase of aquaporin-5, whereas the inhibition of the receptor with oxidized ATP resulted in down regulation of aquaporin-5. The early loss of aquaporin-5 which can be found in different pulmonary fibrosis models does not implicate a specific pathogenetic role during fibrogenesis.

  4. Up-regulation of P2X7 receptors mediating proliferation of Schwann cells after sciatic nerve injury. (United States)

    Song, Xian-min; Xu, Xiao-hui; Zhu, Jiao; Guo, Zhili; Li, Jian; He, Cheng; Burnstock, Geoffrey; Yuan, Hongbin; Xiang, Zhenghua


    Peripheral nerve injury (PNI) is a common disease, which results in a partial or total loss of motor, sensory and autonomic functions, leading to a decrease in quality of life. Schwann cells play a vital role in maintaining the peripheral nervous system and in injury and repair. Using immunohistochemistry, Western blot, calcium assay and bromodeoxyuridine (BrdU) proliferation assay, the present study clearly demonstrated that P2X7 receptors (R) were expressed in myelinating and non-myelinating Schwann cells in longitudinal sections of sciatic nerves. After sciatic nerve injury (SNI), P2X7R expression in Schwann cells of injured sciatic nerves was significantly up-regulated during the early days of SNI. Double immunofluorescence of proliferating cell nuclear antigen (PCNA) and P2X7R implied that P2X7R may be involved in proliferation of Schwann cells. Further experiments on primary cultures of Schwann cells showed that P2X7R are functionally expressed in Schwann cells of rat sciatic nerves; ATP via P2X7R can promote Schwann cell proliferation, possibly via the MAPK/ERK intracellular signalling pathway. Other possible roles of P2X7R on Schwann cells are discussed.

  5. P2X7 receptor activation impairs exogenous MHC class I oligopeptides presentation in antigen presenting cells.

    Directory of Open Access Journals (Sweden)

    Alberto Baroja-Mazo

    Full Text Available Major histocompatibility complex class I (MHC I on antigen presenting cells (APCs is a potent molecule to activate CD8(+ T cells and initiate immunity. P2X7 receptors (P2X7Rs are present on the plasma membrane of APCs to sense the extracellular danger signal adenosine-5'-triphosphate (ATP. P2X7R activates the inflammasome and the release of IL-1β in macrophages and other immune cells to initiate the inflammatory response. Here we show that P2X7R stimulation by ATP in APCs decreased the amount of MHC I at the plasma membrane. Specific antagonism or genetic ablation of P2X7R inhibited the effects of ATP on levels of cellular MHC I. Furthermore, P2X7R stimulation was able to inhibit activation of CD8(+ T cells via specific MHC I-oligopeptide complexes. Our study suggests that P2X7R activation on APCs is a novel inhibitor of adaptive CD8(+ T cell immunity.

  6. Species and agonist dependent zinc modulation of endogenous and recombinant ATP-gated P2X7 receptors. (United States)

    Moore, Samantha F; Mackenzie, Amanda B


    Zinc (Zn2+) and copper (Cu2+) are key signalling molecules in the immune system and regulate the activity of many ion channels. Both Zn2+ and Cu2+ potently inhibit rat P2X7 receptors via a binding site identified by mutagenesis. Here we show that extracellular Cu2+ also potently inhibits mouse P2X7 receptors. By contrast, the receptor expression system and agonist strongly influence the action of extracellular Zn2+ at mouse P2X7 receptors. Consistent with previous reports, Zn2+ inhibits recombinant rat P2X7 receptors. However, recombinant mouse P2X7 receptors are potentiated by Zn2+ when activated by ATP4- but inhibited when stimulated with the ATP analogue BzATP4-. Endogenous murine macrophage P2X7 receptors are not modulated by Zn2+ when stimulated by ATP4- however Zn2+ inhibits BzATP4- mediated responses. In summary, these findings provide a fundamental insight into the differential actions of Zn2+ and Cu2+ between different P2X7 receptor species.

  7. Throughput, Energy and Overhead of Multicast Device-to-Device Communications with Network Coded Cooperation

    DEFF Research Database (Denmark)

    Hernandez, Nestor; Heide, Janus; Roetter, Daniel Enrique Lucani


    Cooperation strategies in mobile networks typically rely in short range technologies, like LTE-A Device to Device (D2D) communications, for data exchange between devices forming mobile clouds. These communications provide a better device experience since the clouds offload the network. Nevertheless...... an analytical framework with numerical results showing: (i) gains of several fold can be attained even if the in-device data rates is moderately larger (2x) than the cellular link data rate and (ii) that is feasible to attain less than 3% total mean overhead with the proposed codes. This is fairly lower than......, a first objective of this work is to assess the operating regions where employing cooperation results in higher throughput and/or energy savings. We consider multicast scenarios with network coded mechanisms employing Random Linear Network Coding (RLNC). However, although RLNC is good for low amount...

  8. Regulation of the P2X7R by microRNA-216b in human breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Luming [Department of Breast and Thyroid, Jinan Military General Hospital, Jinan 250031, Shandong Province (China); Zhang, Xukui [Department of General Surgery, Jinan Military General Hospital, Jinan 250031, Shandong Province (China); Yang, Feng [Department of General Surgery, Shanghai Ninth People’s Hospital, Shanghai 200011 (China); Zhu, Jian; Zhou, Peng; Yu, Fang; Hou, Lei; Xiao, Lei; He, Qingqing [Department of Breast and Thyroid, Jinan Military General Hospital, Jinan 250031, Shandong Province (China); Wang, Baocheng, E-mail: [Department of Oncology, Jinan Military General Hospital, Jinan 250031, Shandong Province (China)


    Highlights: • We suggest the expression level of miR-216b and P2X7R in breast cancer tissues and cell lines. • We demonstrated that miR-216b directly targets and inhibits P2X7R. • We suggested miR-216b can attenuate ATP/P2X7R signaling pathways and induced Bcl-2/caspase-3 pathway. - Abstract: Breast cancer is the most common cancer in women around the world. However, the molecular mechanisms underlying breast cancer pathogenesis are only partially understood. Here, in this study, we found that P2X7R was up-regulated and miR-216b was down-regulated in breast cancer cell lines and tissues. Using bioinformatic analysis and 3′UTR luciferase reporter assay, we determined P2X7R can be directly targeted by miR-216b, which can down-regulate endogenous P2X7R mRNA and protein levels. Ectopic expression of miR-216b mimics leads to inhibited cell growth and apoptosis, while blocking expression of the miR-216b results in increased cell proliferation. Furthermore, our findings demonstrate that knockdown of P2X7R promotes apoptosis in breast cancer cells through down-regulating Bcl-2 and increasing the cleavage caspase-3 protein level. Finally, we confirmed that down-regulation of miR-216b in breast cancer is inversely associated with P2X7R expression level. Together, these findings establish miR-216b as a novel regulator of P2X7R and a potential therapeutic target for breast cancer.

  9. The purinergic receptor P2X7 triggers alpha-secretase-dependent processing of the amyloid precursor protein. (United States)

    Delarasse, Cécile; Auger, Rodolphe; Gonnord, Pauline; Fontaine, Bertrand; Kanellopoulos, Jean M


    The amyloid precursor protein (APP) is cleaved by β- and γ-secretases to generate the β-amyloid (Aβ) peptides, which are present in large amounts in the amyloid plaques of Alzheimer disease (AD) patient brains. Non-amyloidogenic processing of APP by α-secretases leads to proteolytic cleavage within the Aβ peptide sequence and shedding of the soluble APP ectodomain (sAPPα), which has been reported to be endowed with neuroprotective properties. In this work, we have shown that activation of the purinergic receptor P2X7 (P2X7R) stimulates sAPPα release from mouse neuroblastoma cells expressing human APP, from human neuroblastoma cells and from mouse primary astrocytes or neural progenitor cells. sAPPα shedding is inhibited by P2X7R antagonists or knockdown of P2X7R with specific small interfering RNA (siRNA) and is not observed in neural cells from P2X7R-deficient mice. P2X7R-dependent APP-cleavage is independent of extracellular calcium and strongly inhibited by hydroxamate-based metalloprotease inhibitors, TAPI-2 and GM6001. However, knockdown of a disintegrin and metalloproteinase-9 (ADAM9), ADAM10 and ADAM17 by specific siRNA, known to have α-secretase activity, does not block the P2X7R-dependent non-amyloidogenic pathway. Using several specific pharmacological inhibitors, we demonstrate that the mitogen-activated protein kinase modules Erk1/2 and JNK are involved in P2X7R-dependent α-secretase activity. Our study suggests that P2X7R, which is expressed in hippocampal neurons and glial cells, is a potential therapeutic target in AD.

  10. P2X7 receptor-mediated purinergic signaling promotes liver injury in acetaminophen hepatotoxicity in mice. (United States)

    Hoque, Rafaz; Sohail, Muhammed Adnan; Salhanick, Steven; Malik, Ahsan F; Ghani, Ayaz; Robson, Simon C; Mehal, Wajahat Z


    Inflammation contributes to liver injury in acetaminophen (APAP) hepatotoxicity in mice and is triggered by stimulation of immune cells. The purinergic receptor P2X7 is upstream of the nod-like receptor family, pryin domain containing-3 (NLRP3) inflammasome in immune cells and is activated by ATP and NAD that serve as damage-associated molecular patterns. APAP hepatotoxicity was assessed in mice genetically deficient in P2X7, the key inflammatory receptor for nucleotides (P2X7-/-), and in wild-type mice. P2X7-/- mice had significantly decreased APAP-induced liver necrosis. In addition, APAP-poisoned mice were treated with the specific P2X7 antagonist A438079 or etheno-NAD, a competitive antagonist of NAD. Pre- or posttreatment with A438079 significantly decreased APAP-induced necrosis and hemorrhage in APAP liver injury in wild-type but not P2X7-/- mice. Pretreatment with etheno-NAD also significantly decreased APAP-induced necrosis and hemorrhage in APAP liver injury. In addition, APAP toxicity in mice lacking the plasma membrane ecto-NTPDase CD39 (CD39-/-) that metabolizes ATP was examined in parallel with the use of soluble apyrase to deplete extracellular ATP in wild-type mice. CD39-/- mice had increased APAP-induced hemorrhage and mortality, whereas apyrase also decreased APAP-induced mortality. Kupffer cells were treated with extracellular ATP to assess P2X7-dependent inflammasome activation. P2X7 was required for ATP-stimulated IL-1β release. In conclusion, P2X7 and exposure to the ligands ATP and NAD are required for manifestations of APAP-induced hepatotoxicity.

  11. Nonmetallic behavior of out-of-plane conduction in La 2- xSr xCuO 4 (United States)

    Goko, T.; Nakamura, F.; Kikugawa, N.; Uno, Y.; Sakita, S.; Fujita, T.


    Pressure effect on the out-of-plane and in-plane resistivities has been investigated for single-crystalline La 2- xSr xCuO 4 with x = 0.145 and 0.25. The out-of-plane conduction for optimally-doped La 2- xSr xCuO 4 is explained in terms of a hopping process between the CuO 2 planes which have anomalous coherent conduction. For highly-doped La 2- xSr xCuO 4, the out-of-plane conduction is approaching a coherene metallic regime.

  12. Hypoxia induced amoeboid microglial cell activation in postnatal rat brain is mediated by ATP receptor P2X4

    Directory of Open Access Journals (Sweden)

    Li Fan


    Full Text Available Abstract Background Activation of amoeboid microglial cells (AMC and its related inflammatory response have been linked to the periventricular white matter damage after hypoxia in neonatal brain. Hypoxia increases free ATP in the brain and then induces various effects through ATP receptors. The present study explored the possible mechanism in ATP induced AMC activation in hypoxia. Results We first examined the immunoexpression of P2X4, P2X7 and P2Y12 in the corpus callosum (CC and subependyma associated with the lateral ventricles where both areas are rich in AMC. Among the three purinergic receptors, P2X4 was most intensely expressed. By double immunofluorescence, P2X4 was specifically localized in AMC (from P0 to P7 but the immunofluorescence in AMC was progressively diminished with advancing age (P14. It was further shown that P2X4 expression was noticeably enhanced in P0 day rats subjected to hypoxia and killed at 4, 24, 72 h and 7 d versus their matching controls by double labeling and western blotting analysis. P2X4 expression was most intense at 7 d whence the inflammatory response was drastic after hypoxia. We then studied the association of P2X4 with cytokine release in AMC after hypoxic exposure. In primary microglial cells exposed to hypoxia, IL-1β and TNF-α protein levels were up-regulated. Blockade of P2X4 receptor with 2', 3'-0-(2, 4, 6-Trinitrophenyl adenosine 5'-triphosphate, a selective P2X1-7 blocker resulted in partial suppression of IL-1β (24% vs hypoxic group and TNF-α expression (40% vs hypoxic group. However, pyridoxal phosphate-6-azo (benzene-2, 4-disulfonic acid tetrasodium salt hydrate, a selective P2X1-3, 5-7 blocker did not exert any significant effect on the cytokine expression. Conclusions It is concluded that P2X4 which is constitutively expressed by AMC in postnatal rats was enhanced in hypoxia. Hypoxia induced increase in IL-1β and TNF-α expression was reversed by 2', 3'-0-(2, 4, 6-Trinitrophenyl adenosine

  13. "Distinvar" device

    CERN Multimedia


    The alignment of one of the accelerator magnets being checked by the AR Division survey group. A "distinvar" device, invented by the group, using calibrated invar wires stretched between the fixed survey pillar (on the left) and a fixed point on the magnet. In two days it is thus possible to measure the alignment of the 100 magnets with an accuracy better than 1/10.

  14. Magnetohydrodynamic device

    Energy Technology Data Exchange (ETDEWEB)

    Gorlin, S.M.; Ljubimov, G.A.; Bitjurin, V.A.; Kovbasjuk, V.I.; Maximenko, V.I.; Medin, S.A.; Barshak, A.E.


    A magnetohydrodynamic device having a duct for a conducting gas to flow at an angle with the direction of the magnetic field induction vector is described. The duct is situated in the magnetic system and is provided with a plurality of electrodes adapted to interact electrically with the gas, whereas the cross-sectional shape of the duct working space is bounded by a closed contour formed by a curve inscribed into a rectangle. 1 claim.

  15. The regulatory roles of P2X7 receptor in inflammation%P2X7受体在炎症反应中的调节作用

    Institute of Scientific and Technical Information of China (English)

    神谢静; 韩莉


    P2X7 receptors are ATP-gated ion channels, which has strong selectivity for the divalent cations. P2X7 receptors participate in cell signal transduction, involve in cell-mediated cytotoxicity and activation; while, P2X7 receptor is involved in cytokine release, inflammation, apoptosis and is closely related with the tumor. Although the proinflammatory actions of P2RX7 are well recognized, little is known regarding the potential function of P2RX7 in repair responses. In recent years, researchers found that P2RX7 activation promotes the robust release of vascular endothelial growth factor from primary human monocytes. This vascular endothelial growth factor release is calcium dependent and associated with reactive oxygen species production. This paper reviews the P2X7 receptor biology and its molecular mechanism of inflammatory cell and VEGF releasing.%P2X7受体是对二价阳离子有较强选择性的ATP门控的离子通道,参与细胞信号转导,介导细胞毒性作用,活化并诱导宿主细胞凋亡.近几年研究表明,P2X7受体参与炎症反应中细胞因子的释放,特别是P2X7受体活化可促进单核细胞的血管内皮生长因子的释放,该释放依赖钙离子内流与活性氧的产生.本文综述了P2X7受体与炎症细胞及血管内皮生长因子分子机制的相关研究.

  16. The Structure and Function of P2X7 Receptor in Central Nervous System%中枢神经系统P2X7受体的结构与功能

    Institute of Scientific and Technical Information of China (English)

    杜侠莹; 周新妹; 万晓; 李子芳; 朱蒙佳; 陈晓


    中枢神经系统P2X7受体是参与介导胶质细胞和神经元通讯过程的关键介质,激活后可促进促炎因子、谷氨酸及ATP等物质的释放,参与多种炎症及神经损伤所导致的慢性疾病的发生.P2X7受体大量表达在胶质细胞,且在病理性疼痛的发生中起着非常重要的调节作用.现从其结构及药理学特性等方面,分析胶质细胞P2X7 受体在介导病理性疼痛发生、发展中的重要作用.%P2X7 receptor( P2X7 R)in central nervous system functions as an important mediator in the neuron-glia communication. The activation of P2X7 R is involved in the induction of multiple inflammation or nerve injury-induced chronic diseases by increasing the release of proinflammatory cytokines, glutamate and ATP. It has been proposed that P2X7 R,predominantly expressed in glia,play a key role in modulating pathological pain. Here is to focus on analyzing the role of glial P2X7 R in the induction of pathological pain by introducing the configuration, pharmacological profiles and other characteristics.

  17. 以P2X7受体为靶标的高通量筛选方法%Cellular fluorescent high-throughput screening assays of the ATP-gated P2X7 receptor

    Institute of Scientific and Technical Information of China (English)

    蒋亚琴; 尹琪; 粟世铀



  18. P2 X7受体与中枢神经系统疾病的研究进展%Research progress of P2X7 receptor and central nervous system diseases

    Institute of Scientific and Technical Information of China (English)

    曹敏玲; 王慧


    P2 X7受体及其介导的信号通路在中枢神经系统疾病中发挥着关键的调控作用, P2 X7受体可能成为中枢神经系统疾病潜在的药物靶点。本文就P2 X7受体与中枢神经系统疾病如帕金森病、阿尔茨海默病、肌萎缩侧索硬化、抑郁症和失眠等的最新研究进展进行综述。%P2X7 receptor and its mediated signaling pathway play a key role in the regulation of central nervous system diseases. P2X7 receptor may be a potential drug target for diseases of the central nervous system.This article reviews the latest research progress of P2X7 receptor and central nervous system diseases such as Parkinson's disease,Alzheimer's disease,amyotrophic lateral sclerosis, depression and insomnia.

  19. The J-2X Upper Stage Engine: From Heritage to Hardware (United States)

    Byrd, THomas


    NASA's Global Exploration Strategy requires safe, reliable, robust, efficient transportation to support sustainable operations from Earth to orbit and into the far reaches of the solar system. NASA selected the Ares I crew launch vehicle and the Ares V cargo launch vehicle to provide that transportation. Guiding principles in creating the architecture represented by the Ares vehicles were the maximum use of heritage hardware and legacy knowledge, particularly Space Shuttle assets, and commonality between the Ares vehicles where possible to streamline the hardware development approach and reduce programmatic, technical, and budget risks. The J-2X exemplifies those goals. It was selected by the Exploration Systems Architecture Study (ESAS) as the upper stage propulsion for the Ares I Upper Stage and the Ares V Earth Departure Stage (EDS). The J-2X is an evolved version ofthe historic J-2 engine that successfully powered the second stage of the Saturn I launch vehicle and the second and third stages of the Saturn V launch vehicle. The Constellation architecture, however, requires performance greater than its predecessor. The new architecture calls for larger payloads delivered to the Moon and demands greater loss of mission reliability and numerous other requirements associated with human rating that were not applied to the original J-2. As a result, the J-2X must operate at much higher temperatures, pressures, and flow rates than the heritage J-2, making it one of the highest performing gas generator cycle engines ever built, approaching the efficiency of more complex stage combustion engines. Development is focused on early risk mitigation, component and subassembly test, and engine system test. The development plans include testing engine components, including the subscale injector, main igniter, powerpack assembly (turbopumps, gas generator and associated ducting and structural mounts), full-scale gas generator, valves, and control software with hardware

  20. Effects of the stimulation of colorectal distention on expression of P2X4 and P2X7 receptors in dorsal commissural nucleus and dorsal horn of sacral segment of spinal cord in rats with irritable bowel syndrome%结肠扩张刺激对肠易激综合征大鼠DCN核团及骶髓后角中P2X4及P2X7受体表达的影响

    Institute of Scientific and Technical Information of China (English)

    朱琳; 章鹏宇; 王景杰; 黄裕新


    目的 观察肠易激综合征(irritable bowel syndrome,IBS)致内脏高敏感化大鼠在结肠扩张刺激时大鼠腹直肌肌电变化,并观察骶髓后联合核(dorsal commissural nucleus,DCN)和脊髓后角中P2X4和P2X7受体表达的变化情况,为探讨IBS内脏敏化的神经机制提供理论依据.方法 以旋毛虫感染大鼠建立IBS大鼠模型,并以正常大鼠作为对照,实验共分4组:正常大鼠无刺激组,正常大鼠结肠扩张刺激组,IBS大鼠无刺激组,IBS大鼠结肠扩张刺激组.采用免疫组织荧光化学方法,将P2X4和P2X7受体分别标记,观察其在骶髓后角及DCN核团上的表达变化,并同步测定大鼠腹直肌肌电变化.结果 IBS结肠刺激组大鼠腹直肌肌电变化、大鼠骶髓后角及DCN核团中的P2X4和P2X7受体表达较正常大鼠对照组及IBS未刺激组均显著增强.结论 P2X4 和 P2X7受体可能是IBS致内脏敏感性增高的重要因素.%Objective To explore the expression of P2X4 and P2X7 receptors in dorsal commissural nucleus ( DCN ) and dorsal horn of sacral segment of spinal cord in rats with irritable bowel syndrome( IBS ) induced by the stiruulation of colorectal distention,and to provide a theoretical evidence in prevention and treatment of IBS. Methods The rats were gavaged with the Trichinella spiralis to establish the irritable bowel syndrome model,and then divided into 2 groups :IBS without colon distension group and IBS with colon distension group. The normal rats were chosen as controls. and were also divided into 2 groups according to receiving colon distension or not. The expression of P2X4 and P2X7 receptors was detected in neurons of DCN and dorsal horn of the sacral segment of spinal cord in all rats using the immunofluorescent staining method, and the myoelectric changes of the rectus abdominis were recorded at the same time. Result.s The electro-activity of the rectus abdominis and the expression of P2X4 and P2X7 receptors were significantly en

  1. A novel assay to detect nucleotide receptor P2X7 genetic polymorphisms influencing numerous innate immune functions. (United States)

    Denlinger, Loren C; Schell, Kathleen; Angelini, Giuditta; Green, Dawn; Guadarrama, Arturo; Prabhu, Usha; Coursin, Douglas B; Hogan, Kirk; Bertics, Paul J


    The importance of accessory signaling pathways amplifying endotoxin responses has recently been highlighted by genetic studies describing LPS-hyporesponsive individuals despite carrying the common allele for TLR4. The nucleotide receptor P2X7 modulates the production of numerous LPS-stimulated inflammatory mediators. We have recently described the largest phenotypic screen known for genetic polymorphisms associated with the nucleotide receptor P2X7, a global regulator of leukocyte function. This required the development of a novel monocyte pore assay with numerous advantages over previous methods and with the potential to facilitate rapid (< 3 h), multiplex analysis of clinical samples. This paper addresses aspects pertinent to the development of the monocyte pore assay, briefly summarizes our results suggesting that P2X7 alleles modulate LPS-stimulated cytokine production, and discusses a model wherein P2X7 may serve as an amplification loop of innate immunity.

  2. Protein kinase A regulation of P2X(4) receptors: requirement for a specific motif in the C-terminus. (United States)

    Brown, David A; Yule, David I


    The P2X purinergic receptor sub-family of ligand-gated ion channels are subject to protein kinase modulation. We have previously demonstrated that P2X(4)R signaling can be positively regulated by increasing intracellular cAMP levels. The molecular mechanism underlying this effect was, however, unknown. The present study initially addressed whether protein kinase A (PKA) activation was required. Subsequently a mutational approach was utilized to determine which region of the receptor was required for this potentiation. In both DT-40 3KO and HEK-293 cells transiently expressing P2X(4)R, forskolin treatment enhanced ATP-mediated signaling. Specific PKA inhibitors prevented the forskolin-induced enhancement of ATP-mediated inward currents in P2X(4)R expressing HEK-293 cells. To define which region of the P2X(4)R was required for the potentiation, mutations were generated in the cytoplasmic C-terminal tail. It was determined that a limited region of the C-terminus, consisting of a non-canonical tyrosine based sorting motif, was required for the effects of PKA. Of note, this region does not harbor any recognizable PKA phosphorylation motifs, and no direct phosphorylation of P2X(4)R was detected, suggesting that PKA phosphorylation of an accessory protein interacts with the endocytosis motif in the C-terminus of the P2X(4)R. In support of this notion, using Total Internal Reflection Fluorescence Microscopy (TIRF)\\ P2X(4)-EGFP was shown to accumulate at/near the plasma membrane following forskolin treatment. In addition, disrupting the endocytosis machinery using a dominant-negative dynamin construct also prevented the PKA-mediated enhancement of ATP-stimulated Ca(2+) signals. Our results are consistent with a novel mechanism of P2XR regulation, whereby PKA activity, without directly phosphorylating P2X(4)R, markedly enhances ATP-stimulated P2X(4)R currents and hence cytosolic Ca(2+) signals. This may occur at least in part, by altering the trafficking of a population of

  3. Ranked solutions of the matric equation A1X1=A2X2

    Directory of Open Access Journals (Sweden)

    A. Duane Porter


    Full Text Available Let GF(pz denote the finite field of pz elements. Let A1 be s×m of rank r1 and A2 be s×n of rank r2 with elements from GF(pz. In this paper, formulas are given for finding the number of X1,X2 over GF(pz which satisfy the matric equation A1X1=A2X2, where X1 is m×t of rank k1, and X2 is n×t of rank k2. These results are then used to find the number of solutions X1,…,Xn, Y1,…,Ym, m,n>1, of the matric equation A1X1…Xn=A2Y1…Ym.

  4. Effects of charge inhomogeneities on elementary excitations in La2-xSrxCuO4 (United States)

    Park, S. R.; Hamann, A.; Pintschovius, L.; Lamago, D.; Khaliullin, G.; Fujita, M.; Yamada, K.; Gu, G. D.; Tranquada, J. M.; Reznik, D.


    Purely local experimental probes of many copper oxide superconductors show that their electronic states are inhomogeneous in real space. For example, scanning tunneling spectroscopic imaging shows strong variations in real space, and according to nuclear quadrupole resonance (NQR) studies, the charge distribution in the bulk varies on the nanoscale. However, the analysis of the experimental results utilizing spatially averaged probes often ignores this fact. We have performed a detailed investigation of the doping dependence of the energy and linewidth of the zone-boundary Cu-O bond-stretching vibration in La2-xSrxCuO4 by inelastic neutron scattering. Both our results as well as previously reported angle-dependent momentum widths of the electronic spectral function detected by angle-resolved photoemission can be reproduced by including the same distribution of local environments extracted from the NQR analysis.

  5. Manipulating stripes in La2-x Ba x CuO 4 in extreme environments (United States)

    Huecker, Markus; Gu, Genda; Xu, Zhijun; Wen, Jinsheng; Tranquada, John M.; von Zimmermann, Martin


    Competing magnetic and electronic interactions in the copper-oxide high temperature superconductors often result in nanoscale inhomogeneity of the charge and spin density. Such observations motivated a proposal that dynamic electronic inhomogeneities are intrinsic to the copper-oxide planes, and can result in electronic states that break their four-fold symmetry. We have performed high-energy single-crystal X-ray diffraction in high magnetic fields and at high pressure to show that the charge and spin stripe phase in La 2-x Ba x Cu O4 constitutes such a state. In particular, our results provide strong evidence that charge stripe correlations in the cuprates are electronically driven and are enhanced within vortices. The work at Brookhaven was supported by the Office of Science, U.S. Department of Energy under Contract No. DE-AC02-98CH10886.

  6. Downregulation of adenosine and P2X receptor-mediated cardiovascular responses in heart failure rats

    DEFF Research Database (Denmark)

    Zhao, Xin; Sun, X Y; Erlinge, D;


    Neurohormonal changes in congestive heart failure (CHF) include an enhanced peripheral sympathetic nerve activity which results in increased release of noradrenaline, neuropeptide Y and ATP. To examine if such changes in CHF would modulate peripheral pre- and postsynaptic receptors of ATP and its...... effects mediated by the endothelial P2Y receptors are unaffected in CHF. Moreover, the adenosine-mediated inhibitory effects on heart rate and blood pressure were also attenuated in the CHF rats. The most important changes in adenosine and P2-receptor function induced by ischaemic CHF were the reduced...... pressor effect mediated by the P2X receptor and the increased heart rate due to an attenuated inhibitory effect of adenosine....

  7. Crystal structures and phase stability in pseudobinary CaAl 2-xZn x (United States)

    Söderberg, Karin; Boström, Magnus; Kubota, Yoshiki; Nishimatsu, Takeshi; Niewa, Rainer; Häussermann, Ulrich; Grin, Yuri; Terasaki, Osamu


    Samples in the pseudobinary system CaAl 2-xZn x ( 0⩽x⩽2) were synthesised from the elements. Three different structure types, the C15 and C36 Laves phase structures and the KHg 2 (CeCu 2) structure, were observed. The structures and homogeneity ranges of the underlying phases were investigated by electron microscopy and thermal analysis as well as X-ray powder diffraction. The stability ranges for the different structure types were found to be 0⩽x⩽0.18, 0.28⩽x⩽0.68 and 0.93⩽x⩽2 for the C15, C36 and KHg 2 structure types, respectively.

  8. The structure of the Pd(110)(2x1)-CO surface

    Energy Technology Data Exchange (ETDEWEB)

    Kittel, M.; Terborg, R.; Polcik, M.; Bradshaw, A.M.; Toomes, R.L.; Woodruff, D.P.; Rotenberg, E.


    The structure of the Pd(110)(2x1)-CO ordered adsorption phase has been determined by scanned-energy mode photoelectron diffraction. The CO molecules are adsorbed close to short-bridge sites with alternating tilts along the close-packed <110> surface rows. This local geometry is consistent with that found in previous theoretical total energy calculations and an earlier X-ray photoelectron diffraction study, but is in direct contradiction to the results of an earlier quantitative low energy electron diffraction investigation. While the best-fit model structure involves some twist of the CO molecules out of the <100> mirror planes of the surface creating a surface phase of p1g1 symmetry, the more symmetric p2mg falls within the estimated limits of precision of the analysis.

  9. Electron energy loss spectroscopy study of Sr2-xGdxTiMnO6 (United States)

    Biskup, Nevenko; Alvarez-Serrano, Inmaculada; Veiga, Maria Luisa; Garcia-Hernandez, Mar; Lopez, Maria Luisa; Varela, Maria


    The newly synthesized double perovskite family Sr2-xGdxTiMnO6 (0

  10. A measurement of the proton structure function F$_{2}$(x,Q$^{2}$)

    CERN Document Server

    Ahmed, T; Andreev, V; Andrieu, B; Appuhn, R D; Arpagaus, M; Aïd, S; Babaev, A; Baranov, P S; Barrelet, E; Bartel, Wulfrin; Barth, Monique; Bassler, U; Beck, H P; Behrend, H J; Belousov, A; Berger, C; Bergstein, H; Bernardi, G; Bernet, R; Bertrand-Coremans, G H; Besançon, M; Beyer, R; Bizot, J C; Blobel, Volker; Borras, K; Botterweck, F; Boudry, V; Braemer, A; Brasse, F W; Braunschweig, W; Brisson, V; Bruncko, Dusan; Brune, C R; Buchholz, R; Buniatian, A Yu; Burke, S; Burton, M; Buschhorn, G W; Bán, J; Bähr, J; Büngener, L; Bürger, J; Büsser, F W; Campbell, A J; Carli, T; Charles, F; Chernyshov, V; Clarke, D; Clegg, A B; Clerbaux, B; Colombo, M G; Contreras, J G; Cormack, C; Coughlan, J A; Courau, A; Coutures, C; Cozzika, G; Criegee, L; Cussans, D G; Cvach, J; Dagoret, S; Dainton, J B; Danilov, M V; Dau, W D; Daum, K; David, M; De Wolf, E A; Deffur, E; Del Buono, L; Delcourt, B; Di Nezza, P; Dollfus, C; Dowell, John D; Dreis, H B; Droutskoi, A; Duboc, J; Duhm, H; Düllmann, D; Dünger, O; Ebert, J; Ebert, T R; Eckerlin, G; Efremenko, V; Egli, S; Eichenberger, S; Eichler, R; Eisele, Franz; Eisenhandler, Eric F; Ellison, R J; Elsen, E E; Erdmann, M; Erdmann, W; Erlichmann, H; Evrard, E; Favart, L; Fedotov, A; Feeken, D; Felst, R; Feltesse, Joel; Ferencei, J; Ferrarotto, F; Flamm, K; Fleischer, M; Flieser, M; Flügge, G; Fomenko, A; Fominykh, B A; Forbush, M; Formánek, J; Foster, J M; Franke, G; Fretwurst, E; Gabathuler, Erwin; Gabathuler, K; Gamerdinger, K; Garvey, J; Gayler, J; Gebauer, M; Gellrich, A; Genzel, H; Gerhards, R; Goerlach, U; Gogitidze, N; Goldberg, M; Goldner, D; González-Pineiro, B; Gorelov, I V; Goritchev, P A; Grab, C; Greenshaw, T J; Grindhammer, G; Gruber, A; Gruber, C; Grässler, Herbert; Grässler, R; Görlich, L; Haack, J; Haidt, Dieter; Hajduk, L; Hamon, O; Hampel, M; Hanlon, E M; Hapke, M; Haynes, W J; Heatherington, J; Heinzelmann, G; Henderson, R C W; Henschel, H; Herynek, I; Hess, M F; Hildesheim, W; Hill, P; Hiller, K H; Hilton, C D; Hladky, J; Hoeger, K C; Horisberger, R P; Hudgson, V L; Huet, Patrick; Hufnagel, H; Höppner, M; Hütte, M; Ibbotson, M; Itterbeck, H; Jabiol, M A; Jacholkowska, A; Jacobsson, C; Jaffré, M; Janoth, J; Jansen, T; Johannsen, K; Johnson, D P; Johnson, L; Jung, H; Jönsson, L B; Kalmus, Peter I P; Kant, D; Kaschowitz, R; Kasselmann, P; Kathage, U; Katzy, J M; Kaufmann, H H; Kazarian, S; Kenyon, Ian Richard; Kermiche, S; Keuker, C; Kiesling, C; Klein, M; Kleinwort, C; Knies, G; Ko, W; Kolanoski, H; Kole, F; Kolya, S D; Korbel, V; Korn, M; Kostka, P; Kotelnikov, S K; Krasny, M W; Krehbiel, H; Krämerkämper, T; Krücker, D; Krüger, U P; Krüner-Marquis, U; Kubenka, J P; Kuhlen, M; Kurca, T; Kurzhöfer, J; Kuznik, B; Köhler, T; Köhne, J H; Küster, H; Lacour, D; Lamarche, F; Lander, R; Landon, M P J; Lange, W; Lanius, P; Laporte, J F; Lebedev, A; Leverenz, C; Levonian, S; Ley, C; Lindner, A; Lindström, G; Linsel, F; Lipinski, J; List, B; Loch, P; Lohmander, H; Lubimov, V; López, G C; Lüke, D; Magnussen, N; Malinovskii, E I; Mani, S; Maracek, R; Marage, P; Marks, J; Marshall, R; Martens, J; Martin, R D; Martyn, H U; Martyniak, J; Masson, S; Mavroidis, A; Maxfield, S J; McMahon, S J; Mehta, A; Meier, K; Mercer, D; Merz, T; Meyer, C A; Meyer, H; Meyer, J; Mikocki, S; Milstead, D; Moreau, F; Morris, J V; Mroczko, E; Murín, P; Müller, G; Müller, K; Nagovitsin, V; Nahnhauer, R; Naroska, Beate; Naumann, T; Newman, P R; Newton, D; Neyret, D; Nguyen, H K; Nicholls, T C; Niebergall, F; Niebuhr, C B; Nisius, R; Nowak, G; Noyes, G W; Nyberg-Werther, M; Oakden, M N; Oberlack, H; Obrock, U; Olsson, J E; Panaro, E; Panitch, A; Pascaud, C; Patel, G D; Peppel, E; Phillips, J P; Pichler, C; Pitzl, D; Pope, G; Prell, S; Prosi, R; Pérez, E; Raupach, F; Reimer, P; Reinshagen, S; Ribarics, P; Rick, Hartmut; Riech, V; Riedlberger, J; Riess, S; Rietz, M; Rizvi, E; Robertson, S M; Robmann, P; Roloff, H E; Roosen, R; Rosenbauer, K; Rostovtsev, A A; Rouse, F; Royon, C; Rusakov, S V; Rybicki, K; Rylko, R; Rädel, G; Rüter, K; Sahlmann, N; Sankey, D P C; Savitsky, M M; Schacht, P; Schiek, S; Schleper, P; Schmidt, C; Schmidt, D; Schmidt, G; Schröder, V; Schuhmann, E; Schwab, B; Schwind, A; Schöning, A; Seehausen, U; Sefkow, F; Seidel, M; Sell, R; Semenov, A A; Shekelian, V I; Shevyakov, I; Shooshtari, H; Shtarkov, L N; Siegmon, G; Siewert, U; Sirois, Y; Skillicorn, Ian O; Smirnov, P; Smith, J R; Soloviev, Yu V; Spiekermann, J; Spitzer, H; Starosta, R; Steenbock, M; Steffen, P; Steinberg, R; Stella, B; Stephens, K; Stier, J; Stiewe, J; Strachota, J; Straumann, U; Struczinski, W; Stösslein, U; Sutton, J P; Sánchez, E; Tapprogge, Stefan; Taylor, R E; Thiebaux, C; Thompson, G; Truöl, P; Turnau, J; Tutas, J; Uelkes, P; Usik, A; Valkár, S; Valkárová, A; Vallée, C; Van Esch, P; Van Mechelen, P; Vartapetian, A H; Vazdik, Ya A; Vecko, M; Verrecchia, P; Villet, G; Wacker, K; Wagener, A; Wagener, M; Walker, I W; Walther, A; Weber, G; Weber, M; Wegener, D; Wegner, A; Wellisch, H P; West, L R; Willard, S; Winde, M; Winter, G G; Wright, A E; Wulff, N; Wünsch, E; Yiou, T P; Zarbock, D; Zhang, Z; Zhokin, A S; Zimmer, M; Zimmermann, W; Zomer, F; Zuber, K; Zácek, J; de Roeck, A; von Schlippe, W; Niebergall, Friedrich


    A measurement of the proton structure function F_{\\!2}(x,Q^2) is reported for momentum transfer squared Q^2 between 4.5 GeV^2 and 1600 GeV^2 and for Bjorken x between 1.8\\cdot10^{-4} and 0.13 using data collected by the HERA experiment H1 in 1993. It is observed that F_{\\!2} increases significantly with decreasing x, confirming our previous measurement made with one tenth of the data available in this analysis. The Q^2 dependence is approximately logarithmic over the full kinematic range covered. The subsample of deep inelastic events with a large pseudo-rapidity gap in the hadronic energy flow close to the proton remnant is used to measure the "diffractive" contribution to F_{\\!2}.

  11. Nuclear medium modification of the F{sub 2}(x,Q{sup 2}) structure function

    Energy Technology Data Exchange (ETDEWEB)

    Sajjad Athar, M., E-mail: [Department of Physics, Aligarh Muslim University, Aligarh 202 002 (India); Ruiz Simo, I.; Vicente Vacas, M.J. [Departamento de Fisica Teorica and IFIC, Centro Mixto Universidad de Valencia - CSIC, 46100 Burjassot (Valencia) (Spain)


    We study the nuclear effects in the electromagnetic structure function F{sub 2}(x,Q{sup 2}) in the deep inelastic lepton-nucleus scattering process by taking into account Fermi motion, binding, pion and rho meson cloud contributions. Calculations have been done in a local density approximation using relativistic nuclear spectral functions which include nucleon correlations. The ratios R{sub F}{sub 2}{sup A}(x,Q{sup 2})=(2F{sub 2}{sup A}(x,Q{sup 2}))/(AF{sub 2}{sup D}(x,Q{sup 2})) are obtained and compared with recent JLab results for light nuclei with special attention to the slope of the x distributions. This magnitude shows a non-trivial A dependence and it is insensitive to possible normalization uncertainties. The results have also been compared with some of the older experiments using intermediate mass nuclei.

  12. The structure of the Pd(110)(2x1)-CO surface

    CERN Document Server

    Kittel, M; Polcik, M; Bradshaw, A M; Toomes, R L; Woodruff, D P; Rotenberg, E


    The structure of the Pd(110)(2x1)-CO ordered adsorption phase has been determined by scanned-energy mode photoelectron diffraction. The CO molecules are adsorbed close to short-bridge sites with alternating tilts along the close-packed surface rows. This local geometry is consistent with that found in previous theoretical total energy calculations and an earlier X-ray photoelectron diffraction study, but is in direct contradiction to the results of an earlier quantitative low energy electron diffraction investigation. While the best-fit model structure involves some twist of the CO molecules out of the mirror planes of the surface creating a surface phase of p1g1 symmetry, the more symmetric p2mg falls within the estimated limits of precision of the analysis.

  13. Prototipado de un sistema WiMax MIMO 2x2 (I) - Emisor


    Prieto Alonso, Roberto


    El presente proyecto consiste en el diseño de un emisor para el estándar IEEE 802.16d-2004 utilizando MIMO 2x2, OFDM (Multiplexado por División en Frecuencias Ortogonales) en la capa física y BPSK (Modulación Binaria por Salto de Fase) para la modulación de datos, empleando una plataforma de desarrollo sobre FPGA basada en Simulink®, la cual proporciona un alto nivel de abstracción en el diseño de los modelos. Todo ello, como respuesta al creciente interés que las comunicaciones inalámbricas ...

  14. Phase diagram and thermal expansion measurements on the system URu2-xFexSi2. (United States)

    Ran, Sheng; Wolowiec, Christian T; Jeon, Inho; Pouse, Naveen; Kanchanavatee, Noravee; White, Benjamin D; Huang, Kevin; Martien, Dinesh; DaPron, Tyler; Snow, David; Williamsen, Mark; Spagna, Stefano; Riseborough, Peter S; Maple, M Brian


    Thermal expansion, electrical resistivity, magnetization, and specific heat measurements were performed on URu2-xFexSi2 single crystals for various values of Fe concentration x in both the hidden-order (HO) and large-moment antiferromagnetic (LMAFM) regions of the phase diagram. Our results show that the paramagnetic (PM) to HO and LMAFM phase transitions are manifested differently in the thermal expansion coefficient. The uniaxial pressure derivatives of the HO/LMAFM transition temperature T0 change dramatically when crossing from the HO to the LMAFM phase. The energy gap also changes consistently when crossing the phase boundary. In addition, for Fe concentrations at xc ≈ 0.1, we observe two features in the thermal expansion upon cooling, one that appears to be associated with the transition from the PM to the HO phase and another one at lower temperature that may be due to the transition from the HO to the LMAFM phase.

  15. The impact of a 2 X CO2 climate on lightning-caused fires (United States)

    Price, Colin; Rind, David


    Future climate change could have significant repercussions for lightning-caused wildfires. Two empirical fire models are presented relating the frequency of lightning fires and the area burned by these fires to the effective precipitation and the frequency of thunderstorm activity. One model deals with the seasonal variations in lightning fires, while the second model deals with the interannual variations of lightning fires. These fire models are then used with the Goddard Institute for Space Studies General Circulation Model to investigate possible changes in fire frequency and area burned in a 2 X CO2 climate. In the United States, the annual mean number of lightning fires increases by 44%, while the area burned increases by 78%. On a global scale, the largest increase in lightning fires can be expected in untouched tropical ecosystems where few natural fires occur today.

  16. [How I explore the various statistical facets of 2 x 2 tables in medicine]. (United States)

    Albert, A


    In the medical scientific literature, 2 x 2 contingency tables are widely used to display the distribution of binary data. They are associated with the definition of basic concepts in medicine and epidemiology that are universally utilized. They are usually taught in any basic course in biostatistics early in the medical curriculum; their interpretation however is not always straightforward. We have discerned at least eight different facets of such fourfold tables: homogeneity test, independence test, McNemar test, Cohen kappa coefficient, incidence relative risk, prevalence relative risk, odds ratio, diagnostic value of a clinical test. Each facet is illustrated by a clinical problem used as an example. This article should help the reader to understand which table he/she is actually dealing with.

  17. Evidence for Pseudo Bridge Bonding of c (2 x 2)-O on Ni(100) (United States)


    OSTIN1SuTiOIN IT Al CMt ? (0 sofA l~ott smo I** h &t o,& . of ReI..~ I rNt~) :0 SUPOL.IldavdANY miOTETS Published in Physical Review Letters Is KU Y...unlimnited *TA& I 1PCt 133 VOLUME 50, NuMsnul8 PHYSICAL REVIEW LETTERS 2 MAY 1983 Evidence for Pseudo Bridge Bonding of c (2 x 2)-O on Ni(100) J. E...experimental spectra for the 𔃼 -, 1913 The American Physical Society 1373 06 VOLUMESO. NUMBU Is PHYSICAL REVIEW LETTERS 2MAY 1983 7iT•j .t..Z5 ± I .0-45A

  18. Thermodynamic Properties of Heusler Fe2-x C ox M n S i (United States)

    Ito, Masakazu; Furuta, Tatsuya; Kai, Keita; Taira, Atsushi; Onda, Keijiro; Shigeta, Iduru; Hiroi, Masahiko


    We investigated the thermodynamic properties of Heusler compounds Fe2-x C ox m n S i (0.00 ≤ x ≤ 2.00). The specific heats CP(T) for compounds with x ≤ 0.1 exhibit a λ-type anomaly arising from spin rearrangements at TR. With increasing x, TR decreases linearly and vanishes at x ∼ 0.169 . The magnetic entropy, STR, derived from the magnetic specific heat, Cm(T), released at TR decreases by increasing x. This means the canting angle of spins from the [111] direction decreases by the substitution of Fe atoms with Co atoms, based on the magnetic structure model of Fe2MnSi proposed by Miles et al. For compounds with 0.5 ≤ x , CP(T) in the low-T range can be reproduced by Debye T3 law. The electronic specific heat coefficient decreases monotonically with x.

  19. An infinite transfer matrix approach to the product of random 2 x 2 positive matrices

    Energy Technology Data Exchange (ETDEWEB)

    Bai Zaiqiao [Department of Physics, Beijing Normal University, Beijing 100875 (China)], E-mail:


    This paper concerns the efficient and precise determination of the Laypunov exponent (and other statistical properties) of a product of random 2 x 2 matrices. By considering the ensemble average of an infinite series of regular functions and its iteration, we construct a transfer matrix, which is shown to be a trace class operator in a Hilbert space given that the positiveness of the random matrices is assumed. This fact gives a theoretical explanation of the superior convergence of the cycle expansion of the Lyapunov exponent (Bai 2007 J. Phys. A: Math. Theor. 40 8315). A numerical method based on the infinite transfer matrix is applied to a one-dimensional Ising model with a random field and a generalized Fibonacci sequence. It is found that, in the presence of continuous distribution of a disorder or degenerated random matrix, the transfer matrix approach is more efficient than the cycle expansion method.

  20. P2X and P2Y receptor signaling in red blood cells. (United States)

    Sluyter, Ronald


    Purinergic signaling involves the activation of cell surface P1 and P2 receptors by extracellular nucleosides and nucleotides such as adenosine and adenosine triphosphate (ATP), respectively. P2 receptors comprise P2X and P2Y receptors, and have well-established roles in leukocyte and platelet biology. Emerging evidence indicates important roles for these receptors in red blood cells. P2 receptor activation stimulates a number of signaling pathways in progenitor red blood cells resulting in microparticle release, reactive oxygen species formation, and apoptosis. Likewise, activation of P2 receptors in mature red blood cells stimulates signaling pathways mediating volume regulation, eicosanoid release, phosphatidylserine exposure, hemolysis, impaired ATP release, and susceptibility or resistance to infection. This review summarizes the distribution of P2 receptors in red blood cells, and outlines the functions of P2 receptor signaling in these cells and its implications in red blood cell biology.

  1. Endosome-mediated retrograde axonal transport of P2X3 receptor signals in primary sensory neurons

    Institute of Scientific and Technical Information of China (English)

    Xu-Qiao Chen; BinWang; Chengbiao Wu; Jin Pan; Bo Yuan; Yuan-Yuan Su; Xing-Yu Jiang; Xu Zhang; Lan Bao


    Neurotrophins and their receptors adopt signaling endosomes to transmit retrograde signals.However,the mechanisms of retrograde signaling for other ligand/receptor systems are poorly understood.Here,we report that the signals of the purinergic (P)2X3 receptor,an ATP-gated ion channel are retrogradely transported in dorsal root ganglion (DRG) neuron axons.We found that Rab5,a small GTPase,controls the early sorting of P2X3 receptors into endosomes,while Rab7 mediates the fast retrograde transport of P2X3 receptors.Intraplantar injection and axonal application into the microfluidic chamber of α,β-methylene-ATP (α,β-MeATP),a P2X selective agonist,enhanced the endocytosis and retrograde transport of P2X3 receptors.The α,β-MeATP-induced Ca2+ influx activated a pathway comprised of protein kinase C,rat sarcoma viral oncogene and extracellular signal-regulated protein kinase (ERK),which associated with endocytic P2X3 receptors to form signaling endosomes.Disruption of the lipid rafts abolished the α,β-MeATP-induced ERK phosphorylation,endocytosis and retrograde transport of P2X3 receptors.Furthermore,treatment of peripheral axons with α,β-MeATP increased the activation level of ERK and cAMP response element-binding protein in the cell bodies of DRG neurons and enhanced neuronal excitability.Impairment of either microtubule-based axonal transport in vivo or dynein function in vitro blocked α,β-MeATP-induced retrograde signals.These results indicate that P2X3 receptor-activated signals are transmitted via retrogradely transported endosomes in primary sensory neurons and provide a novel signaling mechanism for ligand-gated channels.

  2. Inhibition of Streptococcus pneumoniae penicillin-binding protein 2x and Actinomadura R39 DD-peptidase activities by ceftaroline. (United States)

    Zervosen, Astrid; Zapun, André; Frère, Jean-Marie


    Although the rate of acylation of a penicillin-resistant form of Streptococcus pneumoniae penicillin-binding protein 2x (PBP2x) by ceftaroline is 80-fold lower than that of its penicillin-sensitive counterpart, it remains sufficiently high (k(2)/K = 12,600 M(-1) s(-1)) to explain the sensitivity of the penicillin-resistant strain to this new cephalosporin. Surprisingly, the Actinomadura R39 DD-peptidase is not very sensitive to ceftaroline.

  3. Macrophage P2X7 Receptor Function Is Reduced during Schistosomiasis: Putative Role of TGF-β1

    Directory of Open Access Journals (Sweden)

    Suellen D’arc Santos Oliveira


    Full Text Available Schistosomiasis is a chronic inflammatory disease whose macrophages are involved in immunopathology modulation. Although P2X7 receptor signaling plays an important role in inflammatory responses mediated by macrophages, no reports have examined the role of P2X7 receptors in macrophage function during schistosomiasis. Thus, we evaluated P2X7 receptor function in peritoneal macrophages during schistosomiasis using an ATP-induced permeabilization assay and measurements of the intracellular Ca2+ concentration. ATP treatment induced significantly less permeabilization in macrophages from S. mansoni-infected mice than in control cells from uninfected animals. Furthermore, P2X7-mediated increases in intracellular Ca2+ levels were also reduced in macrophages from infected mice. TGF-β1 levels were increased in the peritoneal cavity of infected animals, and pretreatment of control macrophages with TGF-β1 reduced ATP-induced permeabilization, mimicking the effect of S. mansoni infection. Western blot and qRT-PCR data showed no difference in P2X7 protein and mRNA between uninfected, infected, and TGF-β1-treated groups. However, immunofluorescence analysis revealed reduced cell surface localization of P2X7 receptors in macrophages from infected and TGF-β1-treated mice compared to controls. Therefore, our data suggest that schistosomiasis reduces peritoneal macrophage P2X7 receptor signaling. This effect is likely due to the fact that infected mice have increased levels of TGF-β1, which reduces P2X7 receptor cell surface expression.

  4. Central sensitization of nociceptive neurons in rat medullary dorsal horn involves purinergic P2X7 receptors. (United States)

    Itoh, K; Chiang, C-Y; Li, Z; Lee, J-C; Dostrovsky, J O; Sessle, B J


    Central sensitization is a crucial process underlying the increased neuronal excitability of nociceptive pathways following peripheral tissue injury and inflammation. Our previous findings have suggested that extracellular adenosine 5'-triphosphate (ATP) molecules acting at purinergic receptors located on presynaptic terminals (e.g., P2X2/3, P2X3 subunits) and glial cells are involved in the glutamatergic-dependent central sensitization induced in medullary dorsal horn (MDH) nociceptive neurons by application to the tooth pulp of the inflammatory irritant mustard oil (MO). Since growing evidence indicates that activation of P2X7 receptors located on glia is involved in chronic inflammatory and neuropathic pain, the aim of the present study was to test in vivo for P2X7 receptor involvement in this acute inflammatory pain model. Experiments were carried out in anesthetized Sprague-Dawley male rats. Single unit recordings were made in MDH functionally identified nociceptive neurons for which mechanoreceptive field, mechanical activation threshold and responses to noxious stimuli were tested. We found that continuous intrathecal (i.t.) superfusion over MDH of the potent P2X7 receptor antagonists brilliant blue G and periodated oxidized ATP could each significantly attenuate the MO-induced MDH central sensitization. MDH central sensitization could also be produced by i.t. superfusion of ATP and even more effectively by the P2X7 receptor agonist benzoylbenzoyl ATP. Superfusion of the microglial blocker minocycline abolished the MO-induced MDH central sensitization, consistent with reports that dorsal horn P2X7 receptors are mostly expressed on microglia. In control experiments, superfusion over MDH of vehicle did not produce any significant changes. These novel findings suggest that activation of P2X7 receptors in vivo may be involved in the development of central sensitization in an acute inflammatory pain model.

  5. Pressure induced magneto-structural phase transitions in layered RMn2X2 compounds (invited) (United States)

    Kennedy, Shane; Wang, Jianli; Campbell, Stewart; Hofmann, Michael; Dou, Shixue


    We have studied a range of pseudo-ternaries derived from the parent compound PrMn2Ge2, substituting for each constituent element with a smaller one to contract the lattice. This enables us to observe the magneto-elastic transitions that occur as the Mn-Mn nearest neighbour distance is reduced and to assess the role of Pr on the magnetism. Here, we report on the PrMn2Ge2-xSix, Pr1-xYxMn2Ge2, and PrMn2-xFexGe2 systems. The pressure produced by chemical substitution in these pseudo-ternaries is inherently non-uniform, with local pressure variations dependent on the local atomic distribution. We find that concentrated chemical substitution on the R or X site (e.g., in Pr0.5Y0.5Mn2Ge2 and PrMn2Ge0.8Si1.2) can produce a separation into two distinct magnetic phases, canted ferromagnetic and canted antiferromagnetic, with a commensurate phase gap in the crystalline lattice. This phase gap is a consequence of the combination of phase separation and spontaneous magnetostriction, which is positive on transition to the canted ferromagnetic phase and negative on transition to the canted antiferromagnetic phase. Our results show that co-existence of canted ferromagnetic and antiferromagnetic phases depends on chemical pressure from the rare earth and metalloid sites, on local lattice strain distributions and on applied magnetic field. We demonstrate that the effects of chemical pressure bear close resemblance to those of mechanical pressure on the parent compound.

  6. Impaired P2X signalling pathways in renal microvascular myocytes in genetic hypertension

    KAUST Repository

    Gordienko, Dmitri V.


    Aims P2X receptors (P2XRs) mediate sympathetic control and autoregulation of renal circulation triggering preglomerular vasoconstriction, which protects glomeruli from elevated pressures. Although previous studies established a casual link between glomerular susceptibility to hypertensive injury and decreased preglomerular vascular reactivity to P2XR activation, the mechanisms of attenuation of the P2XR signalling in hypertension remained unknown. We aimed to analyse molecular mechanisms of the impairment of P2XR signalling in renal vascular smooth muscle cells (RVSMCs) in genetic hypertension. Methods and results We compared the expression of pertinent genes and P2XR-linked Ca2+ entry and Ca2+ release mechanisms in RVSMCs of spontaneously hypertensive rats (SHRs) and their normotensive controls, Wistar Kyoto (WKY) rats. We found that, in SHR RVSMCs, P2XR-linked Ca2+ entry and Ca2+ release from the sarcoplasmic reticulum (SR) are both significantly reduced. The former is due to down-regulation of the P2X1 subunit. The latter is caused by a decrease of the SR Ca2+ load. The SR Ca2+ load reduction is caused by attenuated Ca2+ uptake via down-regulated sarco-/endoplasmic reticulum Ca2+-ATPase 2b and elevated Ca2+ leak from the SR via ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors. Spontaneous activity of these Ca2+-release channels is augmented due to up-regulation of RyR type 2 and elevated IP3 production by up-regulated phospholipase C-β1. Conclusions Our study unravels the cellular and molecular mechanisms of attenuation of P2XR-mediated preglomerular vasoconstriction that elevates glomerular susceptibility to harmful hypertensive pressures. This provides an important impetus towards understanding of the pathology of hypertensive renal injury.

  7. Electrooptical devices (United States)

    Hurwitz, C. E.


    This report covers work carried out with support of the Department of the Air Force during the period 1 October 1979 through 31 March 1980. A part of this support was provided by the Rome Air Development Center. CW operation at temperatures up to 55 C has been achieved for GaInAsP/InP double-heterostructure (DH) lasers emitting at 1.5 micrometers, which were grown without a GaInAsP buffer layer. These devices are of interest for use as sources in fiber-optics communications systems, since the lowest transmission loss reported for fused-silica optical fibers occurs at 1.55 micrometers. Surface passivation techniques developed for InP and GaInAsP avalanche photodiodes have resulted in reductions of dark current as large as four orders of magnitude, to values as low as .0000016 A/sq cm at 0.9 V(b) where V(b) is the breakdown voltage. Devices consisting entirely of InP have been passivated with plasma-deposited Si3N4, and those with a GaInAsP layer but with the p-n junction in InP have been passivated with polyimide. Neither of these techniques successfully reduces dark currents in devices with the p-n junction in the GaInAsP, but a film of photoresist sprayed with SF6 as the propellant has given excellent results. The electrical characteristics in InP ion implanted with Sn, Ge, Si, and C have been investigated. All of these column IV elements yielded n-type conductivity and Sn, Ge, and Si showed high electrical activation; however, implanted C was found to have a net electrical activation of only about 5 percent.

  8. Association of IFN-γ and P2X7 Receptor Gene Polymorphisms in Susceptibility to Tuberculosis Among Iranian Patients. (United States)

    Shamsi, Mahdi; Zolfaghari, Mohammad Reza; Farnia, Parissa


    Interferon-gamma (IFN-γ) and P2X7 receptor are crucial for host defence against mycobacterial infections. Recent studies have indicated that IFN-γ, IFN-γ receptor 1 (IFN-γR1) andP2X7 gene polymorphisms are associated with susceptibility to pulmonary tuberculosis (TB). However, the relationship between IFN-γ and P2X7 polymorphism and TB susceptibility remains inconclusive in Iranian population. For this reason, single nucleotide polymorphisms (SNPs) in IFN-γ (G+2109A), IFN-γR1 (G-611A) and P2X7 genes (at -762, 1513 position) in patients (n = 100) were assessed using PCR-RFLP. Data were analysed with SPSS version 18. For the 2109 loci of IFN-γ gene, the frequency of mutant alleles between patients and controls were not statistically significant. However, there was a significant difference between the TB patient and controls for -611 alleles of IFN-γR1 (P = 0.01). Additionally, the frequency of P2X7 gene polymorphisms (SNP-762 and 1513) between patients and controls was statistically significant. In conclusions, our study revealed a significant association of IFN-γR1 and P2X7 genes polymorphisms with risk of developing TB in Iranian population.

  9. Silencing P2X7 receptor downregulates the expression of TCP-1 involved in lymphoma lymphatic metastasis. (United States)

    Jiang, Xudong; Mao, Wenjuan; Yang, Ziyi; Zeng, Jia; Zhang, Yi; Song, Yang; Kong, Ying; Ren, Shuangyi; Zuo, Yunfei


    P2X7R is an ATP-gated cation channel that participates in cell proliferation and apoptosis. TCP-1 assists with the protein folding. According to our previous research, the P2X7R has a potential role in P388D1 lymphoid neoplasm cells dissemination to peripheral lymph nodes. In order to make a further exploration about the probable mechanism, the lymph nodes which metastasized by P2X7R-silenced P388D1 cells or non-silenced cells were analyzed by 2DE and a MALDI-TOF-based proteomics approach. In the 64 proteins which were differentially expressed between two groups, TCP-1 was found to be significantly decreased in P2X7R shRNA group compared to controls. This correlation was also found in subsequent experiments in vivo and in vitro. The positive correlation between P2X7R and TCP-1 was also proved in both lymphoma and benign lymphadenopathy tissues from patients. It indicates that TCP-1 may be a crucial downstream molecular of P2X7R and plays a novel role in lymphoid neoplasm metastasis.

  10. P2X7 receptors on osteoblasts couple to production of lysophosphatidic acid: a signaling axis promoting osteogenesis. (United States)

    Panupinthu, Nattapon; Rogers, Joseph T; Zhao, Lin; Solano-Flores, Luis Pastor; Possmayer, Fred; Sims, Stephen M; Dixon, S Jeffrey


    Nucleotides are released from cells in response to mechanical stimuli and signal in an autocrine/paracrine manner through cell surface P2 receptors. P2rx7-/- mice exhibit diminished appositional growth of long bones and impaired responses to mechanical loading. We find that calvarial sutures are wider in P2rx7-/- mice. Functional P2X7 receptors are expressed on osteoblasts in situ and in vitro. Activation of P2X7 receptors by exogenous nucleotides stimulates expression of osteoblast markers and enhances mineralization in cultures of rat calvarial cells. Moreover, osteogenesis is suppressed in calvarial cell cultures from P2rx7-/- mice compared with the wild type. P2X7 receptors couple to production of the potent lipid mediators lysophosphatidic acid (LPA) and prostaglandin E2. Either an LPA receptor antagonist or cyclooxygenase (COX) inhibitors abolish the stimulatory effects of P2X7 receptor activation on osteogenesis. We conclude that P2X7 receptors enhance osteoblast function through a cell-autonomous mechanism. Furthermore, a novel signaling axis links P2X7 receptors to production of LPA and COX metabolites, which in turn stimulate osteogenesis.

  11. Blockade of murine T cell activation by antagonists of P2Y6 and P2X7 receptors. (United States)

    Tsukimoto, Mitsutoshi; Tokunaga, Akihiro; Harada, Hitoshi; Kojima, Shuji


    Extracellular nucleotides and their metabolites activate ionotropic P2X and metabotropic P2Y receptors on the surface of various types of cells. Here, we investigated the involvement of P2X and P2Y receptor-mediated signaling in TCR-dependent T cell activation. Murine T cells were activated by stimulation of TCR, and both CD25 expression and interleukin (IL)-2 production were observed in activated T cells. Ecto-nucleotidase apyrase and P2Y6 antagonist MRS2578 significantly blocked the increases of both CD25 expression and IL-2 production, and P2X7 antagonists A438079 and oxidized ATP inhibited IL-2 production rather than CD25 expression, suggesting the involvement of P2Y6 and P2X7 receptors in different processes of T cell activation. MRS2578 also blocked TCR-dependent elevation of cytosolic Ca2+ in T cells. The P2X7 and P2Y6 receptors were expressed in murine CD4 T cells. In conclusion, our results indicate that activation of P2Y6 and P2X7 receptors contributes to T cell activation via TCR.

  12. Peripheral mechanisms underlying the essential role of P2X7 receptors in the development of inflammatory hyperalgesia. (United States)

    Teixeira, Juliana Maia; Oliveira, Maria Cláudia G; Parada, Carlos Amílcar; Tambeli, Cláudia Herrera


    Activation of P2X7 receptors by endogenous ATP contributes to the development of inflammatory hyperalgesia. Given the clinical importance of mechanical hyperalgesia in inflammatory states, we hypothesized that the activation of the P2X7 receptor by endogenous ATP contributes to carrageenan-induced mechanical hyperalgesia, and that this contribution is mediated by an indirect sensitization of the primary afferent nociceptors. Co-administration of the selective P2X7 receptor antagonist, A-438079, or the P2X7 receptor antagonist, oATP, with carrageenan blocked the mechanical hyperalgesia induced by carrageenan and significantly reduced the increased concentration of TNF-alpha, IL-6 and CINC-1, but not of IL-1beta induced by carrageenan in the subcutaneous tissue of the rat's hind paw. We concluded that the activation of P2X7 receptors by endogenous ATP is essential to the development of the mechanical hyperalgesia induced by carrageenan in the subcutaneous tissue. It is suggested that this essential role of P2X7 receptors in the development of carrageenan-induced mechanical hyperalgesia is mediated by an indirect sensitization of the primary afferent nociceptors dependent on the previous release of TNF-alpha, IL-6 and CINC-1, but not of IL-1beta.

  13. Lack of functional P2X7 receptor aggravates brain edema development after middle cerebral artery occlusion. (United States)

    Kaiser, Melanie; Penk, Anja; Franke, Heike; Krügel, Ute; Nörenberg, Wolfgang; Huster, Daniel; Schaefer, Michael


    Effective therapeutic measures against the development of brain edema, a life-threatening complication of cerebral ischemia, are necessary to improve the functional outcome for the patient. Here, we identified a beneficial role of purinergic receptor P2X7 activation in acute ischemic stroke. Involvement of P2X7 in the development of neurological deficits, infarct size, brain edema, and glial responses after ischemic cerebral infarction has been analyzed. Neurologic evaluation, magnetic resonance imaging, and immunofluorescence assays were used to characterize the receptor's effect on the disease progress during 72 h after transient middle cerebral artery occlusion (tMCAO). Sham-operated animals were included in all experiments for control purposes. We found P2X7-deficient mice to develop a more prominent brain edema with a trend towards more severe neurological deficits 24 h after tMCAO. Infarct sizes, T2 times, and apparent diffusion coefficients did not differ significantly between wild-type and P2X7(-/-) animals. Our results show a characteristic spatial distribution of reactive glia cells with strongly attenuated microglia activation in P2X7(-/-) mice 72 h after tMCAO. Our data indicate that P2X7 exerts a role in limiting the early edema formation, possibly by modulating glial responses, and supports later microglia activation.

  14. Distribution of P2Y2 receptors in the guinea pig enteric nervous system and its coexistence with P2X2 and P2X3 receptors, neuropeptide Y, nitric oxide synthase and calretinin. (United States)

    Xiang, Zhenghua; Burnstock, Geoffrey


    The distribution of P2Y2 receptor-immunoreactive (ir) neurons and fibers and coexistence of P2Y2 with P2X2 and P2X3 receptors, neuropeptide Y (NPY), calretinin (CR), calbindin (CB) and nitric oxide synthase (NOS) was investigated with immunostaining methods. The results showed that P2Y2-ir neurons and fibers were distributed widely in myenteric and submucous plexuses of the guinea pig stomach corpus, jejunum, ileum and colon. The typical morphology of P2Y2-ir neurons was a long process with strong positive staining on the same side of the cell body. The P2Y2-ir neurons could be Dogiel type 1. About 40-60% P2X3-ir neurons were immunoreactive for P2Y2 in the myenteric plexus and all the P2X3-ir neurons expressed the P2Y2 receptor in the submucosal plexus; almost all the NPY-ir neurons and the majority of CR-ir neurons were also immunoreactive for P2Y2, especially in the myenteric plexus of the small intestine; no P2Y2-ir neurons were immunoreactive for P2X2 receptors, CB and NOS. It is shown for the first time that S type/Dogiel type 1 neurons with fast P2X and slow P2Y receptor-mediated depolarizations could be those neurons expressing both P2Y2-ir and P2X3-ir and that they are widely distributed in myenteric and submucosal plexuses of guinea pig gut.

  15. Potential roles and therapeutic applications of P2 X7 receptor in inflammation and pain%P2 X7受体在炎症和疼痛中的潜在作用及治疗应用

    Institute of Scientific and Technical Information of China (English)

    秦姗姗; 樊波; 徐昌水


    P2X7受体为胞外ATP激活的非选择性阳离子通道,并能触发白介素-1β、白介素-18、肿瘤坏死因子和一氧化氮等前炎性物质的释放。临床研究表明,P2X7受体参与炎症和疼痛机制,调节P2X7受体功能的化合物,具有潜在的新抗炎药物的作用。因此,P2X7受体在炎症和疼痛中发挥重要的生理作用及潜在的临床应用,成为疼痛治疗的药物作用新靶点。%The P2X7 receptor (P2X7 R)is a nonselective cation channel activated by extracellular ATP,and it may trigger the se-cretion of several proinflammatory substances,such as IL-1β, IL-18,TNF-α,and nitric oxide.Several preclinical studies have demonstrated that this receptor participates in inflammation and pain mechanisms,and compounds that modulate the function of this receptor show potential as new anti-inflammatory medicines. Therefore,P2X7 receptors play particularly important physiologi-cal roles and have potential clinical application in inflammation and pain,which proves it a therapeutic target for pain manage-ment.

  16. Scalable devices

    KAUST Repository

    Krüger, Jens J.


    In computer science in general and in particular the field of high performance computing and supercomputing the term scalable plays an important role. It indicates that a piece of hardware, a concept, an algorithm, or an entire system scales with the size of the problem, i.e., it can not only be used in a very specific setting but it\\'s applicable for a wide range of problems. From small scenarios to possibly very large settings. In this spirit, there exist a number of fixed areas of research on scalability. There are works on scalable algorithms, scalable architectures but what are scalable devices? In the context of this chapter, we are interested in a whole range of display devices, ranging from small scale hardware such as tablet computers, pads, smart-phones etc. up to large tiled display walls. What interests us mostly is not so much the hardware setup but mostly the visualization algorithms behind these display systems that scale from your average smart phone up to the largest gigapixel display walls.

  17. The role of P2X7 receptor in ATP-mediated human leukemia cell death:calcium influx-independent

    Institute of Scientific and Technical Information of China (English)

    Xiujun Zhang; Lijun Meng; Baoling He; Jing Chen; Peng Liu; Jie Zhao; Yufen Zhang; Ming Li; Dong An


    Activation of the P2X7 receptor leads to a rapid,bidirectional flux of cations, causing broad range of hiological responses including cytotoxicity.However,the mechanism of P2X7-mediated cytotoxicity remains largely unexplored.In our previous study,the lack of P2X7-mediated calcium response under normal conditions was found in P2X7+ hematopoietic cell lines.In this study, the P2X7-mediated cytotoxicity in different type of cells(P2X7-,P2X7+ with calcium response,and P2X7+ without calcium response)was investigated.Our results showed that P2X7 agonists, adenosine 5'-triphosphate(ATP)or 2'+3'-O-(4 benzoylbenzoyl)ATP,dose-dependently reduced the cell viability in all P2X7+ cells tested,including J6-1,LCL,and Namalva cells which are negative for P2X7-mediated calcium response, although these effects were lower than those observed in KG1a cells which has normal P2X7 functions.The cytotoxic effect could be blocked by P2X7antagonists, oxidized ATP and 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine.In addition,externalization of phosphatidylserine could be detected in a time-dependent manner and apoptotic morphological changes Could be observed after the activation of P2X7 receptor in J6-1 cells.Furthermore,P2X7-mediated pore formation could be detected in KG1a and J6-1 cells under low-ionic conditions,but not under low-divalent conditions.These effects could not be observed in P2X7-Ramos cells.These results suggested that P2X7 receptor-mediated cytotoxic effects may occur independent of calcium response.

  18. Practical microwave electron devices

    CERN Document Server

    Meurant, Gerard


    Practical Microwave Electron Devices provides an understanding of microwave electron devices and their applications. All areas of microwave electron devices are covered. These include microwave solid-state devices, including popular microwave transistors and both passive and active diodes; quantum electron devices; thermionic devices (including relativistic thermionic devices); and ferrimagnetic electron devices. The design of each of these devices is discussed as well as their applications, including oscillation, amplification, switching, modulation, demodulation, and parametric interactions.


    Institute of Scientific and Technical Information of China (English)

    张海燕; 郑国光; 聂坤; 王琳; 林永敏; 种靖慧; 马媛媛; 吴克复


    P2X7受体是ATP门控的离子通道.从白血病细胞系J6-1细胞中扩增P2X7受体编码区全序列,克隆到pTARGET真核表达载体,经DNA序列分析后转染Ramos细胞,获得稳定表达细胞株;应用RT-PCR、Western blot和流式细胞术检测P2X7受体在Ramos中的表达;荧光分光光度计检测P2X7受体介导的胞内钙离子浓度变化.结果显示,J6-1细胞来源的P2X7受体在第559位有一个A→G的有义突变,导致Asn187→Asp187,可在Ramos细胞中表达,在特异性激动剂BzATP作用下可引起胞内钙离子浓度的升高,但所需激动剂浓度高于常规浓度.

  20. 突变型P2X7受体对白血病细胞生物学性质的影响%Effects of Mutant P2X7 Receptor on the Biological Characteristics of Leukemic Cells

    Institute of Scientific and Technical Information of China (English)

    马媛媛; 郑国光; 张海燕; 王琳; 种靖慧; 吴克复


    目的 研究源自白血病细胞系J6-1的突变型P2X7受体对白血病细胞Ramos的影响.方法 用RT-PCR、共聚焦显微镜检测P2X7受体的表达、定位及BzATP刺激下受体的聚集;MTT法测定细胞增殖;流式细胞术检测细胞周期.结果 突变型P2X7受体稳定表达于Ramos细胞细胞膜及细胞质;细胞增殖明显增强;300μmol/L BzATP增加细胞死亡率;100μmol/L BzATP诱导P2X7受体聚集.结论 该突变体促进Ramos细胞增殖;激动剂诱发P2X7受体聚集,过量激动剂导致细胞死亡.

  1. The significance of odontoblast P2X7 receptor expression in pulpitis%牙髓炎成牙本质细胞P2X7受体表达意义

    Institute of Scientific and Technical Information of China (English)

    姜威; 李恩东; 李月玲; 俞明; 陈劼


    Objective To investigate the significance expression of P2X7 receptor(P2X7R)from odontoblast cells in the pathogenesis and progression of pulpitis. Methods Sixty cases with mild pulpitis,severe pulpitis and healthy third molars(20 cases in each group) was enrolled in this study,and P2X7R mRNA expression of which was detected by real time PCR,and P2X7R protein expression of which was detected by Western blotting,and IL-1β,IL-6 and TNF-a level in the serum samples of the third molar donor were detected by ELISA method. Results According to the healthy group,mild pulpitis group and severe pulpitis group order,P2X7R mRNA and protein expression in odontoblast cells of the third molars increased significantly,and IL-1βand IL-6 levels in serum sample increased significantly,and TNF-α of mild pulpitis patients were significantly higher than healthy people(P<0. 05). However,TNF-α of severe pulpitis patients significantly decreased(P<0. 05)than mild pulpitis patients. In mild pulpitis patients,P2X7R mRNA expression was positively correlated with IL-1β levels(P<0. 05),and P2X7R protein expression was positively correlated with IL-1β,IL-6 and TNF-α(P<0.05).In severe pulpitis,P2X7R mRNA expression was positively correlated with IL-1β(P <0.05)and IL-6(P <0.05), P2X7R protein expression was positively correlated with IL-1β(P<0. 05),IL-6(P<0. 05). Conclusion P2X7R expression level in odontoblast cells increased in pulpitis onset and progression,following with inflammatory cytokines IL-1β,IL-6 and TNF-a expression increasing.%目的:探讨成牙本质细胞中P2X7受体(P2X7R)表达在牙髓炎发病及病情进展中的意义。方法取轻度牙髓炎、重度牙髓炎患者和健康者第三磨牙各20例,采用Real-time PCR法检测P2X7R mRNA表达水平,采用Western blotting法检测P2X7R蛋白表达水平;另采用 ELISA 法检测上述第三磨牙供者的血清样本中 IL-1β、IL-6和 TNF-α等炎症因子水平。结果按健康组、轻度牙髓炎组、

  2. Understanding the role of P2X7 in affective disorders – are glial cells the major players?

    Directory of Open Access Journals (Sweden)

    Leanne eStokes


    Full Text Available The pathophysiology of several psychiatric disorders has been linked to biomarkers of inflammation generating a theory of major depressive disorder as an inflammatory disease and infection and autoimmunity as major risk factors for schizophrenia. The idea of pro-inflammatory cytokines altering behavior is now well accepted however many questions remain. Microglia can produce a plethora of inflammatory cytokines and these cells appear to be critical in the link between inflammatory changes and depressive disorders. Microglia play a known role in sickness behavior which has many components of depressive-like behavior such as social withdrawal, sleep alterations, and anorexia. Numerous candidate genes have been identified for psychiatric disorders in the last decade. Single nucleotide polymorphisms in the human P2X7 gene have been linked to bipolar disorder, depression, and to the severity of depressive symptoms. P2X7 is a ligand-gated cation channel expressed on microglia with lower levels found on astrocytes and on some neuronal populations. In microglia P2X7 is a major regulator of pro-inflammatory cytokines of the interleukin-1 family. Genetic deletion of P2X7 in mice is protective for depressive behavior in addition to inflammatory responses. P2X7-/- mice have been shown to demonstrate anti-depressive-like behavior in forced swim and tail suspension behavioral tests and stressor-induced behavioral responses were blunted. Both neurochemical (norepinephrine, serotonin, dopamine and inflammatory changes have been observed in the brains of P2X7-/- mice. This review will discuss the recent evidence for involvement of P2X7 in the pathophysiology of depressive disorders and propose mechanisms by which altered signaling through this ion channel may affect the inflammatory state of the brain.

  3. Targeting P(2)X(7) receptor for the treatment of central post-stroke pain in a rodent model. (United States)

    Kuan, Yung-Hui; Shih, Hsi-Chien; Tang, Sung-Chun; Jeng, Jiann-Shing; Shyu, Bai-Chuang


    Stroke is a leading cause of death and disability in industrialized countries. Approximately 8-14% of stroke survivors suffer from central post-stroke pain (CPSP) when hemorrhagic stroke occurs in lateral thalamic regions, which severely affects their quality of life. Because the mechanisms of CPSP are not well understood, effective treatments have not been developed. In the present study, we tested the hypothesis that persistent CPSP is caused by P(2)X(7)receptor activation after brain tissue damage and subsequent elevations in inflammatory cytokines. A thalamic hemorrhagic rat model was used, characterized by thermal and mechanical allodynia that develops in the subacute to chronic phases upon CPSP onset. We found a significant increase in P(2)X(7) expression in reactive microglia/macrophages in thalamic peri-lesion tissues at 5 weeks post-hemorrhage. Thalamic P(2)X(7) receptors were directly involved in pain transmission and hypersensitivity. The systemic targeting of P(2)X(7) receptors during the acute stage of hemorrhage rescued abnormal pain behaviors and neuronal activity in the thalamocingulate pathway by reducing reactive microglia/macrophage aggregation and associated inflammatory cytokines. After CPSP onset, the targeting of interleukin-1β reversed abnormal pain sensitivity. The aberrant spontaneous thalamocortical oscillations in rats with CPSP were modulated by blocking P(2)X(7) receptors. Taken together, our results suggest that targeting P(2)X(7) may be bi-effective in the treatment of CPSP, as both a pain blocker and immunosuppressant that inhibits inflammatory damage to brain tissue. P(2)X(7)receptors may serve as a potential target to prevent the occurrence of CPSP and may be beneficial for the recovery of patients from stroke.

  4. P2X7 receptor and caspase 1 activation are central to airway inflammation observed after exposure to tobacco smoke.

    Directory of Open Access Journals (Sweden)

    Suffwan Eltom

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is a cigarette smoke (CS-driven inflammatory airway disease with an increasing global prevalence. Currently there is no effective medication to stop the relentless progression of this disease. It has recently been shown that an activator of the P2X7/inflammasome pathway, ATP, and the resultant products (IL-1β/IL-18 are increased in COPD patients. The aim of this study was to determine whether activation of the P2X7/caspase 1 pathway has a functional role in CS-induced airway inflammation. Mice were exposed to CS twice a day to induce COPD-like inflammation and the role of the P2X7 receptor was investigated. We have demonstrated that CS-induced neutrophilia in a pre-clinical model is temporally associated with markers of inflammasome activation, (increased caspase 1 activity and release of IL-1β/IL-18 in the lungs. A selective P2X7 receptor antagonist and mice genetically modified so that the P2X7 receptors were non-functional attenuated caspase 1 activation, IL-1β release and airway neutrophilia. Furthermore, we demonstrated that the role of this pathway was not restricted to early stages of disease development by showing increased caspase 1 activation in lungs from a more chronic exposure to CS and from patients with COPD. This translational data suggests the P2X7/Inflammasome pathway plays an ongoing role in disease pathogenesis. These results advocate the critical role of the P2X7/caspase 1 axis in CS-induced inflammation, highlighting this as a possible therapeutic target in combating COPD.

  5. Shockwaves induce osteogenic differentiation of human mesenchymal stem cells through ATP release and activation of P2X7 receptors. (United States)

    Sun, Dahui; Junger, Wolfgang G; Yuan, Changji; Zhang, Wenyan; Bao, Yi; Qin, Daming; Wang, Chengxue; Tan, Lei; Qi, Baochang; Zhu, Dong; Zhang, Xizheng; Yu, Tiecheng


    Shockwave treatment promotes bone healing of nonunion fractures. In this study, we investigated whether this effect could be due to adenosine 5'-triphosphate (ATP) release-induced differentiation of human mesenchymal stem cells (hMSCs) into osteoprogenitor cells. Cultured bone marrow-derived hMSCs were subjected to shockwave treatment and ATP release was assessed. Osteogenic differentiation and mineralization of hMSCs were evaluated by examining alkaline phosphatase activity, osteocalcin production, and calcium nodule formation. Expression of P2X7 receptors and c-fos and c-jun mRNA was determined with real-time reverse transcription polymerase chain reaction and Western blotting. P2X7-siRNA, apyrase, P2 receptor antagonists, and p38 MAPK inhibitors were used to evaluate the roles of ATP release, P2X7 receptors, and p38 MAPK signaling in shockwave-induced osteogenic hMSCs differentiation. Shockwave treatment released significant amounts (≈ 7 μM) of ATP from hMSCs. Shockwaves and exogenous ATP induced c-fos and c-jun mRNA transcription, p38 MAPK activation, and hMSC differentiation. Removal of ATP with apyrase, targeting of P2X7 receptors with P2X7-siRNA or selective antagonists, or blockade of p38 MAPK with SB203580 prevented osteogenic differentiation of hMSCs. Our findings indicate that shockwaves release cellular ATP that activates P2X7 receptors and downstream signaling events that caused osteogenic differentiation of hMSCs. We conclude that shockwave therapy promotes bone healing through P2X7 receptor signaling, which contributes to hMSC differentiation.

  6. Electrophoresis device (United States)

    Rhodes, P. H.; Snyder, R. S. (Inventor)


    A device for separating cellular particles of a sample substance into fractionated streams of different cellular species includes a casing having a distribution chamber, a separation chamber, and a collection chamber. The electrode chambers are separated from the separation chamber interior by means of passages such that flow variations and membrane variations around the slotted portion of the electrode chamber do not enduce flow perturbations into the laminar buffer curtain flowing in the separation chamber. The cellular particles of the sample are separated under the influence of the electrical field and the separation chamber into streams of different cellular species. The streams of separated cells enter a partition array in the collection chamber where they are fractionated and collected.

  7. Stratification devices

    DEFF Research Database (Denmark)

    Andersen, Elsa; Furbo, Simon


    heating system. High temperatures in the top of the storage tank established by the energy from the solar collector reduce the use of auxiliary energy. Low temperatures in the bottom of the storage tank improve the operation conditions for the solar collector. Using thermal stratified heat storages...... results in longer operation periods and improved utilization of the solar collector. Thermal stratification can be achieved, for example by using inlet stratification devices at all inlets to the storage tank. This paper presents how thermal stratification is established and utilized by means of inlet......Thermal stratification in the storage tank is extremely important in order to achieve high thermal performance of a solar heating system. High temperatures in the top of the storage tank and low temperatures in the bottom of the storage tank lead to the best operation conditions for any solar...

  8. P2X7 Receptor Antagonism Attenuates the Intermittent Hypoxia-induced Spatial Deficits in a Murine Model of Sleep Apnea Via Inhibiting Neuroinflammation and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Yan Deng


    Conclusions: The P2X7R antagonism attenuates the CIH-induced neuroinflammation, oxidative stress, and spatial deficits, demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.

  9. Integrated System Health Management (ISHM) for Test Stand and J-2X Engine: Core Implementation (United States)

    Figueroa, Jorge F.; Schmalzel, John L.; Aguilar, Robert; Shwabacher, Mark; Morris, Jon


    ISHM capability enables a system to detect anomalies, determine causes and effects, predict future anomalies, and provides an integrated awareness of the health of the system to users (operators, customers, management, etc.). NASA Stennis Space Center, NASA Ames Research Center, and Pratt & Whitney Rocketdyne have implemented a core ISHM capability that encompasses the A1 Test Stand and the J-2X Engine. The implementation incorporates all aspects of ISHM; from anomaly detection (e.g. leaks) to root-cause-analysis based on failure mode and effects analysis (FMEA), to a user interface for an integrated visualization of the health of the system (Test Stand and Engine). The implementation provides a low functional capability level (FCL) in that it is populated with few algorithms and approaches for anomaly detection, and root-cause trees from a limited FMEA effort. However, it is a demonstration of a credible ISHM capability, and it is inherently designed for continuous and systematic augmentation of the capability. The ISHM capability is grounded on an integrating software environment used to create an ISHM model of the system. The ISHM model follows an object-oriented approach: includes all elements of the system (from schematics) and provides for compartmentalized storage of information associated with each element. For instance, a sensor object contains a transducer electronic data sheet (TEDS) with information that might be used by algorithms and approaches for anomaly detection, diagnostics, etc. Similarly, a component, such as a tank, contains a Component Electronic Data Sheet (CEDS). Each element also includes a Health Electronic Data Sheet (HEDS) that contains health-related information such as anomalies and health state. Some practical aspects of the implementation include: (1) near real-time data flow from the test stand data acquisition system through the ISHM model, for near real-time detection of anomalies and diagnostics, (2) insertion of the J-2X

  10. Tanshinone II A sulfonate, but not tanshinone II A, acts as potent negative allosteric modulator of the human purinergic receptor P2X7. (United States)

    Kaiser, M; Sobottka, H; Fischer, W; Schaefer, M; Nörenberg, W


    Tanshinone II A sulfonate (TIIAS) was identified as a potent, selective blocker of purinergic receptor P2X7 in a compound library screen. In this study, a detailed characterization of the pharmacologic effects of TIIAS on P2X7 is provided. Because TIIAS is a derivative of tanshinone II A (TIIA) and both compounds have been used interchangeably, TIIA was included in some assays. Fluorometric and electrophysiologic assays were used to characterize effects of TIIAS and TIIA on recombinantly expressed human, rat, and mouse P2X7. Results were confirmed in human monocyte-derived macrophages expressing native P2X7. In all experiments, involvement of P2X7 was verified using established P2X7 antagonists. TIIAS, but not TIIA, reduces Ca(2+) influx via human P2X7 (hP2X7) with an IC50 of 4.3 µM. TIIAS was less potent at mouse P2X7 and poorly inhibited rat P2X7. Monitoring of YO-PRO-1 uptake confirmed these findings, indicating that formation of the hP2X7 pore is also suppressed by TIIAS. Electrophysiologic experiments revealed a noncompetitive mode of action. TIIAS time-dependently inhibits hP2X7 gating, possibly by binding to the intracellular domain of the receptor. Inhibition of native P2X7 in macrophages by TIIAS was confirmed by monitoring Ca(2+) influx, YO-PRO-1 uptake, and release of the proinflammatory cytokine interleukin-1β. Fluorometric experiments involving recombinantly expressed rat P2X2 and human P2X4 were conducted and verified the compound's selectivity. Our data suggest that hP2X7 is a molecular target of TIIAS, but not of TIIA, a compound with different pharmacologic properties.

  11. Tailoring Vacancies Far Beyond Intrinsic Levels Changes the Carrier Type and Optical Response in Monolayer MoSe2-x Crystals. (United States)

    Mahjouri-Samani, Masoud; Liang, Liangbo; Oyedele, Akinola; Kim, Yong-Sung; Tian, Mengkun; Cross, Nicholas; Wang, Kai; Lin, Ming-Wei; Boulesbaa, Abdelaziz; Rouleau, Christopher M; Puretzky, Alexander A; Xiao, Kai; Yoon, Mina; Eres, Gyula; Duscher, Gerd; Sumpter, Bobby G; Geohegan, David B


    Defect engineering has been a critical step in controlling the transport characteristics of electronic devices, and the ability to create, tune, and annihilate defects is essential to enable the range of next-generation devices. Whereas defect formation has been well-demonstrated in three-dimensional semiconductors, similar exploration of the heterogeneity in atomically thin two-dimensional semiconductors and the link between their atomic structures, defects, and properties has not yet been extensively studied. Here, we demonstrate the growth of MoSe2-x single crystals with selenium (Se) vacancies far beyond intrinsic levels, up to ∼20%, that exhibit a remarkable transition in electrical transport properties from n- to p-type character with increasing Se vacancy concentration. A new defect-activated phonon band at ∼250 cm(-1) appears, and the A1g Raman characteristic mode at 240 cm(-1) softens toward ∼230 cm(-1) which serves as a fingerprint of vacancy concentration in the crystals. We show that post-selenization using pulsed laser evaporated Se atoms can repair Se-vacant sites to nearly recover the properties of the pristine crystals. First-principles calculations reveal the underlying mechanisms for the corresponding vacancy-induced electrical and optical transitions.

  12. Engineering amorphous-crystalline interfaces in TiO2-x/TiO2-y-based bilayer structures for enhanced resistive switching and synaptic properties (United States)

    Bousoulas, P.; Asenov, P.; Karageorgiou, I.; Sakellaropoulos, D.; Stathopoulos, S.; Tsoukalas, D.


    The operating principle of resistive random access memories (RRAMs) relies on the distribution of ionic species and their influence on the electron transport. Taking into account that formation and annihilation of conducting filaments (CFs) is the driving mechanism for the switching effect, it is very important to control the regions where these filaments will evolve. Thus, homolayers of titanium oxide with different oxygen contents were fabricated in order to tune the local electrical and thermal properties of the CFs and narrow down the potential percolation paths. We show that the oxygen content in the top layer of the TiO2-x/TiO2-y bilayer memristors can directly influence the morphology of the layers which affect the diffusion barrier and consequently the diffusivity and drift velocity of oxygen vacancies, yielding in important enhancement of switching characteristics, in terms of spatial uniformity (σ/μ < 0.2), enlarged switching ratio (˜104), and synaptic learning. In order to address the experimental data, a physical model was applied, divulging the crucial role of temperature, electric potential and oxygen vacancy density on the switching effect and offering physical insights to the SET/RESET transitions and the analog switching. The forming free nature of all the devices in conjunction with the self-rectifying behavior, should also be regarded as important assets towards RRAM device optimization.

  13. Properties of native P2X receptors in large multipolar neurons dissociated from rat hypothalamic arcuate nucleus. (United States)

    Wakamori, Minoru; Sorimachi, Masaru


    ATP, the ligand of P2X receptors, is a candidate of neurotransmitter or co-transmitter in the peripheral and the central nervous systems. Anatomical studies have revealed the wide distribution of P2X receptors in the brain. So far, P2X-mediated small synaptic responses have been recorded in some brain regions. To determine the physiological significance of postsynaptic ATP receptors in the brain, we have investigated the P2X responses in rat dissociated hypothalamic arcuate neurons by using the patch-clamp technique. ATP evoked inward currents in a concentration-dependent manner (EC(50)=42 microM) at a holding potential of -70 mV. The current-voltage relationship showed a marked inward rectification starting around -10 mV. Although neither 300 microM alphabeta-methylene-ATP nor 300 microM betagamma-methylene-ATP induced any currents, 100 microM ATPgammaS and 100 microM 2-methylthio-ATP evoked inward currents of which amplitude was about 60% of the control currents evoked by 100 microM ATP. PPADS, one of P2 receptor antagonists, inhibited the ATP-evoked currents in a time- and a concentration-dependent manners (IC(50)=19 microM at 2 min). Permeant Ca(2+) inhibited the ATP-evoked currents in the range of millimolars (IC(50)=7 mM); however, Cd(2+) (1-300 microM), a broad cation channel blocker, facilitated the currents with slow off-response. Zn(2+) in the range of 1-100 microM facilitated the currents whereas Zn(2+) at the concentrations over 100 microM inhibited the currents. These observations suggest that functional P2X receptors are expressed in the hypothalamic arcuate nucleus. The most likely subunit combinations of the P2X receptors are P2X(2)-homomultimer and P2X(2)/P2X(6)-heteromultimer.

  14. Neuronal Release of Cytokine IL-3 Triggered by Mechanosensitive Autostimulation of the P2X7 Receptor Is Neuroprotective (United States)

    Lim, Jason C.; Lu, Wennan; Beckel, Jonathan M.; Mitchell, Claire H.


    Mechanical strain due to increased pressure or swelling activates inflammatory responses in many neural systems. As cytokines and chemokine messengers lead to both pro-inflammatory and neuroprotective actions, understanding the signaling patterns triggered by mechanical stress may help improve overall outcomes. While cytokine signaling in neural systems is often associated with glial cells like astrocytes and microglia, the contribution of neurons themselves to the cytokine response is underappreciated and has bearing on any balanced response. Mechanical stretch of isolated neurons was previously shown to trigger ATP release through pannexin hemichannels and autostimulation of P2X7 receptors (P2X7Rs) on the neural membrane. Given that P2X7Rs are linked to cytokine activation in other cells, this study investigates the link between neuronal stretch and cytokine release through a P2X7-dependent pathway. Cytokine assays showed application of a 4% strain to isolated rat retinal ganglion cells (RGCs) released multiple cytokines. The P2X7R agonist BzATP also released multiple cytokines; Interleukin 3 (IL-3), TNF-α, CXCL9, VEGF, L-selectin, IL-4, GM-CSF, IL-10, IL-1Rα, MIP and CCL20 were released by both stimuli, with the release of IL-3 greatest with either stimuli. Stretch-dependent IL-3 release was confirmed with ELISA and blocked by P2X7R antagonists A438079 and Brilliant Blue G (BBG), implicating autostimulation of the P2X7R in stretch-dependent IL-3 release. Neuronal IL-3 release triggered by BzATP required extracellular calcium. The IL-3Rα receptor was expressed on RGCs but not astrocytes, and both IL-3Rα and IL-3 itself were predominantly expressed in the retinal ganglion cell layer of adult retinal sections, implying autostimulation of receptors by released IL-3. While the number of surviving ganglion cells decreased with time in culture, the addition of IL-3 protected against this loss of neurons. Expression of mRNA for IL-3 and IL-3Rα increased in rat

  15. Neuronal release of cytokine IL-3 triggered by mechanosensitive autostimulation of the P2X7 receptor is neuroprotective

    Directory of Open Access Journals (Sweden)

    Jason C Lim


    Full Text Available Mechanical strain due to increased pressure or swelling activates inflammatory responses in many neural systems. As cytokines and chemokine messengers lead to both pro-inflammatory and neuroprotective actions, understanding the signaling patterns triggered by mechanical stress may help improve overall outcomes. While cytokine signaling in neural systems is often associated with glial cells like astrocytes and microglia, the contribution of neurons themselves to the cytokine response is underappreciated and has bearing on any balanced response. Mechanical stretch of isolated neurons was previously shown to trigger ATP release through pannexin hemichannels and autostimulation of P2X7 receptors (P2X7Rs on the neural membrane. Given that P2X7Rs are linked to cytokine activation in other cells, this study investigates the link between neuronal stretch and cytokine release through a P2X7-dependent pathway. Cytokine assays showed application of a 4% strain to isolated rat retinal ganglion cells (RGCs released multiple cytokines. The P2X7R agonist BzATP also released multiple cytokines; IL-3, TNF-α, CXCL9, VEGF, L-selectin, IL-4, GM-CSF, IL-10, IL-1Rα, MIP and CCL20 were released by both stimuli, with the release of IL-3 greatest with either stimulus. Stretch-dependent IL-3 release was confirmed with ELISA and blocked by P2X7R antagonists A438079 and Brilliant Blue G (BBG, implicating autostimulation of the P2X7R in stretch-dependent IL-3 release. Neuronal IL-3 release triggered by BzATP required extracellular calcium. The IL-3Rα receptor was expressed on retinal ganglion cells but not astrocytes, and both IL-3Rα and IL-3 itself were predominantly expressed in the retinal ganglion cell layer of adult retinal sections, implying autostimulation of receptors by released IL-3. While the number of surviving ganglion cells decreased with time in culture, addition of IL-3 protected against this loss of neurons. Expression of mRNA for IL-3 and IL-3R

  16. Testing the role of P2X7 receptors in the development of type 1 diabetes in nonobese diabetic mice. (United States)

    Chen, Yi-Guang; Scheuplein, Felix; Driver, John P; Hewes, Amanda A; Reifsnyder, Peter C; Leiter, Edward H; Serreze, David V


    Although P2rx7 has been proposed as a type 1 diabetes (T1D) susceptibility gene in NOD mice, its potential pathogenic role has not been directly determined. To test this possibility, we generated a new NOD stock deficient in P2X(7) receptors. T1D development was not altered by P2X(7) ablation. Previous studies found CD38 knockout (KO) NOD mice developed accelerated T1D partly because of a loss of CD4(+) invariant NKT (iNKT) cells and Foxp3(+) regulatory T cells (Tregs). These immunoregulatory T cell populations are highly sensitive to NAD-induced cell death activated by ADP ribosyltransferase-2 (ART2)-mediated ADP ribosylation of P2X(7) receptors. Therefore, we asked whether T1D acceleration was suppressed in a double-KO NOD stock lacking both P2X(7) and CD38 by rescuing CD4(+) iNKT cells and Tregs from NAD-induced cell death. We demonstrated that P2X(7) was required for T1D acceleration induced by CD38 deficiency. The CD38 KO-induced defects in homeostasis of CD4(+) iNKT cells and Tregs were corrected by coablation of P2X(7). T1D acceleration in CD38-deficient NOD mice also requires ART2 expression. If increased ADP ribosylation of P2X(7) in CD38-deficient NOD mice underlies disease acceleration, then a comparable T1D incidence should be induced by coablation of both CD38 and ART2, or CD38 and P2X(7). However, a previously established NOD stock deficient in both CD38 and ART2 expression is T1D resistant. This study demonstrated the presence of a T1D resistance gene closely linked to the ablated Cd38 allele in the previously reported NOD stock also lacking ART2, but not in the newly generated CD38/P2X(7) double-KO line.

  17. Activation of P2X7 receptors in the midbrain periaqueductal gray of rats facilitates morphine tolerance. (United States)

    Xiao, Zhi; Li, You-Yan; Sun, Meng-Jie


    Opiates such as morphine exhibit analgesic effect in various pain models, but repeated and chronic morphine administration may develop resistance to antinociception. The purinergic signaling system is involved in the mechanisms of pain modulation and morphine tolerance. This study aimed to determine whether the P2X7 receptor in the ventrolateral midbrain periaqueductal gray (vlPAG) is involved in morphine tolerance. Development of tolerance to the antinociceptive effect of morphine was induced in normal adult male Sprague-Dawley (SD) rats through subcutaneous injection of morphine (10mg/kg). The analgesic effect of morphine (5mg/kg, i.p.) was assessed by measuring mechanical withdrawal thresholds (MWTs) in rats with an electronic von Frey anesthesiometer. The expression levels and distribution of the P2X7 receptor in the vlPAG was evaluated through Western blot analysis and immunohistochemistry. The acute effects of intra-vlPAG injection of the selective P2X7 receptor agonist Bz-ATP, the selective P2X7 receptor antagonist A-740003, or antisense oligodeoxynucleotide (AS ODN) targeting the P2X7 receptor on morphine-treated rats were also observed. Results demonstrated that repeated morphine administration decreased the mechanical pain thresholds. By contrast, the expression of the P2X7 receptor protein was up-regulated in the vlPAG in morphine tolerant rats. The percent changes in MWT were markedly but only transiently attenuated by intra-vlPAG injection of Bz-ATP (9nmol/0.3μL) but elevated by A-740003 at doses of 10 and 100nmol/0.3μL. AS ODN (15nmol/0.3μL) against the P2X7 receptor reduced the development of chronic morphine tolerance in rats. These results suggest that the development of antinociceptive tolerance to morphine is partially mediated by activating the vlPAG P2X7 receptors. The present data also suggest that the P2X7 receptors may be a therapeutic target for improving the analgesic effect of morphine in treatments of pain when morphine tolerance

  18. Effects of visualizing statistical information – An empirical study on tree diagrams and 2 x 2 tables

    Directory of Open Access Journals (Sweden)

    Karin eBinder


    Full Text Available In their research articles, scholars often use 2 x 2 tables or tree diagrams including natural frequencies in order to illustrate Bayesian reasoning situations to their peers. Interestingly, the effect of these visualizations on participants’ performance has not been tested empirically so far (apart from explicit training studies. In the present article, we report on an empirical study (3 x 2 x 2 design in which we systematically vary visualization (no visualization vs. 2 x 2 table vs. tree diagram and information format (probabilities vs. natural frequencies for two contexts (medical vs. economical context; not a factor of interest. Each of N = 259 participants (students of age 16-18 had to solve two typical Bayesian reasoning tasks (mammography problem and economics problem. The hypothesis is that 2 x 2 tables and tree diagrams – especially when natural frequencies are included – can foster insight into the notoriously difficult structure of Bayesian reasoning situations. In contrast to many other visualizations (e. g., icon arrays, Euler diagrams, 2 x 2 tables and tree diagrams have the advantage that they can be constructed easily. The implications of our findings for teaching Bayesian reasoning will be discussed.

  19. The P2X7 receptor regulates cell survival, migration and invasion of pancreatic ductal adenocarcinoma cells

    DEFF Research Database (Denmark)

    Giannuzzo, Andrea; Pedersen, Stine Helene Falsig; Novak, Ivana


    BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is presently one of the cancers with the worst survival rates and least effective treatments. Moreover, total deaths due to PDAC are predicted to increase in the next 15 years. Therefore, novel insights into basic mechanism of PDAC development...... of the ATP receptors, the P2X7 receptor (P2X7R) could be an important player in PDAC behaviour. METHODS: We determined the expression (real time PCR and Western blot) and localization (immunofluorescence) of P2X7R in human PDAC cell lines (AsPC-1, BxPC-3, Capan-1, MiaPaCa-2, Panc-1) and a "normal" human...... pancreatic duct epithelial cell line (HPDE). The function of P2X7R in proliferation (BrdU assay), migration (wound assay) and invasion (Boyden chamber with matrigel) was characterized. Furthermore, we studied P2X7R-dependent pore formation (YoPro-1 assay) and cell death (caspase and annexin V / propidium...

  20. Anoctamin 6 mediates effects essential for innate immunity downstream of P2X7 receptors in macrophages (United States)

    Ousingsawat, Jiraporn; Wanitchakool, Podchanart; Kmit, Arthur; Romao, Ana M.; Jantarajit, Walailak; Schreiber, Rainer; Kunzelmann, Karl


    Purinergic P2X7 receptors (P2X7R) are fundamental to innate immune response. In macrophages, transient stimulation of P2X7R activates several transport mechanisms and induces the scrambling of phospholipids with subsequent membrane blebbing and apoptosis. These processes support phagocytosis and subsequent killing of phagocytosed bacteria. Here we demonstrate that the stimulation of P2X7 receptors activates anoctamin 6 (ANO6, TMEM16F), a protein that functions as Ca2+ dependent phospholipid scramblase and Ca2+-activated Cl- channel. Inhibition or knockdown of ANO6 attenuates ATP-induced cell shrinkage, cell migration and phospholipid scrambling. In mouse macrophages, Ano6 produces large ion currents by stimulation of P2X7 receptors and contributes to ATP-induced membrane blebbing and apoptosis, which is largely reduced in macrophages from Ano6-/- mice. ANO6 supports bacterial phagocytosis and killing by mouse and human THP-1 macrophages. Our data demonstrate that anoctamin 6 is an essential component of the immune defense by macrophages.

  1. Preparation and characterization of LiAlxMn2-xO4 for a supercapacitor in aqueous electrolyte

    Institute of Scientific and Technical Information of China (English)

    Yun Xue; Ye Chen; Mi-lin Zhang; Yong-de Yan


    LiAlxMn2-xO4 (0≤x≤0.5) was synthesized by high temperature solid-state reaction.The structure and morphology of LiAl/Mn2-xO4 were investigated by X-ray diffraction and scanning electron microscopy (SEM).The results indicate that all samples show spinel phase.The polyhedral particles turn to club-shaped,then change to small spherical,and finally become agglomerates with increasing Al content.The supercapacitive performances of LiAlxMn2-xO4 were studied by means of galvanostatic charge-discharge,cyclic voltammetry,and alternating current (AC) impedance in 2 mol.L-l (NH4)2SO4 aqueous solution.The results show that LiAlxMn2-xO4 represents rectangular shape performance in the potential range of 0-1 V.The capacity and cycle perform-ance can be improved by doping Al.The composition of x=0.1 has the maximum special capacitance of 160 F.g-1,which is 1.37 times that of LiMn2O4 electrode.The capacitance loss of LiAlxMn2-xO4 with x=0.1 is only about 14% after 100 cycles.

  2. Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice. (United States)

    Kimbler, Donald E; Shields, Jessica; Yanasak, Nathan; Vender, John R; Dhandapani, Krishnan M


    Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP) and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part to the absence of viable drug targets. In the present study, genetic inhibition (P2X7-/- mice) of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-1β (IL-1β) and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG), a clinically non-toxic P2X7 inhibitor, inhibited IL-1β expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP), a reactive astrocyte marker, and attenuated the expression of aquaporin-4 (AQP4), an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation.

  3. Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.

    Directory of Open Access Journals (Sweden)

    Donald E Kimbler

    Full Text Available Traumatic brain injury (TBI is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part to the absence of viable drug targets. In the present study, genetic inhibition (P2X7-/- mice of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-1β (IL-1β and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG, a clinically non-toxic P2X7 inhibitor, inhibited IL-1β expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP, a reactive astrocyte marker, and attenuated the expression of aquaporin-4 (AQP4, an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation.

  4. Extracellular ATP mediates necrotic cell swelling in SN4741 dopaminergic neurons through P2X7 receptors. (United States)

    Jun, Dong-Jae; Kim, Jaeyoon; Jung, Sang-Yong; Song, Ran; Noh, Ji-Hyun; Park, Yong-Soo; Ryu, Sung-Ho; Kim, Joung-Hun; Kong, Young-Yun; Chung, Jun-Mo; Kim, Kyong-Tai


    Extracellular ATP has recently been identified as an important regulator of cell death in response to pathological insults. When SN4741 cells, which are dopaminergic neurons derived from the substantia nigra of transgenic mouse embryos, are exposed to ATP, cell death occurs. This cell death is associated with prominent cell swelling, loss of ER integrity, the formation of many large cytoplasmic vacuoles, and subsequent cytolysis and DNA release. In addition, the cleavage of caspase-3, a hallmark of apoptosis, is induced by ATP treatment. However, caspase inhibitors do not overcome ATP-induced cell death, indicating that both necrosis and apoptosis are associated with ATP-induced cell death and suggesting that a necrotic event might override the apoptotic process. In this study we also found that P2X(7) receptors (P2X(7)Rs) are abundantly expressed in SN4741 cells, and both ATP-induced swelling and cell death are reversed by pretreatment with the P2X(7)Rs antagonist, KN62, or by knock-down of P2X(7)Rs with small interfering RNAs. Therefore, extracellular ATP release from injured tissues may act as an accelerating factor in necrotic SN4741 dopaminergic cell death via P2X(7)Rs.

  5. Inflammasome activation in bovine monocytes by extracellular ATP does not require the purinergic receptor P2X7. (United States)

    Hussen, Jamal; Düvel, Anna; Koy, Mirja; Schuberth, Hans-Joachim


    Extracellular adenosine triphosphate (ATP) is a second signal for the assembly of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome, which form a framework to activate caspase 1, leading to the processing and secretion of the pro-inflammatory cytokine interleukin-1β (IL-1β). The aim of the present study was to investigate the role of the ATP-gated ion channel subtype P2X7 receptor in the inflammasome activation of bovine monocytes. ATP-induced inflammasome assembly in bovine monocytes was shown by caspase-1 activation and the release of IL-1β by LPS/ATP-stimulated bovine cells. The IL-1β release depended on potassium efflux but was independent of reactive oxygen generation of bovine monocytes. Unlike in the human system, a P2X7 receptor antagonist did not block the ATP-induced release of IL-1β of LPS-primed bovine cells. P2X7 mediated pore formation was observed in subsets of bovine T lymphocytes (CD4+>CD8+) but not in monocytes. In addition, ATP and 2-MeSATP but not the high affinity P2X7 agonist BzATP induced calcium influx in bovine monocytes. The data indicate that ROS generation plays no role in the ATP-induced activation of inflammasome in bovine monocytes and that P2X7-mediated pore formation is not necessary for the release of Interleukin-1β.

  6. ATP inhibits the generation and function of regulatory T cells through the activation of purinergic P2X receptors. (United States)

    Schenk, Ursula; Frascoli, Michela; Proietti, Michele; Geffers, Robert; Traggiai, Elisabetta; Buer, Jan; Ricordi, Camillo; Westendorf, Astrid M; Grassi, Fabio


    Extracellular nucleotides are pleiotropic regulators of mammalian cell function. Adenosine triphosphate (ATP) released from CD4(+) helper T cells upon stimulation of the T cell receptor (TCR) contributes in an autocrine manner to the activation of mitogen-activated protein kinase (MAPK) signaling through purinergic P2X receptors. Increased expression of p2rx7, which encodes the purinergic receptor P2X7, is part of the transcriptional signature of immunosuppressive CD4(+)CD25(+) regulatory T cells (T(regs)). Here, we show that the activation of P2X7 by ATP inhibits the suppressive potential and stability of T(regs). The inflammatory cytokine interleukin-6 (IL-6) increased ATP synthesis and P2X7-mediated signaling in T(regs), which induced their conversion to IL-17-secreting T helper 17 (T(H)17) effector cells in vivo. Moreover, pharmacological antagonism of P2X receptors promoted the cell-autonomous conversion of naïve CD4(+) T cells into T(regs) after TCR stimulation. Thus, ATP acts as an autocrine factor that integrates stimuli from the microenvironment and cellular energetics to tune the developmental and immunosuppressive program of the T cell in adaptive immune responses.

  7. Mellin moments of heavy flavor contributions to F_2(x,Q^2) at NNLO

    CERN Document Server

    Klein, Sebastian


    This thesis is concerned with the calculation of fixed moments of the O(a_s^3) heavy flavor contributions to the Wilson coefficients of the structure function F_2(x,Q^2) in the limit Q^2 >> m^2, neglecting power corrections. The massive Wilson coefficients in the asymptotic region are given as convolutions of massive operator matrix elements (OMEs) and the known light flavor Wilson coefficients. The former derive from the twist--2 operators emerging in the light--cone--expansion and are calculated at the 3--loop level for fixed moments. We also compute the massive OMEs which are needed to evaluate heavy flavor parton distributions in the variable flavor number scheme to the same order. All contributions to the Wilson coefficients and OMEs but the genuine constant terms at O(a_s^3) of the OMEs are derived in terms of quantities, which are known for general values in the Mellin variable N. For the OMEs A_{Qg}^(3), A_{qg,Q}^(3) and A_{gg,Q}^(3) the moments N = 2 to 10, for A_{Qq}^{(3), PS} to N = 12, and for A_{...

  8. Direct proof of static charge stripe correlations in La2-xBaxCuO4 (United States)

    Chen, X. M.; Thampy, V.; Mazzoli, C.; Barbour, A.; Gu, G.; Hill, J. P.; Tranquada, J. M.; Dean, M. P. M.; Wilkins, S. B.

    The nature of charge stripe order in the cuprates, and in particular whether the stripes are static or dynamic, is a key issue in understanding the relationship between stripes and superconductivity. In La2-xBaxCuO4 (LBCO) a low temperature structural distortion is widely believed to pin stripes into fixed, static domains, but such an assertion has never been directly verified. We performed resonant soft x-ray photon correlation spectroscopy (XPCS) to probe the charge order Bragg peak of 1/8 doped LBCO. At low temperatures, we observe time-independent x-ray speckle patterns persisting for more than three hours, proving the static nature of the stripes and we go on to discuss how stripe order melts with increasing temperature. Our results demonstrate that the combination of XPCS with diffraction limited light sources such as the National Synchrotron Light Source II can probe the dynamics of even subtle order parameters such as stripes in the cuprates. Work performed at Brookhaven National Laboratory was supported by the US Department of Energy, Division of Materials Science, under Contract No. DE-AC02-98CH10886. Use of the National Synchrotron Light Source II was supported under Contract No. DE-SC0012704.

  9. Stripe order in La2-xBaxCuO4 at ambient and high pressure. (United States)

    Huecker, M.; Wen, J. S.; Xu, Z. J.; Gu, G. D.; Tranquada, J. M.; Zimmermann, M. V.


    The pronounced stability of the charge and spin stripe order in La2-xBaxCuO4 at x=1/8 doping still is a poorly understood peculiarity. A combination of electronic and structural interactions is likely, however it has been difficult to clearly separate the involved mechanisms. One approach is to explore how stripe order fades away for dopings x !=1/8. We have performed high energy (100 keV) x-ray diffraction and static magnetization experiments on single crystals between x=0.095 and 0.155. To our surprise, at ambient pressure stripes exist in a much broader range of doping around x=1/8 than expected. In the underdoped region charge stripe order always coincides with a structural transition associated with a rotation of the octahedral tilt axis. However, for x=1/8 and high pressure we have been able to show that stripe order also occurs in the absence of this structural phase, which motivates us to discuss stripes in terms of an electronic liquid crystal phase.

  10. Electrochemical fabrication of (TMTSF)2X (X = PF6, BF4, CIO4) nanowires. (United States)

    Jung, Youn Jung; Kim, Yonha; Kim, Gyu Tae; Kang, Woun; Noh, Dong-Youn


    TMTSF-based (TMTSF = tetramethyltetraselenafulvalene = C10H12Se4) charge-transfer salt nanowires were fabricated using the galvanostatic deposition technique that was assisted by an anodic aluminum oxide (AAO) template. By applying a low current density of 1-2 microA/cm2 for more than one month, nanowire arrays with diameters of approximately 150 nm and lengths of approximately 6 microm were obtained. The length of nanowires can be controlled by the duration of the constant current application. Energy-dispersive X-ray spectroscopic (EDX) analysis confirmed that selenium is one of the main components of the nanowires. The micro-Raman (v3C == C) and FT-IR spectra (v3PF6-, v3BF4-, v3CIO4-) indicated that the nanowire arrays had the (TMTSF)2X (X = PF6, BF4, CIO4) phase. The TEM images and the selected area electron diffraction (SAED) patterns indicate that the nanowires were not single crystals, but the current-voltage characteristic that was measured with the four-terminal method showed the conductivity of the (TMTSF)2PF6 single crystals (sigmaRT = 1.6 S/cm) at room temperature.

  11. Thermodynamic and electrical transport investigation of URu2Si2-x P x (United States)

    Gallagher, A.; Chen, K.-W.; Cary, S. K.; Kametani, F.; Graf, D.; Albrecht-Schmitt, T. E.; Shekhter, A.; Baumbach, R. E.


    Magnetic susceptibility, electrical resistivity, and heat capacity results are reported for the chemical substitution series URu2Si2-x P x for 0. This study expands in detail on work recently reported in Gallagher et al (2016 Nat. Commun. 10712), which focused on the small x region of this substitution series. Measurements presented here reveal persistent hybridization between the f- and conduction electrons and strong variation of the low temperature behavior with increasing x. Hidden order and superconductivity are rapidly destroyed for x≲ 0.03 and are replaced for 0.03≲ x≲ 0.26 by a region with Kondo coherence but no ordered state. Antiferromagnetism abruptly appears for x≳ 0.27 . This phase diagram differs significantly from those produced by most other tuning strategies in URu2Si2, including applied pressure, high magnetic fields, and isoelectronic chemical substitution (i.e. Ru  →  Fe and Os), where hidden order and magnetism share a common phase boundary. Besides revealing an intriguing evolution of the low temperature states, this series provides a setting in which to investigate the influence of electronic tuning, where probes that are sensitive to the Fermi surface and the symmetry of the ordered states will be useful to unravel the anomalous behavior of URu2Si2.

  12. Molecular modeling of alkyl monolayers on the Si(100)-2 x 1 surface. (United States)

    Lee, Michael V; Guo, Dawei; Linford, Matthew R; Zuilhof, Han


    Molecular modeling was used to simulate various surfaces derived from the addition of 1-alkenes and 1-alkynes to Si=Si dimers on the Si(100)-2 x 1 surface. The primary aim was to better understand the interactions between adsorbates on the surface and distortions of the underlying silicon crystal due to functionalization. Random addition of ethylene and acetylene was used to determine how the addition of an adduct molecule affects subsequent additions for coverages up to one molecule per silicon dimer, that is, 100% coverage. Randomization subdues the effect that the relative positions of the adsorbates have on the enthalpy of the system. For ethylene and acetylene, the enthalpy of reaction changes less than 3 and 5 kcal/mol, respectively, from the first reacted species up to 100% coverage. As a result, a (near-)complete coverage is predicted, which is in line with experimental data. When 1-alkenes and 1-alkynes add by [2 + 2] addition, the hydrocarbon chains interact differently depending on the direction they project from the surface. These effects were investigated for four-carbon chains: 1-butene and 1-butyne. As expected, the chains that would otherwise intersect bend to avoid each other, raising the enthalpy of the system. For alkyl chains longer than four carbons, the chains are able to reorient themselves in a favorable manner, thus, resulting in a steady reduction in reaction enthalpy of about 2 kcal/mol for each additional methylene unit.

  13. First passage times in M2[X ]|G |1 |R queue with hysteretic overload control policy (United States)

    Pechinkin, Alexander V.; Razumchik, Rostislav R.; Zaryadov, Ivan S.


    One of the reported approaches towards the solution of overload problem in networks of SIP servers is the implementation of multi-level hysteretic control of arrivals in SIP servers. Each level, being the parameter of the policy, specifies operation mode of SIP server i.e. it implicitly indicates what SIP server must do with the arriving packets. The choice of parameters' values is not guided by standards and is usually left for the network owner. In general, all operation modes of the considered policy can be grouped into two groups: normal mode (when all arriving packets are accepted) and congested mode (when part or all arriving packets are being dropped). Such grouping may serve as the criteria for choosing parameters' values of the policy: pick those values which minimize SIP server sojourn time in congested mode. In this short note we propose some analytical results which facilitate the solution of stated minimization problem. The considered mathematical model of SIP server is the queueing system M2[X ]|G |1 |R with batch arrivals and bi-level hysteretic control policy, which specifies three operation modes: normal (customers both flows are accepted), overload (only customers from one flow are accepted), discard (customers from both flows are blocked/lost)). The switching between modes can occur only on service completions. Analytical method allowing computation of stationary sojourn times in different operation modes (as well as first passage times between modes) is presented in brief. Numerical example is given.

  14. A Hypergeometric Formula for Hilbert-Schmidt Generic 2 x 2 Generalized Separability Probabilities

    CERN Document Server

    Slater, Paul B


    We pursue the research agenda set forth in "Moment-Based Evidence for Simple Rational-Valued Hilbert-Schmidt Generic 2 x 2 Separability Probabilities" (J. Phys. A, 45, 095305 [2012]). But in a more thorough, systematic manner, employing--for probability-distribution reconstruction purposes--a substantially greater number (7,501) of moments of the determinant |rho^{PT}| of the partial transpose rho^{PT} of the corresponding 4 x 4 density matrix rho. The results strengthen the conjectures that the two-rebit (alpha= 1/2) and two-qubit (alpha = 1) separability probabilities are 29/64 and 8/33, respectively. Additionally fortified is the conjecture that the presumptive quaternionic (alpha= 2) analog is 26/323. With high accuracy calculations conducted jointly for the sixty-four values alpha = 1/2, 1, 3/2, 2,...,32, we are able to obtain a certain (hypergeometric-related) function of alpha (with argument z = (3/4)^3 = 27/64) that successfully reproduces the three specific conjectures. Additionally, it yields for th...

  15. Phase Structure of lattice $SU(2) x U_{S}(1)$ three-dimensional Gauge Theory

    CERN Document Server

    Farakos, K; McNeill, D


    We discuss a phase diagram for a relativistic SU(2) x U_{S}(1) lattice gauge theory, with emphasis on the formation of a parity-invariant chiral condensate, in the case when the $U_{S}(1)$ field is infinitely coupled, and the SU(2) field is moved away from infinite coupling by means of a strong-coupling expansion. We provide analytical arguments on the existence of (and partially derive) a critical line in coupling space, separating the phase of broken SU(2) symmetry from that where the symmetry is unbroken. We review uncoventional (Kosterlitz-Thouless type) superconducting properties of the model, upon coupling it to external electromagnetic potentials. We discuss the rôle of instantons of the unbroken subgroup U(1) of SU(2), in eventually destroying superconductivity under certain circumstances. The model may have applications to the theory of high-temperature superconductivity. In particular, we argue that in the regime of the couplings leading to the broken SU(2) phase, the model may provide an explanati...

  16. String Theory in the Penrose Limit of AdS_2 x S^2

    CERN Document Server

    Deliduman, C; Deliduman, Cemsinan; Kaynak, Burak T.


    The string theory in the Penrose limit of AdS_2 x S^2 is investigated. The specific Penrose limit is the background known as the Nappi-Witten spacetime, which is a plane-wave background with an axion field. The string theory on it is given as the Wess-Zumino-Novikov-Witten (WZNW) model on non-semi-simple group H_4. It is found that, in the past literature, an important type of irreducible representations of the corresponding algebra, h_4, were missed. We present this "new" representations, which have the type of continuous series representations. All the three types of representations of the previous literature can be obtained from the "new" representations by setting the momenta in the theory to special values. Then we realized the affine currents of the WZNW model in terms of four bosonic free fields and constructed the spectrum of the theory by acting the negative frequency modes of free fields on the ground level states in the h_4 continuous series representation. The spectrum is shown to be free of ghost...

  17. Elucidating the foundations of statistical inference with 2 x 2 tables. (United States)

    Choi, Leena; Blume, Jeffrey D; Dupont, William D


    To many, the foundations of statistical inference are cryptic and irrelevant to routine statistical practice. The analysis of 2 x 2 contingency tables, omnipresent in the scientific literature, is a case in point. Fisher's exact test is routinely used even though it has been fraught with controversy for over 70 years. The problem, not widely acknowledged, is that several different p-values can be associated with a single table, making scientific inference inconsistent. The root cause of this controversy lies in the table's origins and the manner in which nuisance parameters are eliminated. However, fundamental statistical principles (e.g., sufficiency, ancillarity, conditionality, and likelihood) can shed light on the controversy and guide our approach in using this test. In this paper, we use these fundamental principles to show how much information is lost when the tables origins are ignored and when various approaches are used to eliminate unknown nuisance parameters. We present novel likelihood contours to aid in the visualization of information loss and show that the information loss is often virtually non-existent. We find that problems arising from the discreteness of the sample space are exacerbated by p-value-based inference. Accordingly, methods that are less sensitive to this discreteness - likelihood ratios, posterior probabilities and mid-p-values - lead to more consistent inferences.

  18. The metallic transport of (TMTSF){sub 2}X organic conductors close to the superconducting phase

    Energy Technology Data Exchange (ETDEWEB)

    Auban-Senzier, P; Jerome, D [Laboratoire de Physique des Solides, UMR 8502 CNRS Universite Paris-Sud, 91405 Orsay (France); Doiron-Leyraud, N; Rene de Cotret, S; Sedeki, A; Bourbonnais, C; Taillefer, L [Departement de Physique and RQMP, Universite de Sherbrooke, Sherbrooke, QC, J1K 2R1 (Canada); Alemany, P [Departament de Quimica Fisica and Institut de Quimica Teorica i Computacional (IQTCUB), Universitat de Barcelona, Diagonal 647, 08028 Barcelona (Spain); Canadell, E [Institut de Ciencia de Materials de Barcelona (CSIC), Campus de la UAB, 08193 Bellaterra (Spain); Bechgaard, K, E-mail:, E-mail:, E-mail:, E-mail:, E-mail:, E-mail:, E-mail: [Department of Chemistry, HC Oersted Institute, Copenhagen (Denmark)


    Comparing resistivity data of the quasi-one-dimensional superconductors (TMTSF){sub 2}PF{sub 6} and (TMTSF){sub 2}ClO{sub 4} along the least conducting c*-axis and along the high conductivity a-axis as a function of temperature and pressure, a low temperature regime is observed in which a unique scattering time governs the transport along both directions of these anisotropic conductors. However, the pressure dependence of the anisotropy implies a large pressure dependence of the interlayer coupling. This is in agreement with the results of first-principles density functional theory calculations implying methyl group hyperconjugation in the TMTSF molecule. In this low temperature regime, both materials exhibit for {rho}{sub c} a temperature dependence aT + bT{sup 2}. Taking into account the strong pressure dependence of the anisotropy, the T-linear {rho}{sub c} is found to correlate with the suppression of the superconducting T{sub c}, in close analogy with {rho}{sub a} data. This work reveals the domain of existence of the three-dimensional coherent regime in the generic (TMTSF){sub 2}X phase diagram and provides further support for the correlation between T-linear resistivity and superconductivity in non-conventional superconductors. (paper)

  19. Validation of MATRA-S Low Flow Predictions Using PNL 2x6 Mixed Convection Test

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Kyong-Won; Kwon, Hyuk; Kim, Seong-Jin; Hwang, Dae-Hyun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)


    The MATRA-S, a subchannel analysis code has been used to thermal-hydraulic design of SMART core. As the safety enhancement is getting important more and more, some features of the MATRA-S code are required to be validated in order to be applied to nonnominal operating conditions in addition to its applicability to reactor design under normal operating conditions. The MATRA-S code has two numerical schemes, SCHEME for implicit application and XSCHEM for explicit one. The implicit scheme had been developed under assumptions that the axial flow is larger enough than the crossflow. Under certain conditions, especially low flow and low pressure operating conditions, this implicit SCHEME oscillates or becomes unstable numerically and then MATRA-S fails to obtain good solution. These demerits were known as common in implicit schemes of many COBRA families. Efforts have been exerted to resolve these limitations in SCHEME of the MATRA-S such as a once through marching scheme against the multi-pass marching scheme and an adaptive multi-grid method. These remedies can reduce the numerically unstable range for SCHEME but some unstable regions still remain. The XSCHEM, an explicit scheme of MATRA-S was validated using the PNL 2x6 rod bundle flow transient test. The explicit scheme agreed with implicit scheme for steady state calculations. And it showed its capability to predict low flow conditions such as negative flow and recirculation flow.

  20. Metal-Insulator Transition Associated with [0110] Charge Ordering in (EDO-TTF)_2X (United States)

    Drozdova, O.; Tanner, D. B.; Yakushi, K.; Ota, A.; Yamochi, H.; Saito, G.


    Optical (polarized infrared-visible reflectance and Raman) spectra of (EDO-TTF)_2X (X= PF_6, T_MI= 280 K; AsF_6, T_MI= 268 K) have been measured at temperatures above and below T_MI. From the frequencies of three charge-sensitive C=C stretching modes of EDO-TTF, the molecular charge was estimated as uniform +0.5 split below T_MI to (0, +1). In the electronic spectra along the stack, the main conductivity peak vanishes and instead, two charge transfer bands CT1 (4500 cm-1) and CT2 (11150 cm-1) appear corresponding to D^0D^+...D^+D^0 and D^+D^+...D^2+D^0 processes, respectively. For the first time, the electron-molecular vibration (EMV) coupling between two C=C modes of D^+ and CT2 was observed in the polarized Raman spectra. The optical data point out the importance of the EMV coupling in the formation of the [0110] charge-ordering pattern.

  1. Structural and electronic properties of silicene on MgX2 (X = Cl, Br, and I)

    KAUST Repository

    Zhu, Jiajie


    Silicene is a monolayer of Si atoms in a two-dimensional honeycomb lattice, being expected to be compatible with current Si-based nanoelectronics. The behavior of silicene is strongly influenced by the substrate. In this context, its structural and electronic properties on MgX2 (X = Cl, Br, and I) have been investigated using first-principles calculations. Different locations of the Si atoms are found to be energetically degenerate because of the weak van der Waals interaction with the substrates. The Si buckling height is below 0.55 Å, which is close to the value of free-standing silicene (0.49 Å). Importantly, the Dirac cone of silicene is well preserved on MgX2 (located slightly above the Fermi level), and the band gaps induced by the substrate are less than 0.1 eV. Application of an external electric field and stacking can be used to increase the band gap. © 2014 American Chemical Society.

  2. Morphology and electronic properties of Co nanorods on Cu(110)-p(2 x 3)N

    Energy Technology Data Exchange (ETDEWEB)

    Wedekind, Sebastian; Oka, Hirofumi; Rodary, Guillemin; Sander, Dirk; Kirschner, Juergen [Max-Planck-Institut fuer Mikrostrukturphysik, Halle (Germany); Donati, Fabio [Max-Planck-Institut fuer Mikrostrukturphysik, Halle (Germany); NEMAS, Politecnico di Milano, Milano (Italy)


    Copper nitride systems are of high current interest in nanoscience as they offer a venue towards decoupling the electronic properties of nanostructures or adatoms from those of the substrate. We have prepared a Cu(110)-p(2 x 3) (Cu{sub 3}N) substrate by N-ion bombardment (600 eV, 30 min, 550 K) of clean Cu(110). Deposition of Co leads to the formation of several ten nm long Co wires, extending along. Our scanning tunneling microscopy and spectroscopy studies at 8 K reveal the positions of all atoms within the rectangular surface unit cell, where we measure unit vectors of 1.094 and 0.502 nm for the Cu{sub 3}N structure. Surprisingly, spectroscopy on clean Cu{sub 3}N and on Co nanowires on Cu{sub 3}N shows very similar results. No special spectroscopic features are identified near the Fermi energy, but peaks at +1.8 and +3.5 eV of presently unknown electronic character of the unoccupied sample states are observed for both Cu{sub 3}N and Co/Cu{sub 3}N. This suggests a rather strong electronic coupling between substrate and nanowire, questioning the electronic decoupling between this copper nitride system and nanostructures deposited on top.

  3. Two-dimensional Ni(OH)2-XS2 (X = Mo and W) heterostructures (United States)

    Tang, Zhen-Kun; Tong, Chuan-Jia; Geng, Wei; Zhang, Deng-Yu; Liu, Li-Min


    Two-dimensional (2D) van der Waals (vdW) heterostructures have received a lot of attention because of their wide applications in electronics and optoelectronics. In this work, the electronic structures and optical properties of nickel hydroxides (Ni(OH)2) and transition metal dichalcogenides (XS2, X = Mo, W) heterostructures are studied by hybrid density functional theory. The results reveal that all the considered Ni(OH)2-XS2 heterostructures are indirect semiconductors with a band gap of 0.040-0.825 eV. Additionally, the AB stacked Ni(OH)2-XS2 heterostructures are more stable than the AA stacked one. Interestingly, the complete electron-hole separation is found in the Ni(OH)2-XS2 heterostructure, and its conduction band minimum and valence band maximum are located on the XS2 and Ni(OH)2 layers, respectively. Besides, the optical absorption peaks of Ni(OH)2-XS2 heterostructures are mainly located within the visible light region. These fascinating electronic structures and optical absorption of the Ni(OH)2-XS2 heterostructures make them promising candidates for applications in 2D optoelectronics.

  4. Frustrated spin correlations in diluted spin ice Ho2-xLaxTi2O7

    Energy Technology Data Exchange (ETDEWEB)

    Ehlers, Georg; Ehlers, G.; Mamontov, E.; Zamponi, M.; Faraone, A.; Qiu, Y.; Cornelius, A.L.; Booth, C.H.; Kam, K.C.; Le Toquin, R.; Cheetham, A.K.; Gardner, J.S.


    We have studied the evolution of the structural properties as well as the static and dynamic spin correlations of spin ice Ho2Ti2O7, where Ho was partially replaced by non-magnetic La. The crystal structure of diluted samples Ho2-xLaxTi2O7 was characterized by x-ray and neutron diffraction and by Ho L-III-edge and Ti K-edge extended x-ray absorption fine structure (EXAFS) measurements. It is found that the pyrochlore structure remains intact until about x = 0.3, but a systematic increase in local disorder with increasing La concentration is observed in the EXAFS data, especially from the Ti K edge.Quasi-elastic neutron scattering and ac susceptibility measurements show that, in x<= 0.4 samples at temperatures above macroscopic freezing, the spin -spin correlations are short ranged and dynamic in nature. The main difference with pure spin ice in the dynamics is the appearance of a second, faster, relaxation process.


    Directory of Open Access Journals (Sweden)

    Abdul Wahid


    Full Text Available With this study, the design and tuning of multi-loop for multivariable (2x2 CSTR will be made in order to achieve optimum CSTR control performance. This study used Bequette model reactor and MATLAB software and is expected to be able to cope with disturbances in the reactor so that the reactor system is able to stabilize quickly despite the distractions. In this study, the design will be made using multi-loop approach, along with PI controller as the next step. Then, BLT and auto-tune tuning method will be used in PI controller and given disturbances to both of tuning method. The controller performances are then compared. Results of the study are then analyzed for discussions and conclusions. Results from this study have shown that in terms of disturbance rejection, BLT is better than auto-tune based on comparison between both of controller performances. For IAE for the case of temperature, BLT is 30% better than auto-tune, but it is almost the same for the case of concentration. For settling time for the case of concentration, BLT is 30% better than auto-tune, and for the case of temperature, BLT is 18% better than auto-tune. For rise time for the case of concentration and temperature, BLT is 30% better than auto-tune.

  6. Structural and electronic properties of XSi{sub 2} (X = Cr, Mo, and W)

    Energy Technology Data Exchange (ETDEWEB)

    Shugani, Mani, E-mail: [Sadhu Vaswani College, Bairagarh, Department of Physics (India); Aynyas, Mahendra [C. S. A. Govt. P. G. College, Department of Physics (India); Sanyal, S. P. [Barkatullah University, Department of Physics (India)


    The structural and electronic properties of metal silicides XSi{sub 2} (X = Cr, Mo, and W), which crystallize in tetragonal structure, are investigated systematically using the first-principle density functional theory. The total energies are computed as a function of volume and fitted to the Birch equation of state. The ground-state properties such as equilibrium lattice constants a{sub 0} and c{sub 0}, bulk modulus B, its pressure derivative B, B′, and the density of states at the Fermi level, N(E{sub F}), are calculated and compared with other experimental and theoretical results, showing good agreement. The calculated band structure indicates that XSi{sub 2} compounds are semimetallic in nature. From the present study, we predict the structural and electronic properties of CrSi{sub 2} in the tetragonal phase and indicate that CrSi{sub 2} is energetically more stable than MoSi{sub 2} and WSi{sub 2}. Analyzing the bonding properties of the three metal silicides, we observe that WSi{sub 2} has a strong covalent bonding due to W 5d electrons.

  7. Photoelectric properties of defect chalcogenide HgGa2X4 (x=S, Se, Te) (United States)

    Sharma, Ramesh; Dwivedi, Shalini; Sharma, Yamini


    We present results of ab initio study of ordered vacancy compounds of mercury. The electronic structure, charge density, optical and transport properties of the semiconductor family HgGa2X4 (X=S, Se, Te) are calculated using the full potential linearized augmented plane wave method which is based on the density functional theory. A direct bandgap is observed in these compounds, which reduces in the order S>Se>Te. From the density of states it is observed that there is strong hybridization of Hg-d, Ga-d and X-p states. The optical properties show a red shift with increasing size and atomic no. of the chalcogenide atoms. We have also reported the transport properties of mercury thiogallates for the first time. The selenide compound exhibits n-type nature whereas HgGa2S4 and HgGa2Te4 show p-type behavior. The power factor and ZT for the HGS increases at low temperatures, the figure of merit is highest for HgGa2Se4 (1.17) at 19 K.

  8. Ploidy Variation in Hybrids from Interploid 3x X 2x Crosses in Musa

    Directory of Open Access Journals (Sweden)

    Osuji, JO.


    Full Text Available Hybrids were obtained after in vitro germination of embryos from interploid crosses between triploid 'French' plantain cultivars (Musa spp. AAB group 'Ntanga 2' and 'Bobby Tannap' with diploid banana (Ivlusa acuminata subsp. burmannicoidesj 'Calcutta 4'. Cross-pollinated bunches were harvested at full maturity and ripened with acetylene in a room for 4 days. Seeds were extracted from peeled ripe fruits by squashing. Embryos from the seeds were excised aseptically after 2 days and germinated in vitro. Seedlings were subsequently planted in early evaluation trials after acclimatising in the greenhouse. Chromosome counts were carried out on root tips of mature and maiden suckers to determine ploidy levels using a modified squashing technique. Counts showed that two of the hybrids were aneuploids (trisomies with somatic chromosome number of 2n = 2x + 1 = 23, one hybrid was diploid while the other two were tetraploids. Tetraploids are the most promising hybrids for the genetic improvement of plantains. Diploids are valuable material for further improvement of the plantain genome at this ploidy level. Trisomies provide means for further characterisation of the Musa genome and physical gene mapping in plantain and banana.

  9. Thermoelectric properties of the Ca(5)Al(2-x)In(x)Sb(6) solid solution. (United States)

    Zevalkink, Alex; Swallow, Jessica; Ohno, Saneyuki; Aydemir, Umut; Bux, Sabah; Snyder, G Jeffrey


    Zintl phases are attractive for thermoelectric applications due to their complex structures and bonding environments. The Zintl compounds Ca(5)Al(2)In(x)Sb(6)and Ca(5)Al(2)In(x)Sb(6) have both been shown to have promising thermoelectric properties, with zT values of 0.6 and 0.7, respectively, when doped to control the carrier concentration. Alloying can often be used to further improve thermoelectric materials in cases when the decrease in lattice thermal conductivity outweighs reductions to the electronic mobility. Here we present the high temperature thermoelectric properties of the Ca(5)Al(2-x)In(x)Sb(6)solid solution. Undoped and optimally Zn-doped samples were investigated. X-ray diffraction confirms that a full solid solution exists between the Al and In end-members. We find that the Al : In ratio does not greatly influence the carrier concentration or Seebeck effect. The primary effect of alloying is thus increased scattering of both charge carriers and phonons, leading to significantly reduced electronic mobility and lattice thermal conductivity at room temperature. Ultimately, the figure of merit is unaffected by alloying in this system, due to the competing effects of reduced mobility and lattice thermal conductivity.

  10. 嘌呤受体P2X7在人眼小梁网细胞上的表达及分布%Expression and distribution of purinergic receptor P2X7 in human trabecular meshwork cells

    Institute of Scientific and Technical Information of China (English)

    祝芸芸; 左炜; 王恒; 张秀兰


    目的 探讨嘌呤受体P2X7在体外培养正常人眼小梁网细胞上的表达及分布.方法 体外培养、鉴定正常人眼小梁网细胞,利用RT-PCR、Western-blot和免疫荧光法分别检测正常人眼小梁网细胞上P2X7受体mRNA和蛋白的表达情况及受体蛋白的主要分布部位.结果 光镜下观察原代培养的细胞具有人眼小梁网细胞的典型形态;免疫组织化学方法检测结果表明,培养的细胞纤维连接蛋白、层粘连蛋白、神经元特异性烯醇化酶及波形蛋白染色阳性,第Ⅷ因子染色阴性,鉴定为人眼小梁网细胞;RT-PCR扩增到了P2X7mRNA 152 bp大小的基因片段,Western-blot得到了相对分子质量约为74 000的P2X7的蛋白条带,免疫荧光法证实P2X7受体在小梁网细胞膜、细胞质及细胞核内均有广泛分布.结论 人眼小梁网细胞上有P2X7受体表达,其在细胞内分布广泛.

  11. Mechanism for Curie temperature variation in La{sub x}Sr{sub 2-x}FeMoO{sub 6} and Ca{sub x}Sr{sub 2-x}FeMoO{sub 6}

    Energy Technology Data Exchange (ETDEWEB)

    Frontera, C.; Rubi, D.; Navarro, J.; Garcia-Munoz, J.L.; Ritter, C.; Fontcuberta, J


    By means of high-resolution neutron powder diffraction at 10 K, we have characterized the structural details of La{sub x}Sr{sub 2-x}FeMoO{sub 6} (0{<=}x{<=}0.5) and Ca{sub x}Sr{sub 2-x}FeMoO{sub 6} (0{<=}x{<=}0.6) series of compounds. The Curie temperature (T{sub C}) raises in the La series and slightly decreases in the Ca one. The enhancement of T{sub C} in the La series is attributed to the effect of the conduction band-filling when doping with La.

  12. The Special Solutions for the Equation ut=(eu(ux)2)x+P(u)ux+Q(u)%关于方程ut=(eu(ux)2)x+P(u)ux+Q(u)的一种解法

    Institute of Scientific and Technical Information of China (English)



    研究了带有源项的非线性反应扩散方程ut=(eu(ux)2)x+P(u)ux+Q(U)特殊情况的解.利用二阶广义条件对称η=uxx+H(u)u2x+G(u)ux+F(u) 的方法,其中H(u),G(u),F(u)分别是u的光滑函数.得到了上述方程的几个解.该方法也可以用来解决其他偏微分方程.

  13. 方程 utt=a2(utt+(2)/(x)ux) 的 Cauchy 问题的相容性%THE CONSISTENCY OF CAUCHY PROBLEMS IN EQUATION utt=a2(utt+(2)/(x)ux)

    Institute of Scientific and Technical Information of China (English)



    本文就形如 utt=a2(utt+(2)/(x)ux) 的 Cauchy 问题进行了讨论,得到其相容性条件和古典解的存在性定理,进而对于更一般的一类形如 autt+2butt+cutt+(2)/(x)(aux+bux)=0(a、b、c是常量,且b2-ac>0)的方程得到类似结果.

  14. 中枢神经系统离子通道受体P2X7的研究进展%Progress Research on ATP-gate Ionotropic P2X7 Receptor in Central Nervous System

    Institute of Scientific and Technical Information of China (English)

    贺洁宇; 陈晓宇; 潘爱华



  15. Effect of purine receptor P2X7 in pericyte of retinal microvascular apoptosis%嘌呤受体P2X7对视网膜毛细血管周细胞凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    左炜; 祝芸芸; 于洪涛; 利焕廉; 周金文; 王恒


    AIM: To discuss the functional significance of purine receptor P2X7 in retinal capillary pericytes rats. METHODS:The TUNEL test was applied to observe the survival rate of normal retinal capillary pericytes and diabetic retinal capillary pericytes which were affected by P2X7 agonist BzATP and antagonist OxATP in microscopy. RESULTS: Activation of P2X7 receptors caused occurence of apoptosis in retinal capillary pericytes. Compared with normal retinal capillary pericytes, when they were at the same concentration or time, the diabetic retinal capillary pericytes caused much more apoptosis than normal retinal capillary pericytes. The antagonist OxATP could significantly reduce the toxic effects activated by BzATP, and then increased the livability of retinal capillary pericytes. CONCLUSION:The activity of P2X7 receptor plays a regulatory role on RPC apoptosis.%目的:探讨嘌呤受体P2X7在体外培养大鼠视网膜毛细血管周细胞上的功能意义。  方法:利用显微镜下观察结合TUNEL 计数法分别测定P2 X7激动剂BzATP和拮抗剂OxATP对体外培养的正常视网膜毛细血管周细胞以及糖尿病大鼠视网膜毛细血管周细胞存活率的影响。  结果:P2 X 7受体激动后可介导视网膜毛细血管周细胞死亡,糖尿病大鼠视网膜毛细血管周细胞较正常视网膜毛细血管周细胞,在同等激动剂浓度下或在同样的时间点,能引起更多的细胞凋亡。而拮抗剂OxATP 可以明显减轻BzATP对视网膜毛细血管周细胞的毒性作用,提高其存活率。  结论:P2 X 7受体活性对视网膜毛细血管周细胞凋亡有一定调控作用。

  16. Laser device (United States)

    Scott, Jill R.; Tremblay, Paul L.


    A laser device includes a target position, an optical component separated a distance J from the target position, and a laser energy source separated a distance H from the optical component, distance H being greater than distance J. A laser source manipulation mechanism exhibits a mechanical resolution of positioning the laser source. The mechanical resolution is less than a spatial resolution of laser energy at the target position as directed through the optical component. A vertical and a lateral index that intersect at an origin can be defined for the optical component. The manipulation mechanism can auto align laser aim through the origin during laser source motion. The laser source manipulation mechanism can include a mechanical index. The mechanical index can include a pivot point for laser source lateral motion and a reference point for laser source vertical motion. The target position can be located within an adverse environment including at least one of a high magnetic field, a vacuum system, a high pressure system, and a hazardous zone. The laser source and an electro-mechanical part of the manipulation mechanism can be located outside the adverse environment. The manipulation mechanism can include a Peaucellier linkage.

  17. A compact plasmonic MOS-based 2x2 electro-optic switch

    CERN Document Server

    Ye, Chenran; Soref, Richard A; Sorger, Volker J


    We report on a three-waveguide electro-optic switch for compact photonic integrated circuits and data routing applications. The device features a plasmonic metal-oxide-semiconductor (MOS) mode for enhanced light-matter-interactions. The switching mechanism originates from a capacitor-like design where the refractive index of the active medium, Indium-Tin-Oxide, is altered via shifting the plasma frequency due to carrier accumulation inside the waveguide-based MOS structure. This light manipulation mechanism controls the transmission direction of transverse magnetic polarized light into either a CROSS or BAR waveguide port. The extinction ratio of 18 dB (7) dB for the CROSS (BAR) state, respectively, is achieved via a gating voltage bias. The ultrafast broadband fJ/bit device allows for seamless integration with Siliconon- Insulator platforms to for low-cost manufacturing.

  18. Thermal and Electric Properties of the FeAs2-xSbx (x=0, 1, or 2) Marcasite Compounds from First Principles (United States)

    Bang, Semi; Orabi, Rabih Al Rahal Al; Wee, Daehyun


    Thermoelectric energy conversion has been considered as one piece of the future solution to the energy crisis for a long time. In thermoelectric energy conversion, thermoelectric materials, which exhibit strong coupling between heat flow and electric current, are used to convert thermal energy into electrical energy and vice versa. Hence, thermoelectric devices can be potential and present applications for both thermoelectric generation and cooling system. There are significant demands for thermoelectric materials that can be used for environment-friendly cooling applications that need to be met. A few recent studies reported thermoelectric properties of the FeAs2-xSbx (x=0, 1, or 2) marcasite compounds, which has a potential for becoming a good thermoelectric material for low-temperature cooling applications. The compound can be more environment-friendly and more economically viable than other competing materials, for the composition does not involve rare and expensive element like Te or Pt. In this study, we investigate thermoelectric properties of the FeAs2-xSbx (x=0, 1, or 2) marcasite compounds by first-principles calculations in order to demonstrate the feasibility for the use in practical cooling applications. Electronic band structures and density of states are constructed from DFT (density functional theory) calculations, from which electrical properties, including the Seebeck coefficient and the electrical conductivity, are estimated. At the same time, vibrational characteristics are investigated through DFPT (density functional perturbation theory) calculations, from which the thermal conductivity is estimated using semiempirical formulae and the Grüneissen parameters of the compound obtained at the level of the QHA (quasi-harmonic approximation).

  19. Growth mechanisms and origin of localized surface plasmon resonance coupled exciton effects in Cu2_xS thin films

    Energy Technology Data Exchange (ETDEWEB)

    Savariraj, Dennyson A.; Kim, Hee-Je; Viswanathan, Kodakkal K.; Vijayakumar, M.; Prabakar, Kandasamy


    Cu2-xS thin films prepared by template free single step wet chemical method on fluorine doped tin oxide substrate without any surfactant exhibts localized surface plasmon resonance (LSPR) coupled exciton effects. Cu2-xS thin films of unique surface morphology and free carrier density due to copper vacancy is controlled by the growth temperature and time. These selectively grown Cu2-xS thin films possess tunable band gap (2.6 - 1.4 eV) due to quantum size effect. Eventhough, all the samples show satellite peak in the X-ray photoelectron spectra due to Cu vacancies, only the samples with higher oxygen concentration show LSPR in the near infrared region.

  20. Pharmacological insights into the role of P2X4 receptors in behavioral regulation: lessons from ivermectin (United States)

    Bortolato, Marco; Yardley, Megan; Khoja, Sheraz; Godar, Sean C; Asatryan, Liana; Finn, Deborah A.; Alkana, Ronald L.; Louie, Stan G.; Davies, Daryl L.


    Purinergic ionotropic P2X receptors are a family of cation-permeable channels that bind extracellular adenosine 5′-triphosphate (ATP). In particular, convergent lines of evidence have recently highlighted P2X4 receptors as a potentially critical target in the regulation of multiple nervous and behavioral functions, including pain, neuroendocrine regulation and hippocampal plasticity. Nevertheless, the role of the P2X4 receptor in behavioral organization remains poorly investigated. To study the effects of P2X4 activation, we tested the acute effects of its potent positive allosteric modulator ivermectin (IVM, 2.5–10 mg/kg, i.p.) on a broad set of paradigms capturing complementary aspects of perceptual, emotional and cognitive regulation in mice. In a novel open field, IVM did not induce significant changes in locomotor activity, but increased the time spent in the peripheral zone. In contrast, IVM produced anxiolytic-like effects in the elevated plus maze and marble burying tasks, as well as depression-like behaviors in the tail-suspension and forced swim tests. The agent induced no significant behavioral changes in the conditioned place preference test and in the novel object recognition task. Finally, the drug induced a dose-dependent decrease in sensorimotor gating, as assessed by prepulse inhibition (PPI) of the acoustic startle reflex. In P2X4 knockout mice, the effects of IVM in the open field and elevated plus maze were similar to those observed in wild type mice; conversely, the drug significantly increased startle amplitude and failed to reduce PPI. Taken together, these results suggest that P2X4 receptors may play a role in the regulation of sensorimotor gating. PMID:23174033

  1. Diabetic plasticity of non-adrenergic non-cholinergic and P2X-mediated rat bladder contractions. (United States)

    Munoz, Alvaro; Boone, Timothy B; Smith, Christopher P; Somogyi, George T


    We investigated the plasticity effects of diabetes mellitus and diuresis on the non-adrenergic non-cholinergic (NANC) and purinergic (P2X-type) contractile responses in longitudinal rat bladder strips. Female Sprague-Dawley rats received streptozotocin to induce diabetes, or sucrose in water to induce diuresis as a control condition for polyuria. Experiments were carried out at four weeks after treatments, using bladders from non-treated rats as control. Urinary bladder strips were electrically stimulated throughout the experiments to generate neurally evoked contractions (NEC). In all cases, P2X-mediated purinergic contractions were evaluated at the beginning and end of the stimulations with α,β-methylene-adenosine triphosphate (α,βMeATP). The NANC responses were assessed by using two independent protocols. First, cholinergic receptors were activated with carbachol (CCh), followed by inhibition of the muscarinic component with atropine. In the second protocol, the application order for CCh and atropine was reversed. The NANC response, unmasked with the application of atropine, and the P2X purinergic contractions were analyzed. NANC contractions in diabetic bladder strips are more resistant to the desensitizing effects caused by activation of cholinergic receptors. In early stages of experimental diabetes, NANC responses in diabetic strips are less sensitive to functional inhibition mediated by the cholinergic activation. However, P2X-mediated purinergic contractions are more sensitive to desensitization in diabetic or diuretic bladders. For instance preventing muscarinic receptor activation with atropine does not counteract the desensitization of purinergic contractions in either diabetic or diuretic strips. We suggest that diabetes may induce a plasticity of the NANC and P2X-mediated bladder contractile responses. The first one may be associated with diabetic neuropathic damage to bladder nerves, while impaired P2X purinergic contractions might be associated

  2. Valproic acid attenuates microgliosis in injured spinal cord and purinergic P2X4 receptor expression in activated microglia. (United States)

    Lu, Wen-Hsin; Wang, Chih-Yen; Chen, Po-See; Wang, Jing-Wen; Chuang, De-Maw; Yang, Chung-Shi; Tzeng, Shun-Fen


    Peripheral injection with a high dose of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, into animals with mild or moderate spinal cord injury (SCI) for 1 week can reduce spinal cord tissue loss and promote hindlimb locomotor recovery. A purinergic adenosine triphosphate (ATP) receptor subtype, P2X4 receptor (P2X4 R), has been considered as a potential target to diminish SCI-associated inflammatory responses. In this study, using a minipump-based infusion system, we found that intraspinal infusion with VPA for 3 days into injured spinal cord significantly improved hindlimb locomotion of rats with severe SCI induced by a 10-g NYU impactor dropping from the height of 50 mm onto the spinal T9/10 segment. The neuronal fibers in the injured spinal cord tissues were significantly preserved in VPA-treated rats compared with those observed in vehicle-treated animals. Moreover, the accumulation of microglia/macrophages and astrocytes in the injured spinal cord was attenuated in the animal group receiving VPA infusion. VPA also significantly reduced P2X4 R expression post-SCI. Furthermore, in vitro study indicated that VPA, but not the other HDAC inhibitors, sodium butyrate and trichostatin A (TSA), caused downregulation of P2X4 R in microglia activated with lipopolysaccharide (LPS). Moreover, p38 mitogen-activated protein kinase (MAPK)-triggered signaling was involved in the effect of VPA on the inhibition of P2X4 R gene expression. In addition to the findings from others, our results also provide important evidence to show the inhibitory effect of VPA on P2X4 R expression in activated microglia, which may contribute to reduction of SCI-induced gliosis and subsequently preservation of spinal cord tissues. © 2013 Wiley Periodicals, Inc.

  3. Prostaglandin E2 potentiation of P2X3 receptor mediated currents in dorsal root ganglion neurons

    Directory of Open Access Journals (Sweden)

    Huang Li-Yen


    Full Text Available Abstract Prostaglandin E2 (PGE2 is a well-known inflammatory mediator that enhances the excitability of DRG neurons. Homomeric P2X3 and heteromeric P2X2/3 receptors are abundantly expressed in dorsal root ganglia (DRG neurons and participate in the transmission of nociceptive signals. The interaction between PGE2 and P2X3 receptors has not been well delineated. We studied the actions of PGE2 on ATP-activated currents in dissociated DRG neurons under voltage-clamp conditions. PGE2 had no effects on P2X2/3 receptor-mediated responses, but significantly potentiated fast-inactivating ATP currents mediated by homomeric P2X3 receptors. PGE2 exerted its action by activating EP3 receptors. To study the mechanism underlying the action of PGE2, we found that the adenylyl cyclase activator, forskolin and the membrane-permeable cAMP analogue, 8-Br-cAMP increased ATP currents, mimicking the effect of PGE2. In addition, forskolin occluded the enhancement produced by PGE2. The protein kinase A (PKA inhibitors, H89 and PKA-I blocked the PGE2 effect. In contrast, the PKC inhibitor, bisindolymaleimide (Bis did not change the potentiating action of PGE2. We further showed that PGE2 enhanced α,β-meATP-induced allodynia and hyperalgesia and the enhancement was blocked by H89. These observations suggest that PGE2 binds to EP3 receptors, resulting in the activation of cAMP/PKA signaling pathway and leading to an enhancement of P2X3 homomeric receptor-mediated ATP responses in DRG neurons.

  4. Activation of P2X7 receptors causes isoform-specific translocation of protein kinase C in osteoclasts. (United States)

    Armstrong, Souzan; Pereverzev, Alexey; Dixon, S Jeffrey; Sims, Stephen M


    Nucleotides, released in response to mechanical or inflammatory stimuli, signal through P2 nucleotide receptors in many cell types. Osteoclasts express P2X7 receptors (encoded by P2rx7) - Ca(2+)-permeable channels that are activated by high concentrations of extracellular ATP. Genetic disruption of P2rx7 leads to increased resorption and reduced skeletal response to mechanical stimuli. To investigate whether P2X7 receptors couple to activation of protein kinase C (PKC), RAW 264.7 cells were differentiated into multinucleated osteoclast-like cells and live-cell confocal imaging was used to localize enhanced green fluorescent protein (EGFP)-tagged PKC. Benzoylbenzoyl-ATP (BzATP; a P2X7 agonist) induced transient translocation of PKCalpha to the basolateral membrane. UTP or ATP (10 microM), which activate P2 receptors other than P2X7, failed to induce translocation. Moreover, BzATP failed to induce PKC translocation in osteoclasts derived from the bone marrow of P2rx7(-/-) mice, demonstrating specificity for P2X7. BzATP induced a transient rise of cytosolic Ca(2+), and removal of extracellular Ca(2+) abolished the translocation of PKCalpha that was induced by BzATP (but not by phorbol ester). We examined the isoform specificity of this response, and observed translocation of the Ca(2+)-dependent isoforms PKCalpha and PKCbetaI, but not the Ca(2+)-independent isoform PKCdelta. Thus, activation of P2X7 receptors specifically induces Ca(2+)-dependent translocation of PKC to the basolateral membrane domain of osteoclasts, an aspect of spatiotemporal signaling not previously recognized.

  5. Coupling of two pools of P2X7 receptors to distinct intracellular signaling pathways in rat submandibular gland. (United States)

    Garcia-Marcos, Mikel; Pérez-Andrés, Encarnación; Tandel, Séverine; Fontanils, Unai; Kumps, Alain; Kabré, Elie; Gómez-Muñoz, Antonio; Marino, Aida; Dehaye, Jean-Paul; Pochet, Stéphanie


    The plasma membrane of cells from rat submandibular glands was isolated and extensively sonicated. The homogenate was centrifuged at high speed in a discontinuous sucrose gradient. Light fractions contained vesicles analogous to rafts: they were rich in cholesterol, they contained GM1 and caveolin-1, and P2X7 receptors were detected in these fractions. The location of the P2X7 receptors in rafts was abolished when cellular cholesterol was removed by methyl-beta-cyclodextrin (MCD). ATP activated neutral sphingomyelinase (N-SMase), which provoked a decrease of the cellular content of sphingomyelin and an increase of ceramide levels in these cells and in the rafts. Treatment with MCD and filipin (but not with alpha-cyclodextrin) abolished the increase of the intracellular concentration of calcium ([Ca2+]i) in response to epinephrine but not to ATP. MCD and filipin also inhibited the activation by ATP of phospholipase A2 (PLA2). Inhibition of N-SMase with glutathione or GW4869 prevented the activation of PLA2 by P2X7 agonists without affecting [Ca2+]i levels. We conclude that P2X7 receptors are present in both raft and nonraft compartments of plasma membranes; the receptors forming a nonselective cation channel are located in the nonraft fraction. P2X7 receptors in the rafts are coupled to the activation of N-SMase, which increases the content of ceramides in rafts. This may contribute to the activation of PLA2 in response to P2X7 receptor occupancy.

  6. Directly-Modulated VCSELs for 2x2 MIMO-OFDM Radio over Fiber in WDM-PON

    DEFF Research Database (Denmark)

    Binti Othman, Maisara; Deng, Lei; Pang, Xiaodan;


    We demonstrate directly- modulated VCSELs supporting 2x2 MIMO-OFDM 5.6-GHz radio over fiber signaling over 20-km WDM-PON. Error-free signal demodulation of 64-subcarrier 4-QAM signals modulated at 198.5-Mb/s is achieved after fiber and 2-m indoor wireless transmission.......We demonstrate directly- modulated VCSELs supporting 2x2 MIMO-OFDM 5.6-GHz radio over fiber signaling over 20-km WDM-PON. Error-free signal demodulation of 64-subcarrier 4-QAM signals modulated at 198.5-Mb/s is achieved after fiber and 2-m indoor wireless transmission....

  7. Post-translational allosteric activation of the P2X7 receptor through glycosaminoglycan chains of CD44 proteoglycans


    Moura, GEDD; Lucena, SV; Lima, MA; Nascimento, FD; Gesteira, TF; Nader, HB; Paredes-Gamero, EJ; Tersariol, ILS


    Here, we present evidence for the positive allosteric modulation of the P2X7 receptor through glycosaminoglycans (GAGs) in CHO (cell line derived from the ovary of the Chinese hamster) cells. The marked potentiation of P2X7 activity through GAGs in the presence of non-saturating agonists concentrations was evident with the endogenous expression of the receptor in CHO cells. The presence of GAGs on the surface of CHO cells greatly increased the sensitivity to adenosine 5′-triphosphate and chan...

  8. Papel do receptor P2X7 em modelo murino de infecção por Mycobacterium tuberculosis


    Santos Junior,André Avelino dos


    A tuberculose (TB) continua sendo uma das principais causas de morte no mundo, devido à grande capacidade de adaptação do bacilo que pode sobreviver em diferentes condições dentro e fora do hospedeiro humano. Estudos prévios mostraram evidências de que polimorfismos no receptor purinérgico P2X7 estão associados ao aumento da suscetibilidade à TB. O presente estudo objetivou analisar o papel do receptor purinérgico P2X7, na infecção por M. tuberculosis em camundongos, e os possíveis mecanismos...

  9. Synthesis of Monoclinic Form of Gd2-xNaxCuO4 by Direct Precipitation from Molten Salt

    Institute of Scientific and Technical Information of China (English)


    A new phase of Gd2-xNaxCuO4 was synthesized by direct precipitation from the mixture of Gd2O3 and CuO in the molten KOH/NaOH/KNO3 solution at temperature as low as 280° C. The resulting precipitate was characterized by using SEM, XRD, EDX, XPS and magnetic method. The XRD data indicate that the precipitated Gd2-xNaxCuO4 is monoclinic with lattice parameters a=8.6816(A), b=3.7233(A). C=6.0796(A), α =γ =90°, β =108.75° and V=186.1(A)3.

  10. Effects of protein deprivation and re-feeding on P2X_2 receptors in enteric neurons

    Institute of Scientific and Technical Information of China (English)

    Rúbia; Misawa; Priscila; Azevedo; Girotti; Márcia; Sanae; Mizuno; Edson; Aparecido; Liberti; John; Barton; Furness; Patricia; Castelucci


    AIM:To investigate the effects of malnutrition and refeeding on the P2X2 receptor,nitric oxide synthase(NOS),calretinin,calbindin and choline acetyltransferase(ChAT) in neurons of the rat ileum.METHODS:We analyzed the co-localization,numbers and sizes of P2X2-expressing neurons in relation to NOS-immunoreactive(IR),calbindin-IR,ChAT-IR,and calretinin-IR neurons of the myenteric and submucosal plexus.The experimental groups consisted of:(1) rats maintained on normal feed throughout pregnancy until 42 d post-...

  11. “P2X7 Receptor Activation Regulates Microglial Cell Death During Oxygen-Glucose Deprivation”


    Eyo, Ukpong B.; Miner, Sam A.; Ahlers, Katelin E.; Wu, Long-Jun; Dailey, Michael E.


    Brain-resident microglia may promote tissue repair following stroke but, like other cells, they are vulnerable to ischemia. Here we identify mechanisms involved in microglial ischemic vulnerability. Using time-lapse imaging of cultured BV2 microglia, we show that simulated ischemia (oxygen-glucose deprivation; OGD) induces BV2 microglial cell death. Removal of extracellular Ca2+ or application of Brilliant Blue G (BBG), a potent P2X7 receptor (P2X7R) antagonist, protected BV2 microglia from d...

  12. Hierarchical self-assembly of designed 2x2-alpha-helix bundle proteins on Au(111) surfaces

    DEFF Research Database (Denmark)

    Wackerbarth, Hainer; Tofteng, A.P.; Jensen, K.J.


    Self-assembled monolayers of biomolecules on atomically planar surfaces offer the prospect of complex combinations of controlled properties, e. g., for bioelectronics. We have prepared a novel hemi-4-alpha-helix bundle protein by attaching two alpha-helical peptides to a cyclo-dithiothreitol (cyclo...... proteins retained. The surface properties of the DTT and 2 x 2- R-helix bundle protein adlayer were characterized by interfacial capacitance and impedance techniques. Reductive desorption was used to determine the coverage of the adlayers, giving values of 65 and 16 mu C cm(-2) for DTT and 2 x 2-helix...

  13. Inter-subunit disulfide locking of the human P2X3 receptor elucidates ectodomain movements associated with channel gating. (United States)

    Stephan, Gabriele; Kowalski-Jahn, Maria; Zens, Christopher; Schmalzing, Günther; Illes, Peter; Hausmann, Ralf


    P2X3 receptors (P2X3R) are trimeric ATP-gated cation channels involved in sensory neurotransmission and inflammatory pain. We used homology modeling and molecular dynamic simulations of the hP2X3R to identify inter-subunit interactions of residues that are instrumental to elucidate conformational changes associated with gating of the hPX3R. We identified an ionic interaction between E112 and R198 of the head domain and dorsal fin domain, respectively, and E57 and T263 of the lower body domains of adjacent subunits and detected a marked rearrangement of these domains during gating of the hP3X3R. Double-mutant cycle analysis of the inter-subunit residue pairs E112/R198 and E57/T263 revealed significant interaction-free energies. Disulfide locking of the hP2X3R E112C/R198C or the E57C/T263C double cysteine mutants markedly reduced the ATP-induced current responses. The decreased current amplitude following inter-subunit disulfide cross-linking indicates that disulfide locking of the head and dorsal fin domains or at the level of the lower body domains of the hP2X3R prevents the gating-induced conformational rearrangement of the subunits with respect to each other. The distinct reorganization of the subunit interfaces during gating of the hP2X3R is generally consistent with the gating mechanism of other P2XRs. Charge-reversal mutagenesis and methanethiosulfonate (MTS)-modification of substituted cysteines demonstrated that E112 and R198 interact electrostatically. Both disulfide locking and salt bridge breaking of the E112/R198 interaction reduced the hP2X3R function. We conclude that the inter-subunit salt bridge between E112 and R198 of the head and dorsal fin domains, respectively, serves to control the mobility of these domains during agonist-activation of the hP2X3R.

  14. Unbalanced 2 x 2 factorial designs and the interaction effect: a troublesome combination.

    Directory of Open Access Journals (Sweden)

    Johannes A Landsheer

    Full Text Available In this power study, ANOVAs of unbalanced and balanced 2 x 2 datasets are compared (N = 120. Datasets are created under the assumption that H1 of the effects is true. The effects are constructed in two ways, assuming: 1. contributions to the effects solely in the treatment groups; 2. contrasting contributions in treatment and control groups. The main question is whether the two ANOVA correction methods for imbalance (applying Sums of Squares Type II or III; SS II or SS III offer satisfactory power in the presence of an interaction. Overall, SS II showed higher power, but results varied strongly. When compared to a balanced dataset, for some unbalanced datasets the rejection rate of H0 of main effects was undesirably higher. SS III showed consistently somewhat lower power. When the effects were constructed with equal contributions from control and treatment groups, the interaction could be re-estimated satisfactorily. When an interaction was present, SS III led consistently to somewhat lower rejection rates of H0 of main effects, compared to the rejection rates found in equivalent balanced datasets, while SS II produced strongly varying results. In data constructed with only effects in the treatment groups and no effects in the control groups, the H0 of moderate and strong interaction effects was often not rejected and SS II seemed applicable. Even then, SS III provided slightly better results when a true interaction was present. ANOVA allowed not always for a satisfactory re-estimation of the unique interaction effect. Yet, SS II worked better only when an interaction effect could be excluded, whereas SS III results were just marginally worse in that case. Overall, SS III provided consistently 1 to 5% lower rejection rates of H0 in comparison with analyses of balanced datasets, while results of SS II varied too widely for general application.

  15. Thermodynamic Properties of κ-(BEDT-TTF2X Salts: Electron Correlations and Superconductivity

    Directory of Open Access Journals (Sweden)

    Yasuhiro Nakazawa


    Full Text Available Heat capacity measurements of κ-(BEDT-TTF2X (BEDT-TTF: Bis(ethylendithio tetrathiafulvalene, X: counteranions which are classified as two-dimensional (2D dimer-Mott system are reported. At first, we explain structural and electronic features originated from rigid dimerization in donor arrangement in 2D layers. The antiferromagnetic Mott insulating phase located at low-pressure region in the phase diagram shows vanishing γ electronic heat capacity coefficient in the heat capacity, which claims opening of a charge-gap in this insulating state. Then, a systematic change of the γ around the Mott boundary region is reported in relation to the glass freezing of ethylene dynamics. The thermodynamic parameters determined by ∆Cp/γTc of 10 K class superconductors, κ-(BEDT-TTF2Cu(NCS2 and κ-(BEDT-TTF2Cu[N(CN2]Br demonstrate that a rather large gap with a strong coupling character appears around the Fermi-surface. On the other hand, the low temperature heat capacity clearly shows a picture of nodal-gap structure due to an anisotropic pairing. The comparison with lower Tc compounds in the κ-type structure is also performed so as to discuss overall features of the κ-type superconductors. The heat capacity measurements of hole-doped systems containing mercury in the counteranions show an anomalous enhancement of γ, which is consistent with the T1−1 of NMR experiments etc. The results of heat capacity measurements under high pressures are also reported.

  16. Structural and Electrical Properties of Layered Pervoskite Manganites Nd2-2xSr1+2xMn2 O7 (x=0.25, 0.3, 0.4)

    Institute of Scientific and Technical Information of China (English)


    Tetragonally layered perovskite manganites of Nd2-2xSr1+2xMn2O7 (x=0.25, 0.3, 0.4) were fabricated by using solid-state reaction technique.Structural characterization of the compounds was investigated by X-ray diffraction (XRD) and FT-IR absorption spectra.The XRD patterns revealed that all the samples were single phase.X-ray photoemission spectroscopy (XPS) was used to investigate their electronic structures.It was found that manganese was in mixed states of Mn3+ and Mn4+ whereas lattice oxygen and chemical absorbed oxygen were existed in all the samples.The high temperature electrical properties of Nd2-2xSr1+2xMn2O7 (x=0.3, 0.4) were measured by standard four-probe technique.The results showed that both compounds had semi-conductivity behavior in the temperature range of 300~1073 K, and the electrical conduction was dominated by thermally activated behavior above 500 K.

  17. Procedures to characterize and study P2Z/P2X7 purinoceptor: flow cytometry as a promising practical, reliable tool

    Directory of Open Access Journals (Sweden)

    Nihei Oscar Kenji


    Full Text Available The expression of P2Z/P2X7 purinoceptor in different cell types is well established. This receptor is a member of the ionotropic P2X receptor family, which is composed by seven cloned receptor subtypes (P2X1 - P2X7. Interestingly, the P2Z/P2X7 has a unique feature of being linked to a non-selective pore which allows the passage of molecules up to 900 Da depending on the cell type. Early studies of P2Z/P2X7 purinoceptor were exclusively based on classical pharmacological studies but the recent tools of molecular biology have enriched the analysis of the receptor expression. The majority of assays and techniques chosen so far to study the expression of P2Z/P2X7 receptor explore directly or indirectly the effects of the opening of P2Z/P2X7 linked pore. In this review we describe the main techniques used to study the expression and functionality of P2Z/P2X7 receptor. Additionally, the increasing need and importance of a multifunctional analysis of P2Z/P2X7 expression based on flow cytometry technology is discussed, as well as the adoption of a more complete analysis of P2Z/P2X7 expression involving different techniques.

  18. Characterization of (11)C-GSK1482160 for Targeting the P2X7 Receptor as a Biomarker for Neuroinflammation. (United States)

    Territo, Paul R; Meyer, Jill A; Peters, Jonathan S; Riley, Amanda A; McCarthy, Brian P; Gao, Mingzhang; Wang, Min; Green, Mark A; Zheng, Qi-Huang; Hutchins, Gary D


    The purinergic receptor subtype 7 (P2X7R) represents a novel molecular target for imaging neuroinflammation via PET. GSK1482160, a potent P2X7R antagonist, has high receptor affinity, high blood-brain barrier penetration, and the ability to be radiolabeled with (11)C. We report the initial physical and biologic characterization of this novel ligand. Methods:(11)C-GSK1482160 was synthesized according to published methods. Cell density studies were performed on human embryonic kidney cell lines expressing human P2X7R (HEK293-hP2X7R) and underwent Western blotting, an immunofluorescence assay, and radioimmunohistochemistry analysis using P2X7R polyclonal antibodies. Receptor density and binding potential were determined by saturation and association-disassociation kinetics, respectively. Peak immune response to lipopolysaccharide treatment in mice was determined in time course studies and analyzed via Iba1 and P2X7R Western blotting and Iba1 immunohistochemistry. Whole-animal biodistribution studies were performed on saline- or lipopolysaccharide-treated mice at 15, 30, and 60 min after radiotracer administration. Dynamic in vivo PET/CT was performed on the mice at 72 h after administration of saline, lipopolysaccharide, or lipopolysaccharide + blocking, and 2-compartment, 5-parameter tracer kinetic modeling of brain regions was performed. Results: P2X7R changed linearly with concentrations or cell numbers. For high-specific-activity (11)C-GSK1482160, receptor density and Kd were 1.15 ± 0.12 nM and 3.03 ± 0.10 pmol/mg, respectively, in HEK293-hP2X7R membranes. Association constant kon, dissociation constant koff, and binding potential (kon/koff) in HEK293-hP2X7R cells were 0.2312 ± 0.01542 min(-1)⋅nM(-1), 0.2547 ± 0.0155 min(-1), and 1.0277 ± 0.207, respectively. Whole-brain Iba1 e