WorldWideScience

Sample records for gravitationally induced inhibitions

  1. On the Induced Gravitational Collapse

    Directory of Open Access Journals (Sweden)

    M. Becerra Laura

    2018-01-01

    Full Text Available The induced gravitational collapse (IGC paradigm has been applied to explain the long gamma ray burst (GRB associated with type Ic supernova, and recently the Xray flashes (XRFs. The progenitor is a binary systems of a carbon-oxygen core (CO and a neutron star (NS. The CO core collapses and undergoes a supernova explosion which triggers the hypercritical accretion onto the NS companion (up to 10-2 M⊙s-1. For the binary driven hypernova (BdHNe, the binary system is enough bound, the NS reach its critical mass, and collapse to a black hole (BH with a GRB emission characterized by an isotropic energy Eiso > 1052 erg. Otherwise, for binary systems with larger binary separations, the hypercritical accretion onto the NS is not sufficient to induced its gravitational collapse, a X-ray flash is produced with Eiso < 1052 erg. We’re going to focus in identify the binary parameters that limits the BdHNe systems with the XRFs systems.

  2. Induced forces in the gravitational field

    International Nuclear Information System (INIS)

    Voracek, P.

    1979-01-01

    In this paper the expression for the magnitude of the so-called induced force, acting on a mass particle, is deduced. The origin of this force is causally connected to the increase of the rest mass of the particle in the gravitational field. (orig.)

  3. Optical-Gravitation Nonlinearity: A Change of Gravitational Coefficient G induced by Gravitation Field

    OpenAIRE

    R. Vlokh; M. Kostyrko

    2006-01-01

    Nonlinear effect of the gravitation field of spherically symmetric mass on the gravitational coefficient G has been analysed. In frame of the approaches of parametric optics and gravitation nonlinearity we have shown that the gravitation field of spherically symmetric mass can lead to changes in the gravitational coefficient G.

  4. Gravitationally induced neutrino oscillation phases in static spacetimes

    International Nuclear Information System (INIS)

    Bhattacharya, T.; Habib, S.; Mottola, E.

    1999-01-01

    We critically examine the recent claim of a 'new effect' of gravitationally induced quantum mechanical phases in neutrino oscillations. Because this claim has generated some discussion in the literature we present here a straightforward calculation of the phase and clarify some of the conceptual issues involved, particularly in relation to the equivalence principle. When expressed in terms of the asymptotic energy of the neutrinos E and Schwarzschild radial coordinates r, the lowest order at which such a gravitational effect appears is (GMΔm 4 /ℎE 3 )ln(r B /r A ). copyright 1999 The American Physical Society

  5. Influence of norepinephrine transporter inhibition on hemodynamic response to hypergravitation

    OpenAIRE

    Strempel, Sebastian

    2011-01-01

    Background: Sympathetically-mediated tachycardia and vasoconstriction maintain blood pressure during hypergravitational stress, thereby preventing gravitation-induced loss of consciousness (g-LOC). Norepinephrine transporter (NET) inhibition prevents neurally-mediated (pre)syncope during gravitational stress imposed by head-up tilt testing. Thus, it seems reasonable that NET inhibition could increase tolerance to hypergravitational stress. Methods. We performed a double-blind, randomized...

  6. Gravitational Waves from Gravitational Collapse

    Directory of Open Access Journals (Sweden)

    Chris L. Fryer

    2011-01-01

    Full Text Available Gravitational-wave emission from stellar collapse has been studied for nearly four decades. Current state-of-the-art numerical investigations of collapse include those that use progenitors with more realistic angular momentum profiles, properly treat microphysics issues, account for general relativity, and examine non-axisymmetric effects in three dimensions. Such simulations predict that gravitational waves from various phenomena associated with gravitational collapse could be detectable with ground-based and space-based interferometric observatories. This review covers the entire range of stellar collapse sources of gravitational waves: from the accretion-induced collapse of a white dwarf through the collapse down to neutron stars or black holes of massive stars to the collapse of supermassive stars.

  7. Gravitational waves from gravitational collapse

    Energy Technology Data Exchange (ETDEWEB)

    Fryer, Christopher L [Los Alamos National Laboratory; New, Kimberly C [Los Alamos National Laboratory

    2008-01-01

    Gravitational wave emission from stellar collapse has been studied for nearly four decades. Current state-of-the-art numerical investigations of collapse include those that use progenitors with more realistic angular momentum profiles, properly treat microphysics issues, account for general relativity, and examine non-axisymmetric effects in three dimensions. Such simulations predict that gravitational waves from various phenomena associated with gravitational collapse could be detectable with ground-based and space-based interferometric observatories. This review covers the entire range of stellar collapse sources of gravitational waves: from the accretion induced collapse of a white dwarf through the collapse down to neutron stars or black holes of massive stars to the collapse of supermassive stars.

  8. Gravitational Waves from Gravitational Collapse.

    Science.gov (United States)

    Fryer, Chris L; New, Kimberly C B

    2011-01-01

    Gravitational-wave emission from stellar collapse has been studied for nearly four decades. Current state-of-the-art numerical investigations of collapse include those that use progenitors with more realistic angular momentum profiles, properly treat microphysics issues, account for general relativity, and examine non-axisymmetric effects in three dimensions. Such simulations predict that gravitational waves from various phenomena associated with gravitational collapse could be detectable with ground-based and space-based interferometric observatories. This review covers the entire range of stellar collapse sources of gravitational waves: from the accretion-induced collapse of a white dwarf through the collapse down to neutron stars or black holes of massive stars to the collapse of supermassive stars. Supplementary material is available for this article at 10.12942/lrr-2011-1.

  9. The Hall-induced stability of gravitating fluids

    Science.gov (United States)

    Karmakar, P. K.; Goutam, H. P.

    2018-05-01

    We analyze the stability behavior of low-density partially ionized self-gravitating magnetized unbounded dusty plasma fluid in the presence of the Hall diffusion effects (HDEs) in the non-ideal magnetohydrodynamic (MHD) equilibrium framework. The effects of inhomogeneous self-gravity are methodically included in the basic model tapestry. Application of the Fourier plane-wave perturbative treatment decouples the structuration representative parameters into a linear generalized dispersion relation (sextic) in a judicious mean-fluid approximation. The dispersion analysis shows that the normal mode, termed as the gravito-magneto-acoustic (GMA) mode, is drastically modified due to the HDEs. This mode is highly dispersive, and driven unstable by the Hall current resulting from the symmetry-breaking of electrons and ions relative to the magnetic field. The mode feature, which is derived from a modified induction with the positive Hall, is against the ideal MHD. It is further demonstrated that the HDEs play stabilizing roles by supporting the cloud against gravitational collapse. Provided that the HDEs are concurrently switched off, the collapse occurs on the global spatial scale due to enhanced inward accretion of the gravitating dust constituents. It is seen explicitly that the enhanced dust-charge leads to stabilizing effects. Besides, the Hall-induced fluctuations, as propagatory wave modes, exhibit both normal and anomalous dispersions. The reliability checkup of the entailed results as diverse corollaries and special cases are illustratively discussed in the panoptic light of the earlier paradigmatic predictions available in the literature.

  10. HYPERCRITICAL ACCRETION, INDUCED GRAVITATIONAL COLLAPSE, AND BINARY-DRIVEN HYPERNOVAE

    Energy Technology Data Exchange (ETDEWEB)

    Fryer, Chris L. [CCS-2, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Rueda, Jorge A.; Ruffini, Remo [ICRANet, Piazza della Repubblica 10, I-65122 Pescara (Italy)

    2014-10-01

    The induced gravitational collapse (IGC) paradigm has been successfully applied to the explanation of the concomitance of gamma-ray bursts (GRBs) with supernovae (SNe) Ic. The progenitor is a tight binary system composed of a carbon-oxygen (CO) core and a neutron star (NS) companion. The explosion of the SN leads to hypercritical accretion onto the NS companion, which reaches the critical mass, hence inducing its gravitational collapse to a black hole (BH) with consequent emission of the GRB. The first estimates of this process were based on a simplified model of the binary parameters and the Bondi-Hoyle-Lyttleton accretion rate. We present here the first full numerical simulations of the IGC phenomenon. We simulate the core-collapse and SN explosion of CO stars to obtain the density and ejection velocity of the SN ejecta. We follow the hydrodynamic evolution of the accreting material falling into the Bondi-Hoyle surface of the NS all the way up to its incorporation in the NS surface. The simulations go up to BH formation when the NS reaches the critical mass. For appropriate binary parameters, the IGC occurs in short timescales ∼10{sup 2}-10{sup 3} s owing to the combined effective action of the photon trapping and the neutrino cooling near the NS surface. We also show that the IGC scenario leads to a natural explanation for why GRBs are associated only with SNe Ic with totally absent or very little helium.

  11. Erratum: Erratum to: Thermodynamic implications of the gravitationally induced particle creation scenario

    Science.gov (United States)

    Saha, Subhajit; Mondal, Anindita

    2018-04-01

    We would like to rectify an error regarding the validity of the first law of thermodynamics (FLT) on the apparent horizon of a spatially flat Friedmann-Lemaitre-Robertson-Walker (FLRW) universe for the gravitationally induced particle creation scenario with constant specific entropy and an arbitrary particle creation rate (see Sect. 3.1 of original article)

  12. Gravitational Casimir–Polder effect

    Directory of Open Access Journals (Sweden)

    Jiawei Hu

    2017-04-01

    Full Text Available The interaction due to quantum gravitational vacuum fluctuations between a gravitationally polarizable object modelled as a two-level system and a gravitational boundary is investigated. This quantum gravitational interaction is found to be position-dependent, which induces a force in close analogy to the Casimir–Polder force in the electromagnetic case. For a Dirichlet boundary, the quantum gravitational potential for the polarizable object in its ground-state is shown to behave like z−5 in the near zone, and z−6 in the far zone, where z is the distance to the boundary. For a concrete example, where a Bose–Einstein condensate is taken as a gravitationally polarizable object, the relative correction to the radius of the BEC caused by fluctuating quantum gravitational waves in vacuum is found to be of order 10−21. Although the correction is far too small to observe in comparison with its electromagnetic counterpart, it is nevertheless of the order of the gravitational strain caused by a recently detected black hole merger on the arms of the LIGO.

  13. Mechanisms of caffeine-induced inhibition of UVB carcinogenesis

    Directory of Open Access Journals (Sweden)

    Allan H Conney

    2013-06-01

    Full Text Available Sunlight-induced nonmelanoma skin cancer is the most prevalent cancer in the United States with more than 2 million cases per year. Several studies have shown an inhibitory effect of caffeine administration on UVB-induced skin cancer in mice, and these studies are paralleled by epidemiology studies that indicate an inhibitory effect of coffee drinking on nonmelanoma skin cancer in humans. Strikingly, decaffeinated coffee consumption had no such inhibitory effect.Mechanism studies indicate that caffeine has a sunscreen effect that inhibits UVB-induced formation of thymine dimers and sunburn lesions in the epidermis of mice. In addition, caffeine administration has a biological effect that enhances UVB-induced apoptosis thereby enhancing the elimination of damaged precancerous cells, and caffeine administration also enhances apoptosis in tumors. Caffeine administration enhances UVB-induced apoptosis by p53-dependent and p53-independent mechanisms. Exploration of the p53-independent effect indicated that caffeine administration enhanced UVB-induced apoptosis by inhibiting the UVB-induced increase in ATR-mediated formation of phospho-Chk1 (Ser345 and abolishing the UVB-induced decrease in cyclin B1 which resulted in caffeine-induced premature and lethal mitosis in mouse skin. In studies with cultured primary human keratinocytes, inhibition of ATR with siRNA against ATR inhibited Chk1 phosphorylation and enhanced UVB-induced apoptosis. Transgenic mice with decreased epidermal ATR function that were irradiated chronically with UVB had 69% fewer tumors at the end of the study compared with irradiated littermate controls with normal ATR function. These results, which indicate that genetic inhibition of ATR (like pharmacologic inhibition of ATR via caffeine inhibits UVB-induced carcinogenesis and supports the concept that ATR-mediated phosphorylation of Chk1 is an important target for caffeine’s inhibitory effect on UVB-induced carcinogenesis.

  14. Gravitationally self-induced phase transition

    International Nuclear Information System (INIS)

    Novello, M.; Duque, S.L.S.

    1990-01-01

    We propose a new mechanism by means of which a phase transition can be stimulated by self-gravitating matter. We suggest that this model could be used to explain the observed isotropy of the Universe. (orig.)

  15. How to detect the gravitationally induced phase shift of electromagnetic waves by optical-fiber interferometry

    International Nuclear Information System (INIS)

    Tanaka, K.

    1983-01-01

    Attention is called to a laboratory experiment of an optical-fiber interferometer which can show the gravitationally induced phase shift of optical waves. A phase shift of approx.10 -6 rad is anticipated for the Earth's gravitational potential difference of 1 m when a He-Ne laser and two multiple-turn optical-fiber loops of length 5 km are used. The phase shift can be varied by rotating the loops about an axis parallel to the Earth's surface. This order of phase shifts can be detected by current optical-fiber interferometric techniques

  16. Gravitational decoherence

    International Nuclear Information System (INIS)

    Bassi, Angelo; Großardt, André; Ulbricht, Hendrik

    2017-01-01

    We discuss effects of loss of coherence in low energy quantum systems caused by or related to gravitation, referred to as gravitational decoherence. These effects, resulting from random metric fluctuations, for instance, promise to be accessible by relatively inexpensive table-top experiments, way before the scales where true quantum gravity effects become important. Therefore, they can provide a first experimental view on gravity in the quantum regime. We will survey models of decoherence induced both by classical and quantum gravitational fluctuations; it will be manifest that a clear understanding of gravitational decoherence is still lacking. Next we will review models where quantum theory is modified, under the assumption that gravity causes the collapse of the wave functions, when systems are large enough. These models challenge the quantum-gravity interplay, and can be tested experimentally. In the last part we have a look at the state of the art of experimental research. We will review efforts aiming at more and more accurate measurements of gravity ( G and g ) and ideas for measuring conventional and unconventional gravity effects on nonrelativistic quantum systems. (topical review)

  17. Inhibition of ethylene production by putrescine alleviates aluminium-induced root inhibition in wheat plants.

    Science.gov (United States)

    Yu, Yan; Jin, Chongwei; Sun, Chengliang; Wang, Jinghong; Ye, Yiquan; Zhou, Weiwei; Lu, Lingli; Lin, Xianyong

    2016-01-08

    Inhibition of root elongation is one of the most distinct symptoms of aluminium (Al) toxicity. Although putrescine (Put) has been identified as an important signaling molecule involved in Al tolerance, it is yet unknown how Put mitigates Al-induced root inhibition. Here, the possible mechanism was investigated by using two wheat genotypes differing in Al resistance: Al-tolerant Xi Aimai-1 and Al-sensitive Yangmai-5. Aluminium caused more root inhibition in Yangmai-5 and increased ethylene production at the root apices compared to Xi Aimai-1, whereas the effects were significantly reversed by ethylene biosynthesis inhibitors. The simultaneous exposure of wheat seedlings to Al and ethylene donor, ethephon, or ethylene biosynthesis precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), increased ethylene production and aggravated root inhibition, which was more pronounced in Xi Aimai-1. In contrast, Put treatment decreased ethylene production and alleviated Al-induced root inhibition in both genotypes, and the effects were more conspicuous in Yangmai-5. Furthermore, our results indicated that Al-induced ethylene production was mediated by ACC synthase (ACS) and ACC oxidase, and that Put decreased ethylene production by inhibiting ACS. Altogether, these findings indicate that ethylene is involved in Al-induced root inhibition and this process could be alleviated by Put through inhibiting ACS activity.

  18. On the gravitational radiation formula

    International Nuclear Information System (INIS)

    Schaefer, G.; Dehnen, H.

    1980-01-01

    For electromagnetically as well as gravitationally bound quantum mechanical many-body systems the coefficients of absorption and induced emission of gravitational radiation are calculated in the first-order approximation. The results are extended subsequently to systems with arbitrary non-Coulomb-like two-particle interaction potentials;it is shown explicitly that in all cases the perturbation of the binding potentials of the bound systems by the incident gravitational wave field itself must be taken into account. With the help of the thermodynamic equilibrium of gravitational radiation and quantised matter, the coefficients for spontaneous emission of gravitational radiation are derived and the gravitational radiation formula for emission of gravitational quadrupole radiation by bound quantum mechanical many-body systems is given. According to the correspondence principle the present result is completely identical with the well known classical radiation formula, by which recent criticism against this formula is refuted. Finally the quantum mechanical absorption cross section for gravitational quadrupole radiation is deduced and compared with the corresponding classical expressions. As a special example the vibrating two-mass quadrupole is treated explicitly. (author)

  19. Gravitational Anomaly and Transport Phenomena

    International Nuclear Information System (INIS)

    Landsteiner, Karl; Megias, Eugenio; Pena-Benitez, Francisco

    2011-01-01

    Quantum anomalies give rise to new transport phenomena. In particular, a magnetic field can induce an anomalous current via the chiral magnetic effect and a vortex in the relativistic fluid can also induce a current via the chiral vortical effect. The related transport coefficients can be calculated via Kubo formulas. We evaluate the Kubo formula for the anomalous vortical conductivity at weak coupling and show that it receives contributions proportional to the gravitational anomaly coefficient. The gravitational anomaly gives rise to an anomalous vortical effect even for an uncharged fluid.

  20. Gravitational effects of global textures

    International Nuclear Information System (INIS)

    Noetzold, D.

    1990-03-01

    A solution for the dynamics of global textures is obtained. Their gravitational field during the collapse and the subsequent evolution is found to be given solely by a space-time dependent ''deficit solid angle.'' The frequency shift of photons traversing this gravitational field is calculated. The space-time dependent texture metric locally contracts the volume of three-space and thereby induces overdensities in homogeneous matter distributions. There are no gravitational forces unless matter has a nonzero angular momentum with respect to the texture origin which would be the case for moving textures

  1. Observation of Gravitationally Induced Vertical Striation of Polarized Ultracold Neutrons by Spin-Echo Spectroscopy.

    Science.gov (United States)

    Afach, S; Ayres, N J; Ban, G; Bison, G; Bodek, K; Chowdhuri, Z; Daum, M; Fertl, M; Franke, B; Griffith, W C; Grujić, Z D; Harris, P G; Heil, W; Hélaine, V; Kasprzak, M; Kermaidic, Y; Kirch, K; Knowles, P; Koch, H-C; Komposch, S; Kozela, A; Krempel, J; Lauss, B; Lefort, T; Lemière, Y; Mtchedlishvili, A; Musgrave, M; Naviliat-Cuncic, O; Pendlebury, J M; Piegsa, F M; Pignol, G; Plonka-Spehr, C; Prashanth, P N; Quéméner, G; Rawlik, M; Rebreyend, D; Ries, D; Roccia, S; Rozpedzik, D; Schmidt-Wellenburg, P; Severijns, N; Thorne, J A; Weis, A; Wursten, E; Wyszynski, G; Zejma, J; Zenner, J; Zsigmond, G

    2015-10-16

    We describe a spin-echo method for ultracold neutrons (UCNs) confined in a precession chamber and exposed to a |B0|=1  μT magnetic field. We have demonstrated that the analysis of UCN spin-echo resonance signals in combination with knowledge of the ambient magnetic field provides an excellent method by which to reconstruct the energy spectrum of a confined ensemble of neutrons. The method takes advantage of the relative dephasing of spins arising from a gravitationally induced striation of stored UCNs of different energies, and also permits an improved determination of the vertical magnetic-field gradient with an exceptional accuracy of 1.1  pT/cm. This novel combination of a well-known nuclear resonance method and gravitationally induced vertical striation is unique in the realm of nuclear and particle physics and should prove to be invaluable for the assessment of systematic effects in precision experiments such as searches for an electric dipole moment of the neutron or the measurement of the neutron lifetime.

  2. Radiatively-induced gravitational leptogenesis

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, J.I., E-mail: pymcdonald@swansea.ac.uk; Shore, G.M., E-mail: g.m.shore@swansea.ac.uk

    2015-12-17

    We demonstrate how loop effects in gravitational backgrounds lead to a difference in the propagation of matter and antimatter, and show this is forbidden in flat space due to CPT and translation invariance. This mechanism, which is naturally present in beyond the standard model (BSM) theories exhibiting C and CP violation, generates a curvature-dependent chemical potential for leptons in the low-energy effective Lagrangian, allowing a matter–antimatter asymmetry to be generated in thermodynamic equilibrium, below the BSM scale.

  3. Radiatively-induced gravitational leptogenesis

    Directory of Open Access Journals (Sweden)

    J.I. McDonald

    2015-12-01

    Full Text Available We demonstrate how loop effects in gravitational backgrounds lead to a difference in the propagation of matter and antimatter, and show this is forbidden in flat space due to CPT and translation invariance. This mechanism, which is naturally present in beyond the standard model (BSM theories exhibiting C and CP violation, generates a curvature-dependent chemical potential for leptons in the low-energy effective Lagrangian, allowing a matter–antimatter asymmetry to be generated in thermodynamic equilibrium, below the BSM scale.

  4. GSK621 activates AMPK signaling to inhibit LPS-induced TNFα production

    International Nuclear Information System (INIS)

    Wu, Yong-hong; Li, Quan; Li, Ping; Liu, Bei

    2016-01-01

    LPS stimulation in macrophages/monocytes induces TNFα production. We here tested the potential effect of GSK621, a novel AMP-activated protein kinase (AMPK) activator, against the process. In RAW264.7 macrophages, murine bone marrow-derived macrophages (BMDMs), and chronic obstructive pulmonary disease (COPD) patients' monocytes, GSK621 significantly inhibited LPS-induced TNFα protein secretion and mRNA synthesis. Inhibition of AMPK, through AMPKα shRNA knockdown or dominant negative mutation (T172A), almost abolished GSK621's suppression on TNFα in RAW264.7 cells. Reversely, forced-expression of a constitutively-active AMPKα (T172D) mimicked GSK621 actions and reduced LPS-induced TNFα production. Molecularly, GSK621 suppressed LPS-induced reactive oxygen species (ROS) production and nuclear factor kappa B (NFκB) activation. In vivo, GSK621 oral administration inhibited LPS-induced TNFα production and endotoxin shock in mice. In summary, GSK621 activates AMPK signaling to inhibit LPS-induced TNFα production in macrophages/monocytes. - Highlights: • GSK621 inhibits LPS-induced TNFα production/expression in RAW264.7 cells and BMDMs. • GSK621 inhibits LPS-induced TNFα production/expression in COPD patients' PBMCs. • GSK621's inhibition on TNFα production by LPS requires AMPK activation. • GSK621 inhibits LPS-induced ROS production and NFκB activation, dependent on AMPK. • GSK621 oral administration inhibits LPS-induced TNFα production and endotoxin shock in mice.

  5. Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis.

    Science.gov (United States)

    Halder, Sunil K; Beauchamp, R Daniel; Datta, Pran K

    2005-07-01

    Smad proteins play a key role in the intracellular signaling of the transforming growth factor beta (TGF-beta) superfamily of extracellular polypeptides that initiate signaling to regulate a wide variety of biological processes. The inhibitory Smad, Smad7, has been shown to function as intracellular antagonists of TGF-beta family signaling and is upregulated in several cancers. To determine the effect of Smad7-mediated blockade of TGF-beta signaling, we have stably expressed Smad7 in a TGF-beta-sensitive, well-differentiated, and non-tumorigenic cell line, FET, that was derived from human colon adenocarcinoma. Smad7 inhibits TGF-beta-induced transcriptional responses by blocking complex formation between Smad 2/3 and Smad4. While Smad7 has no effect on TGF-beta-induced activation of p38 MAPK and ERK, it blocks the phosphorylation of Akt by TGF-beta and enhances TGF-beta-induced phosphorylation of c-Jun. FET cells expressing Smad7 show anchorage-independent growth and enhance tumorigenicity in athymic nude mice. Smad7 blocks TGF-beta-induced growth inhibition by preventing TGF-beta-induced G1 arrest. Smad7 inhibits TGF-beta-mediated downregulation of c-Myc, CDK4, and Cyclin D1, and suppresses the expression of p21(Cip1). As a result, Smad7 inhibits TGF-beta-mediated downregulation of Rb phosphorylation. Furthermore, Smad7 inhibits the apoptosis of these cells. Together, Smad7 may increase the tumorigenicity of FET cells by blocking TGF-beta-induced growth inhibition and by inhibiting apoptosis. Thus, this study provides a mechanism by which a portion of human colorectal tumors may become refractory to tumor-suppressive actions of TGF-beta that might result in increased tumorigenicity.

  6. Gravitationally induced adiabatic particle production: from big bang to de Sitter

    Science.gov (United States)

    de Haro, Jaume; Pan, Supriya

    2016-08-01

    In the background of a flat homogeneous and isotropic space-time, we consider a scenario of the Universe driven by the gravitationally induced ‘adiabatic’ particle production with constant creation rate. We have shown that this Universe attains a big bang singularity in the past and at late-time it asymptotically becomes de Sitter. To clarify this model Universe, we performed a dynamical analysis and found that the Universe attains a thermodynamic equilibrium in this late de Sitter phase. Finally, for the first time, we have discussed the possible effects of ‘adiabatic’ particle creations in the context of loop quantum cosmology.

  7. Gravitationally induced adiabatic particle production: from big bang to de Sitter

    International Nuclear Information System (INIS)

    Haro, Jaume de; Pan, Supriya

    2016-01-01

    In the background of a flat homogeneous and isotropic space–time, we consider a scenario of the Universe driven by the gravitationally induced ‘adiabatic’ particle production with constant creation rate. We have shown that this Universe attains a big bang singularity in the past and at late-time it asymptotically becomes de Sitter. To clarify this model Universe, we performed a dynamical analysis and found that the Universe attains a thermodynamic equilibrium in this late de Sitter phase. Finally, for the first time, we have discussed the possible effects of ‘adiabatic’ particle creations in the context of loop quantum cosmology. (paper)

  8. Celastrol inhibits TGF-β1-induced epithelial–mesenchymal transition by inhibiting Snail and regulating E-cadherin expression

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hyereen; Lee, Minjae [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Jang, Sung-Wuk, E-mail: swjang@amc.seoul.kr [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of)

    2013-08-09

    Highlights: •We investigated the effects of celastrol on TGF-β1-induced EMT in epithelial cells. •Celastrol regulates TGF-β1-induced morphological changes and E-cadherin expression. •Celastrol inhibits TGF-β1-induced Snail expression. •Celastrol strongly suppresses TGF-β1-induced invasion in MDCK and A549 cells. -- Abstract: The epithelial–mesenchymal transition (EMT) is a pivotal event in the invasive and metastatic potentials of cancer progression. Celastrol inhibits the proliferation of a variety of tumor cells including leukemia, glioma, prostate, and breast cancer; however, the possible role of celastrol in the EMT is unclear. We investigated the effect of celastrol on the EMT. Transforming growth factor-beta 1 (TGF-β1) induced EMT-like morphologic changes and upregulation of Snail expression. The downregulation of E-cadherin expression and upregulation of Snail in Madin–Darby Canine Kidney (MDCK) and A549 cell lines show that TGF-β1-mediated the EMT in epithelial cells; however, celastrol markedly inhibited TGF-β1-induced morphologic changes, Snail upregulation, and E-cadherin expression. Migration and invasion assays revealed that celastrol completely inhibited TGF-β1-mediated cellular migration in both cell lines. These findings indicate that celastrol downregulates Snail expression, thereby inhibiting TGF-β1-induced EMT in MDCK and A549 cells. Thus, our findings provide new evidence that celastrol suppresses lung cancer invasion and migration by inhibiting TGF-β1-induced EMT.

  9. Trichilia monadelpha Bark Extracts Inhibit Carrageenan-Induced ...

    African Journals Online (AJOL)

    The present study was undertaken to evaluate the anti-inflammatory properties of aqueous (TWE), alcoholic (TAE) and petroleum ether extract (TPEE) of T. ... The reference anti-inflammatory drugs (diclofenac and dexamethasone) inhibited the chick-carrageenan-induced footpad oedema, with maximal inhibitions of ...

  10. Scalar field vacuum expectation value induced by gravitational wave background

    Science.gov (United States)

    Jones, Preston; McDougall, Patrick; Ragsdale, Michael; Singleton, Douglas

    2018-06-01

    We show that a massless scalar field in a gravitational wave background can develop a non-zero vacuum expectation value. We draw comparisons to the generation of a non-zero vacuum expectation value for a scalar field in the Higgs mechanism and with the dynamical Casimir vacuum. We propose that this vacuum expectation value, generated by a gravitational wave, can be connected with particle production from gravitational waves and may have consequences for the early Universe where scalar fields are thought to play an important role.

  11. Inhibition by acrolein of light-induced stomatal opening through inhibition of inward-rectifying potassium channels in Arabidopsis thaliana.

    Science.gov (United States)

    Islam, Md Moshiul; Ye, Wenxiu; Matsushima, Daiki; Khokon, Md Atiqur Rahman; Munemasa, Shintaro; Nakamura, Yoshimasa; Murata, Yoshiyuki

    2015-01-01

    Acrolein is a reactive α,β-unsaturated aldehyde derived from lipid peroxides, which are produced in plants under a variety of stress. We investigated effects of acrolein on light-induced stomatal opening using Arabidopsis thaliana. Acrolein inhibited light-induced stomatal opening in a dose-dependent manner. Acrolein at 100 μM inhibited plasma membrane inward-rectifying potassium (Kin) channels in guard cells. Acrolein at 100 μM inhibited Kin channel KAT1 expressed in a heterologous system using Xenopus leaves oocytes. These results suggest that acrolein inhibits light-induced stomatal opening through inhibition of Kin channels in guard cells.

  12. Retrieval-Induced Inhibition in Short-Term Memory.

    Science.gov (United States)

    Kang, Min-Suk; Choi, Joongrul

    2015-07-01

    We used a visual illusion called motion repulsion as a model system for investigating competition between two mental representations. Subjects were asked to remember two random-dot-motion displays presented in sequence and then to report the motion directions for each. Remembered motion directions were shifted away from the actual motion directions, an effect similar to the motion repulsion observed during perception. More important, the item retrieved second showed greater repulsion than the item retrieved first. This suggests that earlier retrieval exerted greater inhibition on the other item being held in short-term memory. This retrieval-induced motion repulsion could be explained neither by reduced cognitive resources for maintaining short-term memory nor by continued inhibition between short-term memory representations. These results indicate that retrieval of memory representations inhibits other representations in short-term memory. We discuss mechanisms of retrieval-induced inhibition and their implications for the structure of memory. © The Author(s) 2015.

  13. Gravitationally induced particle production and its impact on the WIMP abundance

    Directory of Open Access Journals (Sweden)

    I. Baranov

    2015-12-01

    Full Text Available A large set of independent astronomical observations have provided a strong evidence for nonbaryonic dark matter in the Universe. One of the most investigated candidates is an unknown long-lived Weakly Interacting Massive Particle (WIMP which was in thermal equilibrium with the primeval plasma. Here we investigate the WIMP abundance based on the relativistic kinetic treatment for gravitationally induced particle production recently proposed in the literature (Lima and Baranov, 2014 [16]. The new evolution equation is deduced and solved both numerically and through a semi-analytical approach. The predictions of the WIMP observables are discussed and compared with the ones obtained in the standard approach.

  14. Gliclazide directly inhibits arginine-induced glucagon release

    DEFF Research Database (Denmark)

    Cejvan, Kenan; Coy, David H; Holst, Jens Juul

    2002-01-01

    Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect of glicl......Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect....... In islet perifusions with DC-41-33, arginine-induced glucagon release was inhibited by 66%. We therefore concluded that gliclazide inhibits glucagon release by a direct action on the pancreatic A cell....

  15. Thermodynamics of gravitationally induced particle creation scenario in DGP braneworld

    Energy Technology Data Exchange (ETDEWEB)

    Jawad, Abdul; Rani, Shamaila; Rafique, Salman [COMSATS Institute of Information Technology, Department of Mathematics, Lahore (Pakistan)

    2018-01-15

    In this paper, we discuss the thermodynamical analysis for gravitationally induced particle creation scenario in the framework of DGP braneworld model. For this purpose, we consider apparent horizon as the boundary of the universe. We take three types of entropy such as Bakenstein entropy, logarithmic corrected entropy and power law corrected entropy with ordinary creation rate Γ. We analyze the first law and generalized second law of thermodynamics analytically for these entropies which hold under some constraints. The behavior of total entropy in each case is also discussed which implies the validity of generalized second law of thermodynamics. Also, we check the thermodynamical equilibrium condition for two phases of creation rate, that is constant and variable Γ and found its vitality in all cases of entropy. (orig.)

  16. Thermodynamics of gravitationally induced particle creation scenario in DGP braneworld

    International Nuclear Information System (INIS)

    Jawad, Abdul; Rani, Shamaila; Rafique, Salman

    2018-01-01

    In this paper, we discuss the thermodynamical analysis for gravitationally induced particle creation scenario in the framework of DGP braneworld model. For this purpose, we consider apparent horizon as the boundary of the universe. We take three types of entropy such as Bakenstein entropy, logarithmic corrected entropy and power law corrected entropy with ordinary creation rate Γ. We analyze the first law and generalized second law of thermodynamics analytically for these entropies which hold under some constraints. The behavior of total entropy in each case is also discussed which implies the validity of generalized second law of thermodynamics. Also, we check the thermodynamical equilibrium condition for two phases of creation rate, that is constant and variable Γ and found its vitality in all cases of entropy. (orig.)

  17. Naftopidil inhibits 5-hydroxytryptamine-induced bladder contraction in rats.

    Science.gov (United States)

    Sakai, Takumi; Kasahara, Ken-ichi; Tomita, Ken-ichi; Ikegaki, Ichiro; Kuriyama, Hiroshi

    2013-01-30

    Naftopidil is an α(1D) and α(1A) subtype-selective α(1)-adrenoceptor antagonist that has been used to treat lower urinary tract symptoms of benign prostatic hyperplasia. In this study, we investigated the effects of naftopidil on 5-hydroxytryptamine (5-HT)-induced rat bladder contraction (10(-8)-10(-4) M). Naftopidil (0.3, 1, and 3 μM) inhibited 5-HT-induced bladder contraction in a concentration-dependent manner. On the other hand, other α(1)-adrenoceptor antagonists, tamsulosin, silodosin or prazosin, did not inhibit 5-HT-induced bladder contraction. The 5-HT-induced bladder contraction was inhibited by both ketanserin and 4-(4-fluoronaphthalen-1-yl)-6-propan-2-ylpyrimidin-2-amine (RS127445), serotonin 5-HT(2A) and 5-HT(2B) receptor antagonists, respectively. In addition, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and α-methyl-5-HT, 5-HT(2A) and 5-HT(2) receptor agonists, respectively, induced bladder contraction. The 5-HT-induced bladder contraction was not inhibited by N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-yl-cyclohexanecarboxamide (WAY-100635), [1-[2[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl-1-methyl-1H-indole-3-carboxylate (GR113808) or (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulphonyl]phenol (SB269970), 5-HT(1A), 5-HT(4) and 5-HT(7) receptor antagonists, respectively. Naftopidil inhibited both the 5-HT(2A) and 5-HT(2) receptor agonists-induced bladder contractions. Naftopidil binds to the human 5-HT(2A) and 5-HT(2B) receptors with pKi values of 6.55 and 7.82, respectively. These results suggest that naftopidil inhibits 5-HT-induced bladder contraction via blockade of the 5-HT(2A) and 5-HT(2B) receptors in rats. Furthermore, 5-HT-induced bladder contraction was enhanced in bladder strips obtained from bladder outlet obstructed rats, with this contraction inhibited by naftopidil. The beneficial effects of naftopidil on storage symptoms such as urinary frequency and nocturia in patients with benign

  18. Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Khapli, Shruti M.; Tomar, Geetanjali B.; Barhanpurkar, Amruta P.; Gupta, Navita; Yogesha, S.D.; Pote, Satish T. [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India); Wani, Mohan R., E-mail: mohanwani@nccs.res.in [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India)

    2010-09-03

    Research highlights: {yields} IL-3 inhibits receptor activator of NF-{kappa}B ligand (RANKL)-induced osteoclastogenesis. {yields} IL-3 inhibits RANKL-induced JNK activation. {yields} IL-3 down-regulates expression of c-Fos and NFATc1 transcription factors. {yields} IL-3 down-regulates RANK expression posttranscriptionally and irreversibly. {yields} IL-3 inhibits in vivo RANK expression. -- Abstract: IL-3, a cytokine secreted by activated T lymphocytes, stimulates the proliferation, differentiation and survival of pluripotent hematopoietic stem cells. In this study, we investigated the mechanism of inhibitory action of IL-3 on osteoclast differentiation. We show here that IL-3 significantly inhibits receptor activator of NF-{kappa}B (RANK) ligand (RANKL)-induced activation of c-Jun N-terminal kinase (JNK). IL-3 down-regulates expression of c-Fos and nuclear factor of activated T cells (NFATc1) transcription factors. In addition, IL-3 down-regulates RANK expression posttranscriptionally in both purified osteoclast precursors and whole bone marrow cells. Furthermore, the inhibitory effect of IL-3 on RANK expression was irreversible. Interestingly, IL-3 inhibits in vivo RANK expression in mice. Thus, we provide the first evidence that IL-3 irreversibly inhibits RANK expression that results in inhibition of important signaling molecules induced by RANKL.

  19. Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis

    International Nuclear Information System (INIS)

    Khapli, Shruti M.; Tomar, Geetanjali B.; Barhanpurkar, Amruta P.; Gupta, Navita; Yogesha, S.D.; Pote, Satish T.; Wani, Mohan R.

    2010-01-01

    Research highlights: → IL-3 inhibits receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. → IL-3 inhibits RANKL-induced JNK activation. → IL-3 down-regulates expression of c-Fos and NFATc1 transcription factors. → IL-3 down-regulates RANK expression posttranscriptionally and irreversibly. → IL-3 inhibits in vivo RANK expression. -- Abstract: IL-3, a cytokine secreted by activated T lymphocytes, stimulates the proliferation, differentiation and survival of pluripotent hematopoietic stem cells. In this study, we investigated the mechanism of inhibitory action of IL-3 on osteoclast differentiation. We show here that IL-3 significantly inhibits receptor activator of NF-κB (RANK) ligand (RANKL)-induced activation of c-Jun N-terminal kinase (JNK). IL-3 down-regulates expression of c-Fos and nuclear factor of activated T cells (NFATc1) transcription factors. In addition, IL-3 down-regulates RANK expression posttranscriptionally in both purified osteoclast precursors and whole bone marrow cells. Furthermore, the inhibitory effect of IL-3 on RANK expression was irreversible. Interestingly, IL-3 inhibits in vivo RANK expression in mice. Thus, we provide the first evidence that IL-3 irreversibly inhibits RANK expression that results in inhibition of important signaling molecules induced by RANKL.

  20. Autophagy contributes to gefitinib-induced glioma cell growth inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Cheng-Yi [Department of Surgery, Fong-Yuan Hospital, Taichung 420, Taiwan (China); Graduate Institute of Pharmaceutical Science and Technology, Central Taiwan University of Science and Technology, Taichung 406, Taiwan (China); Kuan, Yu-Hsiang [Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Pharmacy, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China); Ou, Yen-Chuan; Li, Jian-Ri [Division of Urology, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Wu, Chih-Cheng [Department of Anesthesiology, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Department of Financial and Computational Mathematics, Providence University, Taichung 433, Taiwan (China); Pan, Pin-Ho [Department of Pediatrics, Tungs’ Taichung MetroHarbor Hospital, Taichung 435, Taiwan (China); Chen, Wen-Ying [Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Huang, Hsuan-Yi [Department of Surgery, Fong-Yuan Hospital, Taichung 420, Taiwan (China); Chen, Chun-Jung, E-mail: cjchen@vghtc.gov.tw [Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan (China); Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Center for General Education, Tunghai University, Taichung 407, Taiwan (China); Department of Nursing, HungKuang University, Taichung 433, Taiwan (China)

    2014-09-10

    Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, have been evaluated in patients with malignant gliomas. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma are incompletely understood. In the present study, the cytostatic potential of gefitinib was demonstrated by the inhibition of glioma cell growth, long-term clonogenic survival, and xenograft tumor growth. The cytostatic consequences were accompanied by autophagy, as evidenced by monodansylcadaverine staining of acidic vesicle formation, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), degradation of p62, punctate pattern of GFP-LC3, and conversion of GFP-LC3 to cleaved-GFP. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 or Beclin 1 attenuated gefitinib-induced growth inhibition. Gefitinib-induced autophagy was not accompanied by the disruption of the Akt/mammalian target of rapamycin signaling. Instead, the activation of liver kinase-B1/AMP-activated protein kinase (AMPK) signaling correlated well with the induction of autophagy and growth inhibition caused by gefitinib. Silencing of AMPK suppressed gefitinib-induced autophagy and growth inhibition. The crucial role of AMPK activation in inducing glioma autophagy and growth inhibition was further supported by the actions of AMP mimetic AICAR. Gefitinib was shown to be capable of reducing the proliferation of glioma cells, presumably by autophagic mechanisms involving AMPK activation. - Highlights: • Gefitinib causes cytotoxic and cytostatic effect on glioma. • Gefitinib induces autophagy. • Gefitinib causes cytostatic effect through autophagy. • Gefitinib induces autophagy involving AMPK.

  1. Autophagy contributes to gefitinib-induced glioma cell growth inhibition

    International Nuclear Information System (INIS)

    Chang, Cheng-Yi; Kuan, Yu-Hsiang; Ou, Yen-Chuan; Li, Jian-Ri; Wu, Chih-Cheng; Pan, Pin-Ho; Chen, Wen-Ying; Huang, Hsuan-Yi; Chen, Chun-Jung

    2014-01-01

    Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, have been evaluated in patients with malignant gliomas. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma are incompletely understood. In the present study, the cytostatic potential of gefitinib was demonstrated by the inhibition of glioma cell growth, long-term clonogenic survival, and xenograft tumor growth. The cytostatic consequences were accompanied by autophagy, as evidenced by monodansylcadaverine staining of acidic vesicle formation, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), degradation of p62, punctate pattern of GFP-LC3, and conversion of GFP-LC3 to cleaved-GFP. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 or Beclin 1 attenuated gefitinib-induced growth inhibition. Gefitinib-induced autophagy was not accompanied by the disruption of the Akt/mammalian target of rapamycin signaling. Instead, the activation of liver kinase-B1/AMP-activated protein kinase (AMPK) signaling correlated well with the induction of autophagy and growth inhibition caused by gefitinib. Silencing of AMPK suppressed gefitinib-induced autophagy and growth inhibition. The crucial role of AMPK activation in inducing glioma autophagy and growth inhibition was further supported by the actions of AMP mimetic AICAR. Gefitinib was shown to be capable of reducing the proliferation of glioma cells, presumably by autophagic mechanisms involving AMPK activation. - Highlights: • Gefitinib causes cytotoxic and cytostatic effect on glioma. • Gefitinib induces autophagy. • Gefitinib causes cytostatic effect through autophagy. • Gefitinib induces autophagy involving AMPK

  2. Norepinephrine transporter inhibition alters the hemodynamic response to hypergravitation.

    Science.gov (United States)

    Strempel, Sebastian; Schroeder, Christoph; Hemmersbach, Ruth; Boese, Andrea; Tank, Jens; Diedrich, André; Heer, Martina; Luft, Friedrich C; Jordan, Jens

    2008-03-01

    Sympathetically mediated tachycardia and vasoconstriction maintain blood pressure during hypergravitational stress, thereby preventing gravitation-induced loss of consciousness. Norepinephrine transporter (NET) inhibition prevents neurally mediated (pre)syncope during gravitational stress imposed by head-up tilt testing. Thus it seems reasonable that NET inhibition could increase tolerance to hypergravitational stress. We performed a double-blind, randomized, placebo-controlled crossover study in 11 healthy men (26 +/- 1 yr, body mass index 24 +/- 1 kg/m2), who ingested the selective NET inhibitor reboxetine (4 mg) or matching placebo 25, 13, and 1 h before testing on separate days. We monitored heart rate, blood pressure, and thoracic impedance in three different body positions (supine, seated, standing) and during a graded centrifuge run (incremental steps of 0.5 g for 3 min each, up to a maximal vertical acceleration load of 3 g). NET inhibition increased supine blood pressure and heart rate. With placebo, blood pressure increased in the seated position and was well maintained during standing. However, with NET inhibition, blood pressure decreased in the seated and standing position. During hypergravitation, blood pressure increased in a graded fashion with placebo. With NET inhibition, the increase in blood pressure during hypergravitation was profoundly diminished. Conversely, the tachycardic responses to sitting, standing, and hypergravitation all were greatly increased with NET inhibition. In contrast to our expectation, short-term NET inhibition did not improve tolerance to hypergravitation. Redistribution of sympathetic activity to the heart or changes in baroreflex responses could explain the excessive tachycardia that we observed.

  3. Global inhibition of reactive oxygen species (ROS inhibits paclitaxel-induced painful peripheral neuropathy.

    Directory of Open Access Journals (Sweden)

    Mehmet Fidanboylu

    Full Text Available Paclitaxel (Taxol® is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS, the aim of this study was to examine whether pharmacological inhibition of ROS could reverse established paclitaxel-induced pain or prevent the development of paclitaxel-induced pain. Using a rat model of paclitaxel-induced pain (intraperitoneal 2 mg/kg paclitaxel on days 0, 2, 4 & 6, the effects of a non-specific ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN and a superoxide selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL were compared. Systemic 100 mg/kg PBN administration markedly inhibited established paclitaxel-induced mechanical hypersensitivity to von Frey 8 g and 15 g stimulation and cold hypersensitivity to plantar acetone application. Daily systemic administration of 50 mg/kg PBN (days -1 to 13 completely prevented mechanical hypersensitivity to von Frey 4 g and 8 g stimulation and significantly attenuated mechanical hypersensitivity to von Frey 15 g. Systemic 100 mg/kg TEMPOL had no effect on established paclitaxel-induced mechanical or cold hypersensitivity. High dose (250 mg/kg systemic TEMPOL significantly inhibited mechanical hypersensitivity to von Frey 8 g & 15 g, but to a lesser extent than PBN. Daily systemic administration of 100 mg/kg TEMPOL (day -1 to 12 did not affect the development of paclitaxel-induced mechanical hypersensitivity. These data suggest that ROS play a causal role in the development and maintenance of paclitaxel-induced pain, but such effects cannot be attributed to superoxide radicals

  4. Jasmonic Acid Enhances Al-Induced Root Growth Inhibition.

    Science.gov (United States)

    Yang, Zhong-Bao; He, Chunmei; Ma, Yanqi; Herde, Marco; Ding, Zhaojun

    2017-02-01

    Phytohormones such as ethylene and auxin are involved in the regulation of the aluminum (Al)-induced root growth inhibition. Although jasmonate (JA) has been reported to play a crucial role in the regulation of root growth and development in response to environmental stresses through interplay with ethylene and auxin, its role in the regulation of root growth response to Al stress is not yet known. In an attempt to elucidate the role of JA, we found that exogenous application of JA enhanced the Al-induced root growth inhibition. Furthermore, phenotype analysis with mutants defective in either JA biosynthesis or signaling suggests that JA is involved in the regulation of Al-induced root growth inhibition. The expression of the JA receptor CORONATINE INSENSITIVE1 (COI1) and the key JA signaling regulator MYC2 was up-regulated in response to Al stress in the root tips. This process together with COI1-mediated Al-induced root growth inhibition under Al stress was controlled by ethylene but not auxin. Transcriptomic analysis revealed that many responsive genes under Al stress were regulated by JA signaling. The differential responsive of microtubule organization-related genes between the wild-type and coi1-2 mutant is consistent with the changed depolymerization of cortical microtubules in coi1 under Al stress. In addition, ALMT-mediated malate exudation and thus Al exclusion from roots in response to Al stress was also regulated by COI1-mediated JA signaling. Together, this study suggests that root growth inhibition is regulated by COI1-mediated JA signaling independent from auxin signaling and provides novel insights into the phytohormone-mediated root growth inhibition in response to Al stress. © 2017 American Society of Plant Biologists. All Rights Reserved.

  5. Fluoxetine-induced inhibition of synaptosomal [3H]5-HT release: Possible Ca2+-channel inhibition

    International Nuclear Information System (INIS)

    Stauderman, K.A.; Gandhi, V.C.; Jones, D.J.

    1992-01-01

    Fluoxetine, a selective 5-Ht uptake inhibitor, inhibited 15 mM K + -induced [ 3 H]5-HT release from rat spinal cord and cortical synaptosomes at concentrations > 0.5 uM. This effect reflected a property shared by another selective 5-HT uptake inhibitor paroxetine but not by less selective uptake inhibitors such as amitriptyline, desipramine, imipramine or nortriptyline. Inhibition of release by fluoxetine was inversely related to both the concentration of K + used to depolarize the synaptosomes and the concentration of external Ca 2+ . Experiments aimed at determining a mechanism of action revealed that fluoxetine did not inhibit voltage-independent release of [ 3 H]5-HT release induced by the Ca 2+ -ionophore A 23187 or Ca 2+ -independent release induced by fenfluramine. Moreover the 5-HT autoreceptor antagonist methiothepin did not reverse the inhibitory actions of fluoxetine on K + -induced release. Further studies examined the effects of fluoxetine on voltage-dependent Ca 2+ channels and Ca 2+ entry

  6. Madecassoside Inhibits Melanin Synthesis by Blocking Ultraviolet-Induced Inflammation

    Directory of Open Access Journals (Sweden)

    Eunsun Jung

    2013-12-01

    Full Text Available Madecassoside (MA, a pentacyclic triterpene isolated from Centella asitica (L., is used as a therapeutic agent in wound healing and also as an anti-inflammatory and anti-aging agent. However, the involvement of MA in skin-pigmentation has not been reported. This study was conducted to investigate the effects of MA on ultraviolet (UV-induced melanogenesis and mechanisms in a co-culture system of keratinocytes and melanocytes. MA significantly inhibited UVR-induced melanin synthesis and melanosome transfer in the co-culture system. These effects were further demonstrated by the MA-induced inhibition of protease-activated receptor-2 expression and its signaling pathway, cyclooxygenase-2, prostaglandin E2 and prostaglandin F2 alpha in keratinocytes. The clinical efficacy of MA was confirmed on artificially tanned human skin. MA significantly reduced UV-induced melanin index at 8 weeks after topical application. Overall, the study demonstrated significant benefits of MA use in the inhibition of hyperpigmentation caused by UV irradiation.

  7. High-Frequency Gravitational Wave Induced Nuclear Fusion

    International Nuclear Information System (INIS)

    Fontana, Giorgio; Baker, Robert M. L. Jr.

    2007-01-01

    Nuclear fusion is a process in which nuclei, having a total initial mass, combine to produce a single nucleus, having a final mass less than the total initial mass. Below a given atomic number the process is exothermic; that is, since the final mass is less than the combined initial mass and the mass deficit is converted into energy by the nuclear fusion. On Earth nuclear fusion does not happen spontaneously because electrostatic barriers prevent the phenomenon. To induce controlled, industrial scale, nuclear fusion, only a few methods have been discovered that look promising, but net positive energy production is not yet possible because of low overall efficiency of the systems. In this paper we propose that an intense burst of High Frequency Gravitational Waves (HFGWs) could be focused or beamed to a target mass composed of appropriate fuel or target material to efficiently rearrange the atomic or nuclear structure of the target material with consequent nuclear fusion. Provided that efficient generation of HFGW can be technically achieved, the proposed fusion reactor could become a viable solution for the energy needs of mankind and alternatively a process for beaming energy to produce a source of fusion energy remotely - even inside solid materials

  8. hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia.

    Science.gov (United States)

    Nogawa, Hisashi; Kawai, Tomoyuki

    2014-10-15

    Acquired long QT syndrome induced by non-cardiovascular drugs can cause lethal cardiac arrhythmia called torsades de points and is a significant problem in drug development. The prolongation of QT interval and cardiac action potential duration are mainly due to reduced physiological function of the rapidly activating voltage-dependent potassium channels encoded by human ether-a-go-go-related gene (hERG). Structurally diverse groups of drugs are known to directly inhibit hERG channel conductance. Therefore, the ability of acute hERG inhibition is routinely assessed at the preclinical stages in pharmaceutical testing. Recent findings indicated that chronic treatment with various drugs not only inhibits hERG channels but also decreases hERG channel expression in the plasma membrane of cardiomyocytes, which has become another concern in safety pharmacology. The mechanisms involve the disruption of hERG trafficking to the surface membrane or the acceleration of hERG protein degradation. From this perspective, we present a brief overview of mechanisms of drug-induced trafficking inhibition and pathological regulation. Understanding of drug-induced hERG trafficking inhibition may provide new strategies for predicting drug-induced QT prolongation and lethal cardiac arrhythmia in pharmaceutical drug development. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Electromagnetic waves in gravitational wave spacetimes

    International Nuclear Information System (INIS)

    Haney, M.; Bini, D.; Ortolan, A.; Fortini, P.

    2013-01-01

    We have considered the propagation of electromagnetic waves in a space-time representing an exact gravitational plane wave and calculated the induced changes on the four-potential field Aμ of a plane electromagnetic wave. By choosing a suitable photon round-trip in a Michelson interferometer, we have been able to identify the physical effects of the exact gravitational wave on the electromagnetic field, i.e. phase shift, change of the polarization vector, angular deflection and delay. These results have been exploited to study the response of an interferometric gravitational wave detector beyond the linear approximation of the general theory of relativity. A much more detailed examination of this problem can be found in our paper recently published in Classical and Quantum Gravity (28 (2011) 235007).

  10. Primordial gravitational waves induced by magnetic fields in an ekpyrotic scenario

    Directory of Open Access Journals (Sweden)

    Asuka Ito

    2017-08-01

    Full Text Available Both inflationary and ekpyrotic scenarios can account for the origin of the large scale structure of the universe. It is often said that detecting primordial gravitational waves is the key to distinguish both scenarios. We show that this is not true if the gauge kinetic function is present in the ekpyrotic scenario. In fact, primordial gravitational waves sourced by the gauge field can be produced in an ekpyrotic universe. We also study scalar fluctuations sourced by the gauge field and show that it is negligible compared to primordial gravitational waves. This comes from the fact that the fast roll condition holds in ekpyrotic models.

  11. Curcumin-induced histone acetylation inhibition improves stress-induced gastric ulcer disease in rats.

    Science.gov (United States)

    He, Ping; Zhou, Renmin; Hu, Guorui; Liu, Zhifeng; Jin, Yu; Yang, Guang; Li, Mei; Lin, Qian

    2015-03-01

    Curcumin is known to possess anti‑inflammatory properties. Despite the fact that curcumin is known to be a strong inhibitor of H+, K+‑ATPase activity, the mechanism underlying the curcumin‑induced inhibition of the transcription of the H+, K+‑ATPase α subunit in gastric mucosal parietal cells remains unclear. The present study investigated the possible mechanism by which curcumin inhibits stomach H+, K+‑ATPase activity during the acute phase of gastric ulcer disease. A rat model of stress‑induced gastric ulcers was produced, in which the anti‑ulcer effects of curcumin were examined. Curcumin‑induced inhibition of the H+, K+‑ATPase promoter via histone acetylation, was verified using a chromatin immunoprecipitation assay. The results showed that curcumin improved stress‑induced gastric ulcer disease in rats, as demonstrated by increased pH values and reduced gastric mucosal hemorrhage and ulcer index. These effects were accompanied by a significant reduction in the level of histone H3 acetylation at the site of the H+, K+‑ATPase promoter and in the expression of the gastric H+,K+‑ATPase α subunit gene and protein. In conclusion, curcumin downregulated the acetylation of histone H3 at the site of the H+, K+‑ATPase promoter gene, thereby inhibiting the transcription and expression of the H+, K+‑ATPase gene. Curcumin was shown to have a preventive and therapeutic effect in gastric ulcer disease.

  12. Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition

    Science.gov (United States)

    Park, Dohyun; Jeong, Heeyoon; Lee, Mi Nam; Koh, Ara; Kwon, Ohman; Yang, Yong Ryoul; Noh, Jungeun; Suh, Pann-Ghill; Park, Hwangseo; Ryu, Sung Ho

    2016-01-01

    Resveratrol (RSV) is a natural polyphenol that has a beneficial effect on health, and resveratrol-induced autophagy has been suggested to be a key process in mediating many beneficial effects of resveratrol, such as reduction of inflammation and induction of cancer cell death. Although various resveratrol targets have been suggested, the molecule that mediates resveratrol-induced autophagy remains unknown. Here, we demonstrate that resveratrol induces autophagy by directly inhibiting the mTOR-ULK1 pathway. We found that inhibition of mTOR activity and presence of ULK1 are required for autophagy induction by resveratrol. In line with this mTOR dependency, we found that resveratrol suppresses the viability of MCF7 cells but not of SW620 cells, which are mTOR inhibitor sensitive and insensitive cancer cells, respectively. We also found that resveratrol-induced cancer cell suppression occurred ULK1 dependently. For the mechanism of action of resveratrol on mTOR inhibition, we demonstrate that resveratrol directly inhibits mTOR. We found that resveratrol inhibits mTOR by docking onto the ATP-binding pocket of mTOR (i.e., it competes with ATP). We propose mTOR as a novel direct target of resveratrol, and inhibition of mTOR is necessary for autophagy induction. PMID:26902888

  13. Measuring Gravitational Flexion in ACS Clusters

    Science.gov (United States)

    Goldberg, David

    2005-07-01

    We propose measurement of the gravitational "Flexion" signal in ACS cluster images. The flexion, or "arciness" of a lensed background galaxy arises from variations in the lensing field. As a result, it is extremely sensitive to small scale perturbations in the field, and thus, to substructure in clusters. Moreover, because flexion represents gravitationally induced asymmetries in the lensed image, it is completely separable from traditional measurements of shear, which focus on the induced ellipticity of the image, and thus, the two signals may be extracted simultaneously. Since typical galaxies are roughly symmetric upon 180 degree rotation, even a small induced flexion can potentially produce a noticeable effect {Goldberg & Bacon, 2005}. We propose the measurement of substructure within approximately 4 clusters with high-quality ACS data, and will further apply a test of a new tomographic technique whereby comparisons of lensed arcs at different redshifts may be used to estimate the background cosmology, and thus place constraints on the equation of state of dark energy.

  14. Oridonin attenuates Aβ1-42-induced neuroinflammation and inhibits NF-κB pathway.

    Directory of Open Access Journals (Sweden)

    Sulei Wang

    Full Text Available Neuroinflammation induced by beta-amyloid (Aβ plays a critical role in the pathogenesis of Alzheimer's disease (AD, and inhibiting Aβ-induced neuroinflammation serves as a potential strategy for the treatment of AD. Oridonin (Ori, a compound of Rabdosia rubescens, has been shown to exert anti-inflammatory effects. In this study, we demonstrated that Ori inhibited glial activation and decreased the release of inflammatory cytokines in the hippocampus of Aβ1-42-induced AD mice. In addition, Ori inhibited the NF-κB pathway and Aβ1-42-induced apoptosis. Furthermore, Ori could attenuate memory deficits in Aβ1-42-induced AD mice. In conclusion, our study demonstrated that Ori inhibited the neuroinflammation and attenuated memory deficits induced by Aβ1-42, suggesting that Ori might be a promising candidate for AD treatment.

  15. Chiral gravitational waves and baryon superfluid dark matter

    Science.gov (United States)

    Alexander, Stephon; McDonough, Evan; Spergel, David N.

    2018-05-01

    We develop a unified model of darkgenesis and baryogenesis involving strongly interacting dark quarks, utilizing the gravitational anomaly of chiral gauge theories. In these models, both the visible and dark baryon asymmetries are generated by the gravitational anomaly induced by the presence of chiral primordial gravitational waves. We provide a concrete model of an SU(2) gauge theory with two massless quarks. In this model, the dark quarks condense and form a dark baryon charge superfluid (DBS), in which the Higgs-mode acts as cold dark matter. We elucidate the essential features of this dark matter scenario and discuss its phenomenological prospects.

  16. Aspirin Inhibits Platelet-Derived Sphingosine-1-Phosphate Induced Endothelial Cell Migration.

    Science.gov (United States)

    Polzin, Amin; Knoop, Betül; Böhm, Andreas; Dannenberg, Lisa; Zurek, Mark; Zeus, Tobias; Kelm, Malte; Levkau, Bodo; Rauch, Bernhard H

    2018-01-01

    Aspirin plays a crucial role in the prevention of cardiovascular diseases. We previously described that aspirin has effects beyond inhibition of platelet aggregation, as it inhibited thrombin-mediated release of sphingosine-1-phosphate (S1P) from human platelets. S1P is a bioactive lipid with important functions on inflammation and apoptosis. In endothelial cells (EC), S1P is a key regulator of cell migration. In this study, we aimed to analyze the effects of aspirin on platelet-induced EC migration. Human umbilical EC migration was measured by Boyden chamber assay. EC migration was induced by platelet supernatants of thrombin receptor-activating peptide-1 (AP1) stimulated platelets. To investigate the S1P receptor subtype that promotes EC migration, specific inhibitors of S1P receptor subtypes were applied. S1P induced EC migration in a concentration-dependent manner. EC migration induced by AP1-stimulated platelet supernatants was reduced by aspirin. S1P1 receptor inhibition almost completely abolished EC migration induced by activated platelets. The inhibition of S1P2 or S1P3 receptor had no effect. Aspirin inhibits EC migration induced by activated platelets that is in part due to S1P and mediated by the endothelial S1P1 receptor. The clinical significance of this novel mechanism of aspirin action has to be investigated in future studies. © 2017 S. Karger AG, Basel.

  17. Cyanidin-3-glucoside inhibits glutamate-induced Zn2+ signaling and neuronal cell death in cultured rat hippocampal neurons by inhibiting Ca2+-induced mitochondrial depolarization and formation of reactive oxygen species.

    Science.gov (United States)

    Yang, Ji Seon; Perveen, Shazia; Ha, Tae Joung; Kim, Seong Yun; Yoon, Shin Hee

    2015-05-05

    Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is a potent natural antioxidant. However, effects of C3G on glutamate-induced [Zn(2+)]i increase and neuronal cell death remain unknown. We studied the effects of C3G on glutamate-induced [Zn(2+)]i increase and cell death in cultured rat hippocampal neurons from embryonic day 17 maternal Sprague-Dawley rats using digital imaging methods for Zn(2+), Ca(2+), reactive oxygen species (ROS), mitochondrial membrane potential and a MTT assay for cell survival. Treatment with glutamate (100 µM) for 7 min induces reproducible [Zn(2+)]i increase at 35 min interval in cultured rat hippocampal neurons. The intracellular Zn(2+)-chelator TPEN markedly blocked glutamate-induced [Zn(2+)]i increase, but the extracellular Zn(2+) chelator CaEDTA did not affect glutamate-induced [Zn(2+)]i increase. C3G inhibited the glutamate-induced [Zn(2+)]i response in a concentration-dependent manner (IC50 of 14.1 ± 1.1 µg/ml). C3G also significantly inhibited glutamate-induced [Ca(2+)]i increase. Two antioxidants such as Trolox and DTT significantly inhibited the glutamate-induced [Zn(2+)]i response, but they did not affect the [Ca(2+)]i responses. C3G blocked glutamate-induced formation of ROS. Trolox and DTT also inhibited the formation of ROS. C3G significantly inhibited glutamate-induced mitochondrial depolarization. However, TPEN, Trolox and DTT did not affect the mitochondrial depolarization. C3G, Trolox and DTT attenuated glutamate-induced neuronal cell death in cultured rat hippocampal neurons, respectively. Taken together, all these results suggest that cyanidin-3-glucoside inhibits glutamate-induced [Zn(2+)]i increase through a release of Zn(2+) from intracellular sources in cultured rat hippocampal neurons by inhibiting Ca(2+)-induced mitochondrial depolarization and formation of ROS, which is involved in neuroprotection against glutamate-induced cell death. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Infinite order quantum-gravitational correlations

    Science.gov (United States)

    Knorr, Benjamin

    2018-06-01

    A new approximation scheme for nonperturbative renormalisation group equations for quantum gravity is introduced. Correlation functions of arbitrarily high order can be studied by resolving the full dependence of the renormalisation group equations on the fluctuation field (graviton). This is reminiscent of a local potential approximation in O(N)-symmetric field theories. As a first proof of principle, we derive the flow equation for the ‘graviton potential’ induced by a conformal fluctuation and corrections induced by a gravitational wave fluctuation. Indications are found that quantum gravity might be in a non-metric phase in the deep ultraviolet. The present setup significantly improves the quality of previous fluctuation vertex studies by including infinitely many couplings, thereby testing the reliability of schemes to identify different couplings to close the equations, and represents an important step towards the resolution of the Nielsen identity. The setup further allows one, in principle, to address the question of putative gravitational condensates.

  19. The tetrapeptide Arg-Leu-Tyr-Glu inhibits VEGF-induced angiogenesis

    International Nuclear Information System (INIS)

    Baek, Yi-Yong; Lee, Dong-Keon; So, Ju-Hoon; Kim, Cheol-Hee; Jeoung, Dooil; Lee, Hansoo; Choe, Jongseon; Won, Moo-Ho; Ha, Kwon-Soo; Kwon, Young-Guen; Kim, Young-Myeong

    2015-01-01

    Kringle 5, derived from plasminogen, is highly capable of inhibiting angiogenesis. Here, we have designed and synthesized 10 tetrapeptides, based on the amino acid properties of the core tetrapeptide Lys-Leu-Tyr-Asp (KLYD) originating from anti-angiogenic kringle 5 of human plasminogen. Of these, Arg-Leu-Tyr-Glu (RLYE) effectively inhibited vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation, migration and tube formation, with an IC 50 of 0.06–0.08 nM, which was about ten-fold lower than that of the control peptide KLYD (0.79 nM), as well as suppressed developmental angiogenesis in a zebrafish model. Furthermore, this peptide effectively inhibited the cellular events that precede angiogenesis, such as ERK and eNOS phosphorylation and nitric oxide production, in endothelial cells stimulated with VEGF. Collectively, these data demonstrate that RLYE is a potent anti-angiogenic peptide that targets the VEGF signaling pathway. - Highlights: • The tetrapeptide RLYE inhibited VEGF-induced angiogenesis in vitro. • RLYE also suppressed neovascularization in a zebrafish model. • Its effect was correlated with inhibition of VEGF-induced ERK and eNOS activation. • RLYE may be used as a therapeutic drug for angiogenesis-related diseases

  20. The tetrapeptide Arg-Leu-Tyr-Glu inhibits VEGF-induced angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Yi-Yong; Lee, Dong-Keon [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); So, Ju-Hoon; Kim, Cheol-Hee [Department of Biology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Jeoung, Dooil [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Lee, Hansoo [Department of Life Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Choe, Jongseon [Department of Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Won, Moo-Ho [Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Ha, Kwon-Soo [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Kwon, Young-Guen [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-752 (Korea, Republic of); Kim, Young-Myeong, E-mail: ymkim@kangwon.ac.kr [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of)

    2015-08-07

    Kringle 5, derived from plasminogen, is highly capable of inhibiting angiogenesis. Here, we have designed and synthesized 10 tetrapeptides, based on the amino acid properties of the core tetrapeptide Lys-Leu-Tyr-Asp (KLYD) originating from anti-angiogenic kringle 5 of human plasminogen. Of these, Arg-Leu-Tyr-Glu (RLYE) effectively inhibited vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation, migration and tube formation, with an IC{sub 50} of 0.06–0.08 nM, which was about ten-fold lower than that of the control peptide KLYD (0.79 nM), as well as suppressed developmental angiogenesis in a zebrafish model. Furthermore, this peptide effectively inhibited the cellular events that precede angiogenesis, such as ERK and eNOS phosphorylation and nitric oxide production, in endothelial cells stimulated with VEGF. Collectively, these data demonstrate that RLYE is a potent anti-angiogenic peptide that targets the VEGF signaling pathway. - Highlights: • The tetrapeptide RLYE inhibited VEGF-induced angiogenesis in vitro. • RLYE also suppressed neovascularization in a zebrafish model. • Its effect was correlated with inhibition of VEGF-induced ERK and eNOS activation. • RLYE may be used as a therapeutic drug for angiogenesis-related diseases.

  1. Detecting free-mass common-mode motion induced by incident gravitational waves

    Science.gov (United States)

    Tobar, Michael Edmund; Suzuki, Toshikazu; Kuroda, Kazuaki

    1999-05-01

    In this paper we show that information on both the differential and common mode free-mass response to a gravitational wave can provide important information on discriminating the direction of the gravitational wave source and between different theories of gravitation. The conventional Michelson interferometer scheme only measures the differential free-mass response. By changing the orientation of the beam splitter, it is possible to configure the detector so it is sensitive to the common-mode of the free-mass motion. The proposed interferometer is an adaptation of the Fox-Smith interferometer. A major limitation to the new scheme is its enhanced sensitivity to laser frequency fluctuations over the conventional, and we propose a method of cancelling these fluctuations. The configuration could be used in parallel to the conventional differential detection scheme with a significant sensitivity and bandwidth.

  2. Gravitational Waves

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Jonah Maxwell [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-10-18

    This report has slides on Gravitational Waves; Pound and Rebka: A Shocking Fact; Light is a Ruler; Gravity is the Curvature of Spacetime; Gravitational Waves Made Simple; How a Gravitational Wave Affects Stuff Here; LIGO; This Detection: Neutron Stars; What the Gravitational Wave Looks Like; The Sound of Merging Neutron Stars; Neutron Star Mergers: More than GWs; The Radioactive Cloud; The Kilonova; and finally Summary, Multimessenger Astronomy.

  3. The gravitational analog of Faraday's induction law

    Science.gov (United States)

    Zile, Daniel; Overduin, James

    2015-04-01

    Michael Faraday, the discoverer of electromagnetic induction, was convinced that there must also be a gravitational analog of this law, and he carried out drop-tower experiments in 1849 to look for the electric current induced in a coil by changes in gravitational flux through the coil. This work, now little remembered, was in some ways the first investigation of what we would now call a unified-field theory. We revisit Faraday's experiments in the light of current knowledge and ask what might be learned if they were to be performed today. We then review the gravitational analog for Faraday's law that arises within the vector (or gravito-electromagnetic) approximation to Einstein's theory of general relativity in the weak-field, low-velocity limit. This law relates spinning masses and induced ``mass currents'' rather than spinning charges and electric currents, but is otherwise remarkably similar to its electromagnetic counterpart. The predicted effects are completely unobservable in everyday settings like those envisioned by Faraday, but are thought to be relevant in astrophysical contexts like the accretion disks around collapsed stars, thus bearing out Faraday's remarkable intuition. Undergraduate student.

  4. Radiosensitive Down syndrome lymphoblastoid lines have normal ionizing-radiation-induced inhibition of DNA synthesis

    International Nuclear Information System (INIS)

    Ganges, M.B.; Robbins, J.H.; Jiang, H.; Hauser, C.; Tarone, R.E.

    1988-01-01

    The extent of X-ray-induced inhibition of DNA synthesis was determined in radiosensitive lymphoblastoid lines from 3 patients with Down syndrome and 3 patients with ataxia telangiectasia (AT). Compared to 6 normal control lines, the 3 AT lines were abnormally resistant to X-ray-induced inhibition of DNA synthesis, while the 3 Down syndrome lines had normal inhibition. These results demonstrate that radiosensitive human cells can have normal X-ray-induced inhibition of DNA synthesis and provide new evidence for the dissociation of radioresistant DNA synthesis. (author). 27 refs.; 1 fig.; 1 tab

  5. Leading gravitational corrections and a unified universe

    DEFF Research Database (Denmark)

    Codello, Alessandro; Jain, Rajeev Kumar

    2016-01-01

    Leading order gravitational corrections to the Einstein-Hilbert action can lead to a consistent picture of the universe by unifying the epochs of inflation and dark energy in a single framework. While the leading local correction induces an inflationary phase in the early universe, the leading...... nonlocal term leads to an accelerated expansion of the universe at the present epoch. We argue that both the leading UV and IR terms can be obtained within the framework of a covariant effective field theory of gravity. The perturbative gravitational corrections therefore provide a fundamental basis...

  6. Myelin-induced inhibition in a spiral ganglion organ culture - Approaching a natural environment in vitro.

    Science.gov (United States)

    Kramer, Benedikt; Tropitzsch, Anke; Müller, Marcus; Löwenheim, Hubert

    2017-08-15

    The performance of a cochlear implant depends on the defined interaction between afferent neurons of the spiral ganglion and the inserted electrode. Neurite outgrowth can be induced by neurotrophins such as brain-derived neurotrophic factor (BDNF) via tropomyosin kinase receptor B (TrkB). However, neurotrophin signaling through the p75 neurotrophin receptor (p75) inhibits neurite outgrowth in the presence of myelin. Organotypic cultures derived from postnatal (P3-5) mice were used to study myelin-induced inhibition in the cochlear spiral ganglion. Neurite outgrowth was analyzed and quantified utilizing an adapted Sholl analysis. Stimulation of neurite outgrowth was quantified after application of BDNF, the selective TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) and a selective inhibitor of the Rho-associated kinase (Y27632), which inhibits the p75 pathway. Myelin-induced inhibition was assessed by application of myelin-associated glycoprotein (MAG-Fc) to stimulate the inhibitory p75 pathway. Inhibition of neurite outgrowth was achieved by the selective TrkB inhibitor K252a. Stimulation of neurite outgrowth was observed after treatment with BDNF, 7,8 DHF and a combination of BDNF and Y27632. The 7,8-DHF-induced growth effects could be inhibited by K252a. Furthermore, inhibition of neurite outgrowth was observed after supplementation with MAG-Fc. Myelin-induced inhibition could be overcome by 7,8-DHF and the combination of BDNF and Y27632. In this study, myelin-induced inhibition of neurite outgrowth was established in a spiral ganglion model. We reveal that 7,8-DHF is a viable novel compound for the stimulation of neurite outgrowth in a myelin-induced inhibitory environment. The combination of TrkB stimulation and ROCK inhibition can be used to overcome myelin inhibition. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Nonlinear metric perturbation enhancement of primordial gravitational waves.

    Science.gov (United States)

    Bastero-Gil, M; Macias-Pérez, J; Santos, D

    2010-08-20

    We present the evolution of the full set of Einstein equations during preheating after inflation. We study a generic supersymmetric model of hybrid inflation, integrating fields and metric fluctuations in a 3-dimensional lattice. We take initial conditions consistent with Einstein's constraint equations. The induced preheating of the metric fluctuations is not large enough to backreact onto the fields, but preheating of the scalar modes does affect the evolution of vector and tensor modes. In particular, they do enhance the induced stochastic background of gravitational waves during preheating, giving an energy density in general an order of magnitude larger than that obtained by evolving the tensor fluctuations in an homogeneous background metric. This enhancement can improve the expectations for detection by planned gravitational wave observatories.

  8. Higher-order geodesic deviation for charged particles and resonance induced by gravitational waves

    Science.gov (United States)

    Heydari-Fard, M.; Hasani, S. N.

    We generalize the higher-order geodesic deviation for the structure-less test particles to the higher-order geodesic deviation equations of the charged particles [R. Kerner, J. W. van Holten and R. Colistete Jr., Class. Quantum Grav. 18 (2001) 4725]. By solving these equations for charged particles moving in a constant magnetic field in the spacetime of a gravitational wave, we show for both cases when the gravitational wave is parallel and perpendicular to the constant magnetic field, a magnetic resonance appears at wg = Ω. This feature might be useful to detect the gravitational wave with high frequencies.

  9. On gravitational wave energy in Einstein gravitational theory

    International Nuclear Information System (INIS)

    Folomeshkin, V.N.; Vlasov, A.A.

    1978-01-01

    By the example of precise wave solutions for the Einstein equations it is shown that a standard commonly adopted formulation of energy-momentum problem with pseudotensors provides us either with a zero or sign-variable values for the energy of gravitational waves. It is shown that if in the Einstein gravitational theory a strict transition to the limits of weak fields is realised then the theory gives us an unambiguous zero result for weak gravitational waves. The well-known non-zero result arises due to incorrect transition to weak field approximation in the Einstein gravitation theory

  10. Gravitational instabilities of the cosmic neutrino background with non-zero lepton number

    Directory of Open Access Journals (Sweden)

    Neil D. Barrie

    2017-09-01

    Full Text Available We argue that a cosmic neutrino background that carries non-zero lepton charge develops gravitational instabilities. Fundamentally, these instabilities are related to the mixed gravity-lepton number anomaly. We have explicitly computed the gravitational Chern–Simons term which is generated quantum-mechanically in the effective action in the presence of a lepton number asymmetric neutrino background. The induced Chern–Simons term has a twofold effect: (i gravitational waves propagating in such a neutrino background exhibit birefringent behaviour leading to an enhancement/suppression of the gravitational wave amplitudes depending on the polarisation, where the magnitude of this effect is related to the size of the lepton asymmetry; (ii Negative energy graviton modes are induced in the high frequency regime, which leads to very fast vacuum decay producing, e.g., positive energy photons and negative energy gravitons. From the constraint on the present radiation energy density, we obtain an interesting bound on the lepton asymmetry of the universe.

  11. Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity

    Directory of Open Access Journals (Sweden)

    Masako Isokawa

    2016-01-01

    Full Text Available GABAergic inhibition plays a critical role in the regulation of neuron excitability; thus, it is subject to modulations by many factors. Recent evidence suggests the elevation of intracellular calcium ([Ca2+]i and calcium-dependent signaling molecules underlie the modulations. Caffeine induces a release of calcium from intracellular stores. We tested whether caffeine modulated GABAergic transmission by increasing [Ca2+]i. A brief local puff-application of caffeine to hippocampal CA1 pyramidal cells transiently suppressed GABAergic inhibitory postsynaptic currents (IPSCs by 73.2 ± 6.98%. Time course of suppression and the subsequent recovery of IPSCs resembled DSI (depolarization-induced suppression of inhibition, mediated by endogenous cannabinoids that require a [Ca2+]i rise. However, unlike DSI, caffeine-induced suppression of IPSCs (CSI persisted in the absence of a [Ca2+]i rise. Intracellular applications of BAPTA and ryanodine (which blocks caffeine-induced calcium release from intracellular stores failed to prevent the generation of CSI. Surprisingly, ruthenium red, an inhibitor of multiple calcium permeable/release channels including those of stores, induced metaplasticity by amplifying the magnitude of CSI independently of calcium. This metaplasticity was accompanied with the generation of a large inward current. Although ionic basis of this inward current is undetermined, the present result demonstrates that caffeine has a robust Ca2+-independent inhibitory action on GABAergic inhibition and causes metaplasticity by opening plasma membrane channels.

  12. Oxygen-induced inhibition of silicon-on-insulator dewetting

    Energy Technology Data Exchange (ETDEWEB)

    Curiotto, S.; Leroy, F.; Cheynis, F.; Müller, P. [Aix Marseille Université, CNRS, CINaM UMR 7325, 13288 Marseille (France)

    2014-02-10

    We report that solid state dewetting of Si thin film on SiO{sub 2} can be reversibly inhibited by exposing the Si surface to a partial pressure of dioxygen (∼10{sup −7}Torr) at high temperature (∼1100K). Coupling in situ Low-Energy Electron Microscopy and ex situ atomic force microscopy we propose that the pinning of the contact line induced by the presence of small amounts of silicon oxide is the main physical process that inhibits the dewetting.

  13. Inhibition of autophagy induced by proteasome inhibition increases cell death in human SHG-44 glioma cells.

    Science.gov (United States)

    Ge, Peng-Fei; Zhang, Ji-Zhou; Wang, Xiao-Fei; Meng, Fan-Kai; Li, Wen-Chen; Luan, Yong-Xin; Ling, Feng; Luo, Yi-Nan

    2009-07-01

    The ubiquitin-proteasome system (UPS) and lysosome-dependent macroautophagy (autophagy) are two major intracellular pathways for protein degradation. Recent studies suggest that proteasome inhibitors may reduce tumor growth and activate autophagy. Due to the dual roles of autophagy in tumor cell survival and death, the effect of autophagy on the destiny of glioma cells remains unclear. In this study, we sought to investigate whether inhibition of the proteasome can induce autophagy and the effects of autophagy on the fate of human SHG-44 glioma cells. The proteasome inhibitor MG-132 was used to induce autophagy in SHG-44 glioma cells, and the effect of autophagy on the survival of SHG-44 glioma cells was investigated using an autophagy inhibitor 3-MA. Cell viability was measured by MTT assay. Apoptosis and cell cycle were detected by flow cytometry. The expression of autophagy related proteins was determined by Western blot. MG-132 inhibited cell proliferation, induced cell death and cell cycle arrest at G(2)/M phase, and activated autophagy in SHG-44 glioma cells. The expression of autophagy-related Beclin-1 and LC3-I was significantly up-regulated and part of LC3-I was converted into LC3-II. However, when SHG-44 glioma cells were co-treated with MG-132 and 3-MA, the cells became less viable, but cell death and cell numbers at G(2)/M phase increased. Moreover, the accumulation of acidic vesicular organelles was decreased, the expression of Beclin-1 and LC3 was significantly down-regulated and the conversion of LC3-II from LC3-I was also inhibited. Inhibition of the proteasome can induce autophagy in human SHG-44 glioma cells, and inhibition of autophagy increases cell death. This discovery may shed new light on the effect of autophagy on modulating the fate of SHG-44 glioma cells.Acta Pharmacologica Sinica (2009) 30: 1046-1052; doi: 10.1038/aps.2009.71.

  14. Relativistic gravitation theory

    International Nuclear Information System (INIS)

    Logunov, A.A.; Mestvirishvili, M.A.

    1984-01-01

    On the basis of the special relativity and geometrization principle a relativistic gravitation theory (RGT) is unambiguously constructed with the help of a notion of a gravitational field as a physical field in Faraday-Maxwell spirit, which posesses energy momentum and spins 2 and 0. The source of gravitation field is a total conserved energy-momentum tensor for matter and for gravitation field in Minkowski space. In the RGT conservation laws for the energy momentum and angular momentum of matter and gravitational field hold rigorously. The theory explains the whole set of gravitation experiments. Here, due to the geometrization principle the Riemannian space is of a field origin since this space arises effectively as a result of the gravitation field origin since this space arises effectively as a result of the gravitation field action on the matter. The RGT astonishing prediction is that the Universe is not closed but ''flat''. It means that in the Universe there should exist a ''missing'' mass in some form of matter

  15. Coherent network detection of gravitational waves: the redundancy veto

    International Nuclear Information System (INIS)

    Wen Linqing; Schutz, Bernard F

    2005-01-01

    A network of gravitational wave detectors is called redundant if, given the direction to a source, the strain induced by a gravitational wave in one or more of the detectors can be fully expressed in terms of the strain induced in others in the network. Because gravitational waves have only two polarizations, any network of three or more differently oriented interferometers with similar observing bands is redundant. The three-armed LISA space interferometer has three outputs that are redundant at low frequencies. The two aligned LIGO interferometers at Hanford WA are redundant, and the LIGO detector at Livingston LA is nearly redundant with either of the Hanford detectors. Redundant networks have a powerful veto against spurious noise, a linear combination of the detector outputs that contains no gravitational wave signal. For LISA, this 'null' output is known as the Sagnac mode, and its use in discriminating between detector noise and a cosmological gravitational wave background is well understood. But the usefulness of the null veto for ground-based detector networks has been ignored until now. We show that it should make it possible to discriminate in a model-independent way between real gravitational waves and accidentally coincident non-Gaussian noise 'events' in redundant networks of two or more broadband detectors. It has been shown that with three detectors, the null output can even be used to locate the direction to the source, and then two other linear combinations of detector outputs give the optimal 'coherent' reconstruction of the two polarization components of the signal. We discuss briefly the implementation of such a detection strategy in realistic networks, where signals are weak, detector calibration is a significant uncertainty, and the various detectors may have different (but overlapping) observing bands

  16. A down to earth model of gravisensing or Newton's Law of Gravitation from the apple's perspective

    Science.gov (United States)

    Wayne, R.; Staves, M. P.

    1996-01-01

    The physiology of gravity perception in plants is examined and a model of gravitational pressure is explained and compared to the statolith model. The gravitational pressure model is based on studies of tension and compression of the plasma membrane against the extracellular matrix. Further studies examine the role of peptides or enzymes that inhibit a compression receptor and calcium channels.

  17. Detection of gravitational waves from inflation

    International Nuclear Information System (INIS)

    Kamionkowski, M.; Jaffe, A.H.

    2001-01-01

    Recent measurements of temperature fluctuations in the cosmic microwave background (CMB) indicate that the Universe is flat and that large-scale structure grew via gravitational infall from primordial adiabatic perturbations. Both of these observations seem to indicate that we are on the right track with inflation. But what is the new physics responsible for inflation? This question can be answered with observations of the polarization of the CMB. Inflation predicts robustly the existence of a stochastic background of cosmological gravitational waves with an amplitude proportional to the square of the energy scale of inflation. This gravitational-wave background induces a unique signature in the polarization of the CMB. If inflation took place at an energy scale much smaller than that of grand unification, then the signal will be too small to be detectable. However, if inflation had something to do with grand unification or Planck-scale physics, then the signal is conceivably detectable in the optimistic case by the Planck satellite, or if not, then by a dedicated post-Planck CMB polarization experiment. Realistic developments in detector technology as well as a proper scan strategy could produce such a post-Planck experiment that would improve on Planck's sensitivity to the gravitational-wave background by several orders of magnitude in a decade timescale. (author)

  18. Testing the gravitational instability hypothesis?

    Science.gov (United States)

    Babul, Arif; Weinberg, David H.; Dekel, Avishai; Ostriker, Jeremiah P.

    1994-01-01

    We challenge a widely accepted assumption of observational cosmology: that successful reconstruction of observed galaxy density fields from measured galaxy velocity fields (or vice versa), using the methods of gravitational instability theory, implies that the observed large-scale structures and large-scale flows were produced by the action of gravity. This assumption is false, in that there exist nongravitational theories that pass the reconstruction tests and gravitational theories with certain forms of biased galaxy formation that fail them. Gravitational instability theory predicts specific correlations between large-scale velocity and mass density fields, but the same correlations arise in any model where (a) structures in the galaxy distribution grow from homogeneous initial conditions in a way that satisfies the continuity equation, and (b) the present-day velocity field is irrotational and proportional to the time-averaged velocity field. We demonstrate these assertions using analytical arguments and N-body simulations. If large-scale structure is formed by gravitational instability, then the ratio of the galaxy density contrast to the divergence of the velocity field yields an estimate of the density parameter Omega (or, more generally, an estimate of beta identically equal to Omega(exp 0.6)/b, where b is an assumed constant of proportionality between galaxy and mass density fluctuations. In nongravitational scenarios, the values of Omega or beta estimated in this way may fail to represent the true cosmological values. However, even if nongravitational forces initiate and shape the growth of structure, gravitationally induced accelerations can dominate the velocity field at late times, long after the action of any nongravitational impulses. The estimated beta approaches the true value in such cases, and in our numerical simulations the estimated beta values are reasonably accurate for both gravitational and nongravitational models. Reconstruction tests

  19. Eicosapentaenoic acid inhibits TNF-α-induced matrix metalloproteinase-9 expression in human keratinocytes, HaCaT cells

    International Nuclear Information System (INIS)

    Kim, Hyeon Ho; Lee, Youngae; Eun, Hee Chul; Chung, Jin Ho

    2008-01-01

    Eicosapentaenoic acid (EPA) is an omega-3 (ω-3) polyunsaturated fatty acid (PUFA), which has anti-inflammatory and anti-cancer properties. Some reports have demonstrated that EPA inhibits NF-κB activation induced by tumor necrosis factor (TNF)-α or lipopolysaccharide (LPS) in various cells. However, its detailed mode of action is unclear. In this report, we investigated whether EPA inhibits the expression of TNF-α-induced matrix metalloproteinases (MMP)-9 in human immortalized keratinocytes (HaCaT). TNF-α induced MMP-9 expression by NF-κB-dependent pathway. Pretreatment of EPA inhibited TNF-α-induced MMP-9 expression and p65 phosphorylation. However, EPA could not affect IκB-α phosphorylation, nuclear translocation of p65, and DNA binding activity of NF-κB. EPA inhibited TNF-α-induced p65 phosphorylation through p38 and Akt inhibition and this inhibition was IKKα-dependent event. Taken together, we demonstrate that EPA inhibits TNF-α-induced MMP-9 expression through inhibition of p38 and Akt activation

  20. Arginase Inhibition Reverses Monocrotaline-Induced Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Christian Jung

    2017-07-01

    Full Text Available Pulmonary hypertension (PH is a heterogeneous disorder associated with a poor prognosis. Thus, the development of novel treatment strategies is of great interest. The enzyme arginase (Arg is emerging as important player in PH development. The aim of the current study was to determine the expression of ArgI and ArgII as well as the effects of Arg inhibition in a rat model of PH. PH was induced in 35 Sprague–Dawley rats by monocrotaline (MCT, 60 mg/kg as single-dose. There were three experimental groups: sham-treated controls (control group, n = 11, MCT-induced PH (MCT group, n = 11 and MCT-induced PH treated with the Arg inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA; MCT/NorNoha group, n = 13. ArgI and ArgII expression was determined by immunohistochemistry and Western blot. Right ventricular systolic pressure (RVPsys was measured and lung tissue remodeling was determined. Induction of PH resulted in an increase in RVPsys (81 ± 16 mmHg compared to the control group (41 ± 15 mmHg, p = 0.002 accompanied by a significant elevation of histological sum-score (8.2 ± 2.4 in the MCT compared to 1.6 ± 1.6 in the control group, p < 0.001. Both, ArgI and ArgII were relevantly expressed in lung tissue and there was a significant increase in the MCT compared to the control group (p < 0.01. Arg inhibition resulted in a significant reduction of RVPsys to 52 ± 19 mmHg (p = 0.006 and histological sum-score to 5.8 ± 1.4 compared to the MCT group (p = 0.022. PH leads to increased expression of Arg. Arg inhibition leads to reduction of RVPsys and diminished lung tissue remodeling and therefore represents a potential treatment strategy in PH.

  1. CMB B-mode auto-bispectrum produced by primordial gravitational waves

    Science.gov (United States)

    Tahara, Hiroaki W. H.; Yokoyama, Jun'ichi

    2018-01-01

    Gravitational waves from inflation induce polarization patterns in the cosmic microwave background (CMB). It is known that there are only two types of non-Gaussianities of the gravitational waves in the most general covariant scalar field theory having second-order field equations, namely, generalized G-inflation. One originates from the inherent non-Gaussianity in general relativity, and the other from a derivative coupling between the Einstein tensor and the scalar field. We calculate polarization bispectra induced by these non-Gaussianities by transforming them into separable forms by virtue of the Laplace transformation. It is shown that future experiments can constrain the new one but cannot detect the general relativistic one.

  2. Polymeric black tea polyphenols inhibit 1,2-dimethylhydrazine induced colorectal carcinogenesis by inhibiting cell proliferation via Wnt/β-catenin pathway

    International Nuclear Information System (INIS)

    Patel, Rachana; Ingle, Arvind; Maru, Girish B.

    2008-01-01

    Tea polyphenols like epigallocatechin gallate and theaflavins are established chemopreventive agents for colorectal carcinogenesis. However, studies on evaluating similar chemopreventive properties of thearubigins or polymeric black tea polyphenols (PBPs), the most abundant polyphenols in black tea, are limited. Hence, in the present study we aim to investigate chemopreventive effects along with probable mechanisms of action of PBP extract employing 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis in Sprague-Dawley rats as experimental model. The present study suggests that PBPs, like other tea polyphenols, also inhibit DMH-induced colorectal tumorigenesis by decreasing tumor volume and multiplicity. This study also shows that although the pretreatment with PBP extract could induce detoxifying enzymes in hepatic and colorectal tissue, it did not show any additional chemopreventive effects when compared to treatments with PBP extract after initiation with DMH. Mechanistically, PBP extract may inhibit colorectal carcinogenesis by decreasing DMH-induced cell proliferation via Wnt/β-catenin pathway. Treatments with PBP extract showed decreased levels of COX-2, c-MYC and cyclin D1 proteins which aid cell proliferation probably by regulating β-catenin by maintaining expression of APC and decreasing inactivation of GSK3β. DMH-induced activation of MAP kinases such as ERK and JNK was also found to be inhibited by treatments with PBP extract. In conclusion, the protective effects of PBP extract could be attributed to inhibition of DMH-induced cellular proliferation probably through β-catenin regulation

  3. Backwards time travel induced by combined magnetic and gravitational fields

    International Nuclear Information System (INIS)

    Novello, M.; Svaiter, N.F.; Guimaraes, M.E.X.

    1990-01-01

    We analyse the behaviour of an elementary microscopic particle submitted to combined Magnetic and Gravitational Fields on Goedel's Universe. The exam is made in a local Gaussian system of coordinates. (author)

  4. Quantum gravitational optics in the field of a gravitomagnetic monopole

    Energy Technology Data Exchange (ETDEWEB)

    Ahmadi, N [Department of Physics, North Karegar Avenue, University of Tehran, P O Box 14395-547, Tehran (Iran, Islamic Republic of); Khoeini-Moghaddam, S [Department of Physics, Sharif University of Technology, P O Box 19365-9161, Tehran (Iran, Islamic Republic of); Nouri-Zonoz, M [Department of Physics, North Karegar Avenue, University of Tehran, P O Box 14395-547, Tehran (Iran, Islamic Republic of)

    2007-05-15

    Vacuum polarization in QED in a background gravitational field induces interactions which effectively modify the classical picture of light rays as the null geodesies of spacetime. After a short introduction on the main aspects of the quantum gravitational optics, as a nontrivial example, we study this effect in the background of NUT space characterizing the spacetime of a spherical mass endowed with a gravitomagnetic monopole charge, the so called NUT factor.

  5. Diclofenac inhibits 27-hydroxycholesterol-induced inflammation.

    Science.gov (United States)

    Kim, Bo-Young; Son, Yonghae; Eo, Seong-Kug; Park, Young Chul; Kim, Koanhoi

    2016-09-23

    27-Hydroxycholesterol (27OHChol) is a cholesterol oxidation product that induces inflammation. In the current study we investigated the effects of diclofenac on inflammatory responses caused by 27OHChol using human monocyte/macrophage (THP-1) cells. Transcription and secretion of CCL2, CCL3, and CCL4 chemokines enhanced by 27OHChol were significantly attenuated by diclofenac in a concentration dependent manner. Migrations of monocytic cells and CCR5-positive Jurkat T cells were reduced proportionally to the concentrations of diclofenac. Superproduction of CCL2 and monocytic cell migration induced by 27OHChol plus LPS were significantly attenuated by diclofenac. Diclofenac also attenuated transcription of MMP-9 and release of its active gene product. These results indicate that diclofenac inhibits 27OHChol-induced inflammatory responses, thereby suppressing inflammation in a milieu rich in cholesterol oxidation products. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma

    International Nuclear Information System (INIS)

    Pei, Qing-Mei; Jiang, Ping; Yang, Min; Qian, Xue-Jiao; Liu, Jiang-Bo; Kim, Sung-Ho

    2016-01-01

    Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodelling, which is associated with increased airway smooth muscle (ASM) mass. Roxithromycin (RXM) has been widely used in asthma treatment; however, its mechanism of action is poorly understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodelling in patients with asthma, and shown to promote ASM cell proliferation. Here, we investigated the effect of RXM on VEGF-induced ASM cell proliferation and attempted to elucidate the underlying mechanisms of action. We tested the effect of RXM on proliferation and cell cycle progression, as well as on the expression of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-Akt, and caveolin-1 in VEGF-stimulated ASM cells. RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed by inhibiting the activity of ERK1/2, but not that of Akt. Furthermore, RXM treatment inhibits VEGF-induced activation of VEGFR2 and ERK and downregulation of caveolin-1 in a dose-dependent manner. RXM also inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. Collectively, our findings suggest that RXM inhibits VEGF-induced ASM cell proliferation by suppression of VEGFR2 and ERK1/2 activation and caveolin-1 down-regulation, which may be involved in airway remodelling. Further elucidation of the mechanisms underlying these observations should enable the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma. - Highlights: • RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. • VEGF-induced cell proliferation was suppressed by inhibiting the activity of ERK1/2. • RXM inhibits activation of VEGFR2 and ERK and downregulation

  7. Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Qing-Mei, E-mail: 34713316@qq.com [Department of Radiology, Tianjin Hospital of Integrated Traditional Chinese and Western Medicine, Tianjin (China); Jiang, Ping, E-mail: jiangping@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Yang, Min, E-mail: YangMin@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Qian, Xue-Jiao, E-mail: qianxuejiao@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Liu, Jiang-Bo, E-mail: LJB1984@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Kim, Sung-Ho, E-mail: chenghao0726@hotmail.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China)

    2016-10-01

    Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodelling, which is associated with increased airway smooth muscle (ASM) mass. Roxithromycin (RXM) has been widely used in asthma treatment; however, its mechanism of action is poorly understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodelling in patients with asthma, and shown to promote ASM cell proliferation. Here, we investigated the effect of RXM on VEGF-induced ASM cell proliferation and attempted to elucidate the underlying mechanisms of action. We tested the effect of RXM on proliferation and cell cycle progression, as well as on the expression of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-Akt, and caveolin-1 in VEGF-stimulated ASM cells. RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed by inhibiting the activity of ERK1/2, but not that of Akt. Furthermore, RXM treatment inhibits VEGF-induced activation of VEGFR2 and ERK and downregulation of caveolin-1 in a dose-dependent manner. RXM also inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. Collectively, our findings suggest that RXM inhibits VEGF-induced ASM cell proliferation by suppression of VEGFR2 and ERK1/2 activation and caveolin-1 down-regulation, which may be involved in airway remodelling. Further elucidation of the mechanisms underlying these observations should enable the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma. - Highlights: • RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. • VEGF-induced cell proliferation was suppressed by inhibiting the activity of ERK1/2. • RXM inhibits activation of VEGFR2 and ERK and downregulation

  8. Perivascular delivery of Notch 1 siRNA inhibits injury-induced arterial remodeling.

    Directory of Open Access Journals (Sweden)

    Eileen M Redmond

    Full Text Available To determine the efficacy of perivascular delivery of Notch 1 siRNA in preventing injury-induced arterial remodeling.Carotid artery ligation was performed to induce arterial remodeling. After 14 days, morphometric analysis confirmed increased vSMC growth and subsequent media thickening and neointimal formation. Laser capture microdissection, quantitative qRT-PCR and immunoblot analysis of medial tissue revealed a significant increase in Notch1 receptor and notch target gene, Hrt 1 and 2 expression in the injured vessels. Perivascular delivery of Notch 1 siRNA by pluronic gel inhibited the injury-induced increase in Notch 1 receptor and target gene expression when compared to scrambled siRNA controls while concomitantly reducing media thickening and neointimal formation to pre-injury, sham-operated levels. Selective Notch 1 knockdown also reversed the injury-induced inhibition of pro-apoptotic Bax expression while decreasing injury-induced anti-apoptotic Bcl-XL expression to sham-operated control levels. In parallel experiments, proliferative cyclin levels, as measured by PCNA expression, were reversed to sham-operated control levels following selective Notch 1 knockdown.These results suggest that injury-induced arterial remodeling can be successfully inhibited by localized perivascular delivery of Notch 1 siRNA.

  9. Gravitational effects in field gravitation theory

    International Nuclear Information System (INIS)

    Denisov, V.I.; Logunov, A.A.; Mestvirishvili, M.A.; Vlasov, A.A.

    1979-01-01

    The possibilities to describe various gravitation effects of field gravitation theory (FGT) are considered. Past-Newtonian approximation of the FGT has been constructed and on the basis of this approximation it has been shown that the field theory allows one to describe the whole set of experimental facts. The comparison of post-Newtonian parameters in FGT with those in the Einstein's theory makes it clear that these two; theories are undistinguishable from the viewpoint of any experiments, realized with post-Newtonian accuracy. Gravitational field of an island type source with spherically symmetrical distribution of matter and unstationary homogeneous model of Universe, which allows to describe the effect of cosmological red shift, are considered

  10. Linear ubiquitin chain induces apoptosis and inhibits tumor growth.

    Science.gov (United States)

    Qin, Zhoushuai; Jiang, Wandong; Wang, Guifen; Sun, Ying; Xiao, Wei

    2018-01-01

    Ubiquitination of proliferating cell nuclear antigen (PCNA) plays an important role in DNA damage response. Ectopic expression of PCNA fused at either terminus with ubiquitin (Ub) lacking two C-terminal glycine residues induces translesion DNA synthesis which resembles synthesis mediated by PCNA monoubiquitination. PCNA fused with Ub containing the C-terminal Gly residues at the C-terminus can be further polyubiquitinated in a Gly-dependent manner, which inhibits cell proliferation and induces ATR-dependent replication checkpoint. In this study, we surprisingly found that PCNA fused to a head-to-tail linear Ub chain induces apoptosis in a Ub chain length-dependent manner. Further investigation revealed that the apoptotic effect is actually induced by the linear Ub chain independently from PCNA, as the Ub chain fused to GFP or an epitope tag still efficiently induces apoptosis. It is revealed that the artificial linear Ub chain differs from endogenously encoded linear Ub chains in that its Ubs contain a Ub-G76S substitution, making the Ub chain resistant to cleavage by deubiquitination enzymes. We demonstrated in this study that ectopic expression of the artificial Ub chain alone in cultured human cancer cells is sufficient to inhibit tumor growth in a xenograft mouse model, making the linear Ub chain a putative anti-cancer agent.

  11. Long-term evolution and gravitational wave radiation of neutron stars with differential rotation induced by r-modes

    International Nuclear Information System (INIS)

    Yu Yunwei; Cao Xiaofeng; Zheng Xiaoping

    2009-01-01

    In a second-order r-mode theory, Sa and Tome found that the r-mode oscillation in neutron stars (NSs) could induce stellar differential rotation, which naturally leads to a saturated state of the oscillation. Based on a consideration of the coupling of the r-modes and the stellar spin and thermal evolution, we carefully investigate the influences of the differential rotation on the long-term evolution of isolated NSs and NSs in low-mass X-ray binaries, where the viscous damping of the r-modes and its resultant effects are taken into account. The numerical results show that, for both kinds of NSs, the differential rotation can significantly prolong the duration of the r-modes. As a result, the stars can keep nearly a constant temperature and constant angular velocity for over a thousand years. Moreover, the persistent radiation of a quasi-monochromatic gravitational wave would also be predicted due to the long-term steady r-mode oscillation and stellar rotation. This increases the detectability of gravitational waves from both young isolated and old accreting NSs. (research papers)

  12. Extracting gravitational waves induced by plasma turbulence in the early Universe through an averaging process

    International Nuclear Information System (INIS)

    Garrison, David; Ramirez, Christopher

    2017-01-01

    This work is a follow-up to the paper, ‘Numerical relativity as a tool for studying the early Universe’. In this article, we determine if cosmological gravitational waves can be accurately extracted from a dynamical spacetime using an averaging process as opposed to conventional methods of gravitational wave extraction using a complex Weyl scalar. We calculate the normalized energy density, strain and degree of polarization of gravitational waves produced by a simulated turbulent plasma similar to what was believed to have existed shortly after the electroweak scale. This calculation is completed using two numerical codes, one which utilizes full general relativity calculations based on modified BSSN equations while the other utilizes a linearized approximation of general relativity. Our results show that the spectrum of gravitational waves calculated from the nonlinear code using an averaging process is nearly indistinguishable from those calculated from the linear code. This result validates the use of the averaging process for gravitational wave extraction of cosmological systems. (paper)

  13. Topics in gravitation and gauge fields

    International Nuclear Information System (INIS)

    Leen, T.K.

    1982-01-01

    The theoretical studies presented here address three distinct topics. The first deals with quantum-mechanical effects of classical gravitational radiation. Specifically, the use of the interstellar medium itself as a remote quantum-mechanical detector of gravitational waves is investigated. This study is motivated by the presumed existence of atomic hydrogen in the vicinity of astrophysical sources of gravitational radiation. Space-time curvature produces uniquely identifiable shifts in atomic hydrogen energy levels. The oscillating level shifts induced by a passing gravitational wave could conceivably be detected spectroscopically. Accordingly the level shifts for both low-lying and highly excited states of single electron atoms immersed in gravitational radiation have been studied. The second two topics deal with the theory of quantized fields on curved space-times. In the first of these studies, a naive model of cosmological baryon synthesis is examined. The model incorporates a hard CP violation as well as a baryon (and lepton) non-conserving interaction and is thus capable of generating an excess of matter over antimatter. The time dependent background geometry of the early universe drives the interaction producing net excess of baryon/lepton pairs. In the final topic, the question of renormalizability of non-Abelian gauge fields theories in a general curved space-time is addressed. All modern theories of elementary particle physics are gauge theories and one would like to know if their perturbative expansions continue to be well defined (i.e. renormalizable) on curved backgrounds. In general, one is interested in knowing if field theories renormalizable in Minkowski space remain so in a general curved space-time

  14. Inhibition of inducible nitric oxide synthesis by azathioprine in a macrophage cell line.

    Science.gov (United States)

    Moeslinger, Thomas; Friedl, Roswitha; Spieckermann, Paul Gerhard

    2006-06-20

    Azathioprine is used as an anti-inflammatory agent. Although there are numerous data demonstrating cytotoxic and immunosuppressive properties of azathioprine and its metabolite 6-mercaptopurine, the mechanism of the anti-inflammatory action of azathioprine has not yet been fully clarified. During our study, we investigated the effects of azathioprine on the inducible nitric oxide synthase (iNOS) in lipopolysaccharide stimulated murine macrophages (RAW 264.7) by measurement of iNOS protein (immunoblotting), iNOS mRNA (semiquantitative competitive RT-PCR), and NO production (nitrite levels). Azathioprine (0-210 muM) induces a concentration dependent inhibition of inducible nitric oxide synthesis (IC50: 33.5 muM). iNOS protein expression showed a concentration dependent reduction as revealed by immunoblotting when cells were incubated with increasing amounts of azathioprine. Azathioprine decreases iNOS mRNA levels as shown by semiquantitative competitive RT-PCR. In contrast, 6-mercaptopurine showed no inhibition of inducible nitric oxide synthesis. Azathioprine did not reduce iNOS mRNA stability after the addition of actinomycin D. Enzymatic activity assays with increasing concentrations of azathioprine (0-210 muM) showed no statistically significant inhibition of iNOS enzyme activity compared to cell lysates without azathioprine. Nuclear translocation of NF-kappaB p65 subunit and binding of NF-kappaB p50 subunit from nuclear extracts to a biotinylated-consensus sequence was unaffected by azathioprine treatment. iNOS inhibition by azathioprine was associated with a decreased expression of IRF-1 (interferon regulatory factor 1) and IFN-beta (beta-interferon) mRNA. Azathioprine induced iNOS inhibition seems to be associated with an action of the methylnitroimidazolyl substituent. This suggests a route to the rational design of nontoxic anti-inflammatory agents by replacing the 6-mercaptopurine component of azathioprine with other substituents. The inhibition of

  15. Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Ruibing [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Lihui [Shandong Normal University, Jinan, Shandong Province 250012 (China); Luo, Zheng; Guo, Xiaolan [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Ming, E-mail: ymylh@163.com [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China)

    2015-08-15

    Extracellular Ca{sup 2+} influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca{sup 2+} entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague–Dawley rats. Our data demonstrated that ethanol (0–400 mM) dose-dependently increased hepatocyte injury and 100 mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72 h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca{sup 2+} overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases. - Highlights: • Blockade of SOCE alleviated overload of Ca{sup 2+} and hepatotoxicity after ethanol application. • Blockade of SOCE inhibited mitochondrial apoptosis after ethanol application. • SOCE might be a useful therapeutic target in alcoholic liver diseases.

  16. Effect of Earth gravitational field on the detection of gravitational waves

    International Nuclear Information System (INIS)

    Denisov, V.I.; Eliseev, V.A.

    1987-01-01

    Results of laboratory detection of high-frequency gravitational waves from the view point of gravitation theories formulated on the basis of pseudoeuclidean space-time are calculated. Peculiarities due to different effects of the Earth gravitational field on the rates of gravitational and electromagnetic wave propagation in these theories are analysed. Experiments on check of predictions of the given class of theories are suggested

  17. Towards gravitational-wave astronomy of core-collapse supernova explosion

    International Nuclear Information System (INIS)

    Kotake, Kei

    2010-01-01

    We study properties of gravitational waves based on the three-dimensional (3D) simulations, which demonstrate the neutrino-driven explosions aided by the standing accretion shock instability (SASI). Pushed by evidence supporting slow rotation prior to core-collapse, we focus on the asphericities in neutrino emissions and matter motions outside the protoneutron star. By performing a ray-tracing calculation in 3D, we estimate accurately the gravitational waveforms from anisotropic neutrino emissions. In contrast to the previous work assuming axisymmetry, we find that the gravitational waveforms vary much more stochastically because the explosion anisotropies depend sensitively on the growth of the SASI which develops chaotically in all directions. Our results show that the gravitational-wave spectrum has its peak near ∼ 100 Hz, reflecting the SASI-induced matter overturns of ∼ O(10) ms. We point out that the detection of such signals, possibly visible to the LIGO-class detectors for a Galactic supernova, could be an important probe into the long-veiled explosion mechanism.

  18. Gravitationally Induced Entanglement between Two Massive Particles is Sufficient Evidence of Quantum Effects in Gravity.

    Science.gov (United States)

    Marletto, C; Vedral, V

    2017-12-15

    All existing quantum-gravity proposals are extremely hard to test in practice. Quantum effects in the gravitational field are exceptionally small, unlike those in the electromagnetic field. The fundamental reason is that the gravitational coupling constant is about 43 orders of magnitude smaller than the fine structure constant, which governs light-matter interactions. For example, detecting gravitons-the hypothetical quanta of the gravitational field predicted by certain quantum-gravity proposals-is deemed to be practically impossible. Here we adopt a radically different, quantum-information-theoretic approach to testing quantum gravity. We propose witnessing quantumlike features in the gravitational field, by probing it with two masses each in a superposition of two locations. First, we prove that any system (e.g., a field) mediating entanglement between two quantum systems must be quantum. This argument is general and does not rely on any specific dynamics. Then, we propose an experiment to detect the entanglement generated between two masses via gravitational interaction. By our argument, the degree of entanglement between the masses is a witness of the field quantization. This experiment does not require any quantum control over gravity. It is also closer to realization than detecting gravitons or detecting quantum gravitational vacuum fluctuations.

  19. Anisotropic gravitational instability

    International Nuclear Information System (INIS)

    Polyachenko, V.L.; Fridman, A.M.

    1988-01-01

    Exact solutions of stability problems are obtained for two anisotropic gravitational systems of different geometries - a layer of finite thickness at rest and a rotating cylinder of finite radius. It is shown that the anisotropic gravitational instability which develops in both cases is of Jeans type. However, in contrast to the classical aperiodic Jeans instability, this instability is oscillatory. The physics of the anisotropic gravitational instability is investigated. It is shown that in a gravitating layer this instability is due, in particular, to excitation of previously unknown interchange-Jeans modes. In the cylinder, the oscillatory Jeans instability is associated with excitation of a rotational branch, this also being responsible for the beam gravitational instability. This is the reason why this instability and the anisotropic gravitational instability have so much in common

  20. Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

    Energy Technology Data Exchange (ETDEWEB)

    Leung, Kin Chung; Hsin, Michael K.Y.; Chan, Joey S.Y.; Yip, Johnson H.Y.; Li, Mingyue; Leung, Billy C.S. [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Mok, Tony S.K. [Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Warner, Timothy D. [The William Harvey Research Institute, Queen Mary University of London, London (United Kingdom); Underwood, Malcolm J. [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Chen, George G., E-mail: gchen@cuhk.edu.hk [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong)

    2009-10-15

    The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB{sub 2}) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB{sub 2} but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

  1. Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

    International Nuclear Information System (INIS)

    Leung, Kin Chung; Hsin, Michael K.Y.; Chan, Joey S.Y.; Yip, Johnson H.Y.; Li, Mingyue; Leung, Billy C.S.; Mok, Tony S.K.; Warner, Timothy D.; Underwood, Malcolm J.; Chen, George G.

    2009-01-01

    The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB 2 ) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB 2 but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

  2. Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shangrong; Wang, Yifan; Li, Shu Jie, E-mail: shujieli@nankai.edu.cn

    2014-06-13

    Highlights: • Lansoprazole (LPZ) induces cell apoptosis in breast cancer cells. • LPZ markedly inhibits intracellular proton extrusion. • LPZ induces an increase in intracellular ATP level, lysosomal alkalinization and ROS accumulation. - Abstract: The increased glycolysis and proton secretion in tumors is proposed to contribute to the proliferation and invasion of cancer cells during the process of tumorigenesis and metastasis. Here, treatment of human breast cancer cells with proton pump inhibitor (PPI) lansoprazole (LPZ) induces cell apoptosis in a dose-dependent manner. In the implantation of the MDA-MB-231 xenografts in nude mice, administration of LPZ significantly inhibits tumorigenesis and induces large-scale apopotosis of tumor cells. LPZ markedly inhibits intracellular proton extrusion, induces an increase in intracellular ATP level, lysosomal alkalinization and accumulation of reactive oxygen species (ROS) in breast cancer cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and diphenyleneiodonium (DPI), a specific pharmacological inhibitor of NADPH oxidases (NOX), significantly abolish LPZ-induced ROS accumulation in breast cancer cells. Our results suggested that LPZ may be used as a new therapeutic drug for breast tumor.

  3. Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion

    International Nuclear Information System (INIS)

    Zhang, Shangrong; Wang, Yifan; Li, Shu Jie

    2014-01-01

    Highlights: • Lansoprazole (LPZ) induces cell apoptosis in breast cancer cells. • LPZ markedly inhibits intracellular proton extrusion. • LPZ induces an increase in intracellular ATP level, lysosomal alkalinization and ROS accumulation. - Abstract: The increased glycolysis and proton secretion in tumors is proposed to contribute to the proliferation and invasion of cancer cells during the process of tumorigenesis and metastasis. Here, treatment of human breast cancer cells with proton pump inhibitor (PPI) lansoprazole (LPZ) induces cell apoptosis in a dose-dependent manner. In the implantation of the MDA-MB-231 xenografts in nude mice, administration of LPZ significantly inhibits tumorigenesis and induces large-scale apopotosis of tumor cells. LPZ markedly inhibits intracellular proton extrusion, induces an increase in intracellular ATP level, lysosomal alkalinization and accumulation of reactive oxygen species (ROS) in breast cancer cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and diphenyleneiodonium (DPI), a specific pharmacological inhibitor of NADPH oxidases (NOX), significantly abolish LPZ-induced ROS accumulation in breast cancer cells. Our results suggested that LPZ may be used as a new therapeutic drug for breast tumor

  4. Catalase inhibits ionizing radiation-induced apoptosis in hematopoietic stem and progenitor cells.

    Science.gov (United States)

    Xiao, Xia; Luo, Hongmei; Vanek, Kenneth N; LaRue, Amanda C; Schulte, Bradley A; Wang, Gavin Y

    2015-06-01

    Hematologic toxicity is a major cause of mortality in radiation emergency scenarios and a primary side effect concern in patients undergoing chemo-radiotherapy. Therefore, there is a critical need for the development of novel and more effective approaches to manage this side effect. Catalase is a potent antioxidant enzyme that coverts hydrogen peroxide into hydrogen and water. In this study, we evaluated the efficacy of catalase as a protectant against ionizing radiation (IR)-induced toxicity in hematopoietic stem and progenitor cells (HSPCs). The results revealed that catalase treatment markedly inhibits IR-induced apoptosis in murine hematopoietic stem cells and hematopoietic progenitor cells. Subsequent colony-forming cell and cobble-stone area-forming cell assays showed that catalase-treated HSPCs can not only survive irradiation-induced apoptosis but also have higher clonogenic capacity, compared with vehicle-treated cells. Moreover, transplantation of catalase-treated irradiated HSPCs results in high levels of multi-lineage and long-term engraftments, whereas vehicle-treated irradiated HSPCs exhibit very limited hematopoiesis reconstituting capacity. Mechanistically, catalase treatment attenuates IR-induced DNA double-strand breaks and inhibits reactive oxygen species. Unexpectedly, we found that the radioprotective effect of catalase is associated with activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway and pharmacological inhibition of STAT3 abolishes the protective activity of catalase, suggesting that catalase may protect HSPCs against IR-induced toxicity via promoting STAT3 activation. Collectively, these results demonstrate a previously unrecognized mechanism by which catalase inhibits IR-induced DNA damage and apoptosis in HSPCs.

  5. Mechanical conditions and modes of paraglacial deep-seated gravitational spreading in Valles Marineris, Mars

    Science.gov (United States)

    Makowska, Magdalena; Mège, Daniel; Gueydan, Frédéric; Chéry, Jean

    2016-09-01

    Deep-seated gravitational spreading (DSGS) affects the slopes of formerly glaciated mountain ridges. On Mars, DSGS has played a key role in shaping the landforms of the giant Valles Marineris troughs. Though less spectacular, DSGS is common in terrestrial orogens, where understanding its mechanics is critical in the light of the ongoing climate change because it is a potential source of catastrophic landslides in deglaciated valleys. We conducted parametric numerical studies in order to identify important factors responsible for DSGS initiation. DSGS models are computed using an elastoviscoplastic finite element code. Using ADELI's software, we reproduce topographic ridge spreading under the effect of valley unloading. Two types of spreading topographic ridges are investigated, homogeneous or with horizontal rheological layering. We find that gravitational instabilities are enhanced by high slopes, which increase gravitational stress, and low friction and cohesion, which decrease yield stress. In the unlayered ridge, instability is triggered by glacial unloading with plastic strain concentration inside the ridge and at the base of the high slopes. Vertical fractures develop in the upper part of the slope, potentially leading to fault scarps. Ridge homogeneity promotes a deformation mode controlled by uphill-facing normal faulting and basal bulging. In the second case, the ridge encompasses horizontal geological discontinuities that induce rock mass anisotropy. Discontinuity located at the base of the slope accumulates plastic strain, leading to the formation of a sliding plane evolving into a landslide. The presence of a weak layer at ridge base therefore promotes another slope deformation mode ending up with catastrophic failure. Mechanical conditions and slope height being equal, these conclusions can probably be extrapolated to Earth. Compared with Mars, DSGS on Earth is inhibited because terrestrial topographic gradients are lower than in Valles Marineris, an

  6. Frequency-dependent squeeze-amplitude attenuation and squeeze-angle rotation by electromagnetically induced transparency for gravitational-wave interferometers

    International Nuclear Information System (INIS)

    Mikhailov, Eugeniy E.; Goda, Keisuke; Corbitt, Thomas; Mavalvala, Nergis

    2006-01-01

    We study the effects of frequency-dependent squeeze-amplitude attenuation and squeeze-angle rotation by electromagnetically induced transparency (EIT) on gravitational-wave (GW) interferometers. We propose the use of low-pass, bandpass, and high-pass EIT filters, an S-shaped EIT filter, and an intracavity EIT filter to generate frequency-dependent squeezing for injection into the antisymmetric port of GW interferometers. We find that the EIT filters have several advantages over the previous filter designs with regard to optical losses, compactness, and the tunability of the filter linewidth

  7. Inhibition of radiation-induced lipid peroxidation by means of gallic polydisulphide

    International Nuclear Information System (INIS)

    Losev, Yu.P.; Amadyan, M.G.; Oganesyan, N.M.; Fedulov, A.S.; Abramyan, A.K.; Shagoyan, A.G.; Khachkavanktsyan, A.S.

    1999-01-01

    Inhibition of radiation-induced lipid peroxidation by means of gallic polydisulphade has been studied. Rats were exposed to X-rays in doses 4,8 and 5,25 Gy. Lipid peroxidation was analysed in blood plasma, membranes of erythrocytes and homogenates of liver and spleen tissues of rats. Polydisulphide of gallic acid was used as inhibitor of lipid peroxidation because of its effective antioxidant properties as have been reported previously. It has been demonstrated that gallic disulphide exhibited high inhibition efficiency in conditions of radiation-induced lipid peroxidation due to the effect of intra-molecular synergism

  8. Neogambogic acid prevents silica-induced fibrosis via inhibition of high-mobility group box 1 and MCP-1-induced protein 1

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wei [Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096 (China); Department of Respiration, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Zhang, Mei, E-mail: meizhang1717@163.com [Department of Respiration, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Wang, Zhongjiang [Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Cheng, Yusi; Liu, Haijun [Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Zhou, Zewei [Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Han, Bing [Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Chen, Baoan [Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Yao, Honghong, E-mail: yaohh@seu.edu.cn [Department of Pharmacology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096 (China); Chao, Jie, E-mail: chaojie@seu.edu.cn [Department of Physiology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China); Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096 (China); Department of Respiration, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009 (China)

    2016-10-15

    Background: Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO{sub 2}); early stages are characterized by alveolar inflammation, and later stages are characterized by progressive lung fibrosis. Mounting evidence indicates that high-mobility group box 1 (HMGB1) is involved in pulmonary fibrosis. Whether neogambogic acid (NGA) inhibits macrophage and fibroblast activation induced by SiO{sub 2} by targeting HMGB1 remains unclear. Methods and results: Experiments using cultured mouse macrophages (RAW264.7 cells) demonstrated that SiO{sub 2} treatment induces the expression of HMGB1 in a time- and dose-dependent manner via mitogen-activated protein kinases (MAPKs) and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway; in turn, this expression causes macrophage apoptosis and fibroblast activation. Pretreating macrophages with NGA inhibited the HMGB1 expression induced by SiO{sub 2} and attenuated both macrophage apoptosis and fibroblast activation. Moreover, NGA directly inhibited MCP-1-induced protein 1 (MCPIP1) expression, as well as markers of fibroblast activation and migration induced by SiO{sub 2}. Furthermore, the effects of NGA on macrophages and fibroblasts were confirmed in vivo by exposing mice to SiO{sub 2}. Conclusion: NGA can prevent SiO{sub 2}-induced macrophage activation and apoptosis via HMGB1 inhibition and SiO{sub 2}-induced fibrosis via the MCPIP1 pathway. Targeting HMGB1 and MCPIP1 with NGA could provide insights into the potential development of a therapeutic approach for alleviating the inflammation and fibrosis induced by SiO{sub 2}. - Highlights: • The SiO{sub 2} induced HMGB1 in alveolar macrophage and MCPIP1 in fibroblast. • NGA rescued the SiO{sub 2}-induced apoptosis of alveolar macrophages via HMGB1 signaling. • NGA inhibited the fibroblast activation induced by SiO{sub 2} via MCPIP1 signaling. • NGA might represent a potential therapeutic approach for silicosis.

  9. Novel Therapeutic Targets to Inhibit Tumor Microenvironment Induced Castration-Resistant Prostate Cancer

    Science.gov (United States)

    2017-12-01

    AWARD NUMBER: W81XWH-13-1-0163 TITLE: Novel Therapeutic Targets to Inhibit Tumor Microenvironment Induced Castration-resistant Prostate Cancer ...Prostate Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Feng Yang, Ph.D. 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: fyang@bcm.edu...W81XWH-13-1-0163 " Novel Therapeutic Targets to Inhibit Tumor Microenvironment Induced Castration-resistant Prostate Cancer " Introduction AR signaling

  10. Manganese (II) induces chemical hypoxia by inhibiting HIF-prolyl hydroxylase: Implication in manganese-induced pulmonary inflammation

    International Nuclear Information System (INIS)

    Han, Jeongoh; Lee, Jong-Suk; Choi, Daekyu; Lee, Youna; Hong, Sungchae; Choi, Jungyun; Han, Songyi; Ko, Yujin; Kim, Jung-Ae; Mi Kim, Young; Jung, Yunjin

    2009-01-01

    Manganese (II), a transition metal, causes pulmonary inflammation upon environmental or occupational inhalation in excess. We investigated a potential molecular mechanism underlying manganese-induced pulmonary inflammation. Manganese (II) delayed HIF-1α protein disappearance, which occurred by inhibiting HIF-prolyl hydroxylase (HPH), the key enzyme for HIF-1α hydroxylation and subsequent von Hippel-Lindau(VHL)-dependent HIF-1α degradation. HPH inhibition by manganese (II) was neutralized significantly by elevated dose of iron. Consistent with this, the induction of cellular HIF-1α protein by manganese (II) was abolished by pretreatment with iron. Manganese (II) induced the HIF-1 target gene involved in pulmonary inflammation, vascular endothelial growth factor (VEGF), in lung carcinoma cell lines. The induction of VEGF was dependent on HIF-1. Manganese-induced VEGF promoted tube formation of HUVEC. Taken together, these data suggest that HIF-1 may be a potential mediator of manganese-induced pulmonary inflammation

  11. A synthetic peptide blocking TRPV1 activation inhibits UV-induced skin responses.

    Science.gov (United States)

    Kang, So Min; Han, Sangbum; Oh, Jang-Hee; Lee, Young Mee; Park, Chi-Hyun; Shin, Chang-Yup; Lee, Dong Hun; Chung, Jin Ho

    2017-10-01

    Transient receptor potential type 1 (TRPV1) can be activated by ultraviolet (UV) irradiation, and mediates UV-induced matrix metalloproteinase (MMP)-1 and proinflammatory cytokines in keratinocytes. Various chemicals and compounds targeting TRPV1 activation have been developed, but are not in clinical use mostly due to their safety issues. We aimed to develop a novel TRPV1-targeting peptide to inhibit UV-induced responses in human skin. We designed and generated a novel TRPV1 inhibitory peptide (TIP) which mimics the specific site in TRPV1 (aa 701-709: Gln-Arg-Ala-Ile-Thr-Ile-Leu-Asp-Thr, QRAITILDT), Thr 705 , and tested its efficacy of blocking UV-induced responses in HaCaT, mouse, and human skin. TIP effectively inhibited capsaicin-induced calcium influx and TRPV1 activation. Treatment of HaCaT with TIP prevented UV-induced increases of MMP-1 and pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-α. In mouse skin in vivo, TIP inhibited UV-induced skin thickening and prevented UV-induced expression of MMP-13 and MMP-9. Moreover, TIP attenuated UV-induced erythema and the expression of MMP-1, MMP-2, IL-6, and IL-8 in human skin in vivo. The novel synthetic peptide targeting TRPV1 can ameliorate UV-induced skin responses in vitro and in vivo, providing a promising therapeutic approach against UV-induced inflammation and photoaging. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  12. Effects of ceramide inhibition on radiation-induced apoptosis in human leukemia MOLT-4 cells

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Eriko; Inanami, Osamu; Asanuma, Taketoshi; Kuwabara, Mikinori [Hokkaido Univ., Graduate School of Veterinary Medicine, Sapporo, Hokkaido (Japan)

    2006-03-15

    In the present study, using inhibitors of ceramide synthase (fumonisin B{sub 1}), ketosphinganine synthetase (L-cycloserine), acid sphingomyelinase (D609 and desipramine) and neutral sphingomyelinase (GW4869), the role of ceramide in X-ray-induced apoptosis was investigated in MOLT-4 cells. The diacylglycerol kinase (DGK) assay showed that the intracellular concentration of ceramide increased time-dependently after X irradiation of cells, and this radiation-induced accumulation of ceramide did not occur prior to the appearance of apoptotic cells. Treatment with D609 significantly inhibited radiation-induced apoptosis, but did not inhibit the increase of intracellular ceramide. Treatment with desipramine or GW4869 prevented neither radiation-induced apoptosis nor the induced increase of ceramide. On the other hand, fumonisin B{sub 1} and L-cycloserine had no effect on the radiation-induced induction of apoptosis, in spite of significant inhibition of the radiation-induced ceramide. From these results, it was suggested that the increase of the intracellular concentration of ceramide was not essential for radiation-induced apoptosis in MOLT-4 cells. (author)

  13. Effects of ceramide inhibition on radiation-induced apoptosis in human leukemia MOLT-4 cells

    International Nuclear Information System (INIS)

    Takahashi, Eriko; Inanami, Osamu; Asanuma, Taketoshi; Kuwabara, Mikinori

    2006-01-01

    In the present study, using inhibitors of ceramide synthase (fumonisin B 1 ), ketosphinganine synthetase (L-cycloserine), acid sphingomyelinase (D609 and desipramine) and neutral sphingomyelinase (GW4869), the role of ceramide in X-ray-induced apoptosis was investigated in MOLT-4 cells. The diacylglycerol kinase (DGK) assay showed that the intracellular concentration of ceramide increased time-dependently after X irradiation of cells, and this radiation-induced accumulation of ceramide did not occur prior to the appearance of apoptotic cells. Treatment with D609 significantly inhibited radiation-induced apoptosis, but did not inhibit the increase of intracellular ceramide. Treatment with desipramine or GW4869 prevented neither radiation-induced apoptosis nor the induced increase of ceramide. On the other hand, fumonisin B 1 and L-cycloserine had no effect on the radiation-induced induction of apoptosis, in spite of significant inhibition of the radiation-induced ceramide. From these results, it was suggested that the increase of the intracellular concentration of ceramide was not essential for radiation-induced apoptosis in MOLT-4 cells. (author)

  14. The gravitational Schwinger effect and attenuation of gravitational waves

    Science.gov (United States)

    McDougall, Patrick Guarneri

    This paper will discuss the possible production of photons from gravitational waves. This process is shown to be possible by examining Feynman diagrams, the Schwinger Effect, and Hawking Radiation. The end goal of this project is to find the decay length of a gravitational wave and assert that this decay is due to photons being created at the expense of the gravitational wave. To do this, we first find the state function using the Klein Gordon equation, then find the current due to this state function. We then take the current to be directly proportional to the production rate per volume. This is then used to find the decay length that this kind of production would produce, gives a prediction of how this effect will change the distance an event creating a gravitational wave will be located, and shows that this effect is small but can be significant near the source of a gravitational wave.

  15. Inhibition of chlorine-induced lung injury by the type 4 phosphodiesterase inhibitor rolipram

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Weiyuan; Chen, Jing; Schlueter, Connie F. [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States); Rando, Roy J. [Department of Environmental Health Sciences, School of Public Health and Tropical Medicine, Tulane University Health Sciences Center, New Orleans, LA (United States); Pathak, Yashwant V. [College of Pharmacy, University of South Florida, Tampa, FL (United States); Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States)

    2012-09-01

    Chlorine is a highly toxic respiratory irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity, inflammation, and pulmonary edema. Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from acute lung injury. The type 4 phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for chlorine-induced lung injury. Rolipram inhibits degradation of the intracellular signaling molecule cyclic AMP. Potential beneficial effects of increased cyclic AMP levels include inhibition of pulmonary edema, inflammation, and airway hyperreactivity. Mice were exposed to chlorine (whole body exposure, 228–270 ppm for 1 h) and were treated with rolipram by intraperitoneal, intranasal, or intramuscular (either aqueous or nanoemulsion formulation) delivery starting 1 h after exposure. Rolipram administered intraperitoneally or intranasally inhibited chlorine-induced pulmonary edema. Minor or no effects were observed on lavage fluid IgM (indicative of plasma protein leakage), KC (Cxcl1, neutrophil chemoattractant), and neutrophils. All routes of administration inhibited chlorine-induced airway hyperreactivity assessed 1 day after exposure. The results of the study suggest that rolipram may be an effective rescue treatment for chlorine-induced lung injury and that both systemic and targeted administration to the respiratory tract were effective routes of delivery. -- Highlights: ► Chlorine causes lung injury when inhaled and is considered a chemical threat agent. ► Rolipram inhibited chlorine-induced pulmonary edema and airway hyperreactivity. ► Post-exposure rolipram treatments by both systemic and local delivery were effective. ► Rolipram shows promise as a rescue treatment for chlorine-induced lung injury.

  16. Interplay of gravitation and linear superposition of different mass eigenstates

    International Nuclear Information System (INIS)

    Ahluwalia, D.V.

    1998-01-01

    The interplay of gravitation and the quantum-mechanical principle of linear superposition induces a new set of neutrino oscillation phases. These ensure that the flavor-oscillation clocks, inherent in the phenomenon of neutrino oscillations, redshift precisely as required by Einstein close-quote s theory of gravitation. The physical observability of these phases in the context of the solar neutrino anomaly, type-II supernova, and certain atomic systems is briefly discussed. copyright 1998 The American Physical Society

  17. The PDE4 inhibitor CHF-6001 and LAMAs inhibit bronchoconstriction-induced remodeling in lung slices.

    Science.gov (United States)

    Kistemaker, Loes E M; Oenema, Tjitske A; Baarsma, Hoeke A; Bos, I Sophie T; Schmidt, Martina; Facchinetti, Fabrizio; Civelli, Maurizio; Villetti, Gino; Gosens, Reinoud

    2017-09-01

    Combination therapy of PDE4 inhibitors and anticholinergics induces bronchoprotection in COPD. Mechanical forces that arise during bronchoconstriction may contribute to airway remodeling. Therefore, we investigated the impact of PDE4 inhibitors and anticholinergics on bronchoconstriction-induced remodeling. Because of the different mechanism of action of PDE4 inhibitors and anticholinergics, we hypothesized functional interactions of these two drug classes. Guinea pig precision-cut lung slices were preincubated with the PDE4 inhibitors CHF-6001 or roflumilast and/or the anticholinergics tiotropium or glycopyorrolate, followed by stimulation with methacholine (10 μM) or TGF-β 1 (2 ng/ml) for 48 h. The inhibitory effects on airway smooth muscle remodeling, airway contraction, and TGF-β release were investigated. Methacholine-induced protein expression of smooth muscle-myosin was fully inhibited by CHF-6001 (0.3-100 nM), whereas roflumilast (1 µM) had smaller effects. Tiotropium and glycopyrrolate fully inhibited methacholine-induced airway remodeling (0.1-30 nM). The combination of CHF-6001 and tiotropium or glycopyrrolate, in concentrations partially effective by themselves, fully inhibited methacholine-induced remodeling in combination. CHF-6001 did not affect airway closure and had limited effects on TGF-β 1 -induced remodeling, but rather, it inhibited methacholine-induced TGF-β release. The PDE4 inhibitor CHF-6001, and to a lesser extent roflumilast, and the LAMAs tiotropium and glycopyrrolate inhibit bronchoconstriction-induced remodeling. The combination of CHF-6001 and anticholinergics was more effective than the individual compounds. This cooperativity might be explained by the distinct mechanisms of action inhibiting TGF-β release and bronchoconstriction. Copyright © 2017 the American Physiological Society.

  18. Effect of the Earth's gravitational field on the detection of gravitational waves

    International Nuclear Information System (INIS)

    Denisov, V.I.; Eliseev, V.A.

    1988-01-01

    We consider the laboratory detection of high-frequency gravitational waves in theories of gravitation based on a pseudo-Euclidean space-time. We analyze the effects due to the Earth's gravitational field on the propagation velocities of gravitational and electromagnetic waves in these theories. Experiments to test the predictions of this class of theories are discussed

  19. Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli.

    Science.gov (United States)

    Bunnell, Bryan E; Escobar, Jillian F; Bair, Kirsten L; Sutton, Mark D; Crane, John K

    2017-01-01

    Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx) and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases. Since zinc inhibited the other aspects of the SOS response, we hypothesized that zinc would also inhibit the mutator response, also known as hypermutation. We explored various different experimental paradigms to induce hypermutation triggered by the SOS response, and found that hypermutation was induced not just by classical inducers such as mitomycin C and the quinolone antibiotics, but also by antiviral drugs such as zidovudine and anti-cancer drugs such as 5-fluorouracil, 6-mercaptopurine, and azacytidine. Zinc salts inhibited the SOS response and the hypermutator phenomenon in E. coli as well as in Klebsiella pneumoniae, and was more effective in inhibiting the SOS response than other metals. We then attempted to determine the mechanism by which zinc, applied externally in the medium, inhibits hypermutation. Our results show that zinc interferes with the actions of RecA, and protects LexA from RecA-mediated cleavage, an early step in initiation of the SOS response. The SOS response may play a role in the development of antibiotic resistance and the effect of zinc suggests ways to prevent it.

  20. Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Bryan E Bunnell

    Full Text Available Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases. Since zinc inhibited the other aspects of the SOS response, we hypothesized that zinc would also inhibit the mutator response, also known as hypermutation. We explored various different experimental paradigms to induce hypermutation triggered by the SOS response, and found that hypermutation was induced not just by classical inducers such as mitomycin C and the quinolone antibiotics, but also by antiviral drugs such as zidovudine and anti-cancer drugs such as 5-fluorouracil, 6-mercaptopurine, and azacytidine. Zinc salts inhibited the SOS response and the hypermutator phenomenon in E. coli as well as in Klebsiella pneumoniae, and was more effective in inhibiting the SOS response than other metals. We then attempted to determine the mechanism by which zinc, applied externally in the medium, inhibits hypermutation. Our results show that zinc interferes with the actions of RecA, and protects LexA from RecA-mediated cleavage, an early step in initiation of the SOS response. The SOS response may play a role in the development of antibiotic resistance and the effect of zinc suggests ways to prevent it.

  1. Quercetin-induced downregulation of phospholipase D1 inhibits proliferation and invasion in U87 glioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Mi Hee [Department of Molecular Biology, College of Natural Science, Pusan National University, 30 Jangjeon dong, Geumjeong gu, Busan 609-735 (Korea, Republic of); Min, Do Sik, E-mail: minds@pusan.ac.kr [Department of Molecular Biology, College of Natural Science, Pusan National University, 30 Jangjeon dong, Geumjeong gu, Busan 609-735 (Korea, Republic of)

    2011-09-09

    Highlights: {yields} Quercetin, a bioactive flavonoid, suppresses expression and enzymatic activity of phospholipase D1. {yields} Quercetin abolishes NFkB-induced phospholipase D1 expression via inhibition of NFkB transactivation. {yields} Quercetin-induced suppression of phospholipase D1 inhibits invasion and proliferation of human glioma cells. -- Abstract: Phospholipase D (PLD) has been recognized as a regulator of cell proliferation and tumorigenesis, but little is known about the molecules regulating PLD expression. Thus, the identification of small molecules inhibiting PLD expression would be an important advance in PLD-mediated physiology. Quercetin, a ubiquitous bioactive flavonoid, is known to inhibit proliferation and induce apoptosis in a variety of cancer cells. In the present study, we examined the effect of quercetin on the expression of PLD in U87 glioma cells. Quercetin significantly suppressed the expression of PLD1 at the transcriptional level. Moreover, quercetin abolished the protein expression of PLD1 in a time and dose-dependent manner, as well as inhibited PLD activity. Quercetin suppressed NF{kappa}B-induced PLD1 expression via inhibition of NFkB transactivation. Furthermore, quercetin inhibited activation and invasion of metalloproteinase-2 (MMP-2), a key modulator of glioma cell invasion, induced by phosphatidic acid (PA), a product of PLD activity. Taken together these data demonstrate that quercetin abolishes PLD1 expression and subsequently inhibits invasion and proliferation of glioma cells.

  2. Gravitation Waves

    CERN Multimedia

    CERN. Geneva

    2005-01-01

    We will present a brief introduction to the physics of gravitational waves and their properties. We will review potential astrophysical sources of gravitational waves, and the physics and astrophysics that can be learned from their study. We will survey the techniques and technologies for detecting gravitational waves for the first time, including bar detectors and broadband interferometers, and give a brief status report on the international search effort, with special emphasis on the LIGO detectors and search results.

  3. ERα inhibited myocardin-induced differentiation in uterine fibroids

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Xing-Hua, E-mail: xinghualiao@hotmail.com [Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065 (China); Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China); Li, Jun-Yan [Henan Vocational College of Applied Technology, Zhengzhou 450042 (China); Dong, Xiu-Mei [Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065 (China); Yuncheng County People' s Hospital, Shandong 274700 (China); Wang, Xiuhong [Xianning Central Hospital, Department of Obstetrics and Gynecology, Xianning, Hubei 437100 (China); Xiang, Yuan; Li, Hui; Yu, Cheng-Xi; Li, Jia-Peng; Yuan, Bai-Yin [Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065 (China); Zhou, Jun, E-mail: zhoujun@wust.edu.cn [Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065 (China); School of Medicine, Wuhan University of Science and Technology, Wuhan 430065 (China); Zhang, Tong-Cun, E-mail: zhangtongcun@wust.edu.cn [Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065 (China); Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China)

    2017-01-01

    Uterine fibroids, also known as uterine leiomyomas, are a benign tumor of the human uterus and the commonest estrogen-dependent benign tumor found in women. Myocardin is an important transcriptional regulator in smooth and cardiac muscle development. The role of myocardin and its relationship with ERα in uterine fibroids have barely been addressed. We noticed that the expression of myocardin was markedly reduced in human uterine fibroid tissue compared with corresponding normal or adjacent myometrium tissue. Here we reported that myocardin induced the transcription and expression of differentiation markers SM22α and alpha smooth muscle actin (α-SMA) in rat primary uterine smooth muscle cells (USMCs) and this effect was inhibited by ERα. Notably, we showed that, ERα induced expression of proliferation markers PCNA and ki-67 in rat primary USMCs. We also found ERα interacted with myocardin and formed complex to bind to CArG box and inhibit the SM22α promoter activity. Furthermore, ERα inhibited the transcription and expression of myocardin, and reduced the levels of transcription and expression of downstream target SM22α, a SMC differentiation marker. Our data thus provided important and novel insights into how ERα and myocardin interact to control the cell differentiation and proliferation of USMCs. Thus, it may provide potential therapeutic target for uterine fibroids.

  4. Einstein-Rosen gravitational waves

    International Nuclear Information System (INIS)

    Astefanoaei, Iordana; Maftei, Gh.

    2001-01-01

    In this paper we analyse the behaviour of the gravitational waves in the approximation of the far matter fields, considering the indirect interaction between the matter sources and the gravitational field, in a cosmological model based on the Einstein-Rosen solution, Because the properties of the gravitational waves obtained as the solutions of Einstein fields equations (the gravitational field equations) are most obvious in the weak gravitational fields we consider here, the gravitational field in the linear approximation. Using the Newman-Penrose formalism, we calculate in the null-tetradic base (e a ), the spin coefficients, the directional derivates and the tetradic components of Ricci and Weyl tensors. From the Einstein field equations we obtained the solution for b(z, t) what described the behaviour of gravitational wave in Einstein-Rosen Universe and in the particular case, when t → ∞, p(z, t) leads us to the primordial gravitational waves in the Einstein-Rosen Universe. (authors)

  5. Prolyl oligopeptidase inhibition-induced growth arrest of human gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Kanayo [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Sakaguchi, Minoru, E-mail: sakaguti@gly.oups.ac.jp [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Tanaka, Satoshi [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Yoshimoto, Tadashi [Department of Life Science, Setsunan University, 17-8 Ikeda-Nakamachi, Neyagawa, Osaka 572-8508 (Japan); Takaoka, Masanori [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)

    2014-01-03

    Highlights: •We examined the effects of prolyl oligopeptidase (POP) inhibition on p53 null gastric cancer cell growth. •POP inhibition-induced cell growth suppression was associated with an increase in a quiescent G{sub 0} state. •POP might regulate the exit from and/or reentry into the cell cycle. -- Abstract: Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G{sub 0}/G{sub 1} cell cycle arrest and increased levels of the CDK inhibitor p27{sup kip1} and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-((4-[2-(E)-styrylphenoxy]butanoyl)-L-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G{sub 0}/G{sub 1} cell cycle phase arrest and increased levels of p27{sup kip1} in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G{sub 0} state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells.

  6. Glycation inhibits trichloroacetic acid (TCA)-induced whey protein precipitation

    Science.gov (United States)

    Four different WPI saccharide conjugates were successfully prepared to test whether glycation could inhibit WPI precipitation induced by trichloroacetic acid (TCA). Conjugates molecular weights after glycation were analyzed with SDS-PAGE. No significant secondary structure change due to glycation wa...

  7. Gravitational waves from inflation

    International Nuclear Information System (INIS)

    Guzzetti, M.C.; Bartolo, N.; Liguori, M.; Matarrese, S.

    2016-01-01

    The production of a stochastic background of gravitational waves is a fundamental prediction of any cosmological inflationary model. The features of such a signal encode unique information about the physics of the Early Universe and beyond, thus representing an exciting, powerful window on the origin and evolution of the Universe. We review the main mechanisms of gravitational-wave production, ranging from quantum fluctuations of the gravitational field to other mechanisms that can take place during or after inflation. These include e.g. gravitational waves generated as a consequence of extra particle production during inflation, or during the (p)reheating phase. Gravitational waves produced in inflation scenarios based on modified gravity theories and second-order gravitational waves are also considered. For each analyzed case, the expected power spectrum is given. We discuss the discriminating power among different models, associated with the validity/violation of the standard consistency relation between tensor-to-scalar ratio r and tensor spectral index ηT. In light of the prospects for (directly/indirectly) detecting primordial gravitational waves, we give the expected present-day gravitational radiation spectral energy-density, highlighting the main characteristics imprinted by the cosmic thermal history, and we outline the signatures left by gravitational waves on the Cosmic Microwave Background and some imprints in the Large-Scale Structure of the Universe. Finally, current bounds and prospects of detection for inflationary gravitational waves are summarized.

  8. Gravitation and relativity

    CERN Document Server

    Hoffmann, William F

    1964-01-01

    Remarks on the observational basis of general relativity ; Riemannian geometry ; gravitation as geometry ; gravitational waves ; Mach's principle and experiments on mass anisotropy ; the many faces of Mach ; the significance for the solar system of time-varying gravitation ; relativity principles and the role of coordinates in physics ; the superdense star and the critical nucleon number ; gravitation and light ; possible effects on the solar system of φ waves if they exist ; the Lyttleton-Bondi universe and charge equality ; quantization of general relativity ; Mach's principle as boundary condition for Einstein's equations.

  9. Dasatinib inhibits both osteoclast activation and prostate cancer PC-3-cell-induced osteoclast formation.

    Science.gov (United States)

    Araujo, John C; Poblenz, Ann; Corn, Paul; Parikh, Nila U; Starbuck, Michael W; Thompson, Jerry T; Lee, Francis; Logothetis, Christopher J; Darnay, Bryant G

    2009-11-01

    Therapies to target prostate cancer bone metastases have only limited effects. New treatments are focused on the interaction between cancer cells, bone marrow cells and the bone matrix. Osteoclasts play an important role in the development of bone tumors caused by prostate cancer. Since Src kinase has been shown to be necessary for osteoclast function, we hypothesized that dasatinib, a Src family kinase inhibitor, would reduce osteoclast activity and prostate cancer (PC-3) cell-induced osteoclast formation. Dasatinib inhibited RANKL-induced osteoclast differentiation of bone marrow-derived monocytes with an EC(50) of 7.5 nM. PC-3 cells, a human prostate cancer cell line, were able to differentiate RAW 264.7 cells, a murine monocytic cell line, into osteoclasts, and dasatinib inhibited this differentiation. In addition, conditioned medium from PC-3 cell cultures was able to differentiate RAW 264.7 cells into osteoclasts and this too, was inhibited by dasatinib. Even the lowest concentration of dasatinib, 1.25 nmol, inhibited osteoclast differentiation by 29%. Moreover, dasatinib inhibited osteoclast activity by 58% as measured by collagen 1 release. We performed in vitro experiments utilizing the Src family kinase inhibitor dasatinib to target osteoclast activation as a means of inhibiting prostate cancer bone metastases. Dasatinib inhibits osteoclast differentiation of mouse primary bone marrow-derived monocytes and PC-3 cell-induced osteoclast differentiation. Dasatinib also inhibits osteoclast degradation activity. Inhibiting osteoclast differentiation and activity may be an effective targeted therapy in patients with prostate cancer bone metastases.

  10. Gravitational waves — A review on the theoretical foundations of gravitational radiation

    Science.gov (United States)

    Dirkes, Alain

    2018-05-01

    In this paper, we review the theoretical foundations of gravitational waves in the framework of Albert Einstein’s theory of general relativity. Following Einstein’s early efforts, we first derive the linearized Einstein field equations and work out the corresponding gravitational wave equation. Moreover, we present the gravitational potentials in the far away wave zone field point approximation obtained from the relaxed Einstein field equations. We close this review by taking a closer look on the radiative losses of gravitating n-body systems and present some aspects of the current interferometric gravitational waves detectors. Each section has a separate appendix contribution where further computational details are displayed. To conclude, we summarize the main results and present a brief outlook in terms of current ongoing efforts to build a spaced-based gravitational wave observatory.

  11. Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jing; Mo, Yiqun; Schlueter, Connie F.; Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu

    2013-10-15

    Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Corticosteroids may inhibit lung injury through their anti-inflammatory actions. • Corticosteroids inhibited chlorine-induced pneumonitis and pulmonary edema. • Mometasone and budesonide are potential rescue treatments for chlorine lung injury.

  12. The impact of particle production on gravitational baryogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Lima, J.A.S., E-mail: jas.lima@iag.usp.br [Departamento de Astronomia, Universidade de São Paulo, Rua do Matão 1226, 05508-900, São Paulo (Brazil); Singleton, D., E-mail: dougs@csufresno.edu [Department of Physics, California State University Fresno, Fresno, CA 93740-8031 (United States); ICTP South American Institute for Fundamental Research, UNESP – Univ. Estadual Paulista, Rua Dr. Bento T. Ferraz 271, 01140-070, São Paulo, SP (Brazil); Institute of Experimental and Theoretical Physics Al-Farabi KazNU, Almaty, 050040 (Kazakhstan)

    2016-11-10

    Baryogenesis driven by curvature effects is investigated by taking into account gravitationally induced particle production in the very early Universe. In our scenario, the baryon asymmetry is generated dynamically during an inflationary epoch powered by ultra-relativistic particles. The adiabatic particle production rate provides both the needed negative pressure to accelerate the radiation dominated Universe and a non-zero chemical potential which distinguishes baryons and anti-baryons thereby producing a baryon asymmetry in agreement with the observed value. Reciprocally, the present day asymmetry may be used to determine the inflationary scale at early times. Successful gravitational baryogenesis is dynamically generated for many different choices of the relevant model parameters.

  13. PPARγ ligand ciglitazone inhibits TNFα-induced ICAM-1 in human airway smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Chien-Da Huang

    2014-08-01

    Full Text Available Background: Modification of human airway smooth muscle (ASM function by proinflammatory cytokines has been regarded as a potential mechanism underlying bronchial hyperresponsiveness in asthma. Human ASM cells express intercellular adhesion molecule (ICAM-1 in response to cytokines. Synthetic ligands for peroxisome proliferator-activated receptor (PPARγ reportedly possess anti-inflammatory and immunomodulatory properties. In this study, we examined whether ciglitazone, a synthetic PPARγ ligand, can modulate the basal and tumor necrosis factor (TNFα-induced ICAM1 gene expression in human ASM cells. Methods: Human ASM cells were treated with TNFα. ICAM-1 expression was assessed by flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR analysis. PPARγ activity was inhibited by target-specific small interfering (si RNA targeting PPARγ and GW9662, a PPARγ antagonist. Activity of nuclear factor (NF-κB was assessed by using immunoblot analysis, immune-confocal images, and electrophoretic mobility shift assay (EMSA. Results: By flow cytometry, ciglitazone alone had no effect on ICAM-1 expression in ASM cells, but inhibited ICAM-1 expression in response to TNFα (10 ng/ml in a dose-dependent manner (1-10 μM. It also inhibited TNFα-induced ICAM1 gene expression by RT-PCR analysis. Knockdown of PPARγ gene by target-specific siRNA targeting PPARγ enhanced ICAM-1 expression and the inhibitory effect of ciglitazone on TNFα-induced ICAM-1 expression was reversed by PPARγ siRNA and GW9662. SN-50 (10 μg/ml, an inhibitor for nuclear translocation of NF-κB, inhibited TNFα-induced ICAM-1 expression. Ciglitazone did not prevent TNFα-induced degradation of the cytosolic inhibitor of NF-κB (IκB, but inhibited the nuclear translocation of p65 induced by TNFα and suppressed the NF-κB/DNA binding activity. Conclusion: These findings suggest that ciglitazone inhibits TNFα-induced ICAM1 gene expression in human ASM cells through

  14. Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

    International Nuclear Information System (INIS)

    Tang, Chunling; Yang, Liqun; Jiang, Xiaolan; Xu, Chuan; Wang, Mei; Wang, Qinrui; Zhou, Zhansong; Xiang, Zhonghuai; Cui, Hongjuan

    2014-01-01

    Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer

  15. Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chunling; Yang, Liqun; Jiang, Xiaolan [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Xu, Chuan [Division of Scientific Research and Training, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083 (China); Wang, Mei; Wang, Qinrui [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Zhou, Zhansong, E-mail: zhouzhans@sina.com [Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Xiang, Zhonghuai [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Cui, Hongjuan, E-mail: hcui@swu.edu.cn [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China)

    2014-03-28

    Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer.

  16. Theory of gravitational interactions

    CERN Document Server

    Gasperini, Maurizio

    2017-01-01

    This is the second edition of a well-received book that is a modern, self-contained introduction to the theory of gravitational interactions. The new edition includes more details on gravitational waves of cosmological origin, the so-called brane world scenario, and gravitational time-delay effects. The first part of the book follows the traditional presentation of general relativity as a geometric theory of the macroscopic gravitational field, while the second, more advanced part discusses the deep analogies (and differences) between a geometric theory of gravity and the “gauge” theories of the other fundamental interactions. This fills a gap within the traditional approach to general relativity which usually leaves students puzzled about the role of gravity. The required notions of differential geometry are reduced to the minimum, allowing room for aspects of gravitational physics of current phenomenological and theoretical interest, such as the properties of gravitational waves, the gravitational inter...

  17. Low grade inflammation inhibits VEGF induced HUVECs migration in p53 dependent manner

    International Nuclear Information System (INIS)

    Panta, Sushil; Yamakuchi, Munekazu; Shimizu, Toshiaki; Takenouchi, Kazunori; Oyama, Yoko; Koriyama, Toyoyasu; Kojo, Tsuyoshi; Hashiguchi, Teruto

    2017-01-01

    In the course of studying crosstalk between inflammation and angiogenesis, high doses of pro-inflammatory factors have been reported to induce apoptosis in cells. Under normal circumstances also the pro-inflammatory cytokines are being released in low doses and are actively involved in cell signaling pathways. We studied the effects of low grade inflammation in growth factor induced angiogenesis using tumor necrosis factor alfa (TNFα) and vascular endothelial growth factor A (VEGF) respectively. We found that low dose of TNFα can inhibit VEGF induced angiogenesis in human umbilical vein endothelial cells (HUVECs). Low dose of TNFα induces mild upregulation and moreover nuclear localization of tumor suppressor protein 53 (P53) which causes decrease in inhibitor of DNA binding-1 (Id1) expression and shuttling to the cytoplasm. In absence of Id1, HUVECs fail to upregulate β 3 -integrin and cell migration is decreased. Connecting low dose of TNFα induced p53 to β 3 -integrin through Id1, we present additional link in cross talk between inflammation and angiogenesis. - Highlights: • Low grade inflammation (low dose of TNF alfa) inhibits VEGF induced endothelial cells migration. • The low grade inflammation with VEGF treatment upregulates P53 to a nonlethal level. • P53 activation inhibits Id1 shuttling to the cytoplasm in endothelial cells. • Inhibition of Id1 resulted in downregulation of β 3 -integrin which cause decrease in cell migration. • Inflammation and angiogenesis might cross-talk by P53 – Id1 – β 3 -integrin pathway in endothelial cells.

  18. Topical W-7 inhibits ultraviolet radiation-induced melanogenesis in Skh:HR2 pigmented hairless mice

    International Nuclear Information System (INIS)

    Dowdy, J.C.; Anthony, F.A.; Costlow, M.E.

    1995-01-01

    We studied the effect of N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide (W-7) on ultraviolet radiation (UVR)-induced melanogenesis (tanning) in Skh:HR2 pigmented hairless mice. Topically pretreated mice were exposed to subminimal edematogenic as well as edematogenic UVR doses to establish whether W-7-UVR-induced edema prophylaxis allows increased melanogenesis while preventing edema. Ultraviolet light-irradiated vehicle control animals developed visible trans; however, both W-7-treated groups failed to tan. Topical W-7 before UVR exposure inhibited UVR induction of dopa oxidase activity in melanocytes by 49% (P=0.029) and inhibited UVR-induced deposition of melanin in the epidermis by 88% (P=0.006). Topical W-7 blocked 23% of the UVR but this blockage could not account for the inhibition of dopa oxidase and melanization. We conclude that, in addition to preventing edema, W-7 inhibits UVR-induced melanogenesis, possibly by affecting Ca 2+ -calmodulin and/or protein kinase C-dependent processes. (au) 30 refs

  19. Topical W-7 inhibits ultraviolet radiation-induced melanogenesis in Skh:HR2 pigmented hairless mice

    Energy Technology Data Exchange (ETDEWEB)

    Dowdy, J.C. [Univ. of Memphis, Div. of Molecular Sciences and Microbiology, Memphis, Tennessee (United States); Anthony, F.A.; Costlow, M.E. [Schering-Plough HealthCare Products, Inc., Advanced Product Research, Memphis, Tennessee (United States)

    1995-08-01

    We studied the effect of N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide (W-7) on ultraviolet radiation (UVR)-induced melanogenesis (tanning) in Skh:HR2 pigmented hairless mice. Topically pretreated mice were exposed to subminimal edematogenic as well as edematogenic UVR doses to establish whether W-7-UVR-induced edema prophylaxis allows increased melanogenesis while preventing edema. Ultraviolet light-irradiated vehicle control animals developed visible trans; however, both W-7-treated groups failed to tan. Topical W-7 before UVR exposure inhibited UVR induction of dopa oxidase activity in melanocytes by 49% (P=0.029) and inhibited UVR-induced deposition of melanin in the epidermis by 88% (P=0.006). Topical W-7 blocked 23% of the UVR but this blockage could not account for the inhibition of dopa oxidase and melanization. We conclude that, in addition to preventing edema, W-7 inhibits UVR-induced melanogenesis, possibly by affecting Ca{sup 2+}-calmodulin and/or protein kinase C-dependent processes. (au) 30 refs.

  20. Excitations of the gravitational field-I

    International Nuclear Information System (INIS)

    Novello, M.

    1978-01-01

    The geometry of spacetime is treated as a stochastic variable. Fluctuations induce a deviation from Einstein's system of equations for the average geometry. A model is presented to deal with the fluctuations by expanding the perturbations on a series in the average geometry. As a consequence, some qualitatively new features appear. The influences on galaxy formation and on the propagation of gravitational waves are analyzed [pt

  1. Thermodynamic implications of the gravitationally induced particle creation scenario

    Energy Technology Data Exchange (ETDEWEB)

    Saha, Subhajit [Indian Institute of Science Education and Research Kolkata, Department of Physical Sciences, Mohanpur, West Bengal (India); Mondal, Anindita [S N Bose National Centre for Basic Sciences, Department of Astrophysics and Cosmology, Kolkata, West Bengal (India)

    2017-03-15

    A rigorous thermodynamic analysis has been done as regards the apparent horizon of a spatially flat Friedmann-Lemaitre-Robertson-Walker universe for the gravitationally induced particle creation scenario with constant specific entropy and an arbitrary particle creation rate Γ. Assuming a perfect fluid equation of state p = (γ - 1)ρ with (2)/(3) ≤ γ ≤ 2, the first law, the generalized second law (GSL), and thermodynamic equilibrium have been studied, and an expression for the total entropy (i.e., horizon entropy plus fluid entropy) has been obtained which does not contain Γ explicitly. Moreover, a lower bound for the fluid temperature T{sub f} has also been found which is given by T{sub f} ≥ 8 (((3γ)/(2)-1)/((2)/(γ)-1)) H{sup 2}. It has been shown that the GSL is satisfied for (Γ)/(3H) ≤ 1. Further, when Γ is constant, thermodynamic equilibrium is always possible for (1)/(2) < (Γ)/(3H) < 1, while for (Γ)/(3H) ≤ min {(1)/(2), (2γ-2)/(3γ-2)} and (Γ)/(3H) ≥ 1, equilibrium can never be attained. Thermodynamic arguments also lead us to believe that during the radiation phase, Γ ≤ H. When Γ is not a constant, thermodynamic equilibrium holds if H ≥ (27)/(4) γ{sup 2}H{sup 3} (1-(Γ)/(3H)){sup 2}, however, such a condition is by no means necessary for the attainment of equilibrium. (orig.)

  2. Thermodynamic implications of the gravitationally induced particle creation scenario

    International Nuclear Information System (INIS)

    Saha, Subhajit; Mondal, Anindita

    2017-01-01

    A rigorous thermodynamic analysis has been done as regards the apparent horizon of a spatially flat Friedmann-Lemaitre-Robertson-Walker universe for the gravitationally induced particle creation scenario with constant specific entropy and an arbitrary particle creation rate Γ. Assuming a perfect fluid equation of state p = (γ - 1)ρ with (2)/(3) ≤ γ ≤ 2, the first law, the generalized second law (GSL), and thermodynamic equilibrium have been studied, and an expression for the total entropy (i.e., horizon entropy plus fluid entropy) has been obtained which does not contain Γ explicitly. Moreover, a lower bound for the fluid temperature T f has also been found which is given by T f ≥ 8 (((3γ)/(2)-1)/((2)/(γ)-1)) H 2 . It has been shown that the GSL is satisfied for (Γ)/(3H) ≤ 1. Further, when Γ is constant, thermodynamic equilibrium is always possible for (1)/(2) < (Γ)/(3H) < 1, while for (Γ)/(3H) ≤ min {(1)/(2), (2γ-2)/(3γ-2)} and (Γ)/(3H) ≥ 1, equilibrium can never be attained. Thermodynamic arguments also lead us to believe that during the radiation phase, Γ ≤ H. When Γ is not a constant, thermodynamic equilibrium holds if H ≥ (27)/(4) γ 2 H 3 (1-(Γ)/(3H)) 2 , however, such a condition is by no means necessary for the attainment of equilibrium. (orig.)

  3. Caffeic acid phenethyl ester inhibits 3-MC-induced CYP1A1 expression through induction of hypoxia-inducible factor-1α

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyung Gyun [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Han, Eun Hee [Division of Life Science, Korea Basic Science Institute, Daejeon (Korea, Republic of); Im, Ji Hye; Lee, Eun Ji; Jin, Sun Woo [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of)

    2015-09-25

    Caffeic acid phenethyl ester (CAPE), a natural component of propolis, is reported to have anticarcinogenic properties, although its precise chemopreventive mechanism remains unclear. In this study, we examined the effects of CAPE on 3-methylcholanthrene (3-MC)-induced CYP1A1 expression and activities. CAPE reduced the formation of the benzo[a]pyrene-DNA adduct. Moreover, CAPE inhibited 3-MC-induced CYP1A1 activity, mRNA expression, protein level, and promoter activity. CAPE treatment also decreased 3-MC-inducible xenobiotic-response element (XRE)-linked luciferase, aryl hydrocarbons receptor (AhR) transactivation and nuclear localization. CAPE induced hypoxia inducible factor-1α (HIF-1α) protein level and HIF-1α responsible element (HRE) transcriptional activity. CAPE-mediated HIF-1α reduced 3-MC-inducible CYP1A1 protein expression. Taken together, CAPE decreases 3-MC-mediated CYP1A1 expression, and this inhibitory response is associated with inhibition of AhR and HIF-1α induction. - Highlights: • CAPE reduced the formation of the benzo[a]pyrene-DNA adduct. • CAPE inhibited 3-MC-induced CYP1A1 expression. • CAPE induced HIF-1α induction. • CAPE-mediated HIF-1α reduced 3-MC-inducible CYP1A1 expression.

  4. Dasatinib inhibits both osteoclast activation and prostate cancer PC-3 cell-induced osteoclast formation

    Science.gov (United States)

    Araujo, John C.; Poblenz, Ann; Corn, Paul G.; Parikh, Nila U.; Starbuck, Michael W.; Thompson, Jerry T.; Lee, Francis; Logothetis, Christopher J.; Darnay, Bryant G.

    2013-01-01

    Purpose Therapies to target prostate cancer bone metastases have only limited effects. New treatments are focused on the interaction between cancer cells, bone marrow cells and the bone matrix. Osteoclasts play an important role in the development of bone tumors caused by prostate cancer. Since Src kinase has been shown to be necessary for osteoclast function, we hypothesized that dasatinib, a Src family kinase inhibitor, would reduce osteoclast activity and prostate cancer (PC-3) cell-induced osteoclast formation. Results Dasatinib inhibited RANKL-induced osteoclast differentiation of bone marrow-derived monocytes with an EC50 of 7.5 nM. PC-3 cells, a human prostate cancer cell line, were able to differentiate RAW 264.7 cells, a murine monocytic cell line, into osteoclasts and dasatinib inhibited this differentiation. In addition, conditioned medium from PC-3 cell cultures was able to differentiate RAW 264.7 cells into osteoclasts and this too, was inhibited by dasatinib. Even the lowest concentration of dasatinib, 1.25 nmol, inhibited osteoclast differentiation by 29%. Moreover, dasatinib inhibited osteoclast activity by 58% as measured by collagen 1 release. Experimental design We performed in vitro experiments utilizing the Src family kinase inhibitor dasatinib to target osteoclast activation as a means of inhibiting prostate cancer bone metastases. Conclusion Dasatinib inhibits osteoclast differentiation of mouse primary bone marrow-derived monocytes and PC-3 cell-induced osteoclast differentiation. Dasatinib also inhibits osteoclast degradation activity. Inhibiting osteoclast differentiation and activity may be an effective targeted therapy in patients with prostate cancer bone metastases. PMID:19855158

  5. Curvature bound from gravitational catalysis

    Science.gov (United States)

    Gies, Holger; Martini, Riccardo

    2018-04-01

    We determine bounds on the curvature of local patches of spacetime from the requirement of intact long-range chiral symmetry. The bounds arise from a scale-dependent analysis of gravitational catalysis and its influence on the effective potential for the chiral order parameter, as induced by fermionic fluctuations on a curved spacetime with local hyperbolic properties. The bound is expressed in terms of the local curvature scalar measured in units of a gauge-invariant coarse-graining scale. We argue that any effective field theory of quantum gravity obeying this curvature bound is safe from chiral symmetry breaking through gravitational catalysis and thus compatible with the simultaneous existence of chiral fermions in the low-energy spectrum. With increasing number of dimensions, the curvature bound in terms of the hyperbolic scale parameter becomes stronger. Applying the curvature bound to the asymptotic safety scenario for quantum gravity in four spacetime dimensions translates into bounds on the matter content of particle physics models.

  6. Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) through inhibiting protein synthesis.

    Science.gov (United States)

    Lee, Dae-Hee; Lee, Yong J

    2008-10-01

    Quercetin, a ubiquitous bioactive plant flavonoid, has been shown to inhibit the proliferation of cancer cells and induce the accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) in normoxia. In this study, under hypoxic conditions (1% O(2)), we examined the effect of quercetin on the intracellular level of HIF-1alpha and extracellular level of vascular endothelial growth factor (VEGF) in a variety of human cancer cell lines. Surprisingly, we observed that quercetin suppressed the HIF-1alpha accumulation during hypoxia in human prostate cancer LNCaP, colon cancer CX-1, and breast cancer SkBr3 cells. Quercetin treatment also significantly reduced hypoxia-induced secretion of VEGF. Suppression of HIF-1alpha accumulation during treatment with quercetin in hypoxia was not prevented by treatment with 26S proteasome inhibitor MG132 or PI3K inhibitor LY294002. Interestingly, hypoxia (1% O(2)) in the presence of 100 microM quercetin inhibited protein synthesis by 94% during incubation for 8 h. Significant quercetin concentration-dependent inhibition of protein synthesis and suppression of HIF-1alpha accumulation were observed under hypoxic conditions. Treatment with 100 microM cycloheximide, a protein synthesis inhibitor, replicated the effect of quercetin by inhibiting HIF-1alpha accumulation during hypoxia. These results suggest that suppression of HIF-1alpha accumulation during treatment with quercetin under hypoxic conditions is due to inhibition of protein synthesis. (c) 2008 Wiley-Liss, Inc.

  7. BMPR2 inhibition induced apoptosis and autophagy via destabilization of XIAP in human chondrosarcoma cells

    Science.gov (United States)

    Jiao, G; Guo, W; Ren, T; Lu, Q; Sun, Y; Liang, W; Ren, C; Yang, K; Sun, K

    2014-01-01

    Bone morphogenetic proteins (BMPs) are multifunctional proteins, and their receptors (BMPRs) have crucial roles in the process of signaling. However, their function in cancer is somewhat inconsistent. It has been demonstrated that more prevalent expression of bone morphogenetic protein receptor 2 (BMPR2) has been detected in dedifferentiated chondrosarcomas than conventional chondrosarcomas. Here, we find that BMPR2 inhibition induces apoptosis and autophagy of chondrosarcoma. We found that BMPR2 expression was correlated with the clinicopathological features of chondrosarcomas, and could predict the treatment outcome. Knockdown of BMPR2 by small interfering RNA results in growth inhibition in chondrosarcoma cells. Silencing BMPR2 promoted G2/M cell cycle arrest, induced chondrosarcoma cell apoptosis through caspase-3-dependent pathway via repression of X-linked inhibitor of apoptosis protein (XIAP) and induced autophagy of chondrosarcoma cells via XIAP-Mdm2-p53 pathway. Inhibition of autophagy induced by BMPR2 small interfering RNA (siBMPR2) sensitized chondrosarcoma cells to siBMPR2-induced apoptotic cell death, suggesting that autophagy has a protective role for chondrosarcoma cells in context of siBMPR2-induced apoptotic cell death. In vivo tumorigenicity assay in mice indicated that inhibition of BMPR2 reduced tumor growth. Taken together, our results suggest that BMPR2 has a significant role in the tumorigenesis of chondrosarcoma, and could be an important prognostic marker for chondrosarcoma. BMPR2 inhibition could eventually provide a promising therapy for chondrosarcoma treatment. PMID:25501832

  8. Silymarin Ameliorates Diabetes-Induced Proangiogenic Response in Brain Endothelial Cells through a GSK-3β Inhibition-Induced Reduction of VEGF Release

    Directory of Open Access Journals (Sweden)

    Ahmed Alhusban

    2017-01-01

    Full Text Available Diabetes mellitus (DM is a major risk factor for cardiovascular disease. Additionally, it was found to induce a dysfunctional angiogenic response in the brain that was attributed to oxidative stress. Milk thistle seed extract (silymarin has potent antioxidant properties, though its potential use in ameliorating diabetes-induced aberrant brain angiogenesis is unknown. Glycogen synthase kinase-3β is a regulator of angiogenesis that is upregulated by diabetes. Its involvement in diabetes-induced angiogenesis is unknown. To evaluate the potential of silymarin to ameliorate diabetes-induced aberrant angiogenesis, human brain endothelial cells (HBEC-5i were treated with 50 μg/mL advanced glycation end (AGE products in the presence or absence of silymarin (50, 100 μM. The angiogenic potential of HBEC-5i was evaluated in terms of migration and in vitro tube formation capacities. The involvement of GSK-3β was also evaluated. AGE significantly increased the migration and tube formation rates of HBEC-5i by about onefold (p=0.0001. Silymarin reduced AGE-induced migration in a dose-dependent manner where 50 μM reduced migration by about 50%, whereas the 100 μM completely inhibited AGE-induced migration. Similarly, silymarin 50 μg/mL blunted AGE-induced tube formation (p=0.001. This effect was mediated through a GSK-3β-dependent inhibition of VEGF release. In conclusion, silymarin inhibits AGE-induced aberrant angiogenesis in a GSK-3β-mediated inhibition of VEGF release.

  9. Gravitational mass and Newton's universal gravitational law under relativistic conditions

    International Nuclear Information System (INIS)

    Vayenas, Constantinos G; Grigoriou, Dimitrios; Fokas, Athanasios

    2015-01-01

    We discuss the predictions of Newton's universal gravitational law when using the gravitational, m g , rather than the rest masses, m o , of the attracting particles. According to the equivalence principle, the gravitational mass equals the inertial mass, m i , and the latter which can be directly computed from special relativity, is an increasing function of the Lorentz factor, γ, and thus of the particle velocity. We consider gravitationally bound rotating composite states, and we show that the ratio of the gravitational force for gravitationally bound rotational states to the force corresponding to low (γ ≈ 1) particle velocities is of the order of (m Pl /m o ) 2 where mpi is the Planck mass (ħc/G) 1/2 . We also obtain a similar result, within a factor of two, by employing the derivative of the effective potential of the Schwarzschild geodesics of GR. Finally, we show that for certain macroscopic systems, such as the perihelion precession of planets, the predictions of this relativistic Newtonian gravitational law differ again by only a factor of two from the predictions of GR. (paper)

  10. Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouse antral follicles in vitro

    International Nuclear Information System (INIS)

    Mahalingam, Sharada; Gao, Liying; Gonnering, Marni; Helferich, William; Flaws, Jodi A.

    2016-01-01

    Equol is a non-steroidal estrogen metabolite produced by microbial conversion of daidzein, a major soy isoflavone, in the gut of some humans and many animal species. Isoflavones and their metabolites can affect endogenous estradiol production, action, and metabolism, potentially influencing ovarian follicle function. However, no studies have examined the effects of equol on intact ovarian antral follicles, which are responsible for sex steroid synthesis and further development into ovulatory follicles. Thus, the present study tested the hypothesis that equol inhibits antral follicle growth, increases follicle atresia, and inhibits steroidogenesis in the adult mouse ovary. To test this hypothesis, antral follicles isolated from adult CD-1 mice were cultured with vehicle control (dimethyl sulfoxide; DMSO) or equol (600 nM, 6 μM, 36 μM, and 100 μM) for 48 and 96 h. Every 24 h, follicle diameters were measured to monitor growth. At 48 and 96 h, the culture medium was subjected to measurement of hormone levels, and the cultured follicles were subjected to gene expression analysis. Additionally, follicles were histologically evaluated for signs of atresia after 96 h of culture. The results indicate that equol (100 μM) inhibited follicle growth, altered the mRNA levels of bcl2-associated X protein and B cell leukemia/lymphoma 2, and induced follicle atresia. Further, equol decreased the levels of estradiol, testosterone, androstenedione, and progesterone, and it decreased mRNA levels of cholesterol side-chain cleavage, steroid 17-α-hydroxalase, and aromatase. Collectively, these data indicate that equol inhibits growth, increases atresia, and inhibits steroidogenesis of cultured mouse antral follicles. - Highlights: • Equol exposure inhibits antral follicle growth. • Equol exposure increases follicle atresia. • Equol exposure inhibits sex steroid hormone levels. • Equol exposure inhibits mRNA levels of certain steroidogenic enzymes.

  11. Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouse antral follicles in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Mahalingam, Sharada, E-mail: mahalin2@illinois.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Gao, Liying, E-mail: lgao@uiuc.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Gonnering, Marni, E-mail: mgonne2@illinois.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States); Helferich, William, E-mail: helferic@illinois.edu [Department of Food Science and Human Nutrition, University of Illinois, 905 S. Goodwin, Urbana, IL 61801 (United States); Flaws, Jodi A., E-mail: jflaws@illinois.edu [Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois, 2001 S. Lincoln Ave, Urbana, IL 61802 (United States)

    2016-03-15

    Equol is a non-steroidal estrogen metabolite produced by microbial conversion of daidzein, a major soy isoflavone, in the gut of some humans and many animal species. Isoflavones and their metabolites can affect endogenous estradiol production, action, and metabolism, potentially influencing ovarian follicle function. However, no studies have examined the effects of equol on intact ovarian antral follicles, which are responsible for sex steroid synthesis and further development into ovulatory follicles. Thus, the present study tested the hypothesis that equol inhibits antral follicle growth, increases follicle atresia, and inhibits steroidogenesis in the adult mouse ovary. To test this hypothesis, antral follicles isolated from adult CD-1 mice were cultured with vehicle control (dimethyl sulfoxide; DMSO) or equol (600 nM, 6 μM, 36 μM, and 100 μM) for 48 and 96 h. Every 24 h, follicle diameters were measured to monitor growth. At 48 and 96 h, the culture medium was subjected to measurement of hormone levels, and the cultured follicles were subjected to gene expression analysis. Additionally, follicles were histologically evaluated for signs of atresia after 96 h of culture. The results indicate that equol (100 μM) inhibited follicle growth, altered the mRNA levels of bcl2-associated X protein and B cell leukemia/lymphoma 2, and induced follicle atresia. Further, equol decreased the levels of estradiol, testosterone, androstenedione, and progesterone, and it decreased mRNA levels of cholesterol side-chain cleavage, steroid 17-α-hydroxalase, and aromatase. Collectively, these data indicate that equol inhibits growth, increases atresia, and inhibits steroidogenesis of cultured mouse antral follicles. - Highlights: • Equol exposure inhibits antral follicle growth. • Equol exposure increases follicle atresia. • Equol exposure inhibits sex steroid hormone levels. • Equol exposure inhibits mRNA levels of certain steroidogenic enzymes.

  12. Insulin-Inducible SMILE Inhibits Hepatic Gluconeogenesis.

    Science.gov (United States)

    Lee, Ji-Min; Seo, Woo-Young; Han, Hye-Sook; Oh, Kyoung-Jin; Lee, Yong-Soo; Kim, Don-Kyu; Choi, Seri; Choi, Byeong Hun; Harris, Robert A; Lee, Chul-Ho; Koo, Seung-Hoi; Choi, Hueng-Sik

    2016-01-01

    The role of a glucagon/cAMP-dependent protein kinase-inducible coactivator PGC-1α signaling pathway is well characterized in hepatic gluconeogenesis. However, an opposing protein kinase B (PKB)/Akt-inducible corepressor signaling pathway is unknown. A previous report has demonstrated that small heterodimer partner-interacting leucine zipper protein (SMILE) regulates the nuclear receptors and transcriptional factors that control hepatic gluconeogenesis. Here, we show that hepatic SMILE expression was induced by feeding in normal mice but not in db/db and high-fat diet (HFD)-fed mice. Interestingly, SMILE expression was induced by insulin in mouse primary hepatocyte and liver. Hepatic SMILE expression was not altered by refeeding in liver-specific insulin receptor knockout (LIRKO) or PKB β-deficient (PKBβ(-/-)) mice. At the molecular level, SMILE inhibited hepatocyte nuclear factor 4-mediated transcriptional activity via direct competition with PGC-1α. Moreover, ablation of SMILE augmented gluconeogenesis and increased blood glucose levels in mice. Conversely, overexpression of SMILE reduced hepatic gluconeogenic gene expression and ameliorated hyperglycemia and glucose intolerance in db/db and HFD-fed mice. Therefore, SMILE is an insulin-inducible corepressor that suppresses hepatic gluconeogenesis. Small molecules that enhance SMILE expression would have potential for treating hyperglycemia in diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. PI3K inhibition enhances doxorubicin-induced apoptosis in sarcoma cells.

    Directory of Open Access Journals (Sweden)

    Diana Marklein

    Full Text Available We searched for a drug capable of sensitization of sarcoma cells to doxorubicin (DOX. We report that the dual PI3K/mTOR inhibitor PI103 enhances the efficacy of DOX in several sarcoma cell lines and interacts with DOX in the induction of apoptosis. PI103 decreased the expression of MDR1 and MRP1, which resulted in DOX accumulation. However, the enhancement of DOX-induced apoptosis was unrelated to DOX accumulation. Neither did it involve inhibition of mTOR. Instead, the combination treatment of DOX plus PI103 activated Bax, the mitochondrial apoptosis pathway, and caspase 3. Caspase 3 activation was also observed in xenografts of sarcoma cells in nude mice upon combination of DOX with the specific PI3K inhibitor GDC-0941. Although the increase in apoptosis did not further impact on tumor growth when compared to the efficient growth inhibition by GDC-0941 alone, these findings suggest that inhibition of PI3K may improve DOX-induced proapoptotic effects in sarcoma. Taken together with similar recent studies of neuroblastoma- and glioblastoma-derived cells, PI3K inhibition seems to be a more general option to sensitize tumor cells to anthracyclines.

  14. δ-Tocopherol inhibits receptor tyrosine kinase-induced AKT activation in prostate cancer cells.

    Science.gov (United States)

    Wang, Hong; Hong, Jungil; Yang, Chung S

    2016-11-01

    The cancer preventive activity of vitamin E is suggested by epidemiological studies and supported by animal studies with vitamin E forms, γ-tocopherol and δ-tocopherol (δ-T). Several recent large-scale cancer prevention trials with high dose of α-tocopherol, however, yielded disappointing results. Whether vitamin E prevents or promotes cancer is a serious concern. A better understanding of the molecular mechanisms of action of the different forms of tocopherols would enhance our understanding of this topic. In this study, we demonstrated that δ-T was the most effective tocopherol form in inhibiting prostate cancer cell growth, by inducing cell cycle arrest and apoptosis. By profiling the effects of δ-T on the cell signaling using the phospho-kinase array, we found that the most inhibited target was the phosphorylation of AKT on T308. Further study on the activation of AKT by EGFR and IGFR revealed that δ-T attenuated the EGF/IGF-induced activation of AKT (via the phosphorylation of AKT on T308 induced by the activation of PIK3). Expression of dominant active PIK3 and AKT in prostate cancer cell line DU145 in which PIK3, AKT, and PTEN are wild type caused the cells to be reflectory to the inhibition of δ-T, supporting that δ-T inhibits the PIK3-mediated activation of AKT. Our data also suggest that δ-T interferes with the EGF-induced EGFR internalization, which leads to the inhibition of the receptor tyrosine kinase-dependent activation of AKT. In summary, our results revealed a novel mechanism of δ-T in inhibiting prostate cancer cell growth, supporting the cancer preventive activity δ-T. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  15. Phase transition and gravitational wave phenomenology of scalar conformal extensions of the Standard Model

    Energy Technology Data Exchange (ETDEWEB)

    Marzola, Luca; Racioppi, Antonio; Vaskonen, Ville [National Institute of Chemical Physics and Biophysics, Tallinn (Estonia)

    2017-07-15

    Thermal corrections in classically conformal models typically induce a strong first-order electroweak phase transition, thereby resulting in a stochastic gravitational background that could be detectable at gravitational wave observatories. After reviewing the basics of classically conformal scenarios, in this paper we investigate the phase transition dynamics in a thermal environment and the related gravitational wave phenomenology within the framework of scalar conformal extensions of the Standard Model. We find that minimal extensions involving only one additional scalar field struggle to reproduce the correct phase transition dynamics once thermal corrections are accounted for. Next-to-minimal models, instead, yield the desired electroweak symmetry breaking and typically result in a very strong gravitational wave signal. (orig.)

  16. Echinocystic acid inhibits RANKL-induced osteoclastogenesis by regulating NF-κB and ERK signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jian-hui, E-mail: jianhui_yangxa@163.com [Rehabilitation Center, First Affiliated Hospital of Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, Shaanxi Province (China); Li, Bing [Department of Dermatology, the 451st Hospital of People’s Liberation Army, Xi’an 710054, Shaanxi Province (China); Wu, Qiong; Lv, Jian-guo; Nie, Hui-Yong [Rehabilitation Center, First Affiliated Hospital of Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, Shaanxi Province (China)

    2016-09-02

    Receptor activator of nuclear factor-κB ligand (RANKL) is a key factor in the differentiation and activation of osteoclasts. Echinocystic acid (EA), a pentacyclic triterpene isolated from the fruits of Gleditsia sinensis Lam, was reported to prevent reduction of bone mass and strength and improve the cancellous bone structure and biochemical properties in ovariectomy rats. However, the molecular mechanism of EA on the osteoclast formation has not been reported. The purpose of this study was to investigate the effects and mechanism of EA on RANKL-induced osteoclastogenesis. Our results showed that EA inhibited the formation of osteoclast, as well as the expression of osteoclastogenesis-related marker proteins in bone marrow macrophages (BMMs). At molecular levels, EA inhibited RANKL-induced NF-κB activation and ERK phosphorylation in BMMs. In conclusion, the present study demonstrated that EA can suppress osteoclastogenesis in vitro. Moreover, we clarified that these inhibitory effects of EA occur through suppression of NF-κB and ERK activation. Therefore, EA may be a potential agent in the treatment of osteoclast-related diseases such as osteoporosis. - Highlights: • EA inhibited the formation of osteoclast in BMMs. • EA inhibits the expression of osteoclastogenesis-related marker proteins in BMMs. • EA inhibits RANKL-induced NF-κB activation in BMMs. • EA inhibits RANKL-induced ERK phosphorylation in BMMs.

  17. Fenspiride inhibits histamine-induced responses in a lung epithelial cell line.

    Science.gov (United States)

    Quartulli, F; Pinelli, E; Broué-Chabbert, A; Gossart, S; Girard, V; Pipy, B

    1998-05-08

    Using the human lung epithelial WI26VA4 cell line, we investigated the capacity of fenspiride, an anti-inflammatory drug with anti-bronchoconstrictor properties, to interfere with histamine-induced intracellular Ca2+ increase and eicosanoid formation. Histamine and a histamine H1 receptor agonist elicited a rapid and transient intracellular Ca2+ increase (0-60 s) in fluo 3-loaded WI26VA4 cells. This response was antagonized by the histamine H1 receptor antagonist, diphenhydramine, the histamine H2 receptor antagonist, cimetidine, having no effect. Fenspiride (10(-7)-10(-5) M) inhibited the histamine H1 receptor-induced Ca2+ increase. In addition, histamine induced a biphasic increase in arachidonic acid release. The initial rise (0-30 s), a rapid and transient arachidonic acid release, was responsible for the histamine-induced intracellular Ca2+ increase. In the second phase release (15-60 min), a sustained arachidonic acid release appeared to be associated with the formation of cyclooxygenase and lipoxygenase metabolites. Fenspiride (10(-5) M) abolished both phases of histamine-induced arachidonic acid release. These results suggest that anti-inflammatory and antibronchoconstrictor properties of fenspiride may result from the inhibition of these effects of histamine.

  18. Quercetogetin protects against cigarette smoke extract-induced apoptosis in epithelial cells by inhibiting mitophagy.

    Science.gov (United States)

    Son, Eun Suk; Kim, Se-Hee; Ryter, Stefan W; Yeo, Eui-Ju; Kyung, Sun Young; Kim, Yu Jin; Jeong, Sung Hwan; Lee, Chang Soo; Park, Jeong-Woong

    2018-04-01

    Recent studies demonstrate that the autophagy-dependent turnover of mitochondria (mitophagy) mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure, and contributes to emphysema development in vivo during chronic cigarette smoke (CS)-exposure, although the underlying mechanisms remain unclear. Here, we investigated the role of mitophagy in regulating apoptosis in CSE-exposed human lung bronchial epithelial cells. Furthermore, we investigated the potential of the polymethoxylated flavone antioxidant quercetogetin (QUE) to inhibit CSE-induced mitophagy-dependent apoptosis. Our results demonstrate that CSE induces mitophagy in epithelial cells via mitochondrial dysfunction, and causes increased expression levels of the mitophagy-regulator protein PTEN-induced putative kinase-1 (PINK1) and the mitochondrial fission protein dynamin-1-like protein (DRP-1). CSE induced epithelial cell death and increased the expression of the apoptosis-related proteins cleaved caspase-3, -8 and -9. Caspase-3 activity was significantly increased in Beas-2B cells exposed to CSE, and decreased by siRNA-dependent knockdown of DRP-1. Treatment of epithelial cells with QUE inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting phospho (p)-DRP-1 and PINK1 expression. QUE suppressed mitophagy-dependent apoptosis by inhibiting the expression of cleaved caspase-3, -8 and -9 and downregulating caspase activity in human bronchial epithelial cells. These findings suggest that QUE may serve as a potential therapeutic in CS-induced pulmonary diseases. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Zinc finger protein 598 inhibits cell survival by promoting UV-induced apoptosis.

    Science.gov (United States)

    Yang, Qiaohong; Gupta, Romi

    2018-01-19

    UV is one of the major causes of DNA damage induced apoptosis. However, cancer cells adopt alternative mechanisms to evade UV-induced apoptosis. To identify factors that protect cancer cells from UV-induced apoptosis, we performed a genome wide short-hairpin RNA (shRNA) screen, which identified Zinc finger protein 598 (ZNF598) as a key regulator of UV-induced apoptosis. Here, we show that UV irradiation transcriptionally upregulates ZNF598 expression. Additionally, ZNF598 knockdown in cancer cells inhibited UV-induced apoptosis. In our study, we observe that ELK1 mRNA level as well as phosphorylated ELK1 levels was up regulated upon UV irradiation, which was necessary for UV irradiation induced upregulation of ZNF598. Cells expressing ELK1 shRNA were also resistant to UV-induced apoptosis, and phenocopy ZNF598 knockdown. Upon further investigation, we found that ZNF598 knockdown inhibits UV-induced apoptotic gene expression, which matches with decrease in percentage of annexin V positive cell. Similarly, ectopic expression of ZNF598 promoted apoptotic gene expression and also increased annexin V positive cells. Collectively, these results demonstrate that ZNF598 is a UV irradiation regulated gene and its loss results in resistance to UV-induced apoptosis.

  20. Relativistic theory of gravitation

    International Nuclear Information System (INIS)

    Logunov, A.A.; Mestvirishvilli, M.A.

    1985-01-01

    In the present paper a relativistic theory of gravitation (RTG) is constructed in a unique way on the basis of the special relativity and geometrization principle. In this, a gravitational field is treated as the Faraday-Maxwell spin-2 and spin-0 physical field possessing energy and momentum. The source of a gravitational field is the total conserved energy-momentum tensor of matter and of a gravitational field in Minkowski space. In the RTG, the conservation laws are strictly fulfilled for the energy-momentum and for the angular momentum of matter and a gravitational field. The theory explains the whole available set of experiments on gravitation. In virtue of the geometrization principle, the Riemannian space in our theory is of field origin, since it appears as an effective force space due to the action of a gravitational field on matter. The RTg leads to an exceptionally strong prediction: The Universe is not closed but just ''flat''. This suggests that in the Universe a ''hidden mass'' should exist in some form of matter

  1. Self-reported Symptoms after Induced and Inhibited Bronchoconstriction in Athletes

    Science.gov (United States)

    SIMPSON, ANDREW J.; ROMER, LEE M.; KIPPELEN, PASCALE

    2015-01-01

    ABSTRACT Purpose A change in the perception of respiratory symptoms after treatment with inhaled beta2 agonists is often used to aid diagnosis of exercise-induced bronchoconstriction (EIB). Our aim was to test the association between subjective ratings of respiratory symptoms and changes in airway caliber after induced and inhibited bronchoconstriction in athletes with EIB. Methods Eighty-five athletes with diagnosed or suspected EIB performed a eucapnic voluntary hyperpnea (EVH) challenge with dry air. Of the 45 athletes with hyperpnea-induced bronchoconstriction [i.e., post-EVH fall in forced expiratory volume in 1 s (FEV1) ≥10%, EVH−], 36 were randomized in a double-blind, placebo-controlled, crossover study. Terbutaline (0.5 mg) or placebo was administered by inhalation 15 min before EVH. Spirometry (for FEV1) was performed before and after EVH, and respiratory symptoms were recorded 15 min after EVH on visual analog scales. Results Terbutaline inhibited bronchoconstriction (i.e., maximal fall in FEV1 athletes, with an average degree of bronchoprotection of 53% (95% confidence interval [CI], 45% to 62%). Terbutaline reduced group mean symptom scores (P athletes who had less than 10% FEV1 fall after EVH in the terbutaline condition, almost half (48%) rated at least one respiratory symptom higher under terbutaline, and more than one quarter (28%) had a higher total symptom score under terbutaline. Conclusion Self-reports of respiratory symptoms in conditions of induced and inhibited bronchoconstriction do not correlate with changes in airway caliber in athletes with EIB. Therefore, subjective ratings of respiratory symptoms after treatment with inhaled beta2 agonists should not be used as the sole diagnostic tool for EIB in athletes. PMID:25710876

  2. Omentin inhibits TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via ERK/NF-{kappa}B pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Xia, E-mail: zhongxia1977@126.com [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Li, Xiaonan; Liu, Fuli; Tan, Hui [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Shang, Deya, E-mail: wenhuashenghuo1@163.com [Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Black-Right-Pointing-Pointer Omentin reduces expression of ICAM-1 and VCAM-1 induced by TNF-{alpha} in HUVECs. Black-Right-Pointing-Pointer Omentin inhibits TNF-{alpha}-induced ERK and NF-{kappa}B activation in HUVECs. Black-Right-Pointing-Pointer Omentin supreeses TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 via ERK/NF-{kappa}B pathway. -- Abstract: In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-{alpha} (TNF-{alpha}) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-{alpha}-activated signal pathway of nuclear factor-{kappa}B (NF-{kappa}B) by preventing NF-{kappa}B inhibitory protein (I{kappa}B{alpha}) degradation and NF-{kappa}B/DNA binding activity. Omentin pretreatment significantly inhibited TNF-{alpha}-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-{alpha}-induced NF-{kappa}B activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-{alpha}. These results suggest that omentin may inhibit TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-{kappa}B pathway.

  3. Hyperin protects against LPS-induced acute kidney injury by inhibiting TLR4 and NLRP3 signaling pathways

    Science.gov (United States)

    Chunzhi, Gong; Zunfeng, Li; Chengwei, Qin; Xiangmei, Bu; Jingui, Yu

    2016-01-01

    Hyperin is a flavonoid compound derived from Ericaceae, Guttifera, and Celastraceae that has been shown to have various biological effects, such as anti-inflammatory and anti-oxidant effects. However, there is no evidence to show the protective effects of hyperin on lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Therefore, we investigated the protective effects and mechanism of hyperin on LPS-induced AKI in mice. The levels of TNF-α, IL-6, and IL-1β were tested by ELISA. The effects of hyperin on blood urea nitrogen (BUN) and serum creatinine were also detected. In addition, the expression of TLR4, NF-κB, and NLRP3 were detected by western blot analysis. The results showed that hyperin significantly inhibited LPS-induced TNF-α, IL-6, and IL-1β production. The levels of BUN and creatinine were also suppressed by hyperin. Furthermore, LPS-induced TLR4 expression and NF-κB activation were also inhibited by hyperin. In addition, treatment of hyperin dose-dependently inhibited LPS-induced NLRP3 signaling pathway. In conclusion, the results showed that hyperin inhibited LPS-induced inflammatory response by inhibiting TLR4 and NLRP3 signaling pathways. Hyperin has potential application prospects in the treatment of sepsis-induced AKI. PMID:27813491

  4. Gravitation Waves seminar

    CERN Multimedia

    CERN. Geneva HR-RFA

    2006-01-01

    We will present a brief introduction to the physics of gravitational waves and their properties. We will review potential astrophysical sources of gravitational waves, and the physics and astrophysics that can be learned from their study. We will survey the techniques and technologies for detecting gravitational waves for the first time, including bar detectors and broadband interferometers, and give a brief status report on the international search effort.

  5. RNCR3 knockdown inhibits diabetes mellitus-induced retinal reactive gliosis

    International Nuclear Information System (INIS)

    Liu, Chang; Li, Chao-peng; Wang, Jia-Jian; Shan, Kun; Liu, Xin; Yan, Biao

    2016-01-01

    Retinal reactive gliosis is an important pathological feature of diabetic retinopathy. Identifying the underlying mechanisms causing reactive gliosis will be important for developing new therapeutic strategies for treating diabetic retinopathy. Herein, we show that long noncoding RNA-RNCR3 knockdown significantly inhibits retinal reactive gliosis. RNCR3 knockdown leads to a marked reduction in the release of several cytokines. RNCR3 knockdown alleviates diabetes mellitus-induced retinal neurodegeneration, as shown by less apoptotic retinal cells and ameliorative visual function. RNCR3 knockdown could also decrease Müller glial cell viability and proliferation, and reduce the expression of glial reactivity-related genes including GFAP and vimentin in vitro. Collectively, this study shows that RNCR3 knockdown may be a promising strategy for the prevention of diabetes mellitus-induced retinal neurodegeneration. - Highlights: • RNCR3 knockdown inhibits retinal reactive gliosis. • RNCR3 knockdown causes a significant change in cytokine profile. • RNCR3 knockdown alleviates diabetes mellitus-induced retinal neurodegeneration. • RNCR3 knockdown affects Müller glial cell function in vitro.

  6. Gingival tissue-produced inhibition of platelet aggregation and the loss of inhibition in streptozotocin-induced diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Keiichiroh; Tamai, Kazuharu; Shirakawa, Masaharu; Okamoto, Hiroshi; Dohi, Toshihiro; Tsujimoto, Akira

    1988-01-01

    Addition of medium incubated with normal rat gingival tissue to platelet-rich plasma inhibited ADP-induced platelet aggregation. The ability of rat gingiva to produce activity inhibiting platelet aggregation was enhanced by the addition of arachidonic acid. Diabetic rat gingiva failed to inhibit platelet aggregation but did produce the anti-platelet aggregating activity in the presence of arachidonic acid. Indomethacin blocked the production of anti-platelet aggregating activity. There was no difference in conversion of (1-/sup 14/C)arachidonic acid to prostaglandins by normal and diabetic rat gingiva. These results suggest that an arachidonic acid metabolite released from gingiva during incubation inhibits platelet aggregation, and the synthesis of the metabolite is impaired in diabetic rat gingiva. A decrease in availability of arachidonic acid may be a causal factor of the defect in diabetic rat gingiva.

  7. Gingival tissue-produced inhibition of platelet aggregation and the loss of inhibition in streptozotocin-induced diabetic rats

    International Nuclear Information System (INIS)

    Kawamura, Keiichiroh; Tamai, Kazuharu; Shirakawa, Masaharu; Okamoto, Hiroshi; Dohi, Toshihiro; Tsujimoto, Akira

    1988-01-01

    Addition of medium incubated with normal rat gingival tissue to platelet-rich plasma inhibited ADP-induced platelet aggregation. The ability of rat gingiva to produce activity inhibiting platelet aggregation was enhanced by the addition of arachidonic acid. Diabetic rat gingiva failed to inhibit platelet aggregation but did produce the anti-platelet aggregating activity in the presence of arachidonic acid. Indomethacin blocked the production of anti-platelet aggregating activity. There was no difference in conversion of [1- 14 C]arachidonic acid to prostaglandins by normal and diabetic rat gingiva. These results suggest that an arachidonic acid metabolite released from gingiva during incubation inhibits platelet aggregation, and the synthesis of the metabolite is impaired in diabetic rat gingiva. A decrease in availability of arachidonic acid may be a causal factor of the defect in diabetic rat gingiva. (author)

  8. (+)-Nootkatone inhibits tumor necrosis factor α/interferon γ-induced production of chemokines in HaCaT cells

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hyeon-Jae; Lee, Jin-Hwee [College of Pharmacy, Ajou University, Suwon 443-749 (Korea, Republic of); Jung, Yi-Sook, E-mail: yisjung@ajou.ac.kr [College of Pharmacy, Ajou University, Suwon 443-749 (Korea, Republic of); Research Institute of Pharmaceutical Sciences and Technology, Ajou University, Suwon 443-749 (Korea, Republic of)

    2014-05-02

    Highlights: • (+)-Nootkatone inhibits TNF-α/IFN-γ-induced TARC and MDC expression in HaCaT cells. • PKCζ, p38 MAPK, or NF-κB mediate TNF-α/IFN-γ-induced TARC and MDC expression. • (+)-Nootkatone inhibits TNF-α/IFN-γ-induced activation of PKCζ, p38 MAPK, or NF-κB. • (+)-Nootkatone suppresses chemokine expression by inhibiting of PKCζ and p38 pathways. - Abstract: Chemokines are important mediators of cell migration, and thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) are well-known typical inflammatory chemokines involved in atopic dermatitis (AD). (+)-Nootkatone is the major component of Cyperus rotundus. (+)-Nootkatone has antiallergic, anti-inflammatory, and antiplatelet activities. The purpose of this study was to investigate the effect of (+)-nootkatone on tumor necrosis factor α (TNF-α)/interferon γ (IFN-γ)-induced expression of Th2 chemokines in HaCaT cells. We found that (+)-nootkatone inhibited the TNF-α/IFN-γ-induced expression of TARC/CCL17 and MDC/CCL22 mRNA in HaCaT cells. It also significantly inhibited TNF-α/IFN-γ-induced activation of nuclear factor kappa B (NF-κB), p38 mitogen-activated protein kinase (MAPK), and protein kinase Cζ (PKCζ). Furthermore, we showed that PKCζ and p38 MAPK contributed to the inhibition of TNF-α/IFN-γ-induced TARC/CCL17 and MDC/CCL22 expression by blocking IκBα degradation in HaCaT cells. Taken together, these results suggest that (+)-nootkatone may suppress TNF-α/IFN-γ-induced TARC/CCL17 and MDC/CCL22 expression in HaCaT cells by inhibiting of PKCζ and p38 MAPK signaling pathways that lead to activation of NF-κB. We propose that (+)-nootkatone may be a useful therapeutic candidate for inflammatory skin diseases such as AD.

  9. Testing gravitational parity violation with coincident gravitational waves and short gamma-ray bursts

    International Nuclear Information System (INIS)

    Yunes, Nicolas; O'Shaughnessy, Richard; Owen, Benjamin J.; Alexander, Stephon

    2010-01-01

    Gravitational parity violation is a possibility motivated by particle physics, string theory, and loop quantum gravity. One effect of it is amplitude birefringence of gravitational waves, whereby left and right circularly polarized waves propagate at the same speed but with different amplitude evolution. Here we propose a test of this effect through coincident observations of gravitational waves and short gamma-ray bursts from binary mergers involving neutron stars. Such gravitational waves are highly left or right circularly polarized due to the geometry of the merger. Using localization information from the gamma-ray burst, ground-based gravitational wave detectors can measure the distance to the source with reasonable accuracy. An electromagnetic determination of the redshift from an afterglow or host galaxy yields an independent measure of this distance. Gravitational parity violation would manifest itself as a discrepancy between these two distance measurements. We exemplify such a test by considering one specific effective theory that leads to such gravitational parity violation, Chern-Simons gravity. We show that the advanced LIGO-Virgo network and all-sky gamma-ray telescopes can be sensitive to the propagating sector of Chern-Simons gravitational parity violation to a level roughly 2 orders of magnitude better than current stationary constraints from the LAGEOS satellites.

  10. Relativity theory and gravitation

    International Nuclear Information System (INIS)

    Bondi, H.

    1986-01-01

    The paper on relativity theory and gravitation is presented as a preface to the first of the articles submitted to the Journal on general relativity. Newtonian gravitation and and observation, relativity, and the sources of the gravitational field, are all discussed. (UK)

  11. EZH2 Inhibition Ameliorates Transverse Aortic Constriction-Induced Pulmonary Arterial Hypertension in Mice

    Directory of Open Access Journals (Sweden)

    Zhan-Li Shi

    2018-01-01

    Full Text Available Background. EPZ005687 is a selective inhibiter of methyltransferase EZH2. In this article, we investigated the protective role and mechanism of EPZ005687 in transverse aortic constriction-induced pulmonary arterial hypertension in mice. Methods. We assigned 15 (6–8 weeks old male balb/c mice to 3 groups randomly: Sham control + DMSO group, TAC + DMSO group, and TAC + EPZ005687 group (10 mg kg−1, once a week for 4 weeks. On day 28 following TAC operation, the right ventricular systolic blood pressure (RVSBP was measured, and lung tissues were collected for laboratory examinations (DHE, Western blot, real-time PCR, and ChIP. Results. Murine PAH model was successfully created by TAC operation as evidenced by increased RVSBP and hypertrophic right ventricle. Compared with the sham control, TAC-induced PAH markedly upregulated the expression of EZH2 and ROS deposition in lungs in PAH mice. The inhibiter of methyltransferase EZH2, EPZ005687 significantly inhibits the development of TAC-induced PAH in an EZH2-SOD1-ROS dependent manner. Conclusion. Our data identified that EZH2 serves a fundamental role in TAC-induced PAH, and administration of EPZ005687 might represent a novel therapeutic target for the treatment of TAC-induced PAH.

  12. Autotaxin is induced by TSA through HDAC3 and HDAC7 inhibition and antagonizes the TSA-induced cell apoptosis.

    Science.gov (United States)

    Li, Song; Wang, Baolu; Xu, Yan; Zhang, Junjie

    2011-02-12

    Autotaxin (ATX) is a secreted glycoprotein with the lysophospholipase D (lysoPLD) activity to convert lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a bioactive lysophospholipid involved in diverse biological actions. ATX is highly expressed in some cancer cells and contributes to their tumorigenesis, invasion, and metastases, while in other cancer cells ATX is silenced or expressed at low level. The mechanism of ATX expression regulation in cancer cells remains largely unknown. In the present study, we demonstrated that trichostatin A (TSA), a well-known HDAC inhibitor (HDACi), significantly induced ATX expression in SW480 and several other cancer cells with low or undetectable endogenous ATX expression. ATX induction could be observed when HDAC3 and HDAC7 were down-regulated by their siRNAs. It was found that HDAC7 expression levels were low in the cancer cells with high endogenous ATX expression. Exogenous over-expression of HDAC7 inhibited ATX expression in these cells in a HDAC3-dependent manner. These data indicate that HDAC3 and HDAC7 collaboratively suppress ATX expression in cancer cells, and suggest that TSA induce ATX expression by inhibiting HDAC3 and HDAC7. The biological significance of this regulation mechanism was revealed by demonstrating that TSA-induced ATX protected cancer cells against TSA-induced apoptosis by producing LPA through its lysoPLD activity, which could be reversed by BrP-LPA and S32826, the inhibitors of the ATX-LPA axis. We have demonstrated that ATX expression is repressed by HDAC3 and HDAC7 in cancer cells. During TSA treatment, ATX is induced due to the HDAC3 and HDAC7 inhibition and functionally antagonizes the TSA-induced apoptosis. These results reveal an internal HDACi-resistant mechanism in cancer cells, and suggest that the inhibition of ATX-LPA axis would be helpful to improve the efficacy of HDACi-based therapeutics against cancer.

  13. Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation.

    Science.gov (United States)

    He, Gang; Wang, Yan; Pang, Xueli; Zhang, Bo

    2014-02-01

    Radiotherapy is one of the main treatments for clinical cancer therapy. However, its application was limited due to lack of radiosensitivity in some cancers. Trichostatin A (TSA) is a classic histone deacetylases inhibitor (HDACi) that specifically inhibits the biochemical functions of HDAC and is demonstrated to be an active anticancer drug. However, whether it could sensitize colon cancer to radiation is not clear. Our results showed that TSA enhanced the radiosensitivity of colon cancer cells as determined by CCK-8 and clonogenic survival assay. Moreover, apoptotic cell death induced by radiation was enhanced by TSA treatment. Additionally, TSA also induced autophagic response in colon cancer cells, while autophagy inhibition led to cell apoptosis and enhanced the radiosensitivity of colon cancer cells. Our data suggested that inhibition of cytoprotective autophagy sensitizes cancer cell to radiation, which might be further investigated for clinical cancer radiotherapy.

  14. Gravitational waves from Abelian gauge fields and cosmic strings at preheating

    International Nuclear Information System (INIS)

    Dufaux, Jean-Francois; Figueroa, Daniel G.; Garcia-Bellido, Juan

    2010-01-01

    Primordial gravitational waves provide a very important stochastic background that could be detected soon with interferometric gravitational wave antennas or indirectly via the induced patterns in the polarization anisotropies of the cosmic microwave background. The detection of these waves will open a new window into the early Universe, and therefore it is important to characterize in detail all possible sources of primordial gravitational waves. In this paper we develop theoretical and numerical methods to study the production of gravitational waves from out-of-equilibrium gauge fields at preheating. We then consider models of preheating after hybrid inflation, where the symmetry breaking field is charged under a local U(1) symmetry. We analyze in detail the dynamics of the system in both momentum and configuration space. We show that gauge fields leave specific imprints in the resulting gravitational wave spectra, mainly through the appearance of new peaks at characteristic frequencies that are related to the mass scales in the problem. We also show how these new features in the spectra correlate with stringlike spatial configurations in both the Higgs and gauge fields that arise due to the appearance of topological winding numbers of the Higgs around Nielsen-Olesen strings. We study in detail the time evolution of the spectrum of gauge fields and gravitational waves as these strings evolve and decay before entering a turbulent regime where the gravitational wave energy density saturates.

  15. Hydrogen sulfide inhibits high glucose-induced NADPH oxidase 4 expression and matrix increase by recruiting inducible nitric oxide synthase in kidney proximal tubular epithelial cells.

    Science.gov (United States)

    Lee, Hak Joo; Lee, Doug Yoon; Mariappan, Meenalakshmi M; Feliers, Denis; Ghosh-Choudhury, Goutam; Abboud, Hanna E; Gorin, Yves; Kasinath, Balakuntalam S

    2017-04-07

    High-glucose increases NADPH oxidase 4 (NOX4) expression, reactive oxygen species generation, and matrix protein synthesis by inhibiting AMP-activated protein kinase (AMPK) in renal cells. Because hydrogen sulfide (H 2 S) inhibits high glucose-induced matrix protein increase by activating AMPK in renal cells, we examined whether H 2 S inhibits high glucose-induced expression of NOX4 and matrix protein and whether H 2 S and NO pathways are integrated. High glucose increased NOX4 expression and activity at 24 h in renal proximal tubular epithelial cells, which was inhibited by sodium hydrosulfide (NaHS), a source of H 2 S. High glucose decreased AMPK phosphorylation and activity, which was restored by NaHS. Compound C, an AMPK inhibitor, prevented NaHS inhibition of high glucose-induced NOX4 expression. NaHS inhibition of high glucose-induced NOX4 expression was abrogated by N (ω)-nitro-l-arginine methyl ester, an inhibitor of NOS. NaHS unexpectedly augmented the expression of inducible NOS (iNOS) but not endothelial NOS. iNOS siRNA and 1400W, a selective iNOS inhibitor, abolished the ameliorative effects of NaHS on high glucose-induced NOX4 expression, reactive oxygen species generation, and, matrix laminin expression. Thus, H 2 S recruits iNOS to generate NO to inhibit high glucose-induced NOX4 expression, oxidative stress, and matrix protein accumulation in renal epithelial cells; the two gasotransmitters H 2 S and NO and their interaction may serve as therapeutic targets in diabetic kidney disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Galvanic Tongue Stimulation Inhibits Five Basic Tastes Induced by Aqueous Electrolyte Solutions

    Directory of Open Access Journals (Sweden)

    Kazuma Aoyama

    2017-12-01

    Full Text Available Galvanic tongue stimulation (GTS modulates taste sensation. However, the effect of GTS is contingent on the electrode polarity in the proximity of the tongue. If an anodal electrode is attached in the proximity of the tongue, an electrical or metallic taste is elicited. On the other hand, if only cathodal electrode is attached in the proximity of the tongue, the salty taste, which is induced by electrolyte materials, is inhibited. The mechanism of this taste inhibition is not adequately understood. In this study, we aim to demonstrate that the inhibition is cause by ions, which elicit taste and which migrate from the taste sensors on the tongue by GTS. We verified the inhibitory effect of GTS on all five basic tastes induced by electrolyte materials. This technology is effective for virtual reality systems and interfaces to support dietary restrictions. Our findings demonstrate that cathodal-GTS inhibits all the five basic tastes. The results also support our hypothesis that the effects of cathodal-GTS are caused by migrating tasting ions in the mouth.

  17. Gravitational Radiation from Post-Newtonian Sources and Inspiralling Compact Binaries

    Directory of Open Access Journals (Sweden)

    Luc Blanchet

    2014-02-01

    Full Text Available To be observed and analyzed by the network of gravitational wave detectors on ground (LIGO, VIRGO, etc. and by the future detectors in space (eLISA, etc., inspiralling compact binaries -- binary star systems composed of neutron stars and/or black holes in their late stage of evolution -- require high-accuracy templates predicted by general relativity theory. The gravitational waves emitted by these very relativistic systems can be accurately modelled using a high-order post-Newtonian gravitational wave generation formalism. In this article, we present the current state of the art on post-Newtonian methods as applied to the dynamics and gravitational radiation of general matter sources (including the radiation reaction back onto the source and inspiralling compact binaries. We describe the post-Newtonian equations of motion of compact binaries and the associated Lagrangian and Hamiltonian formalisms, paying attention to the self-field regularizations at work in the calculations. Several notions of innermost circular orbits are discussed. We estimate the accuracy of the post-Newtonian approximation and make a comparison with numerical computations of the gravitational self-force for compact binaries in the small mass ratio limit. The gravitational waveform and energy flux are obtained to high post-Newtonian order and the binary's orbital phase evolution is deduced from an energy balance argument. Some landmark results are given in the case of eccentric compact binaries -- moving on quasi-elliptical orbits with non-negligible eccentricity. The spins of the two black holes play an important role in the definition of the gravitational wave templates. We investigate their imprint on the equations of motion and gravitational wave phasing up to high post-Newtonian order (restricting to spin-orbit effects which are linear in spins, and analyze the post-Newtonian spin precession equations as well as the induced precession of the orbital plane.

  18. Gravitationally bound BCS state as dark matter

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, Stephon [Department of Physics, Brown University, Providence, RI 20912 (United States); Cormack, Sam, E-mail: stephon_alexander@brown.edu, E-mail: samuel.c.cormack.gr@dartmouth.edu [Department of Physics and Astronomy, Dartmouth College, Hanover, NH 03755 (United States)

    2017-04-01

    We explore the possibility that fermionic dark matter undergoes a BCS transition to form a superfluid. This requires an attractive interaction between fermions and we describe a possible source of this interaction induced by torsion. We describe the gravitating fermion system with the Bogoliubov-de Gennes formalism in the local density approximation. We solve the Poisson equation along with the equations for the density and gap energy of the fermions to find a self-gravitating, superfluid solution for dark matter halos. In order to produce halos the size of dwarf galaxies, we require a particle mass of ∼ 200 eV. We find a maximum attractive coupling strength before the halo becomes unstable. If dark matter halos do have a superfluid component, this raises the possibility that they contain vortex lines.

  19. Autophagy and gap junctional intercellular communication inhibition are involved in cadmium-induced apoptosis in rat liver cells

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Hui [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China); Zhuo, Liling [College of Life Science, Zaozhuang University, Zaozhuang, Shandong, 277160 (China); Han, Tao; Hu, Di; Yang, Xiaokang; Wang, Yi; Yuan, Yan; Gu, Jianhong; Bian, Jianchun; Liu, Xuezhong [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China); Liu, Zongping, E-mail: liuzongping@yzu.edu.cn [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China)

    2015-04-17

    Cadmium (Cd) is known to induce hepatotoxicity, yet the underlying mechanism of how this occurs is not fully understood. In this study, Cd-induced apoptosis was demonstrated in rat liver cells (BRL 3A) with apoptotic nuclear morphological changes and a decrease in cell index (CI) in a time- and concentration-dependent manner. The role of gap junctional intercellular communication (GJIC) and autophagy in Cd-induced apoptosis was investigated. Cd significantly induced GJIC inhibition as well as downregulation of connexin 43 (Cx43). The prototypical gap junction blocker carbenoxolone disodium (CBX) exacerbated the Cd-induced decrease in CI. Cd treatment was also found to cause autophagy, with an increase in mRNA expression of autophagy-related genes Atg-5, Atg-7, Beclin-1, and microtubule-associated protein light chain 3 (LC3) conversion from cytosolic LC3-I to membrane-bound LC3-II. The autophagic inducer rapamycin (RAP) prevented the Cd-induced CI decrease, while the autophagic inhibitor chloroquine (CQ) caused a further reduction in CI. In addition, CBX promoted Cd-induced autophagy, as well as changes in expression of Atg-5, Atg-7, Beclin-1 and LC3. CQ was found to block the Cd-induced decrease in Cx43 and GJIC inhibition, whereas RAP had opposite effect. These results demonstrate that autophagy plays a protective role during Cd-induced apoptosis in BRL 3A cells during 6 h of experiment, while autophagy exacerbates Cd-induced GJIC inhibition which has a negative effect on cellular fate. - Highlights: • GJIC and autophagy is crucial for biological processes. • Cd exposure causes GJIC inhibition and autophagy increase in BRL 3A cells. • Autophagy protects Cd induced BRL 3A cells apoptosis at an early stage. • Autophagy exacerbates Cd-induced GJIC inhibition. • GJIC plays an important role in autophagy induced cell death or survival.

  20. On the effects of gravitational fields on the electrical properties of matter

    International Nuclear Information System (INIS)

    Opat, G.I.

    1993-01-01

    A discussion of the electrical state of a conducting solid in a static gravitational field is presented. The analysis of the stress-gravitational force balance inside the solid is complicated, however, outside the solid, in the evanescent electron field, the analysis of such a balance simplifies greatly. As a consequence of this external analysis, an expression for the electric field external to the body is presented which includes the direct effect of gravity on the electrons, as well as the indirect effect due to the stress induced by gravity acting on the bulk solid. Such fields are an important determinant of the gravitational motion of charged particles within metallic shields. 4 refs., 1 fig

  1. Gravitation

    CERN Document Server

    Misner, Charles W; Wheeler, John Archibald

    2017-01-01

    First published in 1973, Gravitation is a landmark graduate-level textbook that presents Einstein’s general theory of relativity and offers a rigorous, full-year course on the physics of gravitation. Upon publication, Science called it “a pedagogic masterpiece,” and it has since become a classic, considered essential reading for every serious student and researcher in the field of relativity. This authoritative text has shaped the research of generations of physicists and astronomers, and the book continues to influence the way experts think about the subject. With an emphasis on geometric interpretation, this masterful and comprehensive book introduces the theory of relativity; describes physical applications, from stars to black holes and gravitational waves; and portrays the field’s frontiers. The book also offers a unique, alternating, two-track pathway through the subject. Material focusing on basic physical ideas is designated as Track 1 and formulates an appropriate one-semester graduate-level...

  2. Lensing of 21-cm fluctuations by primordial gravitational waves.

    Science.gov (United States)

    Book, Laura; Kamionkowski, Marc; Schmidt, Fabian

    2012-05-25

    Weak-gravitational-lensing distortions to the intensity pattern of 21-cm radiation from the dark ages can be decomposed geometrically into curl and curl-free components. Lensing by primordial gravitational waves induces a curl component, while the contribution from lensing by density fluctuations is strongly suppressed. Angular fluctuations in the 21-cm background extend to very small angular scales, and measurements at different frequencies probe different shells in redshift space. There is thus a huge trove of information with which to reconstruct the curl component of the lensing field, allowing tensor-to-scalar ratios conceivably as small as r~10(-9)-far smaller than those currently accessible-to be probed.

  3. Gravitational wave astronomy

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    In the past year, the LIGO-Virgo Collaboration announced the first secure detection of gravitational waves. This discovery heralds the beginning of gravitational wave astronomy: the use of gravitational waves as a tool for studying the dense and dynamical universe. In this talk, I will describe the full spectrum of gravitational waves, from Hubble-scale modes, through waves with periods of years, hours and milliseconds. I will describe the different techniques one uses to measure the waves in these bands, current and planned facilities for implementing these techniques, and the broad range of sources which produce the radiation. I will discuss what we might expect to learn as more events and sources are measured, and as this field matures into a standard part of the astronomical milieu.

  4. Gravitational Wave Astronomy

    CERN Multimedia

    CERN. Geneva

    2006-01-01

    Gravitational wave astronomy is expected to become an observational field within the next decade. First direct detection of gravitational waves is possible with existing terrestrial-based detectors, and highly probable with proposed upgrades. In this three-part lecture series, we give an overview of the field, including material on gravitional wave sources, detection methods, some details of interferometric detectors, data analysis methods, and current results from observational data-taking runs of the LIGO and GEO projects.

  5. Underdevelopment’s gravitation

    Directory of Open Access Journals (Sweden)

    Marin Dinu

    2013-09-01

    Full Text Available The energy necessary to escape the gravitational pull of underdevelopment and to enter an evolutional trajectory dependent on the gravitational pull of development is unintelligible in economic terms.

  6. Genistein inhibited ammonia induced astrocyte swelling by inhibiting NF-κB activation-mediated nitric oxide formation.

    Science.gov (United States)

    Dai, Hongliang; Jia, Guizhi; Wang, Wei; Liang, Chunguang; Han, Siyu; Chu, Minghui; Mei, Xifan

    2017-06-01

    Our previous study has indicated the involvement of epidermal growth factor receptor (EGFR) transactivation in ammonia-induced astrocyte swelling, which represents a major pathogenesis of brain edema in hepatic encephalopathy. In this study, we examined the effect of genistein, a naturally occurred broad-spectrum protein tyrosine kinase (PTK) inhibitor, on ammonia-induced cell swelling. We found that genistein pretreatment significantly prevented ammonia-induced astrocyte swelling. Mechanistically, ammonia triggered EGFR/extracellular signal-regulated kinase (ERK) association and subsequent ERK phosphorylation were alleviated by genistein pretreatment. Moreover, ammonia-induced NF-κB nuclear location, iNOS expression, and consequent NO production were all prevented by AG1478 and genistein pretreatment. This study suggested that genistein could alleviate ammonia-induced astrocyte swelling, which may be, at least partly, related to its PTK-inhibiting activity and repression of NF-κB mediated iNOS-derived NO accumulation.

  7. Isolation of gravitational waves from displacement noise and utility of a time-delay device

    Energy Technology Data Exchange (ETDEWEB)

    Somiya, Kentaro [Max-Planck Institut fuer Gravitationsphysik, Am Muehlenberg 1, 14476 Potsdam (Germany); Goda, Keisuke [LIGO Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Chen, Yanbei [Max-Planck Institut fuer Gravitationsphysik, Am Muehlenberg 1, 14476 Potsdam (Germany); Mikhailov, Eugeniy E [Department of Physics, College of William and Mary, Williamsburg, VA 23187 (United States)

    2007-05-15

    Interferometers with kilometer-scale arms have been built for gravitational-wave detections on the ground; ones with much longer arms are being planned for space-based detection. One fundamental motivation for long baseline interferometry is from displacement noise. In general, the longer the arm length L, the larger the motion the gravitational-wave induces on the test masses, until L becomes comparable to the gravitational wavelength. Recently, schemes have been invented, in which displacement noise can be evaded by employing differences between the influence of test-mass motions and that of gravitational waves on light propagation. However, in these schemes, such differences only becomes significant when Lapproaches the gravitational wavelength. In this paper, we explore a use of artificial time delay in displacement-noise-free interferometers, which will shift the frequency band of the effect being significant and may improve their shot-noise-limited sensitivity at low frequencies.

  8. Isolation of gravitational waves from displacement noise and utility of a time-delay device

    International Nuclear Information System (INIS)

    Somiya, Kentaro; Goda, Keisuke; Chen, Yanbei; Mikhailov, Eugeniy E

    2007-01-01

    Interferometers with kilometer-scale arms have been built for gravitational-wave detections on the ground; ones with much longer arms are being planned for space-based detection. One fundamental motivation for long baseline interferometry is from displacement noise. In general, the longer the arm length L, the larger the motion the gravitational-wave induces on the test masses, until L becomes comparable to the gravitational wavelength. Recently, schemes have been invented, in which displacement noise can be evaded by employing differences between the influence of test-mass motions and that of gravitational waves on light propagation. However, in these schemes, such differences only becomes significant when Lapproaches the gravitational wavelength. In this paper, we explore a use of artificial time delay in displacement-noise-free interferometers, which will shift the frequency band of the effect being significant and may improve their shot-noise-limited sensitivity at low frequencies

  9. Inhibition of dipeptidyl peptidase 4 regulates microvascular endothelial growth induced by inflammatory cytokines

    International Nuclear Information System (INIS)

    Takasawa, Wataru; Ohnuma, Kei; Hatano, Ryo; Endo, Yuko; Dang, Nam H.; Morimoto, Chikao

    2010-01-01

    Research highlights: → TNF-α or IL-1β induces EC proliferation with reduction of CD26 expression. → CD26 siRNA or DPP-4 inhibition enhances TNF-α or IL-1β-induced EC proliferation. → Loss of CD26/DPP-4 enhances aortic sprouting induced by TNF-α or IL-1β. → Capillary formation induced by TNF-α or IL-1β is enahced in the CD26 -/- mice. -- Abstract: CD26/DPP-4 is abundantly expressed on capillary of inflamed lesion as well as effector T cells. Recently, CD26/dipeptidyl peptidase 4 (DPP-4) inhibition has been used as a novel oral therapeutic approach for patients with type 2 diabetes. While accumulating data indicate that vascular inflammation is a key feature of both micro- and macro-vascular complications in diabetes, the direct role of CD26/DPP-4 in endothelial biology is to be elucidated. We herein showed that proinflammatory cytokines such as tumor necrosis factor or interleukin-1 reduce expression of CD26 on microvascular endothelial cells, and that genetical or pharmacological inhibition of CD26/DPP-4 enhances endothelial growth both in vitro and in vivo. With DPP-4 inhibitors being used widely in the treatment of type 2 diabetes, our data strongly suggest that DPP-4 inhibition plays a pivotal role in endothelial growth and may have a potential role in the recovery of local circulation following diabetic vascular complications.

  10. Leflunomide/teriflunomide inhibit Epstein-Barr virus (EBV)- induced lymphoproliferative disease and lytic viral replication.

    Science.gov (United States)

    Bilger, Andrea; Plowshay, Julie; Ma, Shidong; Nawandar, Dhananjay; Barlow, Elizabeth A; Romero-Masters, James C; Bristol, Jillian A; Li, Zhe; Tsai, Ming-Han; Delecluse, Henri-Jacques; Kenney, Shannon C

    2017-07-04

    EBV infection causes mononucleosis and is associated with specific subsets of B cell lymphomas. Immunosuppressed patients such as organ transplant recipients are particularly susceptible to EBV-induced lymphoproliferative disease (LPD), which can be fatal. Leflunomide (a drug used to treat rheumatoid arthritis) and its active metabolite teriflunomide (used to treat multiple sclerosis) inhibit de novo pyrimidine synthesis by targeting the cellular dihydroorotate dehydrogenase, thereby decreasing T cell proliferation. Leflunomide also inhibits the replication of cytomegalovirus and BK virus via both "on target" and "off target" mechanisms and is increasingly used to treat these viruses in organ transplant recipients. However, whether leflunomide/teriflunomide block EBV replication or inhibit EBV-mediated B cell transformation is currently unknown. We show that teriflunomide inhibits cellular proliferation, and promotes apoptosis, in EBV-transformed B cells in vitro at a clinically relevant dose. In addition, teriflunomide prevents the development of EBV-induced lymphomas in both a humanized mouse model and a xenograft model. Furthermore, teriflunomide inhibits lytic EBV infection in vitro both by preventing the initial steps of lytic viral reactivation, and by blocking lytic viral DNA replication. Leflunomide/teriflunomide might therefore be clinically useful for preventing EBV-induced LPD in patients who have high EBV loads yet require continued immunosuppression.

  11. GSK-3β Inhibition Attenuates LPS-Induced Death but Aggravates Radiation-Induced Death via Down-Regulation of IL-6

    Directory of Open Access Journals (Sweden)

    Bailong Li

    2013-12-01

    Full Text Available Background: Exposure of high dose ionizing radiation is lethal. Signal pathways involved in radiation biology reaction still remain illdefined. Lipopolysaccharides (LPS, the ligands of Toll-like receptor 4(TLR4, could elicit strong immune responses. Glycogen synthase kinase-3β(GSK-3β promotes the production of inflammatory molecules and cell migration. Inhibition of GSK-3β provides protection against inflammation in animal models. The aim of the study was to investigate role of GSK-3β in LPS shock and ionizing radiation. Methods: WT or IL-6-/-mice or cells were pretreated with SB216763, a GSK-3β inhibitor, and survival of the mice was determined. Cell viability was assayed by Cell Counting Kit. Apoptosis was assayed by Annexin V-PI double staining. Serum concentrations of IL-6 and TNF-α were determined by ELISA. Results: SB216763 attenuated LPS induced mice or cell death but aggravated radiation induced mice or cell death. SB216763 reduced IL-6, but not TNF-α levels in vivo. IL-6-/- mice were more resistant to LPS-induced death but less resistant to radiation-induced death than wild type mice. Conclusions: Inhibition of GSK-3β conferred resistance to LPS shock but fostered death induced by ionizing radiation. Inhibition of GSK-3β was effective by reducing IL-6.

  12. Inhibition of LPS-induced splenocyte proliferation by ortho-substituted polychlorinated biphenyl congeners

    International Nuclear Information System (INIS)

    Smithwick, L. Ashley; Smith, Andrew; Quensen, John F.; Stack, Allison; London, Lucille; Morris, Pamela J.

    2003-01-01

    Polychlorinated biphenyls (PCBs) are persistent environmental contaminants, and their ubiquitous nature has prompted studies of their potential health hazards. As a result of their lipophilic nature, PCBs accumulate in breast milk and subsequently affect the health of offspring of exposed individuals. Biological effects of PCBs in animals have mostly been attributed to coplanar congeners, although effects of ortho congeners also have been demonstrated. To investigate the relationship of immunotoxicity and chlorine substitution pattern, the effects of PCB congeners and mixtures of ortho and non-ortho-substituted constituents of Aroclor 1242 on splenocytes from C57B1/6 mice were examined. The immunotoxic endpoints investigated included splenocyte viability, lipopolysaccharide (LPS)-induced splenocyte proliferation, and LPS-induced antibody secretion. Congeners with multiple ortho chlorines preferentially inhibited splenocyte proliferation as compared with non- or mono-ortho-substituted congeners. However, mixtures of non- and mono-ortho-substituted congeners and multi-ortho-substituted congeners inhibited LPS-induced splenocyte proliferation and antibody secretion at similar concentrations. Exposure of splenocytes to these mixtures did not activate the aryl hydrocarbon receptor (AhR) signal transduction pathway. These results suggest individual multi-ortho-substituted congeners preferentially inhibit LPS-induced splenocyte proliferation, while congeners not exhibiting an effect individually may have additive effects in a mixture to produce an immunotoxic response through an AhR-independent pathway

  13. Valsartan Protects Against Contrast-Induced Acute Kidney Injury in Rats by Inhibiting Endoplasmic Reticulum Stress-Induced Apoptosis.

    Science.gov (United States)

    Sun, Yan; Peng, Ping-An; Ma, Yue; Liu, Xiao-Li; Yu, Yi; Jia, Shuo; Xu, Xiao-Han; Wu, Si-Jing; Zhou, Yu-Jie

    2017-01-01

    Contrast-induced acute kidney injury (CI-AKI) is a serious complication of the administration of iodinated contrast media (CM) for diagnostic and interventional cardiovascular procedures and is associated with substantial morbidity and mortality. While the preventative measures can mitigate the risk of CI-AKI, there remains a need for novel and effective therapeutic approaches. The pathogenesis of CI-AKI is complex and not completely understood. CM-induced renal tubular cell apoptosis caused by the activation of endoplasmic reticulum (ER) stress is involved in CIAKI. We previously demonstrated that valsartan alleviated CM-induced human renal tubular cell apoptosis by inhibiting ER stress in vitro. However, the nephroprotective effect of valsartan on CI-AKI in vivo has not been investigated. Therefore, the aim of this study was to explore the protective effect of valsartan in a rat model of CI-AKI by measuring the amelioration of renal damage and the changes in ER stressrelated biomarkers. Our results showed that the radiocontrast agent meglumine diatrizoate caused significant renal insufficiency, renin-angiotensin system (RAS) activation, and renal tubular apoptosis by triggering ER stress through activation of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), caspase 12, CCAAT/enhancer-binding protein-homologous protein (CHOP) and c-Jun N-terminal protein kinase (JNK) (Pvalsartan significantly alleviated renal dysfunction, pathological injury, and apoptosis along with the inhibition of ER stressrelated biomarkers (PValsartan could protect against meglumine diatrizoate-induced kidney injury in rats by inhibiting the ER stress-induced apoptosis, making it a promising strategy for preventing CI-AKI. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Systematic survey for monitor signals to reduce fake burst events in a gravitational-wave detector

    International Nuclear Information System (INIS)

    Ishidoshiro, Koji; Ando, Masaki; Tsubono, Kimio

    2006-01-01

    We present methods and results to reduce fake burst events induced by nonstationary noises. To reduce these fake events, we systematically surveyed monitor signals recorded with a main (or gravitational-wave) signal of a gravitational-wave detector so as to watch the detector. Our survey was to check whether or not there was a coincidence between the main and monitor signals when we found a burst event from the main signal. If there was a coincidence, we rejected this event as a fake event induced by nonstationary noises, regarding the main signal as being dominated by nonstationary noises. As a result, we succeeded to reject about 90% of the burst events of which the SNR values were larger than 10 as fake events, with an accidental probability of about 5% to reject burst-gravitational-wave candidates

  15. Understanding possible electromagnetic counterparts to loud gravitational wave events: Binary black hole effects on electromagnetic fields

    International Nuclear Information System (INIS)

    Palenzuela, Carlos; Lehner, Luis; Yoshida, Shin

    2010-01-01

    In addition to producing loud gravitational waves, the dynamics of a binary black hole system could induce emission of electromagnetic radiation by affecting the behavior of plasmas and electromagnetic fields in their vicinity. We study how the electromagnetic fields are affected by a pair of orbiting black holes through the merger. In particular, we show how the binary's dynamics induce a variability in possible electromagnetically induced emissions as well as an enhancement of electromagnetic fields during the late-merge and merger epochs. These time dependent features will likely leave their imprint in processes generating detectable emissions and can be exploited in the detection of electromagnetic counterparts of gravitational waves.

  16. Furan- and Thiophene-2-Carbonyl Amino Acid Derivatives Activate Hypoxia-Inducible Factor via Inhibition of Factor Inhibiting Hypoxia-Inducible Factor-1

    Directory of Open Access Journals (Sweden)

    Shin-ichi Kawaguchi

    2018-04-01

    Full Text Available Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α is a major transcription factor that orchestrates this protective effect. To activate HIF exogenously, without exposing cells to hypoxic conditions, many small-molecule inhibitors targeting prolyl hydroxylase domain-containing protein have been developed. In addition, suppression of factor inhibiting HIF-1 (FIH-1 has also been shown to have the potential to activate HIF-α. However, few small-molecule inhibitors of FIH-1 have been developed. In this study, we synthesized a series of furan- and thiophene-2-carbonyl amino acid derivatives having the potential to inhibit FIH-1. The inhibitory activities of these compounds were evaluated in SK-N-BE(2c cells by measuring HIF response element (HRE promoter activity. Several furan- and thiophene-2-carbonyl amino acid derivatives inhibited FIH-1 based on correlations among the docking score of the FIH-1 active site, the chemical structure of the compounds, and biological HIF-α/HRE transcriptional activity.

  17. Inhibition of CD38/Cyclic ADP-ribose Pathway Protects Rats against Ropivacaine-induced Convulsion

    Directory of Open Access Journals (Sweden)

    Yu Zou

    2017-01-01

    Conclusions: The CD38/cADPR pathway is activated in ropivacaine-induced convulsion. Inhibiting this pathway alleviates ropivacaine-induced convulsion and protects the brain from apoptosis and oxidative stress.

  18. Potent inhibition of tumoral hypoxia-inducible factor 1α by albendazole

    International Nuclear Information System (INIS)

    Pourgholami, Mohammad H; Cai, Zhao Y; Badar, Samina; Wangoo, Kiran; Poruchynsky, Marianne S; Morris, David L

    2010-01-01

    Emerging reports suggest resistance, increased tumor invasiveness and metastasis arising from treatment with drugs targeting vascular endothelial growth factor (VEGF). It is believed that increased tumoral hypoxia plays a prominent role in the development of these phenomena. Inhibition of tumoral hypoxia inducible factor (HIF-1α) is thus becoming an increasingly attractive therapeutic target in the treatment of cancer. We hypothesized that the anti-VEGF effect of albendazole (ABZ) could be mediated through inhibition of tumoral HIF-1α. In vitro, the effects of ABZ on HIF-1α levels in human ovarian cancer cells (OVCAR-3) were investigated using hypoxic chamber or desferrioxamine (DFO) induced-hypoxia. In vivo, the effects of ABZ (150 mg/kg, i.p., single dose) on the tumor levels of HIF-1α and VEGF protein and mRNA were investigated by western blotting, RT-PCR and real time-PCR. In vitro, ABZ inhibited cellular HIF-1α protein accumulation resulting from placement of cells under hypoxic chamber or exposure to DFO. In vivo, tumors excised from vehicle treated mice showed high levels of both HIF-1α and VEGF. Whereas, tumoral HIF-1α and VEGF protein levels were highly suppressed in ABZ treated mice. Tumoral VEGFmRNA (but not HIF-1αmRNA) was also found to be highly suppressed by ABZ. These results demonstrate for the first time the effects of an acute dose of ABZ in profoundly suppressing both HIF-1α and VEGF within the tumor. This dual inhibition may provide additional value in inhibiting angiogenesis and be at least partially effective in inhibiting tumoral HIF-1α surge, tumor invasiveness and metastasis

  19. Gravitation in Material Media

    Science.gov (United States)

    Ridgely, Charles T.

    2011-01-01

    When two gravitating bodies reside in a material medium, Newton's law of universal gravitation must be modified to account for the presence of the medium. A modified expression of Newton's law is known in the literature, but lacks a clear connection with existing gravitational theory. Newton's law in the presence of a homogeneous material medium…

  20. Detection of gravitational radiation

    Energy Technology Data Exchange (ETDEWEB)

    Holten, J.W. van [ed.

    1994-12-31

    In this report the main contributions presented at the named symposium are collected. These concern astrophysical sources of gravitational radiation, ultracryogenic gravitational wave experiments, read out and data analysis of gravitational wave antennas, cryogenic aspects of large mass cooling to mK temperatures, and metallurgical and engineering aspects of large Cu structure manufacturing. (HSI).

  1. Detection of gravitational radiation

    International Nuclear Information System (INIS)

    Holten, J.W. van

    1994-01-01

    In this report the main contributions presented at the named symposium are collected. These concern astrophysical sources of gravitational radiation, ultracryogenic gravitational wave experiments, read out and data analysis of gravitational wave antennas, cryogenic aspects of large mass cooling to mK temperatures, and metallurgical and engineering aspects of large Cu structure manufacturing. (HSI)

  2. Relativistic theory of gravitation

    International Nuclear Information System (INIS)

    Logunov, A.A.; Mestvirishvili, M.A.

    1986-01-01

    In the present paper a relativistic theory of gravitation (RTG) is unambiguously constructed on the basis of the special relativity and geometrization principle. In this a gravitational field is treated as the Faraday--Maxwell spin-2 and spin-0 physical field possessing energy and momentum. The source of a gravitational field is the total conserved energy-momentum tensor of matter and of a gravitational field in Minkowski space. In the RTG the conservation laws are strictly fulfilled for the energy-moment and for the angular momentum of matter and a gravitational field. The theory explains the whole available set of experiments on gravity. By virtue of the geometrization principle, the Riemannian space in our theory is of field origin, since it appears as an effective force space due to the action of a gravitational field on matter. The RTG leads to an exceptionally strong prediction: The universe is not closed but just ''flat.'' This suggests that in the universe a ''missing mass'' should exist in a form of matter

  3. GSK-3beta inhibition enhances sorafenib-induced apoptosis in melanoma cell lines.

    Science.gov (United States)

    Panka, David J; Cho, Daniel C; Atkins, Michael B; Mier, James W

    2008-01-11

    Glycogen synthase kinase-3beta (GSK-3beta) can participate in the induction of apoptosis or, alternatively, provide a survival signal that minimizes cellular injury. We previously demonstrated that the multikinase inhibitor sorafenib induces apoptosis in melanoma cell lines. In this report, we show that sorafenib activates GSK-3beta in multiple subcellular compartments and that this activation undermines the lethality of the drug. Pharmacologic inhibition and/or down-modulation of the kinase enhances sorafenib-induced apoptosis as determined by propidium iodide staining and by assessing the mitochondrial release of apoptosis-inducing factor and Smac/DIABLO. Conversely, the forced expression of a constitutively active form of the enzyme (GSK-3beta(S9A)) protects the cells from the apoptotic effects of the drug. This protective effect is associated with a marked increase in basal levels of Bcl-2, Bcl-x(L), and survivin and a diminution in the degree to which these anti-apoptotic proteins are down-modulated by sorafenib exposure. Sorafenib down-modulates the pro-apoptotic Bcl-2 family member Noxa in cells with high constitutive GSK-3beta activity. Pharmacologic inhibition of GSK-3beta prevents the disappearance of Noxa induced by sorafenib and enhances the down-modulation of Mcl-1. Down-modulation of Noxa largely eliminates the enhancing effect of GSK-3 inhibition on sorafenib-induced apoptosis. These data provide a strong rationale for the use of GSK-3beta inhibitors as adjuncts to sorafenib treatment and suggest that preservation of Noxa may contribute to their efficacy.

  4. Aspirin inhibits interleukin 1-induced prostaglandin H synthase expression in cultured endothelial cells

    International Nuclear Information System (INIS)

    Wu, K.K.; Sanduja, R.; Tsai, A.L.; Ferhanoglu, B.; Loose-Mitchell, D.S.

    1991-01-01

    Prostaglandin H (PGH) synthase is a key enzyme in the biosynthesis of prostaglandins, thromboxane, and prostacyclin. In cultured human umbilical vein endothelial cells, interleukin 1 (IL-1) is known to induce the synthesis of this enzyme, thereby raising the level of PGH synthase protein severalfold over the basal level. Pretreatment with aspirin at low concentrations inhibited more than 60% of the enzyme mass and also the cyclooxygenase activity in IL-1-induced cells with only minimal effects on the basal level of the synthase enzyme in cells without IL-1. Sodium salicylate exhibited a similar inhibitory action whereas indomethacin had no apparent effect. Similarly low levels of aspirin inhibited the increased L-[ 35 S]methionine incorporation into PGH synthase that was induced by IL0-1 and also suppressed expression of the 2.7-kilobase PGH synthase mRNA. These results suggest that in cultured endothelial cells a potent inhibition of eicosanoid biosynthetic capacity can be effected by aspirin or salicylate at the level of PGH synthase gene expression. The aspirin effect may well be due to degradation of salicylate

  5. The Newton constant and gravitational waves in some vector field adjusting mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Santillán, Osvaldo P. [IMAS (UBA-CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires 1428 (Argentina); Scornavacche, Marina, E-mail: firenzecita@hotmail.com, E-mail: marina.scorna@hotmail.com [Departamento de Física, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires 1428 (Argentina)

    2017-10-01

    At the present, there exist some Lorentz breaking scenarios which explain the smallness of the cosmological constant at the present era [1]–[2]. An important aspect to analyze is the propagation of gravitational waves and the screening or enhancement of the Newton constant G {sub N} in these models. The problem is that the Lorentz symmetry breaking terms may induce an unacceptable value of the Newton constant G {sub N} or introduce longitudinal modes in the gravitational wave propagation. Furthermore this breaking may spoil the standard dispersion relation ω= ck . In [3] the authors have presented a model suggesting that the behavior of the gravitational constant is correct for asymptotic times. In the present work, an explicit checking is made and we finally agree with these claims. Furthermore, it is suggested that the gravitational waves are also well behaved for large times. In the process, some new models with the same behavior are obtained, thus enlarging the list of possible adjustment mechanisms.

  6. Equation of state with scale-invariant hidden local symmetry and gravitational waves

    Directory of Open Access Journals (Sweden)

    Lee Hyun Kyu

    2018-01-01

    Full Text Available The equation of state (EoS for the effective theory proposed recently in the frame work of the scale-invariant hidden local symmetry is discussed briefly. The EoS is found to be relatively stiffer at lower density and but relatively softer at higher density. The particular features of EoS on the gravitational waves are discussed. A relatively stiffer EoS for the neutron stars with the lower density induces a larger deviation of the gravitational wave form from the point-particle-approximation. On the other hand, a relatively softer EoS for the merger remnant of the higher density inside might invoke a possibility of the immediate formation of a black hole for short gamma ray bursts or the appearance of the higher peak frequency for gravitational waves from remnant oscillations. It is anticipated that this particular features could be probed in detail by the detections of gravitational waves from the binary neutron star mergers.

  7. Comment on "Hearing the signal of dark sectors with gravitational wave detectors"

    Science.gov (United States)

    Huang, Da; Lu, Bo-Qiang

    2018-03-01

    We revisit the calculation of the gravitational wave spectra generated in a classically scale-invariant S U (2 ) gauge sector with a scalar field in the adjoint representation, as discussed by J. Jaeckel, et al. The finite-temperature potential at 1-loop level can induce a strong first-order phase transition, during which gravitational waves can be generated. With the accurate numerical computation of the on-shell Euclidean actions of the nucleation bubbles, we find that the triangle approximation employed by J. Jaeckel et al. strongly distorts the actual potential near its maximum and thus greatly underestimates the action values. As a result, the gravitational wave spectra predicted by J. Jaeckel et al. deviate significantly from the exact ones in peak frequencies and shapes.

  8. Traditional Chinese Medicine CFF-1 induced cell growth inhibition, autophagy, and apoptosis via inhibiting EGFR-related pathways in prostate cancer.

    Science.gov (United States)

    Wu, Zhaomeng; Zhu, Qingyi; Yin, Yingying; Kang, Dan; Cao, Runyi; Tian, Qian; Zhang, Yu; Lu, Shan; Liu, Ping

    2018-04-01

    Traditional Chinese medicine (TCM) has a combined therapeutic result in cancer treatment by integrating holistic and local therapeutical effects, by which TCM can enhance the curative effect and reduce the side effect. In this study, we analyzed the effect of CFF-1 (alcohol extract from an anticancer compound Chinese medicine) on prostate cancer (PCa) cell lines and studied in detail the mechanism of cell death induced by CFF-1 in vitro and in vivo. From our data, we found for the first time that CFF-1 obviously arrested cell cycle in G1 phase, decreased cell viability and then increased nuclear rupture in a dose-dependent manner and finally resulted in apoptosis in prostate cancer cells. In molecular level, our data showed that CFF-1 induced inhibition of EGFR auto-phosphorylation and inactivation of EGFR. Disruption of EGFR activity in turn suppressed downstream PI3K/AKT and Raf/Erk signal pathways, resulted in the decrease of p-FOXO1 (Ser256) and regulated the expression of apoptosis-related and cycle-related genes. Moreover, CFF-1 markedly induced cell autophagy through inhibiting PI3K/AKT/mTOR pathway and then up-regulating Beclin-1 and LC-3II and down-regulating phosphorylation of p70S6K. In vivo, CFF-1-treated group exhibited a significant decrease in tumor volume compared with the negative control group in subcutaneous xenograft tumor in nude mice via inhibiting EGFR-related signal pathways. Thus, bio-functions of Chinese medicine CFF-1 in inducing PCa cell growth inhibition, autophagy, and apoptosis suggested that CFF-1 had the clinical potential to treat patients with prostate cancer. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  9. Gravitation in material media

    International Nuclear Information System (INIS)

    Ridgely, Charles T

    2011-01-01

    When two gravitating bodies reside in a material medium, Newton's law of universal gravitation must be modified to account for the presence of the medium. A modified expression of Newton's law is known in the literature, but lacks a clear connection with existing gravitational theory. Newton's law in the presence of a homogeneous material medium is herein derived on the basis of classical, Newtonian gravitational theory and by a general relativistic use of Archimedes' principle. It is envisioned that the techniques presented herein will be most useful to graduate students and those undergraduate students having prior experience with vector analysis and potential theory.

  10. Implication of unfolded protein response in resveratrol-induced inhibition of K562 cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Bao-Qin; Gao, Yan-Yan; Niu, Xiao-Fang [Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001 (China); Xie, Ji-Sheng [Youjiang Medical College for Nationalities, Guangxi 533000 (China); Meng, Xin; Guan, Yifu [Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001 (China); Wang, Hua-Qin, E-mail: wanghq_doctor@hotmail.com [Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001 (China)

    2010-01-01

    Resveratrol (RES), a natural plant polyphenol, is an effective inducer of cell cycle arrest and apoptosis in a variety of carcinoma cell types. In addition, RES has been reported to inhibit tumorigenesis in several animal models suggesting that it functions as a chemopreventive and anti-tumor agent in vivo. The chemopreventive and chemotherapeutic properties associated with resveratrol offer promise for the design of new chemotherapeutic agents. However, the mechanisms by which RES mediates its effects are not yet fully understood. In this study, we showed that RES caused cell cycle arrest and proliferation inhibition via induction of unfolded protein response (UPR) in human leukemia K562 cell line. Treatment of K562 cells with RES induced a number of signature UPR markers, including transcriptional induction of GRP78 and CHOP, phosphorylation of eukaryotic initiation factor 2{alpha} (eIF2{alpha}), ER stress-specific XBP-1 splicing, suggesting the induction of UPR by RES. RES inhibited proliferation of K562 in a concentration-dependent manner. Flow cytometric analyses revealed that K562 cells were arrested in G1 phase upon RES treatment. Salubrinal, an eIF2{alpha} inhibitor, or overexpression of dominant negative mutants of PERK or eIF2{alpha}, effectively restored RES-induced cell cycle arrest, underscoring the important role of PERK/eIF2{alpha} branch of UPR in RES-induced inhibition of cell proliferation.

  11. Implication of unfolded protein response in resveratrol-induced inhibition of K562 cell proliferation

    International Nuclear Information System (INIS)

    Liu, Bao-Qin; Gao, Yan-Yan; Niu, Xiao-Fang; Xie, Ji-Sheng; Meng, Xin; Guan, Yifu; Wang, Hua-Qin

    2010-01-01

    Resveratrol (RES), a natural plant polyphenol, is an effective inducer of cell cycle arrest and apoptosis in a variety of carcinoma cell types. In addition, RES has been reported to inhibit tumorigenesis in several animal models suggesting that it functions as a chemopreventive and anti-tumor agent in vivo. The chemopreventive and chemotherapeutic properties associated with resveratrol offer promise for the design of new chemotherapeutic agents. However, the mechanisms by which RES mediates its effects are not yet fully understood. In this study, we showed that RES caused cell cycle arrest and proliferation inhibition via induction of unfolded protein response (UPR) in human leukemia K562 cell line. Treatment of K562 cells with RES induced a number of signature UPR markers, including transcriptional induction of GRP78 and CHOP, phosphorylation of eukaryotic initiation factor 2α (eIF2α), ER stress-specific XBP-1 splicing, suggesting the induction of UPR by RES. RES inhibited proliferation of K562 in a concentration-dependent manner. Flow cytometric analyses revealed that K562 cells were arrested in G1 phase upon RES treatment. Salubrinal, an eIF2α inhibitor, or overexpression of dominant negative mutants of PERK or eIF2α, effectively restored RES-induced cell cycle arrest, underscoring the important role of PERK/eIF2α branch of UPR in RES-induced inhibition of cell proliferation.

  12. Gravitational radiation reaction

    International Nuclear Information System (INIS)

    Tanaka, Takahiro

    2006-01-01

    We give a short personally-biased review on the recent progress in our understanding of gravitational radiation reaction acting on a point particle orbiting a black hole. The main motivation of this study is to obtain sufficiently precise gravitational waveforms from inspiraling binary compact starts with a large mass ratio. For this purpose, various new concepts and techniques have been developed to compute the orbital evolution taking into account the gravitational self-force. Combining these ideas with a few supplementary new ideas, we try to outline a path to our goal here. (author)

  13. Inhibition of the NAD-dependent protein deacetylase SIRT2 induces granulocytic differentiation in human leukemia cells.

    Directory of Open Access Journals (Sweden)

    Yoshitaka Sunami

    Full Text Available Sirtuins, NAD-dependent protein deacetylases, play important roles in cellular functions such as metabolism and differentiation. Whether sirtuins function in tumorigenesis is still controversial, but sirtuins are aberrantly expressed in tumors, which may keep cancerous cells undifferentiated. Therefore, we investigated whether the inhibition of sirtuin family proteins induces cellular differentiation in leukemic cells. The sirtuin inhibitors tenovin-6 and BML-266 induce granulocytic differentiation in the acute promyelocytic leukemia (APL cell line NB4. This differentiation is likely caused by an inhibition of SIRT2 deacetylase activity, judging from the accumulation of acetylated α-tubulin, a major SIRT2 substrate. Unlike the clinically used differentiation inducer all-trans retinoic acid, tenovin-6 shows limited effects on promyelocytic leukemia-retinoic acid receptor α (PML-RAR-α stability and promyelocytic leukemia nuclear body formation in NB4 cells, suggesting that tenovin-6 does not directly target PML-RAR-α activity. In agreement with this, tenovin-6 induces cellular differentiation in the non-APL cell line HL-60, where PML-RAR-α does not exist. Knocking down SIRT2 by shRNA induces granulocytic differentiation in NB4 cells, which demonstrates that the inhibition of SIRT2 activity is sufficient to induce cell differentiation in NB4 cells. The overexpression of SIRT2 in NB4 cells decreases the level of granulocytic differentiation induced by tenovin-6, which indicates that tenovin-6 induces granulocytic differentiation by inhibiting SIRT2 activity. Taken together, our data suggest that targeting SIRT2 is a viable strategy to induce leukemic cell differentiation.

  14. A gravitational entropy proposal

    International Nuclear Information System (INIS)

    Clifton, Timothy; Tavakol, Reza; Ellis, George F R

    2013-01-01

    We propose a thermodynamically motivated measure of gravitational entropy based on the Bel–Robinson tensor, which has a natural interpretation as the effective super-energy–momentum tensor of free gravitational fields. The specific form of this measure differs depending on whether the gravitational field is Coulomb-like or wave-like, and reduces to the Bekenstein–Hawking value when integrated over the interior of a Schwarzschild black hole. For scalar perturbations of a Robertson–Walker geometry we find that the entropy goes like the Hubble weighted anisotropy of the gravitational field, and therefore increases as structure formation occurs. This is in keeping with our expectations for the behaviour of gravitational entropy in cosmology, and provides a thermodynamically motivated arrow of time for cosmological solutions of Einstein’s field equations. It is also in keeping with Penrose’s Weyl curvature hypothesis. (paper)

  15. Belinostat-induced apoptosis and growth inhibition in pancreatic cancer cells involve activation of TAK1-AMPK signaling axis

    International Nuclear Information System (INIS)

    Wang, Bing; Wang, Xin-bao; Chen, Li-yu; Huang, Ling; Dong, Rui-zen

    2013-01-01

    Highlights: •Belinostat activates AMPK in cultured pancreatic cancer cells. •Activation of AMPK is important for belinostat-induced cytotoxic effects. •ROS and TAK1 are involved in belinostat-induced AMPK activation. •AMPK activation mediates mTOR inhibition by belinostat. -- Abstract: Pancreatic cancer accounts for more than 250,000 deaths worldwide each year. Recent studies have shown that belinostat, a novel pan histone deacetylases inhibitor (HDACi) induces apoptosis and growth inhibition in pancreatic cancer cells. However, the underlying mechanisms are not fully understood. In the current study, we found that AMP-activated protein kinase (AMPK) activation was required for belinostat-induced apoptosis and anti-proliferation in PANC-1 pancreatic cancer cells. A significant AMPK activation was induced by belinostat in PANC-1 cells. Inhibition of AMPK by RNAi knockdown or dominant negative (DN) mutation significantly inhibited belinostat-induced apoptosis in PANC-1 cells. Reversely, AMPK activator AICAR and A-769662 exerted strong cytotoxicity in PANC-1 cells. Belinostat promoted reactive oxygen species (ROS) production in PANC-1 cells, increased ROS induced transforming growth factor-β-activating kinase 1 (TAK1)/AMPK association to activate AMPK. Meanwhile, anti-oxidants N-Acetyl-Cysteine (NAC) and MnTBAP as well as TAK1 shRNA knockdown suppressed belinostat-induced AMPK activation and PANC-1 cell apoptosis. In conclusion, we propose that belinostat-induced apoptosis and growth inhibition require the activation of ROS-TAK1-AMPK signaling axis in cultured pancreatic cancer cells

  16. Belinostat-induced apoptosis and growth inhibition in pancreatic cancer cells involve activation of TAK1-AMPK signaling axis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Bing, E-mail: wangbin69@yahoo.com; Wang, Xin-bao; Chen, Li-yu; Huang, Ling; Dong, Rui-zen

    2013-07-19

    Highlights: •Belinostat activates AMPK in cultured pancreatic cancer cells. •Activation of AMPK is important for belinostat-induced cytotoxic effects. •ROS and TAK1 are involved in belinostat-induced AMPK activation. •AMPK activation mediates mTOR inhibition by belinostat. -- Abstract: Pancreatic cancer accounts for more than 250,000 deaths worldwide each year. Recent studies have shown that belinostat, a novel pan histone deacetylases inhibitor (HDACi) induces apoptosis and growth inhibition in pancreatic cancer cells. However, the underlying mechanisms are not fully understood. In the current study, we found that AMP-activated protein kinase (AMPK) activation was required for belinostat-induced apoptosis and anti-proliferation in PANC-1 pancreatic cancer cells. A significant AMPK activation was induced by belinostat in PANC-1 cells. Inhibition of AMPK by RNAi knockdown or dominant negative (DN) mutation significantly inhibited belinostat-induced apoptosis in PANC-1 cells. Reversely, AMPK activator AICAR and A-769662 exerted strong cytotoxicity in PANC-1 cells. Belinostat promoted reactive oxygen species (ROS) production in PANC-1 cells, increased ROS induced transforming growth factor-β-activating kinase 1 (TAK1)/AMPK association to activate AMPK. Meanwhile, anti-oxidants N-Acetyl-Cysteine (NAC) and MnTBAP as well as TAK1 shRNA knockdown suppressed belinostat-induced AMPK activation and PANC-1 cell apoptosis. In conclusion, we propose that belinostat-induced apoptosis and growth inhibition require the activation of ROS-TAK1-AMPK signaling axis in cultured pancreatic cancer cells.

  17. Vector-tensor interaction of gravitation

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Yuan-zhong; Guo han-ying

    1982-11-01

    In the paper, by using the equation of motion a particle, we show that the antigravity exist in the vector-tensor model of gravitation. Thus the motion of a particle deviates from the geodesic equation. In Newtonian approximation and weak gravitational field, acceleration of a particle in a spherically symmetric and astatic gravitation field is zero. The result is obviously not in agreement with gravitational phenomena.

  18. Projective relativity, cosmology and gravitation

    International Nuclear Information System (INIS)

    Arcidiacono, G.

    1986-01-01

    This book describes the latest applications of projective geometry to cosmology and gravitation. The contents of the book are; the Poincare group and Special Relativity, the thermodynamics and electromagnetism, general relativity, gravitation and cosmology, group theory and models of universe, the special projective relativity, the Fantappie group and Big-Bang cosmology, a new cosmological projective mechanics, the plasma physics and cosmology, the projective magnetohydrodynamics field, projective relativity and waves propagation, the generalizations of the gravitational field, the general projective relativity, the projective gravitational field, the De Sitter Universe and quantum physics, the conformal relativity and Newton gravitation

  19. Enhancing inhibition-induced plasticity in tinnitus--spectral energy contrasts in tailor-made notched music matter.

    Directory of Open Access Journals (Sweden)

    Alwina Stein

    Full Text Available Chronic tinnitus seems to be caused by reduced inhibition among frequency selective neurons in the auditory cortex. One possibility to reduce tinnitus perception is to induce inhibition onto over-activated neurons representing the tinnitus frequency via tailor-made notched music (TMNM. Since lateral inhibition is modifiable by spectral energy contrasts, the question arises if the effects of inhibition-induced plasticity can be enhanced by introducing increased spectral energy contrasts (ISEC in TMNM. Eighteen participants suffering from chronic tonal tinnitus, pseudo randomly assigned to either a classical TMNM or an ISEC-TMNM group, listened to notched music for three hours on three consecutive days. The music was filtered for both groups by introducing a notch filter centered at the individual tinnitus frequency. For the ISEC-TMNM group a frequency bandwidth of 3/8 octaves on each side of the notch was amplified, additionally, by about 20 dB. Before and after each music exposure, participants rated their subjectively perceived tinnitus loudness on a visual analog scale. During the magnetoencephalographic recordings, participants were stimulated with either a reference tone of 500 Hz or a test tone with a carrier frequency representing the individual tinnitus pitch. Perceived tinnitus loudness was significantly reduced after TMNM exposure, though TMNM type did not influence the loudness ratings. Tinnitus related neural activity in the N1m time window and in the so called tinnitus network comprising temporal, parietal and frontal regions was reduced after TMNM exposure. The ISEC-TMNM group revealed even enhanced inhibition-induced plasticity in a temporal and a frontal cortical area. Overall, inhibition of tinnitus related neural activity could be strengthened in people affected with tinnitus by increasing spectral energy contrast in TMNM, confirming the concepts of inhibition-induced plasticity via TMNM and spectral energy contrasts.

  20. Eliminating Legionella by inhibiting BCL-XL to induce macrophage apoptosis.

    Science.gov (United States)

    Speir, Mary; Lawlor, Kate E; Glaser, Stefan P; Abraham, Gilu; Chow, Seong; Vogrin, Adam; Schulze, Keith E; Schuelein, Ralf; O'Reilly, Lorraine A; Mason, Kylie; Hartland, Elizabeth L; Lithgow, Trevor; Strasser, Andreas; Lessene, Guillaume; Huang, David C S; Vince, James E; Naderer, Thomas

    2016-02-24

    Human pathogenic Legionella replicate in alveolar macrophages and cause a potentially lethal form of pneumonia known as Legionnaires' disease(1). Here, we have identified a host-directed therapeutic approach to eliminate intracellular Legionella infections. We demonstrate that the genetic deletion, or pharmacological inhibition, of the host cell pro-survival protein BCL-XL induces intrinsic apoptosis of macrophages infected with virulent Legionella strains, thereby abrogating Legionella replication. BCL-XL is essential for the survival of Legionella-infected macrophages due to bacterial inhibition of host-cell protein synthesis, resulting in reduced levels of the short-lived, related BCL-2 pro-survival family member, MCL-1. Consequently, a single dose of a BCL-XL-targeted BH3-mimetic therapy, or myeloid cell-restricted deletion of BCL-XL, limits Legionella replication and prevents lethal lung infections in mice. These results indicate that repurposing BH3-mimetic compounds, originally developed to induce cancer cell apoptosis, may have efficacy in treating Legionnaires' and other diseases caused by intracellular microbes.

  1. Canine tracheal epithelial cells are more sensitive than rat tracheal epithelial cells to transforming growth factor beta induced growth inhibition

    International Nuclear Information System (INIS)

    Hubbs, A.F.; Hahn, F.F.; Kelly, G.; Thomassen, D.G.

    1988-01-01

    Transforming growth factor beta (TGFβ) markedly inhibited growth of canine tracheal epithelial (CTE) cells. Reduced responsiveness to TGFβ-induced growth inhibition accompanied neoplastic progression of these cells from primary to transformed to neoplastic. This was similar to the relationship between neoplastic progression and increased resistance to TGFβ-induced growth inhibition seen for rat tracheal epithelial (RTE) cells. The canine cells were more sensitive than rat cells to TGFβ-induced growth inhibition at all stages in the neoplastic process. (author)

  2. Gravitational wave generated by mass ejection in protoneutron star neutrino burst

    International Nuclear Information System (INIS)

    Almeida, L. G.; Rodrigues, H.; Portes, D. JR.; Duarte, S. B.

    2010-01-01

    In this work we discuss the mechanism of mass ejection in protoneutron stars induced by diffusion of neutrinos. A dynamical calculation is employed in order to determine the amount of matter ejected and the properties of the remnant compact object [1]. The equations of state of this supra-nuclear regime [2] is properly linked with others describing the different sub-nuclear regimes of density [3, 4, 5]. For specified initial configurations of the protoneutron star, we solve numerically the set of equations of motion together with a schematic treatment of the neutrino transport through the dense stellar medium. We investigate the gravitational waves production accompanying the mass ejection induced by the neutrino burst. It is estimated the gravitational wave intensity and the detection of such wave by the existing detector or near future project for this purpose is discussed.

  3. Does Pressure Accentuate General Relativistic Gravitational Collapse and Formation of Trapped Surfaces?

    Science.gov (United States)

    Mitra, Abhas

    2013-04-01

    It is widely believed that though pressure resists gravitational collapse in Newtonian gravity, it aids the same in general relativity (GR) so that GR collapse should eventually be similar to the monotonous free fall case. But we show that, even in the context of radiationless adiabatic collapse of a perfect fluid, pressure tends to resist GR collapse in a manner which is more pronounced than the corresponding Newtonian case and formation of trapped surfaces is inhibited. In fact there are many works which show such collapse to rebound or become oscillatory implying a tug of war between attractive gravity and repulsive pressure gradient. Furthermore, for an imperfect fluid, the resistive effect of pressure could be significant due to likely dramatic increase of tangential pressure beyond the "photon sphere." Indeed, with inclusion of tangential pressure, in principle, there can be static objects with surface gravitational redshift z → ∞. Therefore, pressure can certainly oppose gravitational contraction in GR in a significant manner in contradiction to the idea of Roger Penrose that GR continued collapse must be unstoppable.

  4. Addendum. Relation for the Light Absorption in the Presence of Gravitation Field

    OpenAIRE

    R.Vlokh; M.Kostyrko

    2005-01-01

    We argue for the validity of relation for electromagnetic wave electric field derived by us earlier. It includes an imaginary part responsible for the absorption induced by gravitation field of spherically symmetric mass.

  5. Gravitationally confined relativistic neutrinos

    Science.gov (United States)

    Vayenas, C. G.; Fokas, A. S.; Grigoriou, D.

    2017-09-01

    Combining special relativity, the equivalence principle, and Newton’s universal gravitational law with gravitational rather than rest masses, one finds that gravitational interactions between relativistic neutrinos with kinetic energies above 50 MeV are very strong and can lead to the formation of gravitationally confined composite structures with the mass and other properties of hadrons. One may model such structures by considering three neutrinos moving symmetrically on a circular orbit under the influence of their gravitational attraction, and by assuming quantization of their angular momentum, as in the Bohr model of the H atom. The model contains no adjustable parameters and its solution, using a neutrino rest mass of 0.05 eV/c2, leads to composite state radii close to 1 fm and composite state masses close to 1 GeV/c2. Similar models of relativistic rotating electron - neutrino pairs give a mass of 81 GeV/c2, close to that of W bosons. This novel mechanism of generating mass suggests that the Higgs mass generation mechanism can be modeled as a latent gravitational field which gets activated by relativistic neutrinos.

  6. Mercuric ions inhibit mitogen-activated protein kinase dephosphorylation by inducing reactive oxygen species

    International Nuclear Information System (INIS)

    Haase, Hajo; Engelhardt, Gabriela; Hebel, Silke; Rink, Lothar

    2011-01-01

    Mercury intoxication profoundly affects the immune system, in particular, signal transduction of immune cells. However, the mechanism of the interaction of mercury with cellular signaling pathways, such as mitogen activated protein kinases (MAPK), remains elusive. Therefore, the objective of this study is to investigate three potential ways in which Hg 2+ ions could inhibit MAPK dephosphorylation in the human T-cell line Jurkat: (1) by direct binding to phosphatases; (2) by releasing cellular zinc (Zn 2+ ); and (3) by inducing reactive oxygen species (ROS). Hg 2+ causes production of ROS, measured by dihydrorhodamine 123, and triggers ROS-mediated Zn 2+ release, detected with FluoZin-3. Yet, phosphatase-inhibition is not mediated by binding of Zn 2+ or Hg 2+ . Rather, phosphatases are inactivated by at least two forms of thiol oxidation; initial inhibition is reversible with reducing agents such as Tris(2-carboxyethyl)phosphine. Prolonged inhibition leads to non-reversible phosphatase oxidation, presumably oxidizing the cysteine thiol to sulfinic- or sulfonic acid. Notably, phosphatases are a particularly sensitive target for Hg 2+ -induced oxidation, because phosphatase activity is inhibited at concentrations of Hg 2+ that have only minor impact on over all thiol oxidation. This phosphatase inhibition results in augmented, ROS-dependent MAPK phosphorylation. MAPK are important regulators of T-cell function, and MAPK-activation by inhibition of phosphatases seems to be one of the molecular mechanisms by which mercury affects the immune system.

  7. Probing gravitational parity violation with gravitational waves from stellar-mass black hole binaries

    Science.gov (United States)

    Yagi, Kent; Yang, Huan

    2018-05-01

    The recent discovery of gravitational-wave events has offered us unique test beds of gravity in the strong and dynamical field regime. One possible modification to General Relativity is the gravitational parity violation that arises naturally from quantum gravity. Such parity violation gives rise to the so-called amplitude birefringence in gravitational waves, in which one of the circularly polarized modes is amplified while the other one is suppressed during their propagation. In this paper, we study how well one can measure gravitational parity violation via the amplitude birefringence effect of gravitational waves sourced by stellar-mass black hole binaries. We choose Chern-Simons gravity as an example and work within an effective field theory formalism to ensure that the approximate theory is well posed. We consider gravitational waves from both individual sources and stochastic gravitational-wave backgrounds. Regarding bounds from individual sources, we estimate such bounds using a Fisher analysis and carry out Monte Carlo simulations by randomly distributing sources over their sky location and binary orientation. We find that the bounds on the scalar field evolution in Chern-Simons gravity from the recently discovered gravitational-wave events are too weak to satisfy the weak Chern-Simons approximation, while aLIGO with its design sensitivity can place meaningful bounds. Regarding bounds from stochastic gravitational-wave backgrounds, we set the threshold signal-to-noise ratio for detection of the parity-violation mode as 5 and estimate projected bounds with future detectors assuming that signals are consistent with no parity violation. In an ideal situation in which all the source parameters and binary black hole merger-rate history are known a priori, we find that a network of two third-generation detectors is able to place bounds that are comparable to or slightly stronger than binary pulsar bounds. In a more realistic situation in which one does not have

  8. General projective relativity and the vector-tensor gravitational field

    International Nuclear Information System (INIS)

    Arcidiacono, G.

    1986-01-01

    In the general projective relativity, the induced 4-dimensional metric is symmetric in three cases, and we obtain the vector-tensor, the scalar-tensor, and the scalar-vector-tensor theories of gravitation. In this work we examine the vector-tensor theory, similar to the Veblen's theory, but with a different physical interpretation

  9. ERK inhibition sensitizes CZ415-induced anti-osteosarcoma activity in vitro and in vivo.

    Science.gov (United States)

    Yin, Gang; Fan, Jin; Zhou, Wei; Ding, Qingfeng; Zhang, Jun; Wu, Xuan; Tang, Pengyu; Zhou, Hao; Wan, Bowen; Yin, Guoyong

    2017-10-10

    mTOR is a valuable oncotarget for osteosarcoma. The anti-osteosarcoma activity by a novel mTOR kinase inhibitor, CZ415, was evaluated. We demonstrated that CZ415 potently inhibited survival and proliferation of known osteosarcoma cell lines (U2OS, MG-63 and SaOs2), and primary human osteosarcoma cells. Further, CZ415 provoked apoptosis and disrupted cell cycle progression in osteosarcoma cells. CZ415 treatment in osteosarcoma cells concurrently blocked mTORC1 and mTORC2 activation. Intriguingly, ERK-MAPK activation could be a major resistance factor of CZ415. ERK inhibition (by MEK162/U0126) or knockdown (by targeted ERK1/2 shRNAs) dramatically sensitized CZ415-induced osteosarcoma cell apoptosis. In vivo , CZ415 oral administration efficiently inhibited U2OS tumor growth in mice. Its activity was further potentiated with co-administration of MEK162. Collectively, we demonstrate that ERK inhibition sensitizes CZ415-induced anti-osteosarcoma activity in vitro and in vivo . CZ415 could be further tested as a promising anti-osteosarcoma agent, alone or in combination of ERK inhibition.

  10. Resveratrol protects vascular endothelial cells from high glucose-induced apoptosis through inhibition of NADPH oxidase activation-driven oxidative stress.

    Science.gov (United States)

    Chen, Feng; Qian, Li-Hua; Deng, Bo; Liu, Zhi-Min; Zhao, Ying; Le, Ying-Ying

    2013-09-01

    Hyperglycemia-induced oxidative stress has been implicated in diabetic vascular complications in which NADPH oxidase is a major source of reactive oxygen species (ROS) generation. Resveratrol is a naturally occurring polyphenol, which has vasoprotective effects in diabetic animal models and inhibits high glucose (HG)-induced oxidative stress in endothelial cells. We aimed to examine whether HG-induced NADPH oxidase activation and ROS production contribute to glucotoxicity to endothelial cells and the effect of resveratrol on glucotoxicity. Using a murine brain microvascular endothelial cell line bEnd3, we found that NADPH oxidase inhibitor (apocynin) and resveratrol both inhibited HG-induced endothelial cell apoptosis. HG-induced elevation of NADPH oxidase activity and production of ROS were inhibited by apocynin, suggesting that HG induces endothelial cell apoptosis through NADPH oxidase-mediated ROS production. Mechanistic studies revealed that HG upregulated NADPH oxidase subunit Nox1 but not Nox2, Nox4, and p22(phox) expression through NF-κB activation, which resulted in elevation of NADPH oxidase activity and consequent ROS production. Resveratrol prevented HG-induced endothelial cell apoptosis through inhibiting HG-induced NF-κB activation, NADPH oxidase activity elevation, and ROS production. HG induces endothelial cell apoptosis through NF-κB/NADPH oxidase/ROS pathway, which was inhibited by resveratrol. Our findings provide new potential therapeutic targets against brain vascular complications of diabetes. © 2013 John Wiley & Sons Ltd.

  11. Presenting Newtonian gravitation

    International Nuclear Information System (INIS)

    Counihan, Martin

    2007-01-01

    The basic principles of the Newtonian theory of gravitation are presented in a way which students may find more logically coherent, mathematically accessible and physically interesting than other approaches. After giving relatively simple derivations of the circular hodograph and the elliptical orbit from the inverse-square law, the concept of gravitational energy is developed from vector calculus. It is argued that the energy density of a gravitational field may reasonably be regarded as -g 2 /8πG, and that the inverse-square law may be replaced by a Schwarzschild-like force law without the need to invoke non-Euclidean geometry

  12. Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth.

    Science.gov (United States)

    Hojman, Pernille; Dethlefsen, Christine; Brandt, Claus; Hansen, Jakob; Pedersen, Line; Pedersen, Bente Klarlund

    2011-09-01

    Regular physical activity protects against the development of breast and colon cancer, since it reduces the risk of developing these by 25-30%. During exercise, humoral factors are released from the working muscles for endocrinal signaling to other organs. We hypothesized that these myokines mediate some of the inhibitory effects of exercise on mammary cancer cell proliferation. Serum and muscles were collected from mice after an exercise bout. Incubation with exercise-conditioned serum inhibited MCF-7 cell proliferation by 52% and increased caspase activity by 54%. A similar increase in caspase activity was found after incubation of MCF-7 cells with conditioned media from electrically stimulated myotubes. PCR array analysis (CAPM-0838E; SABiosciences) revealed that seven genes were upregulated in the muscles after exercise, and of these oncostatin M (OSM) proved to inhibit MCF-7 proliferation by 42%, increase caspase activity by 46%, and induce apoptosis. Blocking OSM signaling with anti-OSM antibodies reduced the induction of caspase activity by 51%. To verify that OSM was a myokine, we showed that it was significantly upregulated in serum and in three muscles, tibialis cranialis, gastronemius, and soleus, after an exercise bout. In contrast, OSM expression remained unchanged in subcutaneous and visceral adipose tissue, liver, and spleen (mononuclear cells). We conclude that postexercise serum inhibits mammary cancer cell proliferation and induces apoptosis of these cells. We suggest that one or more myokines secreted from working muscles may be mediating this effect and that OSM is a possible candidate. These findings emphasize that role of physical activity in cancer treatment, showing a direct link between exercise-induced humoral factors and decreased tumor cell growth.

  13. Gravitational threshold corrections in non-supersymmetric heterotic strings

    Directory of Open Access Journals (Sweden)

    Ioannis Florakis

    2017-03-01

    Full Text Available We compute one-loop quantum corrections to gravitational couplings in the effective action of four-dimensional heterotic strings where supersymmetry is spontaneously broken by Scherk–Schwarz fluxes. We show that in both heterotic and type II theories of this class, no moduli dependent corrections to the Planck mass are generated. We explicitly compute the one-loop corrections to the R2 coupling and find that, despite the absence of supersymmetry, its contributions may still be organised into representations of subgroups of the modular group, and admit a universal form, determined uniquely by the multiplicities of the ground states of the theory. Moreover, similarly to the case of gauge couplings, also the gravitational sector may become strongly coupled in models which dynamically induce large volume for the extra dimensions.

  14. TGF-β2 inhibits AKT activation and FGF-2-induced corneal endothelial cell proliferation

    International Nuclear Information System (INIS)

    Lu Jiawei; Lu Zhenyu; Reinach, Peter

    2006-01-01

    The corneal endothelial cells form a boundary layer between anterior chamber and cornea. This single cell layer is important to maintain cornea transparency by eliciting net fluid transport into the anterior chamber. Injuries of the corneal endothelial layer in humans lead to corneal swelling and translucence. This hindrance is thought to be due to limited proliferative capacity of the endothelial layer. Fibroblast growth factor 2 (FGF-2) and transforming growth factor-beta 2 (TGF-β2) are both found in aqueous humor, and these two cytokines promote and inhibit cell growth, respectively. The intracellular signaling mechanisms by which TGF-β2 suppresses the mitogenic response to FGF-2, however, remain unclear. We have addressed this question by investigating potential crosstalk between FGF-2-induced and TGF-β2-regulated intracellular signaling events in cultured bovine corneal endothelial (BCE) cells. We found that TGF-β2 and FGF-2 oppositely affect BCE cell proliferation and TGF-β2 can override the stimulating effects of FGF-2 by increasing COX-2 expression in these cells. Consistent with these findings, overexpression of COX-2 significantly reduced FGF-2-induced cell proliferation whereas a COX-2 specific inhibitor NS398 reversed the effect of TGF-β2 on FGF-2-induced cell proliferation. The COX-2 product prostaglandin E2 (PGE-2) blocks FGF-2-induced cell proliferation. Whereas FGF-2 stimulates cell proliferation by activating the AKT pathway, TGF-β2 and PGE-2 both inhibit this pathway. In accordance with the effect of PGE-2, cAMP also inhibits FGF-2-induced AKT activation. These findings suggest that the mitogenic response to FGF-2 in vivo in the corneal endothelial layer may be inhibited by TGF-β2-induced suppression of the PI3-kinase/AKT signaling pathway

  15. Thiamine Deficiency Induces Anorexia by Inhibiting Hypothalamic AMPK

    Science.gov (United States)

    Liu, Mei; Alimov, Alexander; Wang, Haiping; Frank, Jacqueline A.; Katz, Wendy; Xu, Mei; Ke, Zun-Ji; Luo, Jia

    2014-01-01

    Obesity and eating disorders are prevailing health concerns worldwide. It is important to understand the regulation of food intake and energy metabolism. Thiamine (vitamin B1) is an essential nutrient. Thiamine deficiency (TD) can cause a number of disorders in humans, such as Beriberi and Wernicke-Korsakoff syndrome. We demonstrated here that TD caused anorexia in C57BL/6 mice. After feeding a TD diet for 16 days, the mice displayed a significant decrease in food intake and an increase in resting energy expenditure (REE), which resulted in a severe weight loss. At the 22nd day, the food intake was reduced by 69% and 74% for male and female mice, respectively in TD group. The REE increased by 9 folds in TD group. The loss of body weight (17–24%) was similar between male and female animals and mainly resulted from the reduction of fat mass (49% decrease). Re-supplementation of thiamine (benfotiamine) restored animal's appetite, leading to a total recovery of body weight. The hypothalamic AMPK is a critical regulator of food intake. TD inhibited the phosphorylation of AMPK in the arcuate nucleus (ARN) and paraventricular nucleus (PVN) of the hypothalamus without affecting its expression. TD-induced inhibition of AMPK phosphorylation was reversed once thiamine was re-supplemented. In contrast, TD increased AMPK phosphorylation in the skeletal muscle and upregulated the uncoupling protein (UCP)-1 in brown adipose tissues which was consistent with increased basal energy expenditure. Re-administration of thiamine stabilized AMPK phosphorylation in the skeletal muscle as well as energy expenditure. Taken together, TD may induce anorexia by inhibiting hypothalamic AMPK activity. With a simultaneous increase in energy expenditure, TD caused an overall body weight loss. The results suggest that the status of thiamine levels in the body may affect food intake and body weight. PMID:24607345

  16. Limonene inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal function and dopamine release.

    Science.gov (United States)

    Yun, Jaesuk

    2014-05-15

    Methamphetamine is a psychomotor stimulant that produces hyperlocomotion in rodents. Limonene (a cyclic terpene from citrus essential oils) has been reported to induce sedative effects. In this study, we demonstrated that limonene administration significantly inhibited serotonin (5-hydroxytryptamine, 5-HT)-induced head twitch response in mice. In rats, pretreatment with limonene decreased hyperlocomotion induced by methamphetamine injection. In addition, limonene reversed the increase in dopamine levels in the nucleus accumbens of rats given methamphetamine. These results suggest that limonene may inhibit stimulant-induced behavioral changes via regulating dopamine levels and 5-HT receptor function. Copyright © 2013 Elsevier GmbH. All rights reserved.

  17. Can observations inside the Solar System reveal the gravitational properties of the quantum vacuum?

    CERN Document Server

    Hajdukovic, Dragan Slavkov

    2013-01-01

    The understanding of the gravitational properties of the quantum vacuum might be the next scientific revolution.It was recently proposed that the quantum vacuum contains the virtual gravitational dipoles; we argue that this hypothesis might be tested within the Solar System. The key point is that quantum vacuum ("enriched" with the gravitational dipoles) induces a retrograde precession of the perihelion. It is obvious that this phenomenon might eventually be revealed by more accurate studies of orbits of planets and orbits of the artificial Earth satellites. However, we suggest that potentialy the best "laboratory" for the study of the gravitational properties of the quantum vacuum is the Dwarf Planet Eris and its satellite Dysnomia; the distance of nearly 100AU makes it the unique system in which the precession of the perihelion of Dysnomia (around Eris) is strongly dominated by the quantum vacuum.

  18. Gravitation and source theory

    International Nuclear Information System (INIS)

    Yilmaz, H.

    1975-01-01

    Schwinger's source theory is applied to the problem of gravitation and its quantization. It is shown that within the framework of a flat-space the source theory implementation leads to a violation of probability. To avoid the difficulty one must introduce a curved space-time hence the source concept may be said to necessitate the transition to a curved-space theory of gravitation. It is further shown that the curved-space theory of gravitation implied by the source theory is not equivalent to the conventional Einstein theory. The source concept leads to a different theory where the gravitational field has a stress-energy tensor t/sup nu//sub mu/ which contributes to geometric curvatures

  19. Nuclear Quantum Gravitation - The Correct Theory

    Science.gov (United States)

    Kotas, Ronald

    2016-03-01

    Nuclear Quantum Gravitation provides a clear, definitive Scientific explanation of Gravity and Gravitation. It is harmonious with Newtonian and Quantum Mechanics, and with distinct Scientific Logic. Nuclear Quantum Gravitation has 10 certain, Scientific proofs and 21 more good indications. With this theory the Physical Forces are obviously Unified. See: OBSCURANTISM ON EINSTEIN GRAVITATION? http://www.santilli- Foundation.org/inconsistencies-gravitation.php and Einstein's Theory of Relativity versus Classical Mechanics http://www.newtonphysics.on.ca/einstein/

  20. The Theory of Vortical Gravitational Fields

    Directory of Open Access Journals (Sweden)

    Rabounski D.

    2007-04-01

    Full Text Available This paper treats of vortical gravitational fields, a tensor of which is the rotor of the general covariant gravitational inertial force. The field equations for a vortical gravitational field (the Lorentz condition, the Maxwell-like equations, and the continuity equation are deduced in an analogous fashion to electrodynamics. From the equations it is concluded that the main kind of vortical gravitational fields is “electric”, determined by the non-stationarity of the acting gravitational inertial force. Such a field is a medium for traveling waves of the force (they are different to the weak deformation waves of the space metric considered in the theory of gravitational waves. Standing waves of the gravitational inertial force and their medium, a vortical gravitational field of the “magnetic” kind, are exotic, since a non-stationary rotation of a space body (the source of such a field is a very rare phenomenon in the Universe.

  1. Glucocorticoids and inhibition of bone formation induced by skeletal unloading

    International Nuclear Information System (INIS)

    Halloran, B.P.; Bikle, D.D.; Cone, C.M.; Morey-Holton, E.

    1988-01-01

    Skeletal unloading or loss of normal weight bearing in the growing animal inhibits bone formation and reduces bone calcium. To determine whether the inhibition of bone formation induced by skeletal unloading is a consequence of an increase in plasma glucocorticoids and/or an increase in bone sensitivity to glucocorticoids, the authors measured plasma corticosterone throughout the day in unloaded and normally loaded rats (hindlimb elevation model) and examined the effect of adrenalectomy on the response of bone to skeletal unloading. Plasma corticosterone levels were similar in normally loaded and unloaded rats at all times. Skeletal unloading in sham-adrenalectomized animals reduced tibial and vertebral calcium by 11.5 and 11.1%, respectively, and in adrenalectomized animals by 15.3 and 20.3%, respectively. Uptake of 45 Ca and [ 3 H]proline in the tibia was reduced by 8 and 14%, respectively, in the sham-adrenalectomized animals and by 13 and 19% in the adrenalectomized animals. Bone formation and apposition rates were reduced to the same level in sham- and adrenalectomized animals. These results suggest that the inhibition of bone formation induced by skeletal unloading is not a consequence of increased plasma glucocorticoids or an increase in bone sensitivity to the glucocorticoids but, rather, point to a local mediator in bone that senses mechanical load and transmits that information to the bone-forming cells directly

  2. Inhibition by anandamide of 6-hydroxydopamine-induced cell death in PC12 cells.

    LENUS (Irish Health Repository)

    Mnich, Katarzyna

    2010-01-01

    6-hydroxydopamine (6-OHDA) is a selective neurotoxin that is widely used to investigate cell death and protective strategies in models of Parkinson\\'s disease. Here, we investigated the effects of the endogenous cannabinoid, anandamide, on 6-OHDA-induced toxicity in rat adrenal phaeochromocytoma PC12 cells. Morphological analysis and caspase-3 activity assay revealed that anandamide inhibited 6-OHDA-induced apoptosis. The protection was not affected by antagonists of either cannabinoid receptors (CB(1) or CB(2)) or the vanilloid receptor TRPV1. Anandamide-dependent protection was reduced by pretreatment with LY294002 (inhibitor of phosphatidylinositol 3-kinase, PI3K) and unaffected by U0126 (inhibitor of extracellularly-regulated kinase). Interestingly, phosphorylation of c-Jun-NH2-terminal kinase (JNK) in cells exposed to 6-OHDA was strongly reduced by anandamide pre-treatment. Furthermore, 6-OHDA induced c-Jun activation and increased Bim expression, both of which were inhibited by anandamide. Together, these data demonstrate antiapoptotic effects of anandamide and also suggest a role for activation of PI3K and inhibition of JNK signalling in anandamide-mediated protection against 6-OHDA.

  3. Pertussis toxin inhibits somatostatin-induced K+ conductance in human pituitary tumor cells

    International Nuclear Information System (INIS)

    Yamashita, N.; Kojima, I.; Shibuya, N.; Ogata, E.

    1987-01-01

    The effect of pertussis toxin on somatostatin-induced K + current was examined in dissociated human pituitary tumor cells obtained from two acromegalic patients. Somatostatin-induced hyperpolarization or K + current was observed in 20 of 23 cells in adenoma 1 and 10 of 11 cells in adenoma 2. After treatment with pertussis toxin for 24 h, these responses were completely suppressed (0/14 in adenoma, 1, 0/10 in adenoma 2). Spontaneous action potentials, K + , Na + , and Ca 2+ currents were well preserved after pertussis toxin treatment. When crude membrane fraction was incubated with [ 32 P]NAD, a 41K protein was ADP-ribosylated by pertussis toxin. Hormone release was inhibited by somatostatin and this inhibition was blocked by pertussis toxin treatment

  4. cGMP-Phosphodiesterase Inhibition Prevents Hypoxia-Induced Cell Death Activation in Porcine Retinal Explants.

    Directory of Open Access Journals (Sweden)

    Lorena Olivares-González

    Full Text Available Retinal hypoxia and oxidative stress are involved in several retinal degenerations including diabetic retinopathy, glaucoma, central retinal artery occlusion, or retinopathy of prematurity. The second messenger cyclic guanosine monophosphate (cGMP has been reported to be protective for neuronal cells under several pathological conditions including ischemia/hypoxia. The purpose of this study was to evaluate whether the accumulation of cGMP through the pharmacological inhibition of phosphodiesterase (PDE with Zaprinast prevented retinal degeneration induced by mild hypoxia in cultures of porcine retina. Exposure to mild hypoxia (5% O2 for 24h reduced cGMP content and induced retinal degeneration by caspase dependent and independent (PARP activation mechanisms. Hypoxia also produced a redox imbalance reducing antioxidant response (superoxide dismutase and catalase activities and increasing superoxide free radical release. Zaprinast reduced mild hypoxia-induced cell death through inhibition of caspase-3 or PARP activation depending on the cell layer. PDE inhibition also ameliorated the effects of mild hypoxia on antioxidant response and the release of superoxide radical in the photoreceptor layer. The use of a PKG inhibitor, KT5823, suggested that cGMP-PKG pathway is involved in cell survival and antioxidant response. The inhibition of PDE, therefore, could be useful for reducing retinal degeneration under hypoxic/ischemic conditions.

  5. Histone deacetylase inhibition reduces hypothyroidism-induced neurodevelopmental defects in rats.

    Science.gov (United States)

    Kumar, Praveen; Mohan, Vishwa; Sinha, Rohit Anthony; Chagtoo, Megha; Godbole, Madan M

    2015-11-01

    Thyroid hormone (TH) through its receptor (TRα/β) influences spatio-temporal regulation of its target gene repertoire during brain development. Though hypothyroidism in WT rodent models of perinatal hypothyroidism severely impairs neurodevelopment, its effect on TRα/β knockout mice is less severe. An explanation to this paradox is attributed to a possible repressive action of unliganded TRs during development. Since unliganded TRs suppress gene expression through the recruitment of histone deacetylase (HDACs) via co-repressor complexes, we tested whether pharmacological inhibition of HDACs may prevent the effects of hypothyroidism on brain development. Using valproate, an HDAC inhibitor, we show that HDAC inhibition significantly blocks the deleterious effects of hypothyroidism on rat cerebellum, evident by recovery of TH target genes like Bdnf, Pcp2 and Mbp as well as improved dendritic structure of cerebellar Purkinje neurons. Together with this, HDAC inhibition also rescues hypothyroidism-induced motor and cognitive defects. This study therefore provides an insight into the role of HDACs in TH insufficiency during neurodevelopment and their inhibition as a possible therapeutics for treatment. © 2015 Society for Endocrinology.

  6. Ursodeoxycholic acid inhibits TNFα-induced IL-8 release from monocytes.

    Science.gov (United States)

    O'Dwyer, Aoife M; Lajczak, Natalia K; Keyes, Jennifer A; Ward, Joseph B; Greene, Catherine M; Keely, Stephen J

    2016-08-01

    Monocytes are critical to the pathogenesis of inflammatory bowel disease (IBD) as they infiltrate the mucosa and release cytokines that drive the inflammatory response. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid with anti-inflammatory actions, has been proposed as a potential new therapy for IBD. However, its effects on monocyte function are not yet known. Primary monocytes from healthy volunteers or cultured U937 monocytes were treated with either the proinflammatory cytokine, TNFα (5 ng/ml) or the bacterial endotoxin, lipopolysaccharide (LPS; 1 μg/ml) for 24 h, in the absence or presence of UDCA (25-100 μM). IL-8 release into the supernatant was measured by ELISA. mRNA levels were quantified by qPCR and changes in cell signaling proteins were determined by Western blotting. Toxicity was assessed by measuring lactate dehydrogenase (LDH) release. UDCA treatment significantly attenuated TNFα-, but not LPS-driven, release of IL-8 from both primary and cultured monocytes. UDCA inhibition of TNFα-driven responses was associated with reduced IL-8 mRNA expression. Both TNFα and LPS stimulated NFκB activation in monocytes, while IL-8 release in response to both cytokines was attenuated by an NFκB inhibitor, BMS-345541. Interestingly, UDCA inhibited TNFα-, but not LPS-stimulated, NFκB activation. Finally, TNFα, but not LPS, induced phosphorylation of TNF receptor associated factor (TRAF2), while UDCA cotreatment attenuated this response. We conclude that UDCA specifically inhibits TNFα-induced IL-8 release from monocytes by inhibiting TRAF2 activation. Since such actions would serve to dampen mucosal immune responses in vivo, our data support the therapeutic potential of UDCA for IBD. Copyright © 2016 the American Physiological Society.

  7. Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity in Vitro and in Vivo by Inhibiting Mitochondrial Dysfunction and Oxidative Damage

    Directory of Open Access Journals (Sweden)

    Cun-dong Fan

    2017-12-01

    Full Text Available Homocysteine (Hcy as an independent risk factor contributes to the occurrence and development of human cardiovascular diseases (CVD. Induction of oxidative stress and apoptosis was commonly accepted as the major mechanism in Hcy-induced cardiotoxicity. Astaxanthin (ATX as one of the most powerful antioxidants exhibits novel cardioprotective potential against Hcy-induced endothelial dysfunction. However, the protective effect and mechanism of ATX against Hcy-induced cardiotoxicity in cardiomyocytes have not been elucidated yet. Herein, H9c2 rat cardiomyocytes and Hcy-injured animal model were employed in the present study. The MTT, flow cytometry analysis (FCM, TUNEL-DAPI and western blotting results all demonstrated that ATX significantly alleviated Hcy-induced cytotoxicity in H9c2 cells through inhibition of mitochondria-mediated apoptosis. The JC-1 and Mito-tracker staining both revealed that ATX pre-treatment blocked Hcy-induced mitochondrial dysfunction by regulating Bcl-2 family expression. Moreover, DCFH-DA and Mito-SOX staining showed that ATX effectively attenuated Hcy-induced oxidative damage via scavenging intracellular reactive oxygen species (ROS. Importantly, the ELISA and immunohistochemical results indicated that Hcy-induced cardiotoxicity in vivo was also significantly inhibited by ATX through inhibition of oxidative damage and apoptosis, and improvement of the angiogenesis. Taken together, our results demonstrated that ATX suppressed Hcy-induced cardiotoxicity in vitro and in vivo by inhibiting mitochondrial dysfunction and oxidative damage. Our findings validated the strategy of using ATX may be a highly efficient way to combat Hcy-mediated human CVD.

  8. Astaxanthin Attenuates Homocysteine-Induced Cardiotoxicity in Vitro and in Vivo by Inhibiting Mitochondrial Dysfunction and Oxidative Damage.

    Science.gov (United States)

    Fan, Cun-Dong; Sun, Jing-Yi; Fu, Xiao-Ting; Hou, Ya-Jun; Li, Yuan; Yang, Ming-Feng; Fu, Xiao-Yan; Sun, Bao-Liang

    2017-01-01

    Homocysteine (Hcy) as an independent risk factor contributes to the occurrence and development of human cardiovascular diseases (CVD). Induction of oxidative stress and apoptosis was commonly accepted as the major mechanism in Hcy-induced cardiotoxicity. Astaxanthin (ATX) as one of the most powerful antioxidants exhibits novel cardioprotective potential against Hcy-induced endothelial dysfunction. However, the protective effect and mechanism of ATX against Hcy-induced cardiotoxicity in cardiomyocytes have not been elucidated yet. Herein, H9c2 rat cardiomyocytes and Hcy-injured animal model were employed in the present study. The MTT, flow cytometry analysis (FCM), TUNEL-DAPI and western blotting results all demonstrated that ATX significantly alleviated Hcy-induced cytotoxicity in H9c2 cells through inhibition of mitochondria-mediated apoptosis. The JC-1 and Mito-tracker staining both revealed that ATX pre-treatment blocked Hcy-induced mitochondrial dysfunction by regulating Bcl-2 family expression. Moreover, DCFH-DA and Mito-SOX staining showed that ATX effectively attenuated Hcy-induced oxidative damage via scavenging intracellular reactive oxygen species (ROS). Importantly, the ELISA and immunohistochemical results indicated that Hcy-induced cardiotoxicity in vivo was also significantly inhibited by ATX through inhibition of oxidative damage and apoptosis, and improvement of the angiogenesis. Taken together, our results demonstrated that ATX suppressed Hcy-induced cardiotoxicity in vitro and in vivo by inhibiting mitochondrial dysfunction and oxidative damage. Our findings validated the strategy of using ATX may be a highly efficient way to combat Hcy-mediated human CVD.

  9. Paeoniflorin inhibits cell growth and induces cell cycle arrest through inhibition of FoxM1 in colorectal cancer cells.

    Science.gov (United States)

    Yue, Meng; Li, Shiquan; Yan, Guoqiang; Li, Chenyao; Kang, Zhenhua

    2018-01-01

    Paeoniflorin (PF) exhibits tumor suppressive functions in a variety of human cancers. However, the function of PF and molecular mechanism in colorectal cancer are elusive. In the present study, we investigated whether PF could exert its antiproliferative activity, anti-migration, and anti-invasive function in colorectal cancer cells. We found that PF inhibited cell growth and induced apoptosis and blocked cell cycle progression in the G0/G1 phase in colorectal cancer cells. Moreover, we found that PF suppressed cell migration and invasion in colorectal cancer cells. FoxM1 has been reported to play an important oncogenic role in human cancers. We also determine whether PF inhibited the expression of FoxM1, leading to its anti-cancer activity. We found that PF treatment in colorectal cancer cells resulted in down-regulation of FoxM1. The rescue experiments showed that overexpression of FoxM1 abrogated the tumor suppressive function induced by PF treatment. Notably, depletion of FoxM1 promoted the anti-tumor activity of PF in colorectal cancer cells. Therefore, inhibition of FoxM1 could participate in the anti-tumor activity of PF in colorectal cancer cells.

  10. Effect of gravitational focusing on annual modulation in dark-matter direct-detection experiments.

    Science.gov (United States)

    Lee, Samuel K; Lisanti, Mariangela; Peter, Annika H G; Safdi, Benjamin R

    2014-01-10

    The scattering rate in dark-matter direct-detection experiments should modulate annually due to Earth's orbit around the Sun. The rate is typically thought to be extremized around June 1, when the relative velocity of Earth with respect to the dark-matter wind is maximal. We point out that gravitational focusing can alter this modulation phase. Unbound dark-matter particles are focused by the Sun's gravitational potential, affecting their phase-space density in the lab frame. Gravitational focusing can result in a significant overall shift in the annual-modulation phase, which is most relevant for dark matter with low scattering speeds. The induced phase shift for light O(10)  GeV dark matter may also be significant, depending on the threshold energy of the experiment.

  11. Inhibition of Rac1 reduces store overload-induced calcium release and protects against ventricular arrhythmia.

    Science.gov (United States)

    Zhang, Lili; Lu, Xiangru; Gui, Le; Wu, Yan; Sims, Stephen M; Wang, Guoping; Feng, Qingping

    2016-08-01

    Rac1 is a small GTPase and plays key roles in multiple cellular processes including the production of reactive oxygen species (ROS). However, whether Rac1 activation during myocardial ischaemia and reperfusion (I/R) contributes to arrhythmogenesis is not fully understood. We aimed to study the effects of Rac1 inhibition on store overload-induced Ca(2+) release (SOICR) and ventricular arrhythmia during myocardial I/R. Adult Rac1(f/f) and cardiac-specific Rac1 knockdown (Rac1(ckd) ) mice were subjected to myocardial I/R and their electrocardiograms (ECGs) were monitored for ventricular arrhythmia. Myocardial Rac1 activity was increased and ventricular arrhythmia was induced during I/R in Rac1(f/f) mice. Remarkably, I/R-induced ventricular arrhythmia was significantly decreased in Rac1(ckd) compared to Rac1(f/f) mice. Furthermore, treatment with Rac1 inhibitor NSC23766 decreased I/R-induced ventricular arrhythmia. Ca(2+) imaging analysis showed that in response to a 6 mM external Ca(2+) concentration challenge, SOICR was induced with characteristic spontaneous intracellular Ca(2+) waves in Rac1(f/f) cardiomyocytes. Notably, SOICR was diminished by pharmacological and genetic inhibition of Rac1 in adult cardiomyocytes. Moreover, I/R-induced ROS production and ryanodine receptor 2 (RyR2) oxidation were significantly inhibited in the myocardium of Rac1(ckd) mice. We conclude that Rac1 activation induces ventricular arrhythmia during myocardial I/R. Inhibition of Rac1 suppresses SOICR and protects against ventricular arrhythmia. Blockade of Rac1 activation may represent a new paradigm for the treatment of cardiac arrhythmia in ischaemic heart disease. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  12. Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation through activating the NR2B subunits of NMDA receptors

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Wen-Zhu [Anesthesia and Operation Center, Hainan Branch of Chinese PLA General Hospital, Hainan 572013 (China); Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China); Miao, Yu-Liang [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Guo, Wen-Zhi [Department of Anesthesiology, Beijing Military General Hospital of Chinese People’s Liberation Army, Beijing 100700 (China); Wu, Wei, E-mail: wwzwgk@163.com [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); Li, Bao-Wei [Department of Head and Neck Surgery of Otolaryngology, PLA No. 306 Hospital, Beijing 100101 (China); An, Li-Na [Department of Anesthesiology, Armed Police General Hospital, Beijing 100039 (China); Fang, Wei-Wu [Department of Anesthesiology, PLA No. 306 Hospital, Beijing 100101 (China); Mi, Wei-Dong, E-mail: elite2005gg@163.com [Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853 (China)

    2014-04-25

    Highlights: • Leptin promotes the proliferation of neural stem cells isolated from embryonic mouse hippocampus. • Leptin reverses corticosterone-induced inhibition of neural stem cell proliferation. • The effects of leptin are partially mediated by upregulating NR2B subunits. - Abstract: Corticosterone inhibits the proliferation of hippocampal neural stem cells (NSCs). The removal of corticosterone-induced inhibition of NSCs proliferation has been reported to contribute to neural regeneration. Leptin has been shown to regulate brain development, improve angiogenesis, and promote neural regeneration; however, its effects on corticosterone-induced inhibition of NSCs proliferation remain unclear. Here we reported that leptin significantly promoted the proliferation of hippocampal NSCs in a concentration-dependent pattern. Also, leptin efficiently reversed the inhibition of NSCs proliferation induced by corticosterone. Interestingly, pre-treatment with non-specific NMDA antagonist MK-801, specific NR2B antagonist Ro 25-6981, or small interfering RNA (siRNA) targeting NR2B, significantly blocked the effect of leptin on corticosterone-induced inhibition of NSCs proliferation. Furthermore, corticosterone significantly reduced the protein expression of NR2B, whereas pre-treatment with leptin greatly reversed the attenuation of NR2B expression caused by corticosterone in cultured hippocampal NSCs. Our findings demonstrate that leptin reverses the corticosterone-induced inhibition of NSCs proliferation. This process is, at least partially mediated by increased expression of NR2B subunits of NMDA receptors.

  13. Gravitational lensing

    CERN Document Server

    Dodelson, Scott

    2017-01-01

    Gravitational lensing is a consequence of general relativity, where the gravitational force due to a massive object bends the paths of light originating from distant objects lying behind it. Using very little general relativity and no higher level mathematics, this text presents the basics of gravitational lensing, focusing on the equations needed to understand the phenomena. It then applies them to a diverse set of topics, including multiply imaged objects, time delays, extrasolar planets, microlensing, cluster masses, galaxy shape measurements, cosmic shear, and lensing of the cosmic microwave background. This approach allows undergraduate students and others to get quickly up to speed on the basics and the important issues. The text will be especially relevant as large surveys such as LSST and Euclid begin to dominate the astronomical landscape. Designed for a one semester course, it is accessible to anyone with two years of undergraduate physics background.

  14. The role of somatostatin in GLP-1-induced inhibition of glucagon secretion in mice

    DEFF Research Database (Denmark)

    Ørgaard, Anne; Holst, Jens J

    2017-01-01

    AIMS/HYPOTHESIS: Glucagon-like peptide-1 (GLP-1) receptor agonists are currently used for the treatment of type 2 diabetes. Their main mechanism of action is enhancement of glucose-induced insulin secretion (from increased beta cell glucose sensitivity) and inhibition of glucagon secretion...... on glucagon secretion is heavily debated. Glucagon inhibition is also said to be glucose-dependent, although it is unclear what is meant by this. We hypothesise here that GLP-1 does not inhibit glucagon secretion during hypoglycaemia because the inhibition depends on somatostatin secretion, which in turn...

  15. Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro

    International Nuclear Information System (INIS)

    Xue, Gang; Zou, Xi; Zhou, Jin-Yong; Sun, Wei; Wu, Jian; Xu, Jia-Li; Wang, Rui-Ping

    2013-01-01

    Highlights: •Raddeanin A is a triterpenoid saponin in herb medicine Anemone raddeana Regel. •Raddeanin A can inhibit 3 kinds of gastric cancer cells’ proliferation and invasion. •Caspase-cascades’ activation indicates apoptosis induced by Raddeanin A. •MMPs, RECK, Rhoc and E-cad are involved in Raddeanin A-induced invasion inhibition. -- Abstract: Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A’s dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug

  16. Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Gang [Department of Oncology, Nanjing University of Chinese Medicine, Nanjing (China); Zou, Xi [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Zhou, Jin-Yong [Laboratory Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Sun, Wei [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Wu, Jian [Laboratory Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Xu, Jia-Li [Department of Oncology, Nanjing University of Chinese Medicine, Nanjing (China); Wang, Rui-Ping, E-mail: ruipingwang61@hotmail.com [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China)

    2013-09-20

    Highlights: •Raddeanin A is a triterpenoid saponin in herb medicine Anemone raddeana Regel. •Raddeanin A can inhibit 3 kinds of gastric cancer cells’ proliferation and invasion. •Caspase-cascades’ activation indicates apoptosis induced by Raddeanin A. •MMPs, RECK, Rhoc and E-cad are involved in Raddeanin A-induced invasion inhibition. -- Abstract: Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A’s dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug.

  17. Camptothecin inhibits platelet-derived growth factor-BB-induced proliferation of rat aortic vascular smooth muscle cells through inhibition of PI3K/Akt signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun-Seok [Department of Applied Biochemistry, Division of Life Science, College of Health and Biomedical Science, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Kang, Shin-il [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of); Yoo, Kyu-dong [Hazardous Substances Analysis Division, Gwangju Regional Food and Drug Administration, Gwangju (Korea, Republic of); Lee, Mi-Yea [Department of Nursing Kyungbok University, Pocheon (Korea, Republic of); Yoo, Hwan-Soo; Hong, Jin-Tae [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of); Shin, Hwa-Sup [Department of Applied Biochemistry, Division of Life Science, College of Health and Biomedical Science, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Kim, Bokyung [Department of Physiology, Konkuk Medical School, Konkuk University, Chungju, Chungbuk (Korea, Republic of); Yun, Yeo-Pyo, E-mail: ypyun@chungbuk.ac.kr [College of Pharmacy Medical Research Center, Chungbuk National University, Cheongju (Korea, Republic of)

    2013-04-15

    The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial wall is a major cause of vascular disorders such as atherosclerosis and restenosis after angioplasty. In this study, we investigated not only the inhibitory effects of camptothecin (CPT) on PDGF-BB-induced VSMC proliferation, but also its molecular mechanism of this inhibition. CPT significantly inhibited proliferation with IC50 value of 0.58 μM and the DNA synthesis of PDGF-BB-stimulated VSMCs in a dose-dependent manner (0.5–2 μM ) without any cytotoxicity. CPT induced the cell cycle arrest at G0/G1 phase. Also, CPT decreased the expressions of G0/G1-specific regulatory proteins including cyclin-dependent kinase (CDK)2, cyclin D1 and PCNA in PDGF-BB-stimulated VSMCs. Pre-incubation of VSMCs with CPT significantly inhibited PDGF-BB-induced Akt activation, whereas CPT did not affect PDGF-receptor beta phosphorylation, extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and phospholipase C (PLC)-γ1 phosphorylation in PDGF-BB signaling pathway. Our data showed that CPT pre-treatment inhibited VSMC proliferation, and that the inhibitory effect of CPT was enhanced by LY294002, a PI3K inhibitor, on PDGF-BB-induced VSMC proliferation. In addition, inhibiting the PI3K/Akt pathway by LY294002 significantly enhanced the suppression of PCNA expression and Akt activation by CPT. These results suggest that the anti-proliferative activity of CPT is mediated in part by downregulating the PI3K/Akt signaling pathway. - Highlights: ► CPT inhibits proliferation of PDGF-BB-induced VSMC without cytotoxicity. ► CPT arrests the cell cycle in G0/G1 phase by downregulation of cyclin D1 and CDK2. ► CPT significantly attenuates Akt phosphorylation in PDGF-BB signaling pathway. ► LY294002 enhanced the inhibitory effect of CPT on VSMC proliferation. ► Thus, CPT is mediated by downregulating the PI3K/Akt signaling pathway.

  18. Camptothecin inhibits platelet-derived growth factor-BB-induced proliferation of rat aortic vascular smooth muscle cells through inhibition of PI3K/Akt signaling pathway

    International Nuclear Information System (INIS)

    Park, Eun-Seok; Kang, Shin-il; Yoo, Kyu-dong; Lee, Mi-Yea; Yoo, Hwan-Soo; Hong, Jin-Tae; Shin, Hwa-Sup; Kim, Bokyung; Yun, Yeo-Pyo

    2013-01-01

    The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial wall is a major cause of vascular disorders such as atherosclerosis and restenosis after angioplasty. In this study, we investigated not only the inhibitory effects of camptothecin (CPT) on PDGF-BB-induced VSMC proliferation, but also its molecular mechanism of this inhibition. CPT significantly inhibited proliferation with IC50 value of 0.58 μM and the DNA synthesis of PDGF-BB-stimulated VSMCs in a dose-dependent manner (0.5–2 μM ) without any cytotoxicity. CPT induced the cell cycle arrest at G0/G1 phase. Also, CPT decreased the expressions of G0/G1-specific regulatory proteins including cyclin-dependent kinase (CDK)2, cyclin D1 and PCNA in PDGF-BB-stimulated VSMCs. Pre-incubation of VSMCs with CPT significantly inhibited PDGF-BB-induced Akt activation, whereas CPT did not affect PDGF-receptor beta phosphorylation, extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and phospholipase C (PLC)-γ1 phosphorylation in PDGF-BB signaling pathway. Our data showed that CPT pre-treatment inhibited VSMC proliferation, and that the inhibitory effect of CPT was enhanced by LY294002, a PI3K inhibitor, on PDGF-BB-induced VSMC proliferation. In addition, inhibiting the PI3K/Akt pathway by LY294002 significantly enhanced the suppression of PCNA expression and Akt activation by CPT. These results suggest that the anti-proliferative activity of CPT is mediated in part by downregulating the PI3K/Akt signaling pathway. - Highlights: ► CPT inhibits proliferation of PDGF-BB-induced VSMC without cytotoxicity. ► CPT arrests the cell cycle in G0/G1 phase by downregulation of cyclin D1 and CDK2. ► CPT significantly attenuates Akt phosphorylation in PDGF-BB signaling pathway. ► LY294002 enhanced the inhibitory effect of CPT on VSMC proliferation. ► Thus, CPT is mediated by downregulating the PI3K/Akt signaling pathway

  19. Quantum phenomena in gravitational field

    Science.gov (United States)

    Bourdel, Th.; Doser, M.; Ernest, A. D.; Voronin, A. Yu.; Voronin, V. V.

    2011-10-01

    The subjects presented here are very different. Their common feature is that they all involve quantum phenomena in a gravitational field: gravitational quantum states of ultracold antihydrogen above a material surface and measuring a gravitational interaction of antihydrogen in AEGIS, a quantum trampoline for ultracold atoms, and a hypothesis on naturally occurring gravitational quantum states, an Eötvös-type experiment with cold neutrons and others. Considering them together, however, we could learn that they have many common points both in physics and in methodology.

  20. Quantum phenomena in gravitational field

    International Nuclear Information System (INIS)

    Bourdel, Th.; Doser, M.; Ernest, A.D.; Voronin, A.Y.; Voronin, V.V.

    2010-01-01

    The subjects presented here are very different. Their common feature is that they all involve quantum phenomena in a gravitational field: gravitational quantum states of ultracold anti-hydrogen above a material surface and measuring a gravitational interaction of anti-hydrogen in AEGIS, a quantum trampoline for ultracold atoms, and a hypothesis on naturally occurring gravitational quantum states, an Eoetvoes-type experiment with cold neutrons and others. Considering them together, however, we could learn that they have many common points both in physics and in methodology. (authors)

  1. DMH1 (4-[6-(4-isopropoxyphenylpyrazolo[1,5-a]pyrimidin-3-yl]quinoline inhibits chemotherapeutic drug-induced autophagy

    Directory of Open Access Journals (Sweden)

    Yue Sheng

    2015-07-01

    Full Text Available Our previous work found that DMH1 (4-[6-(4-isopropoxyphenylpyrazolo [1,5-a]pyrimidin-3-yl]quinoline was a novel autophagy inhibitor. Here, we aimed to investigate the effects of DMH1 on chemotherapeutic drug-induced autophagy as well as the efficacy of chemotherapeutic drugs in different cancer cells. We found that DMH1 inhibited tamoxifen- and cispcis-diaminedichloroplatinum (II (CDDP-induced autophagy responses in MCF-7 and HeLa cells, and potentiated the anti-tumor activity of tamoxifen and CDDP for both cells. DMH1 inhibited 5-fluorouracil (5-FU-induced autophagy responses in MCF-7 and HeLa cells, but did not affect the anti-tumor activity of 5-FU for these two cell lines. DMH1 itself did not induce cell death in MCF-7 and HeLa cells, but inhibited the proliferation of these cells. In conclusion, DMH1 inhibits chemotherapeutic drug-induced autophagy response and the enhancement of efficacy of chemotherapeutic drugs by DMH1 is dependent on the cell sensitivity to drugs.

  2. Aloin Suppresses Lipopolysaccharide-Induced Inflammatory Response and Apoptosis by Inhibiting the Activation of NF-κB

    Directory of Open Access Journals (Sweden)

    Xuan Luo

    2018-02-01

    Full Text Available Numerous herbal-derived natural products are excellent anti-inflammatory agents. Several studies have reported that aloin, the major anthraquinone glycoside obtained from the Aloe species, exhibits anti-inflammatory activity. However, the molecular mechanism of this activity is not well understood. In this report, we found that aloin suppresses lipopolysaccharide-induced pro-inflammatory cytokine secretion and nitric oxide production, and downregulates the expression of tumor necrosis factor alpha (TNF-α, interleukin 6 (IL-6, inducible nitric oxide synthase (iNOS, and cyclooxygenase-2 (COX-2. Aloin inhibits the phosphorylation and acetylation of the NF-κB p65 subunit by suppressing the upstream kinases p38 and Msk1, preventing LPS-induced p65 translocation to the nucleus. We have also shown that aloin inhibits LPS-induced caspase-3 activation and apoptotic cell death. Collectively, these findings suggest that aloin effectively suppresses the inflammatory response, primarily through the inhibition of NF-κB signaling.

  3. Partial protection from organophosphate-induced cholinesterase inhibition by metyrapone treatment

    Directory of Open Access Journals (Sweden)

    Radosław Świercz

    2013-08-01

    Full Text Available Background: Organophosphates are cholinesterase (ChE inhibitors with worldwide use as insecticides. Stress response, evidenced by a dramatic and relatively long-lasting (several hours rise in the plasma glucocorticoid concentration is an integral element of the organophosphate (OP poisoning symptomatology. In rodents, corticosterone (CORT is the main glucocorticoid. There are several reports suggesting a relationship between the stressor-induced rise in CORT concentraion (the CORT response and the activity of the cerebral and peripheral ChE. Thus, it seems reasonable to presume that, in OP intoxication, the rise in plasma CORT concentration may somehow affect the magnitude of the OP-induced ChE inhibition. Metyrapone (MET [2-methyl-1,2-di(pyridin-3-ylpropan-1-one] blocks CORT synthesis by inhibiting steoid 11β-hydroxylase, thereby preventing the CORT response. Chlorfenvinphos (CVP [2-chloro-1-(2,4-dichlorophenyl ethenyl diethyl phosphate] is an organophosphate insecticide still in use in some countries. Material and Methods: The purose of the present work was to compare the CVP-induced effects - the rise of the plasma CORT concentration and the reduction in ChE activity - in MET-treated and MET-untreated rats. Chlorfenvinphos was administered once at 0.0, 0.5, 1.0 and 3.0 mg/kg i.p. Metyrapone, at 100 mg/kg i.p., was administered five times, at 24-h intervals. The first MET dose was given two hours before CVP. Conclusion: The following was observed in the MET-treated rats: i no rise in plasma CORT concentration after the CVP administration, ii a reduced inhibition and a faster restitution of blood and brain ChE activities. The results suggest that MET treatment may confer significant protection against at least some effects of OP poisoning. The likely mechanism of the protective MET action has been discussed.

  4. Drug-induced Inhibition and Trafficking Disruption of ion Channels: Pathogenesis of QT Abnormalities and Drug-induced Fatal Arrhythmias

    Science.gov (United States)

    Cubeddu, Luigi X.

    2016-01-01

    Risk of severe and fatal ventricular arrhythmias, presenting as Torsade de Pointes (TdP), is increased in congenital and acquired forms of long QT syndromes (LQTS). Drug-induced inhibition of K+ currents, IKs, IKr, IK1, and/or Ito, delay repolarization, prolong QT, and increase the risk of TdP. Drug-induced interference with IKr is the most common cause of acquired LQTS/TdP. Multiple drugs bind to KNCH2-hERG-K+ channels affecting IKr, including antiarrythmics, antibiotics, antivirals, azole-antifungals, antimalarials, anticancer, antiemetics, prokinetics, antipsychotics, and antidepressants. Azithromycin has been recently added to this list. In addition to direct channel inhibition, some drugs interfere with the traffic of channels from the endoplasmic reticulum to the cell membrane, decreasing mature channel membrane density; e.g., pentamidine, geldalamicin, arsenic trioxide, digoxin, and probucol. Other drugs, such as ketoconazole, fluoxetine, norfluoxetine, citalopram, escitalopram, donepezil, tamoxifen, endoxifen, atazanavir, and roxitromycin, induce both direct channel inhibition and impaired channel trafficking. Although many drugs prolong the QT interval, TdP is a rare event. The following conditions increase the risk of drug-induced TdP: a) Disease states/electrolyte levels (heart failure, structural cardiac disease, bradycardia, hypokalemia); b) Pharmacogenomic variables (presence of congenital LQTS, subclinical ion-channel mutations, history of or having a relative with history of drug-induced long QT/TdP); c) Pharmacodynamic and kinetic factors (high doses, women, elderly, metabolism inhibitors, combining two or more QT prolonging drugs, drugs that prolong the QT and increase QT dispersion, and drugs with multiple actions on ion channels). Because most of these conditions are preventable, careful evaluation of risk factors and increased knowledge of drug use associated with repolarization abnormalities are strongly recommended. PMID:26926294

  5. Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts

    International Nuclear Information System (INIS)

    Tsang, Chi Man; Cheung, Yuk Chun; Lui, Vivian Wai-Yan; Yip, Yim Ling; Zhang, Guitao; Lin, Victor Weitao; Cheung, Kenneth Chat-Pan; Feng, Yibin; Tsao, Sai Wah

    2013-01-01

    Cortidis rhizoma (Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation, has also been documented. In this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using both in vivo and in vitro models. Berberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cells in vivo was correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice. In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R. Our observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC

  6. Cepharanthine Prevents Estrogen Deficiency-Induced Bone Loss by Inhibiting Bone Resorption

    Directory of Open Access Journals (Sweden)

    Chen-he Zhou

    2018-03-01

    Full Text Available Osteoporosis is a common health problem worldwide caused by an imbalance of bone formation vs. bone resorption. However, current therapeutic approaches aimed at enhancing bone formation or suppressing bone resorption still have some limitations. In this study, we demonstrated for the first time that cepharanthine (CEP, derived from Stephania cepharantha Hayata exerted a protective effect on estrogen deficiency-induced bone loss. This protective effect was confirmed to be achieved through inhibition of bone resorption in vivo, rather than through enhancement of bone formation in vivo. Furthermore, the in vitro study revealed that CEP attenuated receptor activator of nuclear factor κB ligand (RANKL-induced osteoclast formation, and suppressed bone resorption by impairing the c-Jun N-terminal kinase (JNK and phosphatidylinositol 3-kinase (PI3K-AKT signaling pathways. The inhibitory effect of CEP could be partly reversed by treatment with anisomycin (a JNK and p38 agonist and/or SC79 (an AKT agonist in vitro. Our results thus indicated that CEP could prevent estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis. Hence, CEP might be a novel therapeutic agent for anti-osteoporosis therapy.

  7. Gravitational capture

    International Nuclear Information System (INIS)

    Bondi, H.

    1979-01-01

    In spite of the strength of gravitational focres between celestial bodies, gravitational capture is not a simple concept. The principles of conservation of linear momentum and of conservation of angular momentum, always impose severe constraints, while conservation of energy and the vital distinction between dissipative and non-dissipative systems allows one to rule out capture in a wide variety of cases. In complex systems especially those without dissipation, long dwell time is a more significant concept than permanent capture. (author)

  8. Antioxidant Activity of Lawsonia inermis Extracts Inhibits Chromium(VI-Induced Cellular and DNA Toxicity

    Directory of Open Access Journals (Sweden)

    Gunjan Guha

    2011-01-01

    Full Text Available Hexavalent chromium Cr(VI is a very strong oxidant which consequently causes high cytotoxicity through oxidative stress. Prevention of Cr(VI-induced cellular damage has been sought in this study in aqueous and methanolic extracts of Lawsonia inermis Linn. (Lythraceae, commonly known as Henna. The extracts showed significant (P < .05 potential in scavenging free radicals (DPPH• and ABTS•+ and Fe3+, and in inhibiting lipid peroxidation. DNA damage caused by exposure of pBR322 to Cr(VI-UV is markedly inhibited by both extracts in varying degrees. A distinct decline in Cr(VI-induced cytotoxicity was noticed in MDA-MB-435S (human breast carcinoma cells with an increase in dosage of both extracts individually. Furthermore, both extracts proved to contain a high content of phenolic compounds which were found to have a strong and significant (P < .05 positive correlation to the radical scavenging potential, lipid peroxidation inhibition capacity and cyto-protective efficiency against Cr(VI-induced oxidative cellular damage. HPLC analysis identified some of the major phenolic compounds in both extracts, which might be responsible for the antioxidant potential and the properties of DNA and cyto-protection. This study contributes to the search for natural resources that might yield potent therapeutic drugs against Cr(VI-induced oxidative cell damage.

  9. Interaction of gravitational waves with superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Inan, N.A.; Thompson, J.J. [University of California, Schools of Natural Sciences, Merced, CA (United States); Chiao, R.Y. [University of California, Schools of Natural Sciences and Engineering, Merced, CA (United States)

    2017-06-15

    Applying the Helmholtz Decomposition theorem to linearized General Relativity leads to a gauge-invariant formulation where the transverse-traceless part of the metric perturbation describes gravitational waves in matter. Gravitational waves incident on a superconductor can be described by a linear London-like constituent equation characterized by a ''gravitational shear modulus'' and a corresponding plasma frequency and penetration depth. Electric-like and magnetic-like gravitational tensor fields are defined in terms of the strain field of a gravitational wave. It is shown that in the DC limit, the magnetic-like tensor field is expelled from the superconductor in a gravitational Meissner-like effect. The Cooper pair density is described by the Ginzburg-Landau theory embedded in curved space-time. The ionic lattice is modeled by quantum harmonic oscillators coupled to gravitational waves and characterized by quasi-energy eigenvalues for the phonon modes. The formulation predicts the possibility of a dynamical Casimir effect since the zero-point energy of the ionic lattice phonons is found to be modulated by the gravitational wave, in a quantum analog of a ''Weber-bar effect.'' Applying periodic thermodynamics and the Debye model in the low-temperature limit leads to a free energy density for the ionic lattice. Lastly, we relate the gravitational strain of space to the strain of matter to show that the response to a gravitational wave is far less for the Cooper pair density than for the ionic lattice. This predicts a charge separation effect in the superconductor as a result of the gravitational wave. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  10. Inhibition of HSP27 alone or in combination with pAKT inhibition as therapeutic approaches to target SPARC-induced glioma cell survival

    Directory of Open Access Journals (Sweden)

    Schultz Chad R

    2012-04-01

    Full Text Available Abstract Background The current treatment regimen for glioma patients is surgery, followed by radiation therapy plus temozolomide (TMZ, followed by 6 months of adjuvant TMZ. Despite this aggressive treatment regimen, the overall survival of all surgically treated GBM patients remains dismal, and additional or different therapies are required. Depending on the cancer type, SPARC has been proposed both as a therapeutic target and as a therapeutic agent. In glioma, SPARC promotes invasion via upregulation of the p38 MAPK/MAPKAPK2/HSP27 signaling pathway, and promotes tumor cell survival by upregulating pAKT. As HSP27 and AKT interact to regulate the activity of each other, we determined whether inhibition of HSP27 was better than targeting SPARC as a therapeutic approach to inhibit both SPARC-induced glioma cell invasion and survival. Results Our studies found the following. 1 SPARC increases the expression of tumor cell pro-survival and pro-death protein signaling in balance, and, as a net result, tumor cell survival remains unchanged. 2 Suppressing SPARC increases tumor cell survival, indicating it is not a good therapeutic target. 3 Suppressing HSP27 decreases tumor cell survival in all gliomas, but is more effective in SPARC-expressing tumor cells due to the removal of HSP27 inhibition of SPARC-induced pro-apoptotic signaling. 4 Suppressing total AKT1/2 paradoxically enhanced tumor cell survival, indicating that AKT1 or 2 are poor therapeutic targets. 5 However, inhibiting pAKT suppresses tumor cell survival. 6 Inhibiting both HSP27 and pAKT synergistically decreases tumor cell survival. 7 There appears to be a complex feedback system between SPARC, HSP27, and AKT. 8 This interaction is likely influenced by PTEN status. With respect to chemosensitization, we found the following. 1 SPARC enhances pro-apoptotic signaling in cells exposed to TMZ. 2 Despite this enhanced signaling, SPARC protects cells against TMZ. 3 This protection can be reduced

  11. Inhibition of STAT3 activity delays obesity-induced thyroid carcinogenesis in a mouse model

    Science.gov (United States)

    Park, Jeong Won; Han, Cho Rong; Zhao, Li; Willingham, Mark C.; Cheng, Sheue-yann

    2015-01-01

    Compelling epidemiologic studies indicate that obesity is a risk factor for many human cancers, including thyroid cancer. In recent decades, the incidence of thyroid cancer has dramatically increased along with a marked rise in obesity prevalence. We previously demonstrated that a high fat diet (HFD) effectively induced the obese phenotype in a mouse model of thyroid cancer (ThrbPV/PVPten+/− mice). Moreover, HFD activates the STAT3 signal pathway to promote more aggressive tumor phenotypes. The aim of the present study was to evaluate the effect of S3I-201, a specific inhibitor of STAT3 activity, on HFD-induced aggressive cancer progression in the mouse model of thyroid cancer. Wild type and ThrbPV/PVPten+/− mice were treated with HFD together with S3I-201 or vehicle-only as controls. We assessed the effects of S3I-201 on HFD-induced thyroid cancer progression, the leptin-JAK2-STAT3 signaling pathway, and key regulators of epithelial-mesenchymal transition. S3I-201 effectively inhibited HFD-induced aberrant activation of STAT3 and its downstream targets to markedly inhibit thyroid tumor growth and to prolong survival. Decreased protein levels of cyclins D1 and B1, cyclin dependent kinase (CDK) 4, CDK 6, and phosphorylated retinoblastoma protein led to the inhibition of tumor cell proliferation in S3I-201-treated ThrbPV/PVPten+/− mice. Reduced occurrence of vascular invasion and blocking of anaplasia and lung metastasis in thyroid tumors of S3I-201-treated ThrbPV/PVPten+/− mice were mediated via decreased expression of vimentin and matrix metalloproteinases, two key effectors of epithelial-mesenchymal transition. The present findings suggest that inhibition of the STAT3 activity would be a novel treatment strategy for obesity-induced thyroid cancer. PMID:26552408

  12. Are the gravitational waves quantised?

    International Nuclear Information System (INIS)

    Lovas, Istvan

    1997-01-01

    If the gravitational waves are classical objects then the value of their correlation function is 1. If they are quantised, then there exist two possibilities: the gravitational waves are either completely coherent, then their correlation function is again 1, or they are only partially coherent, then their correlation function is expected to deviate from 1. Unfortunately such a deviation is not a sufficient proof for the quantised character of the gravitational waves. If the gravitational waves are quantised and generated by the change of the background metrical then they can be in a squeezed state. In a squeezed state there is a chance for the correlation between the phase of the wave and the quantum fluctuations. The observation of such a correlation would be a genuine proof of the quantised character of the gravitational wave

  13. GSK-3β Inhibition Attenuates CLP-Induced Liver Injury by Reducing Inflammation and Hepatic Cell Apoptosis

    Directory of Open Access Journals (Sweden)

    Hui Zhang

    2014-01-01

    Full Text Available Liver dysfunction has been known to occur frequently in cases of sepsis. Excessive inflammation and apoptosis are pathological features of acute liver failure. Recent studies suggest that activation of glycogen synthase kinase- (GSK- 3β is involved in inflammation and apoptosis. We aimed to investigate the protective effects of GSK-3β inhibition on polymicrobial sepsis-induced liver injury and to explore the possible mechanisms. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP, and SB216763 was used to inhibit GSK-3β in C57BL/6 mice. GSK-3β was activated following CLP. Administration of SB216763 decreased mortality, ameliorated liver injury, and reduced hepatic apoptosis. The inhibition of GSK-3β also reduced leukocyte infiltration and hepatic inflammatory cytokine expression and release. Moreover, GSK-3β inhibition suppressed the transcriptional activity of nuclear factor-kappa B (NF-κB but enhanced the transcriptional activity of cAMP response element binding protein (CREB in the liver. In in vitro studies, GSK-3β inhibition reduced inflammatory cytokine production via modulation of NF-κB and CREB signaling pathways in lipopolysaccharide-stimulated macrophages. In conclusion, these findings suggest that GSK-3β blockade protects against CLP-induced liver via inhibition of inflammation by modulating NF-κB and CREB activity and suppression of hepatic apoptosis.

  14. Relativistic gravitational instabilities

    International Nuclear Information System (INIS)

    Schutz, B.F.

    1987-01-01

    The purpose of these lectures is to review and explain what is known about the stability of relativistic stars and black holes, with particular emphases on two instabilities which are due entirely to relativistic effects. The first of these is the post-Newtonian pulsational instability discovered independently by Chandrasekhar (1964) and Fowler (1964). This effectively ruled out the then-popular supermassive star model for quasars, and it sets a limit to the central density of white dwarfs. The second instability was also discovered by Chandrasekhar (1970): the gravitational wave induced instability. This sets an upper bound on the rotation rate of neutron stars, which is near that of the millisecond pulsar PSR 1937+214, and which is beginning to constrain the equation of state of neutron matter. 111 references, 5 figures

  15. Adaptability and specificity of inhibition processes in distractor-induced blindness.

    Science.gov (United States)

    Winther, Gesche N; Niedeggen, Michael

    2017-12-01

    In a rapid serial visual presentation task, inhibition processes cumulatively impair processing of a target possessing distractor properties. This phenomenon-known as distractor-induced blindness-has thus far only been elicited using dynamic visual features, such as motion and orientation changes. In three ERP experiments, we used a visual object feature-color-to test for the adaptability and specificity of the effect. In Experiment I, participants responded to a color change (target) in the periphery whose onset was signaled by a central cue. Presentation of irrelevant color changes prior to the cue (distractors) led to reduced target detection, accompanied by a frontal ERP negativity that increased with increasing number of distractors, similar to the effects previously found for dynamic targets. This suggests that distractor-induced blindness is adaptable to color features. In Experiment II, the target consisted of coherent motion contrasting the color distractors. Correlates of distractor-induced blindness were found neither in the behavioral nor in the ERP data, indicating a feature specificity of the process. Experiment III confirmed the strict distinction between congruent and incongruent distractors: A single color distractor was embedded in a stream of motion distractors with the target consisting of a coherent motion. While behavioral performance was affected by the distractors, the color distractor did not elicit a frontal negativity. The experiments show that distractor-induced blindness is also triggered by visual stimuli predominantly processed in the ventral stream. The strict specificity of the central inhibition process also applies to these stimulus features. © 2017 Society for Psychophysiological Research.

  16. IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression

    Energy Technology Data Exchange (ETDEWEB)

    Kiyomiya, Hiroyasu [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Ariyoshi, Wataru; Okinaga, Toshinori [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Kaneuji, Takeshi [Division of Oral Medicine, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Mitsugi, Sho [Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Sakurai, Takuma [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Habu, Manabu [Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Yoshioka, Izumi [Division of Oral Medicine, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); Tominaga, Kazuhiro [Division of Oral and Maxillofacial Surgery, Department of Science of Physical Functions, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580 (Japan); and others

    2015-05-01

    Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression. - Highlights: • IL-33 inhibits RANKL-induced osteoclast formation. • IL-33 has inhibitory effect on the RANKL-induced NFATc1 expression. • IL-33-induced NFATc1 suppression depends on the regulation of Blimp-1 and IRF-8.

  17. IL-33 inhibits RANKL-induced osteoclast formation through the regulation of Blimp-1 and IRF-8 expression

    International Nuclear Information System (INIS)

    Kiyomiya, Hiroyasu; Ariyoshi, Wataru; Okinaga, Toshinori; Kaneuji, Takeshi; Mitsugi, Sho; Sakurai, Takuma; Habu, Manabu; Yoshioka, Izumi; Tominaga, Kazuhiro

    2015-01-01

    Interleukin (IL)-33 is a recently discovered proinflammatory cytokine that belongs to the IL-1 family. Several studies have reported that IL-33 inhibits osteoclast differentiation. However, the mechanism of IL-33 regulation of osteoclastogenesis remains unclear. In the present study, we examined the effect of IL-33 on osteoclast formation in vitro. IL-33 suppressed osteoclast formation in both mouse bone marrow cells and monocyte/macrophage cell line RAW264.7 cells induced by receptor activator of NF-κB ligand (RANKL) and/or macrophage stimulating factor (M-CSF). IL-33 also inhibited the expression of RANKL-induced nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), thereby decreasing the expression of osteoclastogenesis-related marker genes, including Cathepsin K, Osteoclast stimulatory transmembrane protein (Oc-stamp) and Tartrate-resistant acid phosphatase (Trap). Blockage of IL-33-ST2 binding suppressed the IL-33-mediated inhibition of NFATc1. RANKL-induced B-lymphocyte-induced maturation protein-1 (Blimp-1) expression was also suppressed by IL-33, which was followed by the stimulation of anti-osteoclastic genes such as interferon regulatory factor-8 (IRF-8). These results suggest that IL-33-ST2 interactions down-regulate both RANKL-induced NFATc1 activation and osteoclast differentiation via the regulation of Blimp-1 and IRF-8 expression. - Highlights: • IL-33 inhibits RANKL-induced osteoclast formation. • IL-33 has inhibitory effect on the RANKL-induced NFATc1 expression. • IL-33-induced NFATc1 suppression depends on the regulation of Blimp-1 and IRF-8

  18. LY294002 inhibits glucocorticoid-induced COX-2 gene expression in cardiomyocytes through a phosphatidylinositol 3 kinase-independent mechanism

    International Nuclear Information System (INIS)

    Sun Haipeng; Xu Beibei; Sheveleva, Elena; Chen, Qin M.

    2008-01-01

    Glucocorticoids induce COX-2 expression in rat cardiomyocytes. While investigating whether phosphatidylinositol 3 kinase (PI3K) plays a role in corticosterone (CT)-induced COX-2, we found that LY294002 (LY29) but not wortmannin (WM) attenuates CT from inducing COX-2 gene expression. Expression of a dominant-negative mutant of p85 subunit of PI3K failed to inhibit CT from inducing COX-2 expression. CT did not activate PI3K/AKT signaling pathway whereas LY29 and WM decreased the activity of PI3K. LY303511 (LY30), a structural analogue and a negative control for PI3K inhibitory activity of LY29, also suppressed COX-2 induction. These data suggest PI3K-independent mechanisms in regulating CT-induced COX-2 expression. LY29 and LY30 do not inhibit glucocorticoid receptor transactivity. Both compounds have been reported to inhibit Casein Kinase 2 activity and modulate potassium and calcium levels independent of PI3K, while LY29 has been reported to inhibit mammalian Target of Rapamycin (mTOR), and DNA-dependent Protein Kinase (DNA-PK). Inhibitor of Casein Kinase 2 (CK2), mTOR or DNA-PK failed to prevent CT from inducing COX-2 expression. Tetraethylammonium (TEA), a potassium channel blocker, and nimodipine, a calcium channel blocker, both attenuated CT from inducing COX-2 gene expression. CT was found to increase intracellular Ca 2+ concentration, which can be inhibited by LY29, TEA or nimodipine. These data suggest a possible role of calcium instead of PI3K in CT-induced COX-2 expression in cardiomyocytes

  19. General relativity and gravitation, 1989

    International Nuclear Information System (INIS)

    Ashby, N.; Bartlett, D.F.; Wyss, W.

    1990-01-01

    This volume records the lectures and symposia of the 12th International Conference on General Relativity and Gravitation. Plenary lecturers reviewed the major advances since the previous conference in 1986. The reviews cover classical and quantum theory of gravity, colliding gravitational waves, gravitational lensing, relativistic effects on pulsars, tests of the inverse square law, numerical relativity, cosmic microwave background radiation, experimental tests of gravity theory, gravitational wave detectors, and cosmology. The plenary lectures are complemented by summaries of symposia, provided by the chairmen. Almost 700 contributed papers were presented at these and they cover an even wider range of topics than the plenary talks. The book provides a comprehensive guide to research activity in both experimental and theoretical gravitation and its applications in astrophysics and cosmology. It will be essential reading for research workers in these fields, as well as theoretical and experimental physicists, astronomers, and mathematicians who wish to be acquainted with modern developments in gravitational theory and general relativity. All the papers and summaries of the workshop sessions are indexed separately. (16 united talks, 20 workshop sessions). (author)

  20. Pulsar timing residuals due to individual non-evolving gravitational wave sources

    International Nuclear Information System (INIS)

    Tong Ming-Lei; Zhao Cheng-Shi; Yan Bao-Rong; Yang Ting-Gao; Gao Yu-Ping

    2014-01-01

    The pulsar timing residuals induced by gravitational waves from non-evolving single binary sources are affected by many parameters related to the relative positions of the pulsar and the gravitational wave sources. We will analyze the various effects due to different parameters. The standard deviations of the timing residuals will be calculated with a variable parameter fixing a set of other parameters. The orbits of the binary sources will be generally assumed to be elliptical. The influences of different eccentricities on the pulsar timing residuals will also be studied in detail. We find that the effects of the related parameters are quite different, and some of them display certain regularities

  1. Gangliosides inhibit bee venom melittin cytotoxicity but not phospholipase A2-induced degranulation in mast cells

    International Nuclear Information System (INIS)

    Nishikawa, Hirofumi; Kitani, Seiichi

    2011-01-01

    Sting accident by honeybee causes severe pain, inflammation and allergic reaction through IgE-mediated anaphylaxis. In addition to this hypersensitivity, an anaphylactoid reaction occurs by toxic effects even in a non-allergic person via cytolysis followed by similar clinical manifestations. Auto-injectable epinephrine might be effective for bee stings, but cannot inhibit mast cell lysis and degranulation by venom toxins. We used connective tissue type canine mast cell line (CM-MC) for finding an effective measure that might inhibit bee venom toxicity. We evaluated degranulation and cytotoxicity by measurement of β-hexosaminidase release and MTT assay. Melittin and crude bee venom induced the degranulation and cytotoxicity, which were strongly inhibited by mono-sialoganglioside (G M1 ), di-sialoganglioside (G D1a ) and tri-sialoganglioside (G T1b ). In contrast, honeybee venom-derived phospholipase A 2 induced the net degranulation directly without cytotoxicity, which was not inhibited by G M1 , G D1a and G T1b . For analysis of distribution of Gα q and Gα i protein by western blotting, lipid rafts were isolated by using discontinuous sucrose gradient centrifuge. Melittin disrupted the localization of Gα q and Gα i at lipid raft, but gangliosides stabilized the rafts. As a result from this cell-based study, bee venom-induced anaphylactoid reaction can be explained with melittin cytotoxicity and phospholipase A 2 -induced degranulation. Taken together, gangliosides inhibit the effect of melittin such as degranulation, cytotoxicity and lipid raft disruption but not phospholipase A 2 -induced degranulation in mast cells. Our study shows a potential of gangliosides as a therapeutic tool for anaphylactoid reaction by honeybee sting.

  2. Evolution of an electron-positron plasma produced by induced gravitational collapse in binary-driven hypernovae

    Directory of Open Access Journals (Sweden)

    Melon Fuksman J. D.

    2018-01-01

    Full Text Available The binary-driven hypernova (BdHN model has been introduced in the past years, to explain a subfamily of gamma-ray bursts (GRBs with energies Eiso ≥ 1052 erg associated with type Ic supernovae. Such BdHNe have as progenitor a tight binary system composed of a carbon-oxigen (CO core and a neutron star undergoing an induced gravitational collapse to a black hole, triggered by the CO core explosion as a supernova (SN. This collapse produces an optically-thick e+e- plasma, which expands and impacts onto the SN ejecta. This process is here considered as a candidate for the production of X-ray flares, which are frequently observed following the prompt emission of GRBs. In this work we follow the evolution of the e+e- plasma as it interacts with the SN ejecta, by solving the equations of relativistic hydrodynamics numerically. Our results are compatible with the Lorentz factors estimated for the sources that produce the flares, of typically Γ ≲ 4.

  3. Asymmetric gravitational spreading - Analogue experiments on the Svecofennian orogen

    Science.gov (United States)

    Nikkilä, Kaisa; Korja, Annakaisa; Koyi, Hemin; Eklund, Olav

    2015-04-01

    Over-thickened orogenic crust may suffer from rheological, gravitational and topographical unbalancing resulting in discharging via gravitational spreading. If the thickened orogen is also hot, then increased temperature may reduce the viscosity of the crust that may induce large-scale horizontal flow. The effect of flow on the crustal architecture has previously been modeled with symmetric two-way spreading or asymmetric one- or two-way spreading (like channel flow) experiments. Most models do not take into account of the contrasting mechanical properties of the juxtaposed terranes. We have made analogue experiments to study gravitational one-way spreading and the interplay between two crustal blocks with contrasting rheological properties. The models are 3 cm thick replicas of 60 km thick crust. They have three horizontal layers representing strong lower, weak middle and brittle upper crust. The models have cuts to study the effect of inherited crustal-scale weakness zones. The experiments have been conducted within a large centrifuge in the Hans Ramberg Tectonic Laboratory at Uppsala University. The analogue models propose that asymmetric, unilateral flow has different effect on the contrasting crustal units, in both horizontal and vertical directions. The laterally heterogeneous crust flows towards the direction of extension, and it rotates and extends the pre-existing weakness zones. The weakness zones facilitate exhumation and they increase strain rate. The weakness zones split the crust into subblocks, which stretch individually and which may show signatures of compression or rotation. The changes in thickness of the model reflect changes in the layers, which may thin or thicken depending on the mechanical properties of crustal layers. A consequence of this the total amount of flattening is less than the model extension. The results are compared to geophysical and geological data from Precambrian Svecofennian orogen in Fennoscandia. The comparison suggest

  4. Gravitational Physics

    OpenAIRE

    Schäfer, G.; Schutz, B.

    1996-01-01

    Gravity is truly universal. It is the force that pulls us to the Earth, that keeps the planets and moons in their orbits, and that causes the tides on the Earth to ebb and flow. It even keeps the Sun shining. Yet on a laboratory scale gravity is extremely weak. The Coulomb force between two protons is 1039 times stronger than the gravitational force between them. Moreover, Newton's gravitational constant is the least accurately known of the fundamental constants: it has been measured to 1 par...

  5. Dietary spices protect against hydrogen peroxide-induced DNA damage and inhibit nicotine-induced cancer cell migration.

    Science.gov (United States)

    Jayakumar, R; Kanthimathi, M S

    2012-10-01

    Spices are rich sources of antioxidants due to the presence of phenols and flavonoids. In this study, the DNA protecting activity and inhibition of nicotine-induced cancer cell migration of 9 spices were analysed. Murine fibroblasts (3T3-L1) and human breast cancer (MCF-7) cells were pre-treated with spice extracts and then exposed to H₂O₂ and nicotine. The comet assay was used to analyse the DNA damage. Among the 9 spices, ginger, at 50 μg/ml protected against 68% of DNA damage in 3T3-L1 cells. Caraway, cumin and fennel showed statistically significant (pspices reduced this migration. Pepper, long pepper and ginger exhibited a high rate of inhibition of cell migration. The results of this study prove that spices protect DNA and inhibit cancer cell migration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Mechanisms involved in growth inhibition induced by clofibrate in hepatoma cells

    International Nuclear Information System (INIS)

    Muzio, Giuliana; Maggiora, Marina; Trombetta, Antonella; Martinasso, Germana; Reffo, Patrizia; Colombatto, Sebastiano; Canuto, Rosa Angela

    2003-01-01

    Low concentrations of some peroxisome proliferators have been found to decrease apoptosis in rat liver cells, whereas higher but pharmacological concentrations have been found to inhibit cell proliferation or to induce apoptosis in human and rat hepatoma cells. The highly deviated JM2 rat hepatoma cell line was used to examine the mechanisms underlying the inhibitory effect on cell proliferation. Clofibrate chiefly inhibited cell proliferation in these cells. Parallel to the decrease in cell proliferation there was an increase of peroxisome proliferator activated receptor (PPAR) gamma and of protein phosphatase 2A, whose importance was confirmed, respectively, by using antisense oliginucleotides (AS-ODN) or okadaic acid. The increase of protein phosphatase 2A induced by PPARgamma caused a decrease of MAPK, an intracellular signaling transduction pathway, as shown by evaluation of Erk1,2 and c-myc. In light of these results, clofibrate, like conventional synthetic ligands of PPARgamma, may be regarded as a possible prototype anti-tumour drug

  7. Statin therapy exacerbates alcohol-induced constriction of cerebral arteries via modulation of ethanol-induced BK channel inhibition in vascular smooth muscle.

    Science.gov (United States)

    Simakova, Maria N; Bisen, Shivantika; Dopico, Alex M; Bukiya, Anna N

    2017-12-01

    Statins constitute the most commonly prescribed drugs to decrease cholesterol (CLR). CLR is an important modulator of alcohol-induced cerebral artery constriction (AICAC). Using rats on a high CLR diet (2% CLR) we set to determine whether atorvastatin administration (10mg/kg daily for 18-23weeks) modified AICAC. Middle cerebral arteries were pressurized in vitro at 60mmHg and AICAC was evoked by 50mM ethanol, that is within the range of blood alcohol detected in humans following moderate-to-heavy drinking. AICAC was evident in high CLR+atorvastatin group but not in high CLR diet+placebo. Statin exacerbation of AICAC persisted in de-endothelialized arteries, and was blunted by CLR enrichment in vitro. Fluorescence imaging of filipin-stained arteries showed that atorvastatin decreased vascular smooth muscle (VSM) CLR when compared to placebo, this difference being reduced by CLR enrichment in vitro. Voltage- and calcium-gated potassium channels of large conductance (BK) are known VSM targets of ethanol, with their beta1 subunit being necessary for ethanol-induced channel inhibition and resulting AICAC. Ethanol-induced BK inhibition in excised membrane patches from freshly isolated myocytes was exacerbated in the high CLR diet+atorvastatin group when compared to high CLR diet+placebo. Unexpectedly, atorvastatin decreased the amount and function of BK beta1 subunit as documented by immunofluorescence imaging and functional patch-clamp studies. Atorvastatin exacerbation of ethanol-induced BK inhibition disappeared upon artery CLR enrichment in vitro. Our study demonstrates for the first time statin's ability to exacerbate the vascular effect of a widely consumed drug of abuse, this exacerbation being driven by statin modulation of ethanol-induced BK channel inhibition in the VSM via CLR-mediated mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Measurement of gravitational acceleration of antimatter

    International Nuclear Information System (INIS)

    Rouhani, S.

    1989-12-01

    The minute yet effective impact of gravitational potential in the central region of a long tube magnetic container of non-neutral plasmas can be utilized for the measurement of the gravitational acceleration of antimatter particles. The slight change in distribution of plasma particles along the gravitational field affects the internal electric field of the plasma, which in turn affects the frequency of the magnetron motion of its particles. Thus, a rather straightforward relation is established between the gravitational acceleration of the particles and their magnetron frequencies, which is measurable directly, determining the value of the gravitational acceleration. (author). 7 refs, 3 figs

  9. Changes in peroxidases associated with radiation-induced sprout inhibition in garlic (Allium sativum L.)

    International Nuclear Information System (INIS)

    Croci, C.A.; Curvetto, N.R.; Orioli, G.A.; Arguello, J.A.

    1991-01-01

    The effects of an acute dose of γ-rays (10 Gy) to post-dormant garlic cloves on inner sprout growth and changes in peroxidases and soluble proteins were evaluated up to 100 days of storage in darkness at 19±1 0 C and 42±2% relative humidity. Radiation-induced inhibition of sprout growth became evident after 25 days of treatment and was synchronous with a marked increase in peroxidase activity. Thin-layer isoelectric focusing revealed that radiation induced an increase in the number of anodic peroxidase isoenzymes at 100 days, suggesting modifications in the vascularization process. Neither the soluble protein content nor the protein pattern were affected by irradiation. These results are discussed in terms of a possible mediating effect of peroxidase on radiation-induced sprout inhibition in garlic. (author)

  10. Changes in peroxidases associated with radiation-induced sprout inhibition in garlic (Allium sativum L. )

    Energy Technology Data Exchange (ETDEWEB)

    Croci, C.A.; Curvetto, N.R.; Orioli, G.A. (Universidad Nacional del Sur, Bahia Blanca (Argentina)); Arguello, J.A. (Universidad Nacional de Cordoba (Argentina). Dept. de Biologia Aplicada)

    1991-02-01

    The effects of an acute dose of {gamma}-rays (10 Gy) to post-dormant garlic cloves on inner sprout growth and changes in peroxidases and soluble proteins were evaluated up to 100 days of storage in darkness at 19+-1{sup 0}C and 42+-2% relative humidity. Radiation-induced inhibition of sprout growth became evident after 25 days of treatment and was synchronous with a marked increase in peroxidase activity. Thin-layer isoelectric focusing revealed that radiation induced an increase in the number of anodic peroxidase isoenzymes at 100 days, suggesting modifications in the vascularization process. Neither the soluble protein content nor the protein pattern were affected by irradiation. These results are discussed in terms of a possible mediating effect of peroxidase on radiation-induced sprout inhibition in garlic. (author).

  11. Prevention of gravitational collapse

    International Nuclear Information System (INIS)

    Moffat, J.W.; Taylor, J.G.

    1981-01-01

    We apply a new theory of gravitation to the question of gravitational collapse to show that collapse is prevented in this theory under very reasonable conditions. This result also extends to prevent ultimate collapse of the Universe. (orig.)

  12. Tetrahydroxystilbene glucoside improves TNF-α-induced endothelial dysfunction: involvement of TGFβ/Smad pathway and inhibition of vimentin expression.

    Science.gov (United States)

    Yao, Wenjuan; Gu, Chengjing; Shao, Haoran; Meng, Guoliang; Wang, Huiming; Jing, Xiang; Zhang, Wei

    2015-01-01

    Endothelial dysfunction plays an important role in the pathogenesis of atherogenesis. 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component of the rhizome extract from Polygonum multiflorum (PM), exhibits significant anti-atherosclerotic activity. Here, we used human umbilical vein endothelial cells (HUVECs) induced by tumor necrosis factor-α (TNF-α) in vitro to investigate the cytoprotective effects of TSG on TNF-α-induced endothelial injury and the related mechanisms. Pretreatment with 50 and 100 μM TSG markedly attenuated TNF-α-induced loss of cell viability and release of lactate dehydrogenase (LDH) and inhibited TNF-α-induced cell apoptosis. The inhibition of vimentin expression was involved in the cytoprotection afforded by TSG. Using inhibitors for PI3K and TGFβ or siRNA for Akt and Smad2, we found that vimentin production in HUVECs is regulated by TGFβ/Smad signaling, but not by PI3K-Akt-mTOR signaling. Meanwhile, TSG inhibited both the expression of TGFβ1 and the phosphorylation of Smad2 and Smad3, and TSG suppressed the nuclear translocation of Smad4 induced by TNF-α. These results suggest that TSG protects HUVECs against TNF-α-induced cell damage by inhibiting vimentin expression via the interruption of the TGFβ/Smad signaling pathway.

  13. Weight, gravitation, inertia, and tides

    Science.gov (United States)

    Pujol, Olivier; Lagoute, Christophe; Pérez, José-Philippe

    2015-11-01

    This paper deals with the factors that influence the weight of an object near the Earth's surface. They are: (1) the Earth's gravitational force, (2) the centrifugal force due to the Earth's diurnal rotation, and (3) tidal forces due to the gravitational field of the Moon and Sun, and other solar system bodies to a lesser extent. Each of these three contributions is discussed and expressions are derived. The relationship between weight and gravitation is thus established in a direct and pedagogical manner readily understandable by undergraduate students. The analysis applies to the Newtonian limit of gravitation. The derivation is based on an experimental (or operational) definition of weight, and it is shown that it coincides with the Earth’s gravitational force modified by diurnal rotation around a polar axis and non-uniformity of external gravitational bodies (tidal term). Two examples illustrate and quantify these modifications, respectively the Eötvös effect and the oceanic tides; tidal forces due to differential gravitation on a spacecraft and an asteroid are also proposed as examples. Considerations about inertia are also given and some comments are made about a widespread, yet confusing, explanation of tides based on a centrifugal force. Finally, the expression of the potential energy of the tide-generating force is established rigorously in the appendix.

  14. Weight, gravitation, inertia, and tides

    International Nuclear Information System (INIS)

    Pujol, Olivier; Lagoute, Christophe; Pérez, José-Philippe

    2015-01-01

    This paper deals with the factors that influence the weight of an object near the Earth's surface. They are: (1) the Earth's gravitational force, (2) the centrifugal force due to the Earth's diurnal rotation, and (3) tidal forces due to the gravitational field of the Moon and Sun, and other solar system bodies to a lesser extent. Each of these three contributions is discussed and expressions are derived. The relationship between weight and gravitation is thus established in a direct and pedagogical manner readily understandable by undergraduate students. The analysis applies to the Newtonian limit of gravitation. The derivation is based on an experimental (or operational) definition of weight, and it is shown that it coincides with the Earth’s gravitational force modified by diurnal rotation around a polar axis and non-uniformity of external gravitational bodies (tidal term). Two examples illustrate and quantify these modifications, respectively the Eötvös effect and the oceanic tides; tidal forces due to differential gravitation on a spacecraft and an asteroid are also proposed as examples. Considerations about inertia are also given and some comments are made about a widespread, yet confusing, explanation of tides based on a centrifugal force. Finally, the expression of the potential energy of the tide-generating force is established rigorously in the appendix. (paper)

  15. Gravitational Grating

    Science.gov (United States)

    Rahvar, Sohrab

    2018-05-01

    In this work, we study the interaction of the electromagnetic wave (EW) from a distant quasar with the gravitational wave (GW) sourced by the binary stars. While in the regime of geometric optics, the light bending due to this interaction is negligible, we show that the phase shifting on the wavefront of an EW can produce the diffraction pattern on the observer plane. The diffraction of the light (with the wavelength of λe) by the gravitational wave playing the role of gravitational grating (with the wavelength of λg) has the diffraction angle of Δβ ˜ λe/λg. The relative motion of the observer, the source of gravitational wave and the quasar results in a relative motion of the observer through the interference pattern on the observer plane. The consequence of this fringe crossing is the modulation in the light curve of a quasar with the period of few hours in the microwave wavelength. The optical depth for the observation of this phenomenon for a Quasar with the multiple images strongly lensed by a galaxy where the light trajectory of some of the images crosses the lensing galaxy is τ ≃ 0.2. By shifting the time-delay of the light curves of the multiple images in a strong lensed quasar and removing the intrinsic variations of a quasar, our desired signals, as a new method for detection of GWs can be detected.

  16. Inhibition of Estrogen-induced Growth of Breast Cancer by Targeting Mitochondrial Oxidants

    National Research Council Canada - National Science Library

    Roy, Deodutta; Felty, Quentin; Kunkle, Brian

    2008-01-01

    ...) Anchorage-independent cell growth, and (c) tumor spheroid formation using new 3D HuBiogel bioassay whether estrogen induced conversion of normal cells to transformed cells is inhibited by treatment with antioxidants, over expression of MnSOD...

  17. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    Energy Technology Data Exchange (ETDEWEB)

    Hannon, Patrick R., E-mail: phannon2@illinois.edu; Brannick, Katherine E., E-mail: kbran@illinois.edu; Wang, Wei, E-mail: Wei.Wang2@covance.com; Gupta, Rupesh K., E-mail: drrupesh@yahoo.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2015-04-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

  18. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    International Nuclear Information System (INIS)

    Hannon, Patrick R.; Brannick, Katherine E.; Wang, Wei; Gupta, Rupesh K.; Flaws, Jodi A.

    2015-01-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

  19. Electromagnetic Waves in a Uniform Gravitational Field and Planck's Postulate

    Science.gov (United States)

    Acedo, Luis; Tung, Michael M.

    2012-01-01

    The gravitational redshift forms the central part of the majority of the classical tests for the general theory of relativity. It could be successfully checked even in laboratory experiments on the earth's surface. The standard derivation of this effect is based on the distortion of the local structure of spacetime induced by large masses. The…

  20. Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Pratheeshkumar, Poyil; Son, Young-Ok; Divya, Sasidharan Padmaja; Roy, Ram Vinod; Hitron, John Andrew; Wang, Lei [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Kim, Donghern; Dai, Jin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Asha, Padmaja [National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Cochin (India); Zhang, Zhuo [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Wang, Yitao [State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau (China); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States)

    2014-12-01

    Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with the incidence of lung cancer. Inhibition of metal induced carcinogenesis by a dietary antioxidant is a novel approach. Luteolin, a natural dietary flavonoid found in fruits and vegetables, possesses potent antioxidant and anti-inflammatory activity. We found that short term exposure of human bronchial epithelial cells (BEAS-2B) to Cr(VI) (5 μM) showed a drastic increase in ROS generation, NADPH oxidase (NOX) activation, lipid peroxidation, and glutathione depletion, which were significantly inhibited by the treatment with luteolin in a dose dependent manner. Treatment with luteolin decreased AP-1, HIF-1α, COX-2, and iNOS promoter activity induced by Cr(VI) in BEAS-2B cells. In addition, luteolin protected BEAS-2B cells from malignant transformation induced by chronic Cr(VI) exposure. Moreover, luteolin also inhibited the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and VEGF in chronic Cr(VI) exposed BEAS-2B cells. Western blot analysis showed that luteolin inhibited multiple gene products linked to survival (Akt, Fak, Bcl-2, Bcl-xL), inflammation (MAPK, NF-κB, COX-2, STAT-3, iNOS, TNF-α) and angiogenesis (HIF-1α, VEGF, MMP-9) in chronic Cr(VI) exposed BEAS-2B cells. Nude mice injected with BEAS-2B cells chronically exposed to Cr(VI) in the presence of luteolin showed reduced tumor incidence compared to Cr(VI) alone treated group. Overexpression of catalase (CAT) or SOD2, eliminated Cr(VI)-induced malignant transformation. Overall, our results indicate that luteolin protects BEAS-2B cells from Cr(VI)-induced carcinogenesis by scavenging ROS and modulating multiple cell signaling mechanisms that are linked to ROS. Luteolin, therefore, serves as a potential chemopreventive agent against Cr(VI)-induced carcinogenesis. - Highlights: • Luteolin inhibited Cr(VI)-induced oxidative stress. • Luteolin inhibited chronic Cr(VI)-induced malignant transformation.

  1. Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

    International Nuclear Information System (INIS)

    Pratheeshkumar, Poyil; Son, Young-Ok; Divya, Sasidharan Padmaja; Roy, Ram Vinod; Hitron, John Andrew; Wang, Lei; Kim, Donghern; Dai, Jin; Asha, Padmaja; Zhang, Zhuo; Wang, Yitao; Shi, Xianglin

    2014-01-01

    Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with the incidence of lung cancer. Inhibition of metal induced carcinogenesis by a dietary antioxidant is a novel approach. Luteolin, a natural dietary flavonoid found in fruits and vegetables, possesses potent antioxidant and anti-inflammatory activity. We found that short term exposure of human bronchial epithelial cells (BEAS-2B) to Cr(VI) (5 μM) showed a drastic increase in ROS generation, NADPH oxidase (NOX) activation, lipid peroxidation, and glutathione depletion, which were significantly inhibited by the treatment with luteolin in a dose dependent manner. Treatment with luteolin decreased AP-1, HIF-1α, COX-2, and iNOS promoter activity induced by Cr(VI) in BEAS-2B cells. In addition, luteolin protected BEAS-2B cells from malignant transformation induced by chronic Cr(VI) exposure. Moreover, luteolin also inhibited the production of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) and VEGF in chronic Cr(VI) exposed BEAS-2B cells. Western blot analysis showed that luteolin inhibited multiple gene products linked to survival (Akt, Fak, Bcl-2, Bcl-xL), inflammation (MAPK, NF-κB, COX-2, STAT-3, iNOS, TNF-α) and angiogenesis (HIF-1α, VEGF, MMP-9) in chronic Cr(VI) exposed BEAS-2B cells. Nude mice injected with BEAS-2B cells chronically exposed to Cr(VI) in the presence of luteolin showed reduced tumor incidence compared to Cr(VI) alone treated group. Overexpression of catalase (CAT) or SOD2, eliminated Cr(VI)-induced malignant transformation. Overall, our results indicate that luteolin protects BEAS-2B cells from Cr(VI)-induced carcinogenesis by scavenging ROS and modulating multiple cell signaling mechanisms that are linked to ROS. Luteolin, therefore, serves as a potential chemopreventive agent against Cr(VI)-induced carcinogenesis. - Highlights: • Luteolin inhibited Cr(VI)-induced oxidative stress. • Luteolin inhibited chronic Cr(VI)-induced malignant transformation.

  2. cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes

    International Nuclear Information System (INIS)

    Bhattacharjee, Rajesh; Xiang, Wenpei; Wang, Yinna; Zhang, Xiaoying; Billiar, Timothy R.

    2012-01-01

    Highlights: ► cAMP blocks cell death induced by TNF and actinomycin D in cultured hepatocytes. ► cAMP blocks NF-κB activation induced by TNF and actinomycin D. ► cAMP blocks DISC formation following TNF and actinomycin D exposure. ► cAMP blocks TNF signaling at a proximal step. -- Abstract: Tumor necrosis factor α (TNF) is a pleiotropic proinflammatory cytokine that plays a role in immunity and the control of cell proliferation, cell differentiation, and apoptosis. The pleiotropic nature of TNF is due to the formation of different signaling complexes upon the binding of TNF to its receptor, TNF receptor type 1 (TNFR1). TNF induces apoptosis in various mammalian cells when the cells are co-treated with a transcription inhibitor like actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein, TNF receptor-associated protein with death domain (TRADD), through its cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling proteins, including TNF receptor-associated protein 2 (TRAF2) and receptor-associated protein kinase (RIPK) 1, to form a complex. Subsequently, this complex combines with FADD and procaspase-8, converts into a death-inducing signaling complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second messenger that regulates various cellular processes such as cell proliferation, gene expression, and apoptosis. cAMP analogues are reported to act as anti-apoptotic agents in various cell types, including hepatocytes. We found that a cAMP analogue, dibutyryl cAMP (db-cAMP), inhibits TNF + ActD-induced apoptosis in rat hepatocytes. The protein kinase A (PKA) inhibitor KT-5720 reverses this inhibitory effect of cAMP on apoptosis. Cytoprotection by cAMP involves down-regulation of various apoptotic signal regulators like TRADD and FADD and inhibition of caspase-8 and caspase-3 cleavage. We also found that cAMP exerts its affect at the proximal level of TNF signaling by inhibiting the formation of the DISC

  3. cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharjee, Rajesh [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Xiang, Wenpei [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People' s Republic of China (China); Wang, Yinna [Vascular Medicine Institute, University of Pittsburgh School of Medicine, 10051-5A BST 3, 3501 Fifth Avenue, Pittsburgh, PA 15261 (United States); Zhang, Xiaoying [Department of Medicine/Endocrinology Division, University of Pittsburgh Medical Center, 200 Lothrop St., Pittsburgh, PA 15213 (United States); Billiar, Timothy R., E-mail: billiartr@upmc.edu [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer cAMP blocks cell death induced by TNF and actinomycin D in cultured hepatocytes. Black-Right-Pointing-Pointer cAMP blocks NF-{kappa}B activation induced by TNF and actinomycin D. Black-Right-Pointing-Pointer cAMP blocks DISC formation following TNF and actinomycin D exposure. Black-Right-Pointing-Pointer cAMP blocks TNF signaling at a proximal step. -- Abstract: Tumor necrosis factor {alpha} (TNF) is a pleiotropic proinflammatory cytokine that plays a role in immunity and the control of cell proliferation, cell differentiation, and apoptosis. The pleiotropic nature of TNF is due to the formation of different signaling complexes upon the binding of TNF to its receptor, TNF receptor type 1 (TNFR1). TNF induces apoptosis in various mammalian cells when the cells are co-treated with a transcription inhibitor like actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein, TNF receptor-associated protein with death domain (TRADD), through its cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling proteins, including TNF receptor-associated protein 2 (TRAF2) and receptor-associated protein kinase (RIPK) 1, to form a complex. Subsequently, this complex combines with FADD and procaspase-8, converts into a death-inducing signaling complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second messenger that regulates various cellular processes such as cell proliferation, gene expression, and apoptosis. cAMP analogues are reported to act as anti-apoptotic agents in various cell types, including hepatocytes. We found that a cAMP analogue, dibutyryl cAMP (db-cAMP), inhibits TNF + ActD-induced apoptosis in rat hepatocytes. The protein kinase A (PKA) inhibitor KT-5720 reverses this inhibitory effect of cAMP on apoptosis. Cytoprotection by cAMP involves down-regulation of various apoptotic signal regulators like TRADD and FADD and inhibition of caspase-8 and caspase-3 cleavage. We also found

  4. Quantum Scalar Corrections to the Gravitational Potentials on de Sitter Background

    NARCIS (Netherlands)

    Park, Sohyun; Prokopec, Tomislav; Woodard, R. P.

    We employ the graviton self-energy induced by a massless, minimally coupled (MMC) scalar on de Sitter background to compute the quantum corrections to the gravitational potentials of a static point particle with a mass $M$. The Schwinger-Keldysh formalism is used to derive real and causal effective

  5. Gravitational radiation quadrupole formula is valid for gravitationally interacting systems

    International Nuclear Information System (INIS)

    Walker, M.; Will, C.M.

    1980-01-01

    An argument is presented for the validity of the quadrupole formula for gravitational radiation energy loss in the far field of nearly Newtonian (e.g., binary stellar) systems. This argument differs from earlier ones in that it determines beforehand the formal accuracy of approximation required to describe gravitationally self-interacting systems, uses the corresponding approximate equation of motion explicitly, and evaluate the appropriate asymptotic quantities by matching along the correct space-time light cones

  6. ADA-07 Suppresses Solar Ultraviolet-Induced Skin Carcinogenesis by Directly Inhibiting TOPK.

    Science.gov (United States)

    Gao, Ge; Zhang, Tianshun; Wang, Qiushi; Reddy, Kanamata; Chen, Hanyong; Yao, Ke; Wang, Keke; Roh, Eunmiri; Zykova, Tatyana; Ma, Weiya; Ryu, Joohyun; Curiel-Lewandrowski, Clara; Alberts, David; Dickinson, Sally E; Bode, Ann M; Xing, Ying; Dong, Zigang

    2017-09-01

    Cumulative exposure to solar ultraviolet (SUV) irradiation is regarded as the major etiologic factor in the development of skin cancer. The activation of the MAPK cascades occurs rapidly and is vital in the regulation of SUV-induced cellular responses. The T-LAK cell-originated protein kinase (TOPK), an upstream activator of MAPKs, is heavily involved in inflammation, DNA damage, and tumor development. However, the chemopreventive and therapeutic effects of specific TOPK inhibitors in SUV-induced skin cancer have not yet been elucidated. In the current study, ADA-07, a novel TOPK inhibitor, was synthesized and characterized. Pull-down assay results, ATP competition, and in vitro kinase assay data revealed that ADA-07 interacted with TOPK at the ATP-binding pocket and inhibited its kinase activity. Western blot analysis showed that ADA-07 suppressed SUV-induced phosphorylation of ERK1/2, p38, and JNKs and subsequently inhibited AP-1 activity. Importantly, topical treatment with ADA-07 dramatically attenuated tumor incidence, multiplicity, and volume in SKH-1 hairless mice exposed to chronic SUV. Our findings suggest that ADA-07 is a promising chemopreventive or potential therapeutic agent against SUV-induced skin carcinogenesis that acts by specifically targeting TOPK. Mol Cancer Ther; 16(9); 1843-54. ©2017 AACR . ©2017 American Association for Cancer Research.

  7. Gravitational waves and electrodynamics: new perspectives.

    Science.gov (United States)

    Cabral, Francisco; Lobo, Francisco S N

    2017-01-01

    Given the recent direct measurement of gravitational waves (GWs) by the LIGO-VIRGO collaboration, the coupling between electromagnetic fields and gravity have a special relevance since it opens new perspectives for future GW detectors and also potentially provides information on the physics of highly energetic GW sources. We explore such couplings using the field equations of electrodynamics on (pseudo) Riemann manifolds and apply it to the background of a GW, seen as a linear perturbation of Minkowski geometry. Electric and magnetic oscillations are induced that propagate as electromagnetic waves and contain information as regards the GW which generates them. The most relevant results are the presence of longitudinal modes and dynamical polarization patterns of electromagnetic radiation induced by GWs. These effects might be amplified using appropriate resonators, effectively improving the signal to noise ratio around a specific frequency. We also briefly address the generation of charge density fluctuations induced by GWs and the implications for astrophysics.

  8. Gravitational waves and electrodynamics: new perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Cabral, Francisco; Lobo, Francisco S.N. [Faculdade de Ciencias da Universidade de Lisboa, Instituto de Astrofisica e Ciencias do Espaco, Lisbon (Portugal)

    2017-04-15

    Given the recent direct measurement of gravitational waves (GWs) by the LIGO-VIRGO collaboration, the coupling between electromagnetic fields and gravity have a special relevance since it opens new perspectives for future GW detectors and also potentially provides information on the physics of highly energetic GW sources. We explore such couplings using the field equations of electrodynamics on (pseudo) Riemann manifolds and apply it to the background of a GW, seen as a linear perturbation of Minkowski geometry. Electric and magnetic oscillations are induced that propagate as electromagnetic waves and contain information as regards the GW which generates them. The most relevant results are the presence of longitudinal modes and dynamical polarization patterns of electromagnetic radiation induced by GWs. These effects might be amplified using appropriate resonators, effectively improving the signal to noise ratio around a specific frequency. We also briefly address the generation of charge density fluctuations induced by GWs and the implications for astrophysics. (orig.)

  9. Huaier Extract Induces Autophagic Cell Death by Inhibiting the mTOR/S6K Pathway in Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Xiaolong Wang

    Full Text Available Huaier extract is attracting increased attention due to its biological activities, including antitumor, anti-parasite and immunomodulatory effects. Here, we investigated the role of autophagy in Huaier-induced cytotoxicity in MDA-MB-231, MDA-MB-468 and MCF7 breast cancer cells. Huaier treatment inhibited cell viability in all three cell lines and induced various large membranous vacuoles in the cytoplasm. In addition, electron microscopy, MDC staining, accumulated expression of autophagy markers and flow cytometry revealed that Huaier extract triggered autophagy. Inhibition of autophagy attenuated Huaier-induced cell death. Furthermore, Huaier extract inhibited the mammalian target of the rapamycin (mTOR/S6K pathway in breast cancer cells. After implanting MDA-MB-231 cells subcutaneously into the right flank of BALB/c nu/nu mice, Huaier extract induced autophagy and effectively inhibited xenograft tumor growth. This study is the first to show that Huaier-induced cytotoxicity is partially mediated through autophagic cell death in breast cancer cells through suppression of the mTOR/S6K pathway.

  10. Gangliosides inhibit bee venom melittin cytotoxicity but not phospholipase A(2)-induced degranulation in mast cells.

    Science.gov (United States)

    Nishikawa, Hirofumi; Kitani, Seiichi

    2011-05-01

    Sting accident by honeybee causes severe pain, inflammation and allergic reaction through IgE-mediated anaphylaxis. In addition to this hypersensitivity, an anaphylactoid reaction occurs by toxic effects even in a non-allergic person via cytolysis followed by similar clinical manifestations. Auto-injectable epinephrine might be effective for bee stings, but cannot inhibit mast cell lysis and degranulation by venom toxins. We used connective tissue type canine mast cell line (CM-MC) for finding an effective measure that might inhibit bee venom toxicity. We evaluated degranulation and cytotoxicity by measurement of β-hexosaminidase release and MTT assay. Melittin and crude bee venom induced the degranulation and cytotoxicity, which were strongly inhibited by mono-sialoganglioside (G(M1)), di-sialoganglioside (G(D1a)) and tri-sialoganglioside (G(T1b)). In contrast, honeybee venom-derived phospholipase A(2) induced the net degranulation directly without cytotoxicity, which was not inhibited by G(M1), G(D1a) and G(T1b). For analysis of distribution of Gα(q) and Gα(i) protein by western blotting, lipid rafts were isolated by using discontinuous sucrose gradient centrifuge. Melittin disrupted the localization of Gα(q) and Gα(i) at lipid raft, but gangliosides stabilized the rafts. As a result from this cell-based study, bee venom-induced anaphylactoid reaction can be explained with melittin cytotoxicity and phospholipase A(2)-induced degranulation. Taken together, gangliosides inhibit the effect of melittin such as degranulation, cytotoxicity and lipid raft disruption but not phospholipase A(2)-induced degranulation in mast cells. Our study shows a potential of gangliosides as a therapeutic tool for anaphylactoid reaction by honeybee sting. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression by dietary curcumin

    Directory of Open Access Journals (Sweden)

    Lipigorngoson Suwiwek

    2001-01-01

    Full Text Available Abstract Background We investigated the chemopreventive action of dietary curcumin on 7,12-dimethylbenz(aanthracene (DMBA-initiated and 12,0-tetradecanoylphorbol-13-acetate (TPA-promoted skin tumor formation in Swiss albino mice. Curcumin, a yellow coloring matter isolated from roots of Curcuma longa Linn, is a phenolic compound possessing antioxidant, free radical scavenger, and antiinflammatory properties. It has been shown by previously reported work that TPA-induced skin tumors were inhibited by topical application of curcumin, and curcumin has been shown to inhibit a variety of biological activities of TPA. Topical application of curcumin was reported to inhibit TPA-induced c-fos, c-jun and c-myc gene expression in mouse skin. This paper reports the effects of orally administered curcumin, which was consumed as a dietary component at concentrations of 0.2 % or 1 %, in ad libitum feeding. Results Animals in which tumors had been initiated with DMBA and promoted with TPA experienced significantly fewer tumors and less tumor volume if they ingested either 0.2% or 1% curcumin diets. Also, the dietary consumption of curcumin resulted in a significantly decreased expression of ras and fos proto-oncogenes in the tumorous skin, as measured by enhanced chemiluminesence Western blotting detection system (Amersham. Conclusions Whereas earlier work demonstrated that topical application of curcumin to mouse skin inhibited TPA-induced expression of c-fos, c-jun and c-myc oncogenes, our results are the first to show that orally consumed curcumin significantly inhibited DMBA- and TPA-induced ras and fos gene expression in mouse skin.

  12. Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression by dietary curcumin

    International Nuclear Information System (INIS)

    Limtrakul, Porn-ngarm; Anuchapreeda, Songyot; Lipigorngoson, Suwiwek; Dunn, Floyd W

    2001-01-01

    We investigated the chemopreventive action of dietary curcumin on 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12,0-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor formation in Swiss albino mice. Curcumin, a yellow coloring matter isolated from roots of Curcuma longa Linn, is a phenolic compound possessing antioxidant, free radical scavenger, and antiinflammatory properties. It has been shown by previously reported work that TPA-induced skin tumors were inhibited by topical application of curcumin, and curcumin has been shown to inhibit a variety of biological activities of TPA. Topical application of curcumin was reported to inhibit TPA-induced c-fos, c-jun and c-myc gene expression in mouse skin. This paper reports the effects of orally administered curcumin, which was consumed as a dietary component at concentrations of 0.2 % or 1 %, in ad libitum feeding. Animals in which tumors had been initiated with DMBA and promoted with TPA experienced significantly fewer tumors and less tumor volume if they ingested either 0.2% or 1% curcumin diets. Also, the dietary consumption of curcumin resulted in a significantly decreased expression of ras and fos proto-oncogenes in the tumorous skin, as measured by enhanced chemiluminesence Western blotting detection system (Amersham). Whereas earlier work demonstrated that topical application of curcumin to mouse skin inhibited TPA-induced expression of c-fos, c-jun and c-myc oncogenes, our results are the first to show that orally consumed curcumin significantly inhibited DMBA- and TPA-induced ras and fos gene expression in mouse skin

  13. Synergistic Interactions with PI3K Inhibition that Induce Apoptosis. | Office of Cancer Genomics

    Science.gov (United States)

    Activating mutations involving the PI3K pathway occur frequently in human cancers. However, PI3K inhibitors primarily induce cell cycle arrest, leaving a significant reservoir of tumor cells that may acquire or exhibit resistance. We searched for genes that are required for the survival of PI3K mutant cancer cells in the presence of PI3K inhibition by conducting a genome scale shRNA-based apoptosis screen in a PIK3CA mutant human breast cancer cell. We identified 5 genes (PIM2, ZAK, TACC1, ZFR, ZNF565) whose suppression induced cell death upon PI3K inhibition.

  14. Celecoxib Induced Tumor Cell Radiosensitization by Inhibiting Radiation Induced Nuclear EGFR Transport and DNA-Repair: A COX-2 Independent Mechanism

    International Nuclear Information System (INIS)

    Dittmann, Klaus H.; Mayer, Claus; Ohneseit, Petra A.; Raju, Uma; Andratschke, Nickolaus H.; Milas, Luka; Rodemann, H. Peter

    2008-01-01

    Purpose: The purpose of the study was to elucidate the molecular mechanisms mediating radiosensitization of human tumor cells by the selective cyclooxygenase (COX)-2 inhibitor celecoxib. Methods and Materials: Experiments were performed using bronchial carcinoma cells A549, transformed fibroblasts HH4dd, the FaDu head-and-neck tumor cells, the colon carcinoma cells HCT116, and normal fibroblasts HSF7. Effects of celecoxib treatment were assessed by clonogenic cell survival, Western analysis, and quantification of residual DNA damage by γH 2 AX foci assay. Results: Celecoxib treatment resulted in a pronounced radiosensitization of A549, HCT116, and HSF7 cells, whereas FaDu and HH4dd cells were not radiosensitized. The observed radiosensitization could neither be correlated with basal COX-2 expression pattern nor with basal production of prostaglandin E2, but was depended on the ability of celecoxib to inhibit basal and radiation-induced nuclear transport of epidermal growth factor receptor (EGFR). The nuclear EGFR transport was strongly inhibited in A549-, HSF7-, and COX-2-deficient HCT116 cells, which were radiosensitized, but not in FaDu and HH4dd cells, which resisted celecoxib-induced radiosensitization. Celecoxib inhibited radiation-induced DNA-PK activation in A549, HSF7, and HCT116 cells, but not in FaDu and HH4dd cells. Consequentially, celecoxib increased residual γH2AX foci after irradiation, demonstrating that inhibition of DNA repair has occurred in responsive A549, HCT116, and HSF7 cells only. Conclusions: Celecoxib enhanced radiosensitivity by inhibition of EGFR-mediated mechanisms of radioresistance, a signaling that was independent of COX-2 activity. This novel observation may have therapeutic implications such that COX-2 inhibitors may improve therapeutic efficacy of radiation even in patients whose tumor radioresistance is not dependent on COX-2

  15. Ursodeoxycholic Acid (UDCA) Exerts Anti-Atherogenic Effects by Inhibiting Endoplasmic Reticulum (ER) Stress Induced by Disturbed Flow.

    Science.gov (United States)

    Chung, Jihwa; Kim, Kyoung Hwa; Lee, Seok Cheol; An, Shung Hyun; Kwon, Kihwan

    2015-10-01

    Disturbed blood flow with low-oscillatory shear stress (OSS) is a predominant atherogenic factor leading to dysfunctional endothelial cells (ECs). Recently, it was found that disturbed flow can directly induce endoplasmic reticulum (ER) stress in ECs, thereby playing a critical role in the development and progression of atherosclerosis. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid, has long been used to treat chronic cholestatic liver disease and is known to alleviate endoplasmic reticulum (ER) stress at the cellular level. However, its role in atherosclerosis remains unexplored. In this study, we demonstrated the anti-atherogenic activity of UDCA via inhibition of disturbed flow-induced ER stress in atherosclerosis. UDCA effectively reduced ER stress, resulting in a reduction in expression of X-box binding protein-1 (XBP-1) and CEBP-homologous protein (CHOP) in ECs. UDCA also inhibits the disturbed flow-induced inflammatory responses such as increases in adhesion molecules, monocyte adhesion to ECs, and apoptosis of ECs. In a mouse model of disturbed flow-induced atherosclerosis, UDCA inhibits atheromatous plaque formation through the alleviation of ER stress and a decrease in adhesion molecules. Taken together, our results revealed that UDCA exerts anti-atherogenic activity in disturbed flow-induced atherosclerosis by inhibiting ER stress and the inflammatory response. This study suggests that UDCA may be a therapeutic agent for prevention or treatment of atherosclerosis.

  16. Gravitational wave reception by a sphere

    International Nuclear Information System (INIS)

    Ashby, N.; Dreitlein, J.

    1975-01-01

    The reception of gravitational waves by an elastic self-gravitating spherical detector is studied in detail. The equations of motion of a detector driven by a gravitational wave are presented in the intuitively convenient coordinate system of Fermi. An exact analytic solution is given for the homogeneous isotropic sphere. Nonlinear effects of a massive self-gravitating system are computed for a body of mass equal to that of the earth, and are shown to be numerically important

  17. Mechanical characterisation of the TorPeDO: a low frequency gravitational force sensor

    Science.gov (United States)

    McManus, D. J.; Forsyth, P. W. F.; Yap, M. J.; Ward, R. L.; Shaddock, D. A.; McClelland, D. E.; Slagmolen, B. J. J.

    2017-07-01

    Newtonian noise is likely to be a future challenge at low frequencies for Advanced LIGO and other second generation gravitational wave detectors. We present the TorPeDO system: a dual torsion pendulum sensor designed to measure local gravitational forces to high precision. Gravitational forces induce a differential rotation between the two torsion beams, which is measured with an optical read-out. Both torsion pendulums have a common suspension point, tunable centre of mass, and resonant frequency. This produces a high level of mechanical common mode noise cancellation. We report on a controls prototype of the TorPeDO system, presenting the frequency response and tuning range of both pendulums. A noise budget and mechanical cross-coupling model for this system are also presented. We demonstrate frequency tuning of the two torsion pendulums to a difference of 4.3 μHz.

  18. Accretion-induced spin-wandering effects on the neutron star in Scorpius X-1: Implications for continuous gravitational wave searches

    Science.gov (United States)

    Mukherjee, Arunava; Messenger, Chris; Riles, Keith

    2018-02-01

    The LIGO's discovery of binary black hole mergers has opened up a new era of transient gravitational wave astronomy. The potential detection of gravitational radiation from another class of astronomical objects, rapidly spinning nonaxisymmetric neutron stars, would constitute a new area of gravitational wave astronomy. Scorpius X-1 (Sco X-1) is one of the most promising sources of continuous gravitational radiation to be detected with present-generation ground-based gravitational wave detectors, such as Advanced LIGO and Advanced Virgo. As the sensitivity of these detectors improve in the coming years, so will power of the search algorithms being used to find gravitational wave signals. Those searches will still require integration over nearly year long observational spans to detect the incredibly weak signals from rotating neutron stars. For low mass X-ray binaries such as Sco X-1 this difficult task is compounded by neutron star "spin wandering" caused by stochastic accretion fluctuations. In this paper, we analyze X-ray data from the R X T E satellite to infer the fluctuating torque on the neutron star in Sco X-1. We then perform a large-scale simulation to quantify the statistical properties of spin-wandering effects on the gravitational wave signal frequency and phase evolution. We find that there are a broad range of expected maximum levels of frequency wandering corresponding to maximum drifts of between 0.3 - 50 μ Hz /sec over a year at 99% confidence. These results can be cast in terms of the maximum allowed length of a coherent signal model neglecting spin-wandering effects as ranging between 5-80 days. This study is designed to guide the development and evaluation of Sco X-1 search algorithms.

  19. Inhibition of HDAC6 protects against rhabdomyolysis-induced acute kidney injury.

    Science.gov (United States)

    Shi, Yingfeng; Xu, Liuqing; Tang, Jinhua; Fang, Lu; Ma, Shuchen; Ma, Xiaoyan; Nie, Jing; Pi, Xiaoling; Qiu, Andong; Zhuang, Shougang; Liu, Na

    2017-03-01

    Histone deacetylase 6 (HDAC6) inhibition has been reported to protect against ischemic stroke and prolong survival after sepsis in animal models. However, it remains unknown whether HDAC6 inhibition offers a renoprotective effect after acute kidney injury (AKI). In this study, we examined the effect of tubastatin A (TA), a highly selective inhibitor of HDAC6, on AKI in a murine model of glycerol (GL) injection-induced rhabdomyolysis. Following GL injection, the mice developed severe acute tubular injury as indicated by renal dysfunction; expression of neutrophil gelatinase-associated lipocalin (NGAL), an injury marker of renal tubules; and an increase of TdT-mediated dUTP nick-end labeling (TUNEL)-positive tubular cells. These changes were companied by increased HDAC6 expression in the cytoplasm of renal tubular cells. Administration of TA significantly reduced serum creatinine and blood urea nitrogen levels as well as attenuated renal tubular damage in injured kidneys. HDAC6 inhibition also resulted in decreased expression of NGAL, reduced apoptotic cell, and inactivated caspase-3 in the kidney after acute injury. Moreover, injury to the kidney increased phosphorylation of nuclear factor (NF)-κB and expression of multiple cytokines/chemokines including tumor necrotic factor-α and interleukin-6 and monocyte chemoattractant protein-1, as well as macrophage infiltration. Treatment with TA attenuated all those responses. Finally, HDAC6 inhibition reduced the level of oxidative stress by suppressing malondialdehyde (MDA) and preserving expression of superoxide dismutase (SOD) in the injured kidney. Collectively, these data indicate that HDAC6 contributes to the pathogenesis of rhabdomyolysis-induced AKI and suggest that HDAC6 inhibitors have therapeutic potential for AKI treatment. Copyright © 2017 the American Physiological Society.

  20. Are the gravitational waves quantised?

    International Nuclear Information System (INIS)

    Lovas, I.

    1998-01-01

    The question whether gravitational waves are quantised or not can be investigated by the help of correlation measurements. If the gravitational waves are classical objects then the value of their correlation function is 1. However, if they are quantised, then there exist two possibilities: the gravitational waves are either completely coherent, then the correlation function is again 1, or they are partially coherent, then the correlation function is expected to deviate from 1. If the gravitational waves are generated by the change of the background metrics then they can be in a squeezed state. In a squeezed state there is a chance for the correlation between the phase of the wave and the quantum fluctuations. (author)

  1. Transient multimessenger astronomy with gravitational waves

    International Nuclear Information System (INIS)

    Marka, S

    2011-01-01

    Comprehensive multimessenger astronomy with gravitational waves is a pioneering field bringing us interesting results and presenting us with exciting challenges for the future. During the era of the operation of advanced interferometric gravitational wave detectors, we will have the opportunity to investigate sources of gravitational waves that are also expected to be observable through other messengers, such as gamma rays, x-rays, optical, radio, and/or neutrino emission. Multimessenger searches for gravitational waves with the LIGO-GEO600-Virgo interferometer network have already produced insights on cosmic events and it is expected that the simultaneous observation of electromagnetic or neutrino emission could be a crucial aspect for the first direct detection of gravitational waves in the future. Trigger time, direction and expected frequency range enhances our ability to search for gravitational wave signatures with amplitudes closer to the noise floor of the detector. Furthermore, multimessenger observations will enable the extraction of otherwise unaccessible scientific insight. We summarize the status of transient multimessenger detection efforts as well as mention some of the open questions that might be resolved by advanced or third generation gravitational wave detector networks.

  2. Fatty acid synthase inhibition in human breast cancer cells leads to malonyl-CoA-induced inhibition of fatty acid oxidation and cytotoxicity.

    Science.gov (United States)

    Thupari, J N; Pinn, M L; Kuhajda, F P

    2001-07-13

    Inhibition of fatty acid synthase (FAS) induces apoptosis in human breast cancer cells in vitro and in vivo without toxicity to proliferating normal cells. We have previously shown that FAS inhibition causes a rapid increase in malonyl-CoA levels identifying malonyl-CoA as a potential trigger of apoptosis. In this study we further investigated the role of malonyl-CoA during FAS inhibition. We have found that: [i] inhibition of FAS with cerulenin causes carnitine palmitoyltransferase-1 (CPT-1) inhibition and fatty acid oxidation inhibition in MCF-7 human breast cancer cells likely mediated by elevation of malonyl-CoA; [ii] cerulenin cytotoxicity is due to the nonphysiological state of increased malonyl-CoA, decreased fatty acid oxidation, and decreased fatty acid synthesis; and [iii] the cytotoxic effect of cerulenin can be mimicked by simultaneous inhibition of CPT-1, with etomoxir, and fatty acid synthesis with TOFA, an acetyl-CoA carboxylase (ACC) inhibitor. This study identifies CPT-1 and ACC as two new potential targets for cancer chemotherapy. Copyright 2001 Academic Press.

  3. Gravitational lensing of quasars

    CERN Document Server

    Eigenbrod, Alexander

    2013-01-01

    The universe, in all its richness, diversity and complexity, is populated by a myriad of intriguing celestial objects. Among the most exotic of them are gravitationally lensed quasars. A quasar is an extremely bright nucleus of a galaxy, and when such an object is gravitationally lensed, multiple images of the quasar are produced – this phenomenon of cosmic mirage can provide invaluable insights on burning questions, such as the nature of dark matter and dark energy. After presenting the basics of modern cosmology, the book describes active galactic nuclei, the theory of gravitational lensing, and presents a particular numerical technique to improve the resolution of astronomical data. The book then enters the heart of the subject with the description of important applications of gravitational lensing of quasars, such as the measurement of the famous Hubble constant, the determination of the dark matter distribution in galaxies, and the observation of the mysterious inner parts of quasars with much higher r...

  4. Effects of smoke and tea on radiation-induced bone marrow cell mutation and marrow inhibition

    International Nuclear Information System (INIS)

    Gao Yong; Zhang Weiguang

    2004-01-01

    Objective: To provide scientific information for the prevention and treatment of the radiation damage by analyzing the effects of smoke and tea on radiation-induced bone marrow cell mutation and marrow inhibition. Methods: 7 group mice were exposed to smoke and/or tea and/or radiation respectively. There were also b blank control group and a cyclophosphamide positive control group. The frequencies of micronucleated polychromatic erythrocytes (MPCE), the ratio of polychromatic erythrocytes (PCE) to mature erythrocytes (RBC) in marrow, and the count of peripheral blood hemoleukocyte were observed. Results: The frequencies of MPCE in the groups irradiated with γ-rays were significantly higher than that in the blank control group (P<0.05 or 0.01). The smoke + radiation group's frequency was significantly higher than single radiation group (P<0.05). The ratios of PCE to RBC in the groups irradiated were significantly lower than that in the blank control group (P<0.01). The counts of peripheral blood hemoleukocyte in the groups irradiated were significantly lower than the blank control group (P<0.01). Conclusion: Radiation were able to cause marrow cell mutation and induce marrow inhibition. Smoke increases the effect of radiation-induced marrow cell mutation. Tea and smoke could not affect radiation-induced bone marrow inhibition

  5. Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons.

    Science.gov (United States)

    Mardinly, A R; Spiegel, I; Patrizi, A; Centofante, E; Bazinet, J E; Tzeng, C P; Mandel-Brehm, C; Harmin, D A; Adesnik, H; Fagiolini, M; Greenberg, M E

    2016-03-17

    Inhibitory neurons regulate the adaptation of neural circuits to sensory experience, but the molecular mechanisms by which experience controls the connectivity between different types of inhibitory neuron to regulate cortical plasticity are largely unknown. Here we show that exposure of dark-housed mice to light induces a gene program in cortical vasoactive intestinal peptide (VIP)-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibitory neuron. We identify Igf1 as one of several activity-regulated genes that are specific to VIP neurons, and demonstrate that IGF1 functions cell-autonomously in VIP neurons to increase inhibitory synaptic input onto these neurons. Our findings further suggest that in cortical VIP neurons, experience-dependent gene transcription regulates visual acuity by activating the expression of IGF1, thus promoting the inhibition of disinhibitory neurons and affecting inhibition onto cortical pyramidal neurons.

  6. Gravitation and spacetime

    CERN Document Server

    Ohanian, Hans C

    2013-01-01

    The third edition of this classic textbook is a quantitative introduction for advanced undergraduates and graduate students. It gently guides students from Newton's gravitational theory to special relativity, and then to the relativistic theory of gravitation. General relativity is approached from several perspectives: as a theory constructed by analogy with Maxwell's electrodynamics, as a relativistic generalization of Newton's theory, and as a theory of curved spacetime. The authors provide a concise overview of the important concepts and formulas, coupled with the experimental results underpinning the latest research in the field. Numerous exercises in Newtonian gravitational theory and Maxwell's equations help students master essential concepts for advanced work in general relativity, while detailed spacetime diagrams encourage them to think in terms of four-dimensional geometry. Featuring comprehensive reviews of recent experimental and observational data, the text concludes with chapters on cosmology an...

  7. SIGNATURES OF GRAVITATIONAL INSTABILITY IN RESOLVED IMAGES OF PROTOSTELLAR DISKS

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Ruobing [Lawrence Berkeley National Lab, Berkeley, CA 94720 (United States); Vorobyov, Eduard [Department of Astrophysics, The University of Vienna, Vienna, A-1180 (Austria); Pavlyuchenkov, Yaroslav [Institute of Astronomy, Russian Academy of Sciences, Moscow (Russian Federation); Chiang, Eugene [Department of Astronomy, University of California at Berkeley, Berkeley, CA 94720 (United States); Liu, Hauyu Baobab, E-mail: rdong2013@berkeley.edu [European Southern Observatory (ESO), Karl-Schwarzschild-Strasse 2, D-85748 Garching (Germany)

    2016-06-01

    Protostellar (class 0/I) disks, which have masses comparable to those of their nascent host stars and are fed continuously from their natal infalling envelopes, are prone to gravitational instability (GI). Motivated by advances in near-infrared (NIR) adaptive optics imaging and millimeter-wave interferometry, we explore the observational signatures of GI in disks using hydrodynamical and Monte Carlo radiative transfer simulations to synthesize NIR scattered light images and millimeter dust continuum maps. Spiral arms induced by GI, located at disk radii of hundreds of astronomical units, are local overdensities and have their photospheres displaced to higher altitudes above the disk midplane; therefore, arms scatter more NIR light from their central stars than inter-arm regions, and are detectable at distances up to 1 kpc by Gemini/GPI, VLT/SPHERE, and Subaru/HiCIAO/SCExAO. In contrast, collapsed clumps formed by disk fragmentation have such strong local gravitational fields that their scattering photospheres are at lower altitudes; such fragments appear fainter than their surroundings in NIR scattered light. Spiral arms and streamers recently imaged in four FU Ori systems at NIR wavelengths resemble GI-induced structures and support the interpretation that FUors are gravitationally unstable protostellar disks. At millimeter wavelengths, both spirals and clumps appear brighter in thermal emission than the ambient disk and can be detected by ALMA at distances up to 0.4 kpc with one hour integration times at ∼0.″1 resolution. Collapsed fragments having masses ≳1 M {sub J} can be detected by ALMA within ∼10 minutes.

  8. Thymoquinone inhibits TNF-α-induced inflammation and cell adhesion in rheumatoid arthritis synovial fibroblasts by ASK1 regulation

    Energy Technology Data Exchange (ETDEWEB)

    Umar, Sadiq; Hedaya, Omar; Singh, Anil K.; Ahmed, Salahuddin, E-mail: salah.ahmed@wsu.edu

    2015-09-15

    Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine produced by monocytes/macrophage that plays a pathological role in rheumatoid arthritis (RA). In this study, we investigate the effect of thymoquinone (TQ), a phytochemical found in Nigella sativa, in regulating TNF-α-induced RA synovial fibroblast (RA-FLS) activation. Treatment with TQ (1–5 μM) had no marked effect on the viability of human RA-FLS. Pre-treatment of TQ inhibited TNF-α-induced interleukin-6 (IL-6) and IL-8 production and ICAM-1, VCAM-1, and cadherin-11 (Cad-11) expression in RA-FLS (p < 0.01). Evaluation of the signaling events showed that TQ inhibited TNF-α-induced phospho-p38 and phospho-JNK expression, but had no inhibitory effect on NF-κB pathway, in RA-FLS (p < 0.05; n = 4). Interestingly, we observed that selective down-regulation of TNF-α-induced phospho-p38 and phospho-JNK activation by TQ is elicited through inhibition of apoptosis-regulated signaling kinase 1 (ASK1). Furthermore, TNF-α selectively induced phosphorylation of ASK1 at Thr845 residue in RA-FLS, which was inhibited by TQ pretreatment in a dose dependent manner (p < 0.01). Pre-treatment of RA-FLS with ASK1 inhibitor (TC ASK10), blocked TNF-α induced expression of ICAM-1, VCAM-1, and Cad-11. Our results suggest that TNF-α-induced ASK1-p38/JNK pathway is an important mediator of cytokine synthesis and enhanced expression of adhesion molecule in RA-FLS and TQ, by selectively inhibiting this pathway, may have a potential therapeutic value in regulating tissue destruction observed in RA. - Highlights: • Evolving evidence suggests that ASK1 plays a central role in rheumatic arthritis (RA). • TNF-α activates ASK1, which regulate downstream signaling through JNK/p38 activation in RA-FLS. • ASK1 may be used as a potential therapeutic target in RA. • Thymoquinone was able to selectively inhibit TNF-α-induced phosphorylation of ASK1 in RA-FLS. • Thymoquinone might serve as a potential small

  9. Prevention of wear particle-induced osteolysis by a novel V-ATPase inhibitor saliphenylhalamide through inhibition of osteoclast bone resorption.

    Directory of Open Access Journals (Sweden)

    An Qin

    Full Text Available Wear particle-induced peri-implant loosening (Aseptic prosthetic loosening is one of the most common causes of total joint arthroplasty. It is well established that extensive bone destruction (osteolysis by osteoclasts is responsible for wear particle-induced peri-implant loosening. Thus, inhibition of osteoclastic bone resorption should prevent wear particle induced osteolysis and may serve as a potential therapeutic avenue for prosthetic loosening. Here, we demonstrate for the first time that saliphenylhalamide, a new V-ATPase inhibitor attenuates wear particle-induced osteolysis in a mouse calvarial model. In vitro biochemical and morphological assays revealed that the inhibition of osteolysis is partially attributed to a disruption in osteoclast acidification and polarization, both a prerequisite for osteoclast bone resorption. Interestingly, the V-ATPase inhibitor also impaired osteoclast differentiation via the inhibition of RANKL-induced NF-κB and ERK signaling pathways. In conclusion, we showed that saliphenylhalamide affected multiple physiological processes including osteoclast differentiation, acidification and polarization, leading to inhibition of osteoclast bone resorption in vitro and wear particle-induced osteolysis in vivo. The results of the study provide proof that the new generation V-ATPase inhibitors, such as saliphenylhalamide, are potential anti-resorptive agents for treatment of peri-implant osteolysis.

  10. Gravitation and vacuum field

    International Nuclear Information System (INIS)

    Tevikyan, R.V.

    1986-01-01

    This paper presents equations that describe particles with spins s = 0, 1/2, 1 completely and which also describe 2s + 2 limiting fields as E → ∞. It is shown that the ordinary Hilbert-Einstein action for the gravitation field must be augmented by the action for the Bose vacuum field. This means that one must introduce in the gravitational equations a cosmological term proportional to the square of the strength of the Bose vacuum field. It is shown that the theory of gravitation describes three realities: matter, field, and vacuum field. A new form of matter--the vacuum field--is introduced into field theory

  11. Those Elusive Gravitational Waves

    Science.gov (United States)

    MOSAIC, 1976

    1976-01-01

    The presence of gravitational waves was predicted by Einstein in his theory of General Relativity. Since then, scientists have been attempting to develop a detector sensitive enough to measure these cosmic signals. Once the presence of gravitational waves is confirmed, scientists can directly study star interiors, galaxy cores, or quasars. (MA)

  12. Lithium ions induce prestalk-associated gene expression and inhibit prespore gene expression in Dictyostelium discoideum

    NARCIS (Netherlands)

    Peters, Dorien J.M.; Lookeren Campagne, Michiel M. van; Haastert, Peter J.M. van; Spek, Wouter; Schaap, Pauline

    1989-01-01

    We investigated the effect of Li+ on two types of cyclic AMP-regulated gene expression and on basal and cyclic AMP-stimulated inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) levels. Li+ effectively inhibits cyclic AMP-induced prespore gene expression, half-maximal inhibition occurring at about 2mM-LiCl.

  13. Doxycycline attenuates acrolein-induced mucin production, in part by inhibiting MMP-9.

    Science.gov (United States)

    Ren, Shuang; Guo, Ling-Li; Yang, Jie; Liu, Dai-Shun; Wang, Tao; Chen, Lei; Chen, Ya-Juan; Xu, Dan; Feng, Yu-Lin; Wen, Fu-Qiang

    2011-01-10

    Matrix metalloproteinases (MMPs), especially MMP-9, have been found to increase the expression of epidermal growth factor (EGF) receptor, a possible regulator of acrolein-induced mucin expression in the airway epithelium. The aim of this study was to investigate whether doxycycline, a tetracycline antibiotic that inhibits MMPs, attenuates mucus production and synthesis of mucin MUC5AC in acrolein-exposed rats. Sprague-Dawley rats were exposed to acrolein aerosol [3.0parts/million (ppm), 6h/day, 12days] and they received 20mg/kg doxycycline daily by gavage, beginning two days before exposure to acrolein until the end of the experiment. The production of mucin glycoproteins and expression of the MMP-9 and MUC5AC genes were measured in rat trachea. The increase in levels of MMP-9 mRNA and protein in airway epithelium after acrolein exposure was accompanied by an increase in MUC5AC mRNA expression. Doxycycline significantly prevented these increases in acrolein-induced expression of MMP-9 and MUC5AC and attenuated mucus production in tracheal epithelium. These results indicate that doxycycline attenuated acrolein-induced mucin synthesis, in part by inhibiting expression of MMP-9. Thus doxycycline may have a prophylactic effect in the treatment of smoking-induced mucus hypersecretion. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  14. Probing Positron Gravitation at HERA

    International Nuclear Information System (INIS)

    Gharibyan, Vahagn

    2015-07-01

    An equality of particle and antiparticle gravitational interactions holds in general relativity and is supported by indirect observations. Here I develop a method based on high energy Compton scattering to measure the gravitational interaction of accelerated charged particles. Within that formalism the Compton spectra measured at HERA rule out the positron's anti-gravity and hint for a positron's 1.3(0.2)% weaker coupling to the gravitational field relative to an electron.

  15. Quantum Emulation of Gravitational Waves.

    Science.gov (United States)

    Fernandez-Corbaton, Ivan; Cirio, Mauro; Büse, Alexander; Lamata, Lucas; Solano, Enrique; Molina-Terriza, Gabriel

    2015-07-14

    Gravitational waves, as predicted by Einstein's general relativity theory, appear as ripples in the fabric of spacetime traveling at the speed of light. We prove that the propagation of small amplitude gravitational waves in a curved spacetime is equivalent to the propagation of a subspace of electromagnetic states. We use this result to propose the use of entangled photons to emulate the evolution of gravitational waves in curved spacetimes by means of experimental electromagnetic setups featuring metamaterials.

  16. Probing Positron Gravitation at HERA

    Energy Technology Data Exchange (ETDEWEB)

    Gharibyan, Vahagn

    2015-07-15

    An equality of particle and antiparticle gravitational interactions holds in general relativity and is supported by indirect observations. Here I develop a method based on high energy Compton scattering to measure the gravitational interaction of accelerated charged particles. Within that formalism the Compton spectra measured at HERA rule out the positron's anti-gravity and hint for a positron's 1.3(0.2)% weaker coupling to the gravitational field relative to an electron.

  17. The energy-momentum problem and gravitation theory

    International Nuclear Information System (INIS)

    Logunov, A.A.; Folomeshkin, V.N.

    1977-01-01

    General properties of geometrized gravitation theories are considered. A covariant formulation of conservation laws in an arbitrary Riemann space-time is presented. In the Einstein theory both symmetric and canonical energy-momentum tensors of the matter and gravitational field system and, in particular, energy-momentum of free gravitational waves prove to be equal to zero. Since gravitational waves carry the curvature and, consequently, affect the detector, this bears witness to an intrinsic contradiction of the Einstein theory. To realize the sources of difficulties concerning energy-momentum in the Einstein theory the gravitational field is treated in the same way as all the other physical fields, i.e. in terms of usual Lorentz-invariant field theory. Unification of this approach with the Einstein idea of geometrization enables to construct the geometrized theory, which is free from contradictions, has clearly defined the notions of gravitation field energy-momentum and satisfactorily describes all known experimental facts. To construct a logically consistent theory one should geometrize only the density of the matter Lagrangian. The gravitation field equations are formulated in terms of the Euclidean space-time with a metric tensor γsub(ik), while the matter motion may be completely described in terms of the non-Euclidean space-time with a metric tensor gsub(ik). For strong gravitational fields the predictions of the quasi-linear theory under consideration appriciably differ from those of the Einstein formulation of the gravitation theory. No black holes are present in the theory. The results of the calculation for the energy flow of gravitational waves are rigorously unambiguous and show that gravitational waves carry positively definite energy

  18. Metformin inhibits 7,12-dimethylbenz[a]anthracene-induced breast carcinogenesis and adduct formation in human breast cells by inhibiting the cytochrome P4501A1/aryl hydrocarbon receptor signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Maayah, Zaid H. [Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451 (Saudi Arabia); Ghebeh, Hazem [Stem Cell & Tissue Re-Engineering, King Faisal Specialist Hospital and Research Center, Riyadh 11211 (Saudi Arabia); Alhaider, Abdulqader A. [Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451 (Saudi Arabia); Camel Biomedical Research Unit, College of Pharmacy and Medicine, King Saud University, Riyadh 11451 (Saudi Arabia); El-Kadi, Ayman O.S. [Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton (Canada); Soshilov, Anatoly A.; Denison, Michael S. [Department of Environmental Toxicology, University of California at Davis, Davis, CA 95616 (United States); Ansari, Mushtaq Ahmad [Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451 (Saudi Arabia); Korashy, Hesham M., E-mail: hkorashy@ksu.edu.sa [Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451 (Saudi Arabia)

    2015-04-15

    Recent studies have established that metformin (MET), an oral anti-diabetic drug, possesses antioxidant activity and is effective against different types of cancer in several carcinogen-induced animal models and cell lines. However, whether MET can protect against breast cancer has not been reported before. Therefore, the overall objectives of the present study are to elucidate the potential chemopreventive effect of MET in non-cancerous human breast MCF10A cells and explore the underlying mechanism involved, specifically the role of cytochrome P4501A1 (CYP1A1)/aryl hydrocarbon receptor (AhR) pathway. Transformation of the MCF10A cells into initiated breast cancer cells with DNA adduct formation was conducted using 7,12-dimethylbenz[a]anthracene (DMBA), an AhR ligand. The chemopreventive effect of MET against DMBA-induced breast carcinogenesis was evidenced by the capability of MET to restore the induction of the mRNA levels of basic excision repair genes, 8-oxoguanine DNA glycosylase (OGG1) and apurinic/apyrimidinic endonuclease1 (APE1), and the level of 8-hydroxy-2-deoxyguanosine (8-OHdG). Interestingly, the inhibition of DMBA-induced DNA adduct formation was associated with proportional decrease in CYP1A1 and in NAD(P)H:quinone oxidoreductase 1 (NQO1) gene expression. Mechanistically, the involvements of AhR and nuclear factor erythroid 2-related factor-2 (Nrf2) in the MET-mediated inhibition of DMBA-induced CYP1A1 and NQO1 gene expression were evidenced by the ability of MET to inhibit DMBA-induced xenobiotic responsive element and antioxidant responsive element luciferase reporter gene expression which suggests an AhR- and Nrf2-dependent transcriptional control. However, the inability of MET to bind to AhR suggests that MET is not an AhR ligand. In conclusion, the present work shows a strong evidence that MET inhibits the DMBA-mediated carcinogenicity and adduct formation by inhibiting the expression of CYP1A1 through an AhR ligand-independent mechanism

  19. Metformin inhibits 7,12-dimethylbenz[a]anthracene-induced breast carcinogenesis and adduct formation in human breast cells by inhibiting the cytochrome P4501A1/aryl hydrocarbon receptor signaling pathway

    International Nuclear Information System (INIS)

    Maayah, Zaid H.; Ghebeh, Hazem; Alhaider, Abdulqader A.; El-Kadi, Ayman O.S.; Soshilov, Anatoly A.; Denison, Michael S.; Ansari, Mushtaq Ahmad; Korashy, Hesham M.

    2015-01-01

    Recent studies have established that metformin (MET), an oral anti-diabetic drug, possesses antioxidant activity and is effective against different types of cancer in several carcinogen-induced animal models and cell lines. However, whether MET can protect against breast cancer has not been reported before. Therefore, the overall objectives of the present study are to elucidate the potential chemopreventive effect of MET in non-cancerous human breast MCF10A cells and explore the underlying mechanism involved, specifically the role of cytochrome P4501A1 (CYP1A1)/aryl hydrocarbon receptor (AhR) pathway. Transformation of the MCF10A cells into initiated breast cancer cells with DNA adduct formation was conducted using 7,12-dimethylbenz[a]anthracene (DMBA), an AhR ligand. The chemopreventive effect of MET against DMBA-induced breast carcinogenesis was evidenced by the capability of MET to restore the induction of the mRNA levels of basic excision repair genes, 8-oxoguanine DNA glycosylase (OGG1) and apurinic/apyrimidinic endonuclease1 (APE1), and the level of 8-hydroxy-2-deoxyguanosine (8-OHdG). Interestingly, the inhibition of DMBA-induced DNA adduct formation was associated with proportional decrease in CYP1A1 and in NAD(P)H:quinone oxidoreductase 1 (NQO1) gene expression. Mechanistically, the involvements of AhR and nuclear factor erythroid 2-related factor-2 (Nrf2) in the MET-mediated inhibition of DMBA-induced CYP1A1 and NQO1 gene expression were evidenced by the ability of MET to inhibit DMBA-induced xenobiotic responsive element and antioxidant responsive element luciferase reporter gene expression which suggests an AhR- and Nrf2-dependent transcriptional control. However, the inability of MET to bind to AhR suggests that MET is not an AhR ligand. In conclusion, the present work shows a strong evidence that MET inhibits the DMBA-mediated carcinogenicity and adduct formation by inhibiting the expression of CYP1A1 through an AhR ligand-independent mechanism

  20. Inhibition of Cariogenic Plaque Formation on Root Surface with Polydopamine-Induced-Polyethylene Glycol Coating

    Directory of Open Access Journals (Sweden)

    May Lei Mei

    2016-05-01

    Full Text Available Root caries prevention has been a challenge for clinicians due to its special anatomical location, which favors the accumulation of dental plaque. Researchers are looking for anti-biofouling material to inhibit bacterial growth on exposed root surfaces. This study aimed to develop polydopamine-induced-polyethylene glycol (PEG and to study its anti-biofouling effect against a multi-species cariogenic biofilm on the root dentine surface. Hydroxyapatite disks and human dentine blocks were divided into four groups for experiments. They received polydopamine-induced-PEG, PEG, polydopamine, or water application. Contact angle, quartz crystal microbalance, and Fourier transform infrared spectroscopy were used to study the wetting property, surface affinity, and an infrared spectrum; the results indicated that PEG was induced by polydopamine onto a hydroxyapatite disk. Salivary mucin absorption on hydroxyapatite disks with polydopamine-induced-PEG was confirmed using spectrophotometry. The growth of a multi-species cariogenic biofilm on dentine blocks with polydopamine-induced-PEG was assessed and monitored by colony-forming units, confocal laser scanning microscopy, and scanning electron microscopy. The results showed that dentine with polydopamine-induced-PEG had fewer bacteria than other groups. In conclusion, a novel polydopamine-induced-PEG coating was developed. Its anti-biofouling effect inhibited salivary mucin absorption and cariogenic biofilm formation on dentine surface and thus may be used for the prevention of root dentine caries.

  1. Do pH and flavonoids influence hypochlorous acid-induced catalase inhibition and heme modification?

    Science.gov (United States)

    Krych-Madej, Justyna; Gebicka, Lidia

    2015-09-01

    Hypochlorous acid (HOCl), highly reactive oxidizing and chlorinating species, is formed in the immune response to invading pathogens by the reaction of hydrogen peroxide with chloride catalyzed by the enzyme myeloperoxidase. Catalase, an important antioxidant enzyme, catalyzing decomposition of hydrogen peroxide to water and molecular oxygen, hampers in vitro HOCl formation, but is also one of the main targets for HOCl. In this work we have investigated HOCl-induced catalase inhibition at different pH, and the influence of flavonoids (catechin, epigallocatechin gallate and quercetin) on this process. It has been shown that HOCl-induced catalase inhibition is independent on pH in the range 6.0-7.4. Preincubation of catalase with epigallocatechin gallate and quercetin before HOCl treatment enhances the degree of catalase inhibition, whereas catechin does not affect this process. Our rapid kinetic measurements of absorption changes around the heme group have revealed that heme modification by HOCl is mainly due to secondary, intramolecular processes. The presence of flavonoids, which reduce active catalase intermediate, Compound I to inactive Compound II have not influenced the kinetics of HOCl-induced heme modification. Possible mechanisms of the reaction of hypochlorous acid with catalase are proposed and the biological consequences are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Relic gravitational waves and cosmology

    International Nuclear Information System (INIS)

    Grishchuk, Leonid P

    2005-01-01

    The paper begins with a brief recollection of interactions of the author with Ya B Zeldovich in the context of the study of relic gravitational waves. The principles and early results on the quantum-mechanical generation of cosmological perturbations are then summarized. The expected amplitudes of relic gravitational waves differ in various frequency windows, and therefore the techniques and prospects of their detection are distinct. One section of the paper describes the present state of efforts in direct detection of relic gravitational waves. Another section is devoted to indirect detection via the anisotropy and polarization measurements of the cosmic microwave background (CMB) radiation. It is emphasized throughout the paper that the inference about the existence and expected amount of relic gravitational waves is based on a solid theoretical foundation and the best available cosmological observations. It is also explained in great detail what went wrong with the so-called 'inflationary gravitational waves', whose amount is predicted by inflationary theorists to be negligibly small, thus depriving them of any observational significance. (reviews of topical problems)

  3. Modified entropic gravitation in superconductors

    International Nuclear Information System (INIS)

    Matos, Clovis Jacinto de

    2012-01-01

    Verlinde recently developed a theoretical account of gravitation in terms of an entropic force. The central element in Verlinde’s derivation is information and its relation with entropy through the holographic principle. The application of this approach to the case of superconductors requires to take into account that information associated with superconductor’s quantum vacuum energy is not stored on Planck size surface elements, but in four volume cells with Planck-Einstein size. This has profound consequences on the type of gravitational force generated by the quantum vacuum condensate in superconductors, which is closely related with the cosmological repulsive acceleration responsible for the accelerated expansion of the Universe. Remarkably this new gravitational type force depends on the level of breaking of the weak equivalence principle for cooper pairs in a given superconducting material, which was previously derived by the author starting from similar principles. It is also shown that this new gravitational force can be interpreted as a surface force. The experimental detection of this new repulsive gravitational-type force appears to be challenging.

  4. Thread Embedding Acupuncture Inhibits Ultraviolet B Irradiation-Induced Skin Photoaging in Hairless Mice

    Directory of Open Access Journals (Sweden)

    Yoon-Jung Kim

    2015-01-01

    Full Text Available Thread embedding acupuncture (TEA is an acupuncture treatment applied to many diseases in Korean medical clinics because of its therapeutic effects by continuous stimulation to tissues. It has recently been used to enhance facial skin appearance and antiaging, but data from evidence-based medicine are limited. To investigate whether TEA therapy can inhibit skin photoaging by ultraviolet B (UVB irradiation, we performed analyses for histology, histopathology, in situ zymography and western blot analysis in HR-1 hairless mice. TEA treatment resulted in decreased wrinkle formation and skin thickness (Epidermis; P=0.001 versus UV in UVB irradiated mice and also inhibited degradation of collagen fibers (P=0.010 versus normal by inhibiting proteolytic activity of gelatinase matrix-metalloproteinase-9 (MMP-9. Western blot data showed that activation of c-Jun N-terminal kinase (JNK induced by UVB (P=0.002 versus normal group was significantly inhibited by TEA treatment (P=0.005 versus UV with subsequent alleviation of MMP-9 activation (P=0.048 versus UV. These results suggest that TEA treatment can have anti-photoaging effects on UVB-induced skin damage by maintenance of collagen density through regulation of expression of MMP-9 and related JNK signaling. Therefore, TEA therapy may have potential roles as an alternative treatment for protection against skin damage from aging.

  5. Gravitational waveforms for neutron star binaries from binary black hole simulations

    Science.gov (United States)

    Barkett, Kevin; Scheel, Mark; Haas, Roland; Ott, Christian; Bernuzzi, Sebastiano; Brown, Duncan; Szilagyi, Bela; Kaplan, Jeffrey; Lippuner, Jonas; Muhlberger, Curran; Foucart, Francois; Duez, Matthew

    2016-03-01

    Gravitational waves from binary neutron star (BNS) and black-hole/neutron star (BHNS) inspirals are primary sources for detection by the Advanced Laser Interferometer Gravitational-Wave Observatory. The tidal forces acting on the neutron stars induce changes in the phase evolution of the gravitational waveform, and these changes can be used to constrain the nuclear equation of state. Current methods of generating BNS and BHNS waveforms rely on either computationally challenging full 3D hydrodynamical simulations or approximate analytic solutions. We introduce a new method for computing inspiral waveforms for BNS/BHNS systems by adding the post-Newtonian (PN) tidal effects to full numerical simulations of binary black holes (BBHs), effectively replacing the non-tidal terms in the PN expansion with BBH results. Comparing a waveform generated with this method against a full hydrodynamical simulation of a BNS inspiral yields a phase difference of < 1 radian over ~ 15 orbits. The numerical phase accuracy required of BNS simulations to measure the accuracy of the method we present here is estimated as a function of the tidal deformability parameter λ.

  6. Statins induce apoptosis in rat and human myotube cultures by inhibiting protein geranylgeranylation but not ubiquinone

    International Nuclear Information System (INIS)

    Johnson, Timothy E.; Zhang, Xiaohua; Bleicher, Kimberly B.; Dysart, Gary; Loughlin, Amy F.; Schaefer, William H.; Umbenhauer, Diane R.

    2004-01-01

    Statins are widely used to treat lipid disorders. These drugs are safe and well tolerated; however, in <1% of patients, myopathy and/or rhabdomyolysis can develop. To better understand the mechanism of statin-induced myopathy, we examined the ability of structurally distinct statins to induce apoptosis in an optimized rat myotube model. Compound A (a lactone) and Cerivastatin (an open acid) induced apoptosis, as measured by TUNEL and active caspase 3 staining, in a concentration- and time-dependent manner. In contrast, an epimer of Compound A (Compound B) exhibited a much weaker apoptotic response. Statin-induced apoptosis was completely prevented by mevalonate or geranylgeraniol, but not by farnesol. Zaragozic acid A, a squalene synthase inhibitor, caused no apoptosis on its own and had no effect on Compound-A-induced myotoxicity, suggesting the apoptosis was not a result of cholesterol synthesis inhibition. The geranylgeranyl transferase inhibitors GGTI-2133 and GGTI-2147 caused apoptosis in myotubes; the farnesyl transferase inhibitor FTI-277 exhibited a much weaker effect. In addition, the prenylation of rap1a, a geranylgeranylated protein, was inhibited by Compound A in myotubes at concentrations that induced apoptosis. A similar statin-induced apoptosis profile was seen in human myotube cultures but primary rat hepatocytes were about 200-fold more resistant to statin-induced apoptosis. Although the statin-induced hepatotoxicity could be attenuated with mevalonate, no effect was found with either geranylgeraniol or farnesol. In studies assessing ubiquinone levels after statin treatment in rat and human myotubes, there was no correlation between ubiquinone levels and apoptosis. Taken together, these observations suggest that statins cause apoptosis in myotube cultures in part by inhibiting the geranylgeranylation of proteins, but not by suppressing ubiquinone concentration. Furthermore, the data from primary hepatocytes suggests a cell-type differential

  7. Sensitivity of a combined gravitational antenna

    International Nuclear Information System (INIS)

    Kulagin, V.V.; Rudenko, V.N.

    1986-01-01

    A modification of a combined optico-acoustic gravitational antenna: a long-base laser interferometer, where free masses are changed by Weber resonators, is suggested. The combined gravitational antenna can possess sensitivity h min ∼ 10 -18 without deep cooling of Weber resonators and h min ∼ 10 -19 at helium temperaure of the resonators. This antenna has the following new quantities: presence of three independent responses, that permits to a considerable extent to exclude non-gravitational effects; presence of responses of two separated Weber resonators, that permits to register the wave character of gravitational perturbation by measuring phase shift between relaxation ''tails''. It means that one may with certainty register the wave structure of gravitational radiation for perturbation of metrics h, exceeding the threshold sensitivity of the known detectors by an order

  8. Theory and experiment in gravitational physics

    Science.gov (United States)

    Will, C. M.

    New technological advances have made it feasible to conduct measurements with precision levels which are suitable for experimental tests of the theory of general relativity. This book has been designed to fill a new need for a complete treatment of techniques for analyzing gravitation theory and experience. The Einstein equivalence principle and the foundations of gravitation theory are considered, taking into account the Dicke framework, basic criteria for the viability of a gravitation theory, experimental tests of the Einstein equivalence principle, Schiff's conjecture, and a model theory devised by Lightman and Lee (1973). Gravitation as a geometric phenomenon is considered along with the parametrized post-Newtonian formalism, the classical tests, tests of the strong equivalence principle, gravitational radiation as a tool for testing relativistic gravity, the binary pulsar, and cosmological tests.

  9. Gravitational waves from self-ordering scalar fields

    CERN Document Server

    Fenu, Elisa; Durrer, Ruth; Garcia-Bellido, Juan

    2009-01-01

    Gravitational waves were copiously produced in the early Universe whenever the processes taking place were sufficiently violent. The spectra of several of these gravitational wave backgrounds on subhorizon scales have been extensively studied in the literature. In this paper we analyze the shape and amplitude of the gravitational wave spectrum on scales which are superhorizon at the time of production. Such gravitational waves are expected from the self ordering of randomly oriented scalar fields which can be present during a thermal phase transition or during preheating after hybrid inflation. We find that, if the gravitational wave source acts only during a small fraction of the Hubble time, the gravitational wave spectrum at frequencies lower than the expansion rate at the time of production behaves as $\\Omega_{\\rm GW}(f) \\propto f^3$ with an amplitude much too small to be observable by gravitational wave observatories like LIGO, LISA or BBO. On the other hand, if the source is active for a much longer tim...

  10. Gravitational Waves: The Evidence Mounts

    Science.gov (United States)

    Wick, Gerald L.

    1970-01-01

    Reviews the work of Weber and his colleagues in their attempts at detecting extraterrestial gravitational waves. Coincidence events recorded by special detectors provide the evidence for the existence of gravitational waves. Bibliography. (LC)

  11. Rotation of the cosmic microwave background polarization from weak gravitational lensing.

    Science.gov (United States)

    Dai, Liang

    2014-01-31

    When a cosmic microwave background (CMB) photon travels from the surface of last scatter through spacetime metric perturbations, the polarization vector may rotate about its direction of propagation. This gravitational rotation is distinct from, and occurs in addition to, the lensing deflection of the photon trajectory. This rotation can be sourced by linear vector or tensor metric perturbations and is fully coherent with the curl deflection field. Therefore, lensing corrections to the CMB polarization power spectra as well as the temperature-polarization cross correlations due to nonscalar perturbations are modified. The rotation does not affect lensing by linear scalar perturbations, but needs to be included when calculations go to higher orders. We present complete results for weak lensing of the full-sky CMB power spectra by general linear metric perturbations, taking into account both deflection of the photon trajectory and rotation of the polarization. For the case of lensing by gravitational waves, we show that the B modes induced by the rotation largely cancel those induced by the curl component of deflection.

  12. Gemcitabine inhibits proliferation and induces apoptosis in human pancreatic cancer PANC-1 cells.

    Science.gov (United States)

    Yong-Xian, Gui; Xiao-Huan, Li; Fan, Zhang; Guo-Fang, Tian

    2016-10-01

    The aim of the study is to investigate the underlying molecular mechanisms by which gemcitabine (gem) inhibits proliferation and induces apoptosis in human pancreatic cancer PANC-1 cells in vitro. After PANC-1 cells had been treated by indicated concentration (0, 5, and 25 mg/L) of gem for 48 h, cell proliferation was evaluated by 3'-(4, 5 dimethyl-thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay; cell morphology was observed by transmission electron microscopy; Expression of c-IAP2 and Bcl-2 proteins was analyzed by Western blot; the activity of caspase-3 and -9 was detected by spectrophotometry. Gem significantly inhibited cell proliferation and could induce apoptosis of human pancreatic cancer PANC-1 cells, with a dose-dependent manner. Western blot analysis showed that gem significantly reduced c-IAP2 and Bcl-2 proteins expression level (P PANC-1 cells. Gem could induce apoptosis of human pancreatic cancer PANC-1 cells, probably through downregulating c-IAP2 and Bcl-2 expression levels, and at the same time activating caspase-3 and -9.

  13. Thromboxane synthase suppression induces lung cancer cell apoptosis via inhibiting NF-κB

    International Nuclear Information System (INIS)

    Leung, Kin Chung; Li, Ming-Yue; Leung, Billy C.S.; Hsin, Michael K.Y.; Mok, Tony S.K.; Underwood, Malcolm J.; Chen, George G.

    2010-01-01

    Accumulating evidence shows that the inhibition of thromboxane synthase (TXS) induced apoptosis in cancer cells. TXS inhibitor 1-Benzylimidzole (1-BI) can trigger apoptosis in lung cancer cells but the mechanism is not fully defined. In this study, lung cancer cells were treated with 1-BI. In this study, the level of reactive oxygen species (ROS) was measured and NF-κB activity was determined in human lung cancer cells. The roles of ROS and NF-κB in 1-BI-mediated cell death were analyzed. The results showed that 1-BI induced ROS generation but decreased the activity of NF-κB by reducing phosphorylated IκBα (p-IκBα) and inhibiting the translocation of p65 into the nucleus. In contrast to 1-BI, antioxidant N-acetyl cysteine (NAC) stimulated cell proliferation and significantly protected the cells from 1-BI-mediated cell death by neutralizing ROS. Collectively, apoptosis induced by 1-BI is associated with the over-production of ROS and the reduction of NF-κB. Antioxidants can significantly block the inhibitory effect of 1-BI.

  14. Constraining neutron-star tidal Love numbers with gravitational-wave detectors

    International Nuclear Information System (INIS)

    Flanagan, Eanna E.; Hinderer, Tanja

    2008-01-01

    Ground-based gravitational wave detectors may be able to constrain the nuclear equation of state using the early, low frequency portion of the signal of detected neutron star-neutron star inspirals. In this early adiabatic regime, the influence of a neutron star's internal structure on the phase of the waveform depends only on a single parameter λ of the star related to its tidal Love number, namely, the ratio of the induced quadrupole moment to the perturbing tidal gravitational field. We analyze the information obtainable from gravitational wave frequencies smaller than a cutoff frequency of 400 Hz, where corrections to the internal-structure signal are less than 10%. For an inspiral of two nonspinning 1.4M · neutron stars at a distance of 50 Megaparsecs, LIGO II detectors will be able to constrain λ to λ≤2.0x10 37 g cm 2 s 2 with 90% confidence. Fully relativistic stellar models show that the corresponding constraint on radius R for 1.4M · neutron stars would be R≤13.6 km (15.3 km) for a n=0.5 (n=1.0) polytrope with equation of state p∝ρ 1+1/n

  15. Gravitational Wave Speed: Undefined. Experiments Proposed

    Directory of Open Access Journals (Sweden)

    Daniel Russell

    2018-04-01

    Full Text Available Since changes in all 4 dimensions of spacetime are components of displacement for gravitational waves, a theoretical result is presented that their speed is undefined, and that the Theory of Relativity is not reliable to predict their speed. Astrophysical experiments are proposed with objectives to directly measure gravitational wave speed, and to verify these theoretical results. From the circumference of two merging black hole's final orbit, it is proposed to make an estimate of a total duration of the last ten orbits, before gravitational collapse, for comparison with durations of reported gravitational wave signals. It is proposed to open a new field of engineering of spacetime wave modulation with an objective of faster and better data transmission and communication through the Earth, the Sun, and deep space. If experiments verify that gravitational waves have infinite speed, it is concluded that a catastrophic gravitational collapse, such as a merger of quasars, today, would re-define the geometry and curvature of spacetime on Earth, instantly, without optical observations of this merger visible, until billions of years in the future.

  16. Resonant-bar gravitational radiation antennas

    International Nuclear Information System (INIS)

    Blair, D.G.

    1987-01-01

    This paper reviews the concept of gravitational radiation, and describes the worldwide research programme for the development of high-sensitivity resonant-bar antennas which are aimed at detecting gravitational radiation from astrophysical sources. (author)

  17. Problem of energy-momentum and theory of gravitation

    International Nuclear Information System (INIS)

    Logunov, A.A.; Folomeshkin, V.N.

    1977-01-01

    General properties of geometrised theories of gravitation are considered. Covariant formulation of conservation laws in arbitrary riemannian space-time is given. In the Einstein theory the symmetric as well as canonical energy-momentum tensor of the system ''matter plus gravitational field'' and in particular, the energy-momentum of free gravitational waves, turns out to be equal to zero. To understand the origin of the problems and difficulties concerning the energy-momentum in the Einstein theory, the gravitational filed is considered in the usual framework of the Lorentz invariant field theory, just like any other physical field. Combination of the approach proposed with the Einstein's idea of geometrization makes it possible to formulate the geometrised gravitation theory, in which there are no inner contradictions, the energy-momentum of gravitational field is defined precisely and all the known experimental facts are described successfully. For strong gravitational fields the predictions of the quasilinear geometrised theory under consideration are different from those of the gravitational theory in the Einstein formulation. Black holes are absent in the theory. Evaluation of the energy-flux of gravitational waves leads to unambiguous results and shows that the gravitational waves transfer the positive-definite energy

  18. Sulindac, a nonsteroidal anti-inflammatory drug, selectively inhibits interferon-γ-induced expression of the chemokine CXCL9 gene in mouse macrophages

    International Nuclear Information System (INIS)

    Sakaeda, Yoshiichi; Hiroi, Miki; Shimojima, Takahiro; Iguchi, Mayumi; Kanegae, Haruhide; Ohmori, Yoshihiro

    2006-01-01

    Sulindac, a non-steroidal anti-inflammatory drug, has been shown to exert an anti-tumor effect on several types of cancer. To determine the effect of sulindac on intracellular signaling pathways in host immune cells such as macrophages, we investigated the effect of the drug on interferon gamma (IFNγ)-induced expression of signal transducer and activator of transcription 1 (STAT1) and other genes in mouse macrophage-like cell line RAW264.7 cells. Sulindac, but not aspirin or sodium salicylate, inhibited IFNγ-induced expression of the CXC ligand 9 (CXCL9) mRNA, a chemokine for activated T cells, whereas the interferon-induced expression of CXCL10 or IFN regulatory factor-1 was not affected by sulindac. Luciferase reporter assay demonstrated that sulindac inhibited IFNγ-induced promoter activity of the CXCL9 gene. Surprisingly, sulindac had no inhibitory effect on IFNγ-induced STAT1 activation; however, constitutive nuclear factor κB activity was suppressed by the drug. These results indicate that sulindac selectively inhibited IFNγ-inducible gene expression without inhibiting STAT1 activation

  19. Potential role of an antimicrobial peptide, KLK in inhibiting lipopolysaccharide-induced macrophage inflammation.

    Directory of Open Access Journals (Sweden)

    Pornpimon Jantaruk

    Full Text Available Antimicrobial peptides (AMPs are attractive alternatives to antibiotics. Due to their immune modulatory properties, AMPs are at present emerging as promising agents for controlling inflammatory-mediated diseases. In this study, anti-inflammatory potential of an antimicrobial peptide, KLK (KLKLLLLLKLK and its analogs was evaluated in lipopolysaccharide (LPS-induced RAW 264.7 macrophages. The results herein demonstrated that KLK peptide as well as its analogs significantly inhibited the pro-inflammatory mediator nitric oxide (NO, interleukin-1β (IL-1β and tumor necrosis factor-α (TNF-α production in LPS-stimulated RAW 264.7 macrophages in dose-dependent manners, and such inhibitory effects were not due to direct cytotoxicity. When considering inhibition potency, KLK among the test peptides exhibited the most effective activity. The inhibitory activity of KLK peptide also extended to include suppression of LPS-induced production of prostaglandin E2 (PGE2. KLK significantly decreased mRNA and protein expression of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 as well as mRNA expression of IL-1β and TNF-α. Moreover, KLK inhibited nuclear translocation of nuclear factor-κB (NF-κB p65 and blocked degradation and phosphorylation of inhibitor of κB (IκB. Taken together, these results suggested that the KLK peptide inhibited inflammatory response through the down-regulation of NF-κB mediated activation in macrophages. Since peptide analogs with different amino acid sequences and arrangement were investigated for their anti-inflammatory activities, the residues/structures required for activity were also discussed. Our findings therefore proved anti-inflammatory potential of the KLK peptide and provide direct evidence for therapeutic application of KLK as a novel anti-inflammatory agent.

  20. β-carotene and canthaxanthin inhibit chemically- and physically-induced transformation in 10T1/2 cells

    International Nuclear Information System (INIS)

    Pung, A.; Rundhaug, J.E.; Yoshizawa, C.N.; Bertram, J.S.

    1988-01-01

    We have studied the effects of β-carotene (β-C), a vitamin A precursor of plant origin, and canthaxanthin (CTX), a non-provitamin A carotenoid, on the neoplastic transformation of C3H/10T1/2 murine fibroblast cells. We show that both β-C and CTX inhibit 3-methylcholanthrene (MCA)-induced transformation. Both carotenoids failed to inhibit X-ray-induced transformation when the cells were treated prior to and during irradiation. However, when the drugs were added 1 week after X-irradiation and maintained in the medium thereafter, both carotenoids inhibited subsequent development of transformed foci in a dose-dependent manner. Again, CTX was more effective than β-C. The inhibition of MCA-induced transformation was reversible; upon removal of the drug, transformed foci developed within 2 weeks, indicating that the carotenoids were not specifically toxic to initiated cells. Although both carotenoids caused a small dose-dependent decrease in the growth rate of both parental and initiated 10T1/2 cells, they did not markedly affect colony size or number when the cells were treated as in the transformation assays, nor did they influence the expression of neoplasia of two transformed cell lines. We suggest that the carotenoids' lipid anti-oxidant properties may be responsible for their inhibitory actions on transformation. (author)

  1. Fisetin Inhibits Hyperglycemia-Induced Proinflammatory Cytokine Production by Epigenetic Mechanisms

    Directory of Open Access Journals (Sweden)

    Hye Joo Kim

    2012-01-01

    Full Text Available Diabetes is characterized by a proinflammatory state, and several inflammatory processes have been associated with both type 1 and type 2 diabetes and the resulting complications. High glucose levels induce the release of proinflammatory cytokines. Fisetin, a flavonoid dietary ingredient found in the smoke tree (Cotinus coggygria, and is also widely distributed in fruits and vegetables. Fisetin is known to exert anti-inflammatory effects via inhibition of the NF-κB signaling pathway. In this study, we analyzed the effects of fisetin on proinflammatory cytokine secretion and epigenetic regulation, in human monocytes cultured under hyperglycemic conditions. Human monocytic (THP-1 cells were cultured under control (14.5 mmol/L mannitol, normoglycemic (NG, 5.5 mmol/L glucose, or hyperglycemic (HG, 20 mmol/L glucose conditions, in the absence or presence of fisetin. Fisetin was added (3–10 μM for 48 h. While the HG condition significantly induced histone acetylation, NF-κB activation, and proinflammatory cytokine (IL-6 and TNF-α release from THP-1 cells, fisetin suppressed NF-κB activity and cytokine release. Fisetin treatment also significantly reduced CBP/p300 gene expression, as well as the levels of acetylation and HAT activity of the CBP/p300 protein, which is a known NF-κB coactivator. These results suggest that fisetin inhibits HG-induced cytokine production in monocytes, through epigenetic changes involving NF-κB. We therefore propose that fisetin supplementation be considered for diabetes prevention.

  2. Inhibition by hyperthermia of repair synthesis and chromatin reassembly of ultraviolet-induced damage to DNA

    International Nuclear Information System (INIS)

    Bodell, W.J.; Cleaver, J.E.; Roti Roti, J.L.

    1984-01-01

    The authors have investigated the effects of hyperthermia treatment on sequential steps of the repair of UV-induced DNA damage in HeLa cells. DNA repair synthesis was inhibited by 40% after 15 min of hyperthermia treatment at 45 0 C; greater inhibition of repair synthesis occurred with prolonged incubation at 45 0 C. Enzymatic digestion of repair-labeled DNA with Exonuclease III indicated that once DNA repair was initiated, the DNA repair patch was synthesized to completion and that ligation of the DNA repair patch occurred. Thus, the observed inhibition of UV-induced DNA repair synthesis by hyperthermia treatment may be the result of inhibition of enzymes involved in the initiating steps(s) of DNA repair. DNA repair patches synthesized in UV-irradiated cells labeled at 37 0 C with[ 3 H]Thd were 2.2-fold more sensitive to micrococcal nuclease digestion than was parental DNA; if the length of the labeling period was prolonged, the nuclease sensitivity of the repair patch synthesized approached that of the parental DNA. DNA repair patches synthesized at 45 0 C, however, remained sensitive to micrococcal nuclease digestion even after long labeling periods, indicating that heat treatment inhibits the reassembly of the DNA repair patch into nucleosomal structures. 23 references, 3 figures, 2 tables

  3. On black holes and gravitational waves

    CERN Document Server

    Loinger, Angelo

    2002-01-01

    Black holes and gravitational waves are theoretical entities of today astrophysics. Various observed phenomena have been associated with the concept of black hole ; until now, nobody has detected gravitational waves. The essays contained in this book aim at showing that the concept of black holes arises from a misinterpretation of general relativity and that gravitational waves cannot exist.

  4. The Japanese space gravitational wave antenna - DECIGO

    International Nuclear Information System (INIS)

    Kawamura, S; Seto, N; Sato, S; Arai, K; Ando, M; Tsubono, K; Agatsuma, K; Akutsu, T; Akutsu, T; Arase, Y; Nakamura, T; Tanaka, T; Funaki, I; Takashima, T; Numata, K; Ioka, K; Kanda, N; Aoyanagi, Koh-Suke; Araya, A; Asada, H

    2008-01-01

    DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. The goal of DECIGO is to detect gravitational waves from various kinds of sources mainly between 0.1 Hz and 10 Hz and thus to open a new window of observation for gravitational wave astronomy. DECIGO will consist of three drag-free spacecraft, 1000 km apart from each other, whose relative displacements are measured by a Fabry-Perot Michelson interferometer. We plan to launch DECIGO pathfinder first to demonstrate the technologies required to realize DECIGO and, if possible, to detect gravitational waves from our galaxy or nearby galaxies

  5. Theoretical approaches to laser spectroscopy in the presence of gravitational fields

    International Nuclear Information System (INIS)

    Borde, C.J.; Sharma, J.; Tourrenc, P.; Damour, T.

    1983-01-01

    We present a general framework in which non-linear optical phenomena for an ensemble of accelerated atoms can be studied. We show the equivalence of various approaches through frame transformations. This equivalence is understood within the context of a covariant formalism which is briefly sketched. The choice of the frame, in which the atoms are not accelerated but where the light spectrum and the atomic source term are correspondingly modified, leads to the simplest calculated. It enables one to use the usual density matrix diagrams and associated rules. Explicit examples are given in the case of a sinusoidal gravitational wave. Finally a brief discussion of the signal-to-noise of the sidebands induced by gravitational waves on saturation resonances is outlined

  6. The ovarian DNA damage repair response is induced prior to phosphoramide mustard-induced follicle depletion, and ataxia telangiectasia mutated inhibition prevents PM-induced follicle depletion

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2016-02-01

    Phosphoramide mustard (PM) is an ovotoxic metabolite of cyclophosphamide and destroys primordial and primary follicles potentially by DNA damage induction. The temporal pattern by which PM induces DNA damage and initiation of the ovarian response to DNA damage has not yet been well characterized. This study investigated DNA damage initiation, the DNA repair response, as well as induction of follicular demise using a neonatal rat ovarian culture system. Additionally, to delineate specific mechanisms involved in the ovarian response to PM exposure, utility was made of PKC delta (PKCδ) deficient mice as well as an ATM inhibitor (KU 55933; AI). Fisher 344 PND4 rat ovaries were cultured for 12, 24, 48 or 96 h in medium containing DMSO ± 60 μM PM or KU 55933 (48 h; 10 nM). PM-induced activation of DNA damage repair genes was observed as early as 12 h post-exposure. ATM, PARP1, E2F7, P73 and CASP3 abundance were increased but RAD51 and BCL2 protein decreased after 96 h of PM exposure. PKCδ deficiency reduced numbers of all follicular stages, but did not have an additive impact on PM-induced ovotoxicity. ATM inhibition protected all follicle stages from PM-induced depletion. In conclusion, the ovarian DNA damage repair response is active post-PM exposure, supporting that DNA damage contributes to PM-induced ovotoxicity. - Highlights: • PM exposure induces DNA damage repair gene expression. • Inhibition of ATM prevented PM-induced follicle depletion. • PKCδ deficiency did not impact PM-induced ovotoxicity.

  7. Huperzine A prophylaxis against pentylenetetrazole-induced seizures in rats is associated with increased cortical inhibition.

    Science.gov (United States)

    Gersner, R; Ekstein, D; Dhamne, S C; Schachter, S C; Rotenberg, A

    2015-11-01

    Huperzine A (HupA) is a naturally occurring compound found in the firmoss Huperzia serrata. While HupA is a potent acetylcholinesterase inhibitor, its full pharmacologic profile is incompletely described. Since previous works suggested a capacity for HupA to prophylax against seizures, we tested the HupA antiepileptic potential in pentylenetetrazole (PTZ) rat epilepsy model and explored its mechanism of action by spectral EEG analysis and by paired-pulse transcranial magnetic stimulation (ppTMS), a measure of GABA-mediated intracortical inhibition. We tested whether HupA suppresses seizures in the rat PTZ acute seizure model, and quantified latency to first myoclonus and to generalized tonic-clonic seizure, and spike frequency on EEG. Additionally, we measured power in the EEG gamma frequency band which is associated with GABAergic cortical interneuron activation. Then, as a step toward further examining the HupA antiepileptic mechanism of action, we tested long-interval intracortical inhibition (LICI) using ppTMS coupled with electromyography to assess whether HupA augments GABA-mediated paired-pulse inhibition of the motor evoked potential. We also tested whether the HupA effect on paired-pulse inhibition was central or peripheral by comparison of outcomes following administration of HupA or the peripheral acetylcholinesterase inhibitor pyridostigmine. We also tested whether the HupA effect was dependent on central muscarinic or GABAA receptors by co-administration of HupA and atropine or PTZ, respectively. In tests of antiepileptic potential, HupA suppressed seizures and epileptic spikes on EEG. Spectral EEG analysis also revealed enhanced gamma frequency band power with HupA treatment. By ppTMS we found that HupA increases intracortical inhibition and blocks PTZ-induced cortical excitation. Atropine co-administration with HupA did not alter HupA-induced intracortical inhibition suggesting independent of muscarinic acetylcholine receptors mechanism in this model

  8. Medullary Reticular Neurons Mediate Neuropeptide Y-Induced Metabolic Inhibition and Mastication.

    Science.gov (United States)

    Nakamura, Yoshiko; Yanagawa, Yuchio; Morrison, Shaun F; Nakamura, Kazuhiro

    2017-02-07

    Hypothalamic neuropeptide Y (NPY) elicits hunger responses to increase the chances of surviving starvation: an inhibition of metabolism and an increase in feeding. Here we elucidate a key central circuit mechanism through which hypothalamic NPY signals drive these hunger responses. GABAergic neurons in the intermediate and parvicellular reticular nuclei (IRt/PCRt) of the medulla oblongata, which are activated by NPY-triggered neural signaling from the hypothalamus, potentially through the nucleus tractus solitarius, mediate the NPY-induced inhibition of metabolic thermogenesis in brown adipose tissue (BAT) via their innervation of BAT sympathetic premotor neurons. Intriguingly, the GABAergic IRt/PCRt neurons innervating the BAT sympathetic premotor region also innervate the masticatory motor region, and stimulation of the IRt/PCRt elicits mastication and increases feeding as well as inhibits BAT thermogenesis. These results indicate that GABAergic IRt/PCRt neurons mediate hypothalamus-derived hunger signaling by coordinating both autonomic and feeding motor systems to reduce energy expenditure and to promote feeding. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Gravitational waves in cold dark matter

    Science.gov (United States)

    Flauger, Raphael; Weinberg, Steven

    2018-06-01

    We study the effects of cold dark matter on the propagation of gravitational waves of astrophysical and primordial origin. We show that the dominant effect of cold dark matter on gravitational waves from astrophysical sources is a small frequency dependent modification of the propagation speed of gravitational waves. However, the magnitude of the effect is too small to be detected in the near future. We furthermore show that the spectrum of primordial gravitational waves in principle contains detailed information about the properties of dark matter. However, depending on the wavelength, the effects are either suppressed because the dark matter is highly nonrelativistic or because it contributes a small fraction of the energy density of the universe. As a consequence, the effects of cold dark matter on primordial gravitational waves in practice also appear too small to be detectable.

  10. Radiation-induced inhibition of human lymphocyte blastogenesis: the effect of superoxide dismutase and catalase

    International Nuclear Information System (INIS)

    Knox, S.; Misra, H.P.; Shifrine, M.

    1982-01-01

    Mitogen-induced lymphocyte blastogenesis was measured following X-irradiation (0-4 Gy) in the presence or absence of superoxide dismutase (SOD), under aerobic and anaerobic conditions. There were no significant differences between radiation survival curves under these different conditions, nor did SOD have any radioprotective effect. This demonstrates lack of oxygen dependence of radiation-induced inhibition of lymphocyte blastogenesis. Following X-irradiation at 2 Gy, neither SOD nor catalase, alone or together, added before or after irradiation, were radioprotective. In comparison to controls, both enzymes depressed lymphocyte proliferation when added at levels as low as 25 μg catalase or 100 μg SOD/ml media. When SOD and catalase were added together, the greatest depression of blastogenesis was obtained with increasing levels of SOD relative to increasing levels of catalase, indicating that SOD was largely responsible for this depression. The suppressive effect of administration of SOD (p 2 - and/or H 2 O 2 are not involved in radiation-induced inhibition of lymphocyte blastogenesis. (author)

  11. Anisotropic solutions by gravitational decoupling

    Science.gov (United States)

    Ovalle, J.; Casadio, R.; da Rocha, R.; Sotomayor, A.

    2018-02-01

    We investigate the extension of isotropic interior solutions for static self-gravitating systems to include the effects of anisotropic spherically symmetric gravitational sources by means of the gravitational decoupling realised via the minimal geometric deformation approach. In particular, the matching conditions at the surface of the star with the outer Schwarzschild space-time are studied in great detail, and we describe how to generate, from a single physically acceptable isotropic solution, new families of anisotropic solutions whose physical acceptability is also inherited from their isotropic parent.

  12. Anisotropic solutions by gravitational decoupling

    Energy Technology Data Exchange (ETDEWEB)

    Ovalle, J. [Silesian University in Opava, Institute of Physics and Research Centre of Theoretical Physics and Astrophysics, Faculty of Philosophy and Science, Opava (Czech Republic); Universidad Simon Bolivar, Departamento de Fisica, Caracas (Venezuela, Bolivarian Republic of); Casadio, R. [Alma Mater Universita di Bologna, Dipartimento di Fisica e Astronomia, Bologna (Italy); Istituto Nazionale di Fisica Nucleare, Bologna (Italy); Rocha, R. da [Universidade Federal do ABC (UFABC), Centro de Matematica, Computacao e Cognicao, Santo Andre, SP (Brazil); Sotomayor, A. [Universidad de Antofagasta, Departamento de Matematicas, Antofagasta (Chile)

    2018-02-15

    We investigate the extension of isotropic interior solutions for static self-gravitating systems to include the effects of anisotropic spherically symmetric gravitational sources by means of the gravitational decoupling realised via the minimal geometric deformation approach. In particular, the matching conditions at the surface of the star with the outer Schwarzschild space-time are studied in great detail, and we describe how to generate, from a single physically acceptable isotropic solution, new families of anisotropic solutions whose physical acceptability is also inherited from their isotropic parent. (orig.)

  13. Gravitation and Electricity

    Directory of Open Access Journals (Sweden)

    Stavroulakis N.

    2008-04-01

    Full Text Available The equations of gravitation together with the equations of electromagnetism in terms of the General Theory of Relativity allow to conceive an interdependence between the gravitational field and the electromagnetic field. However the technical difficulties of the relevant problems have precluded from expressing clearly this interdependence. Even the simple problem related to the field generated by a charged spherical mass is not correctly solved. In the present paper we reexamine from the outset this problem and propose a new solution.

  14. Gravitational states of antihydrogen near material surface

    Energy Technology Data Exchange (ETDEWEB)

    Voronin, Alexei Yu., E-mail: dr.a.voronin@gmail.com [P.N. Lebedev Physical Institute (Russian Federation); Froelich, Piotr [Uppsala University, Department of Quantum Chemistry (Sweden); Nesvizhevsky, Valery V. [Institut Laue-Langevin (ILL) (France)

    2012-12-15

    We present a theoretical study of the motion of antihydrogen atoms in the Earth's gravitational field near a material surface. We predict the existence of long-living quasistationary states of antihydrogen in a superposition of the gravitational and Casimir-van der Waals potentials of the surface. We suggest an interferometric method of measuring the energy difference between such gravitational states, hence the gravitational mass of antihydrogen.

  15. Fisetin Inhibits Hyperglycemia-Induced Proinflammatory Cytokine Production by Epigenetic Mechanisms

    OpenAIRE

    Hye Joo Kim; Seong Hwan Kim; Jung-Mi Yun

    2012-01-01

    Diabetes is characterized by a proinflammatory state, and several inflammatory processes have been associated with both type 1 and type 2 diabetes and the resulting complications. High glucose levels induce the release of proinflammatory cytokines. Fisetin, a flavonoid dietary ingredient found in the smoke tree (Cotinus coggygria), and is also widely distributed in fruits and vegetables. Fisetin is known to exert anti-inflammatory effects via inhibition of the NF-?B signaling pathway. In this...

  16. Progranulin Inhibits Human T Lymphocyte Proliferation by Inducing the Formation of Regulatory T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Kyu Hwan Kwack

    2017-01-01

    Full Text Available We have examined the effect of progranulin (PGRN on human T cell proliferation and its underlying mechanism. We show that PGRN inhibits the PHA-induced multiplication of T lymphocytes. It increases the number of iTregs when T lymphocytes are activated by PHA but does not do so in the absence of PHA. PGRN-mediated inhibition of T lymphocyte proliferation, as well as the induction of iTregs, was completely reversed by a TGF-β inhibitor or a Treg inhibitor. PGRN induced TGF-β secretion in the presence of PHA whereas it did not in the absence of PHA. Our findings indicate that PGRN suppresses T lymphocyte proliferation by enhancing the formation of iTregs from activated T lymphocytes in response to TGF-β.

  17. A new theory of space-time and gravitation

    International Nuclear Information System (INIS)

    Denisov, V.I.; Logunov, A.A.

    1982-01-01

    Field theory of gravitation is constructed. It uses a symmetrical second rank tensor field in pseudoeuclidean space-time for describing the gravitational field. The theory is based on the condition of the presence of conservation laws for gravitational field and matter taken together and on the geometrization principle. The field theory of gravitation has the same post-newtonian parame-- ters as the general relativity theory (GRT) which implies that both theories are indistinguishable from the viewpoint of any post- newtonian experiment. The description of the effects in strong gravitational fields as well as properties of gravitational waves in the field theory of gravitation and GRT differ significantly from each other. The distinctions between two theories include also the itational red shifti curving of light trajectories and timabsence in the field theory of gravitation of the effects of grav.. delay/ in processes of propagation of gravitational waves in external fields. These distinctions made it possible to suggest a number of experiments with gravitational waves in which the predictions of the field theory of gravitation can be compared with those of the GRT. Model of the Universe in the field theory of gravitation makes it possible to describe the cosmological red shift of the frequency. Character of the evolution in this mode is determined by the delay parameter q 0 : at q 0 0 >4-3/2xα the ''expansion'' at some moment will ''change'' to contraction'' and the Universe will return to the singular state, where α=8πepsilon 0 /3M 2 (H is the Hubble constant) [ru

  18. Tob1 induces apoptosis and inhibits proliferation, migration and invasion of gastric cancer cells by activating Smad4 and inhibiting β‑catenin signaling.

    Science.gov (United States)

    Kundu, Juthika; Wahab, S M Riajul; Kundu, Joydeb Kumar; Choi, Yoon-La; Erkin, Ozgur Cem; Lee, Hun Seok; Park, Sang Gyu; Shin, Young Kee

    2012-09-01

    Transducer of ErbB-2.1 (Tob1), a tumor suppressor protein, is inactivated in a variety of cancers including stomach cancer. However, the role of Tob1 in gastric carcinogenesis remains elusive. The present study aimed to investigate whether Tob1 could inhibit gastric cancer progression in vitro, and to elucidate its underlying molecular mechanisms. We found differential expression of Tob1 in human gastric cancer (MKN28, AGS and MKN1) cells. The overexpression of Tob1 induced apoptosis in MKN28 and AGS cells, which was associated with sub-G1 arrest, activation of caspase-3, induction of Bax, inhibition of Bcl-2 and cleavage of poly (ADP-ribose) polymerase (PARP). In addition, Tob1 inhibited proliferation, migration and invasion, which were reversed in MKN1 and AGS cells transfected with Tob1 siRNA. Overexpression of Tob1 in MKN28 and AGS cells induced the expression of Smad4, leading to the increased expression and the promoter activity of p15, which was diminished by silencing of Tob1 using specific siRNA. Tob1 decreased the phosphorylation of Akt and glycogen synthase kinase-3β (GSK3β) in MKN28 and AGS cells, resulting in the reduced protein expression and the transcriptional activity of β‑catenin, which in turn decreased the expression of cyclin D1, cyclin-dependent kinase-4 (CDK4), urokinase plasminogen activator receptor (uPAR) and peroxisome proliferator and activator receptor-δ (PPARδ). Conversely, silencing of Tob1 induced the phosphorylation of Akt and GSK-3β, and increased the expression of β‑catenin and its target genes. Collectively, our study demonstrates that the overexpression of Tob1 inhibits gastric cancer progression by activating Smad4- and inhibiting β‑catenin-mediated signaling pathways.

  19. Gravitational waves from self-ordering scalar fields

    International Nuclear Information System (INIS)

    Fenu, Elisa; Durrer, Ruth; Figueroa, Daniel G.; García-Bellido, Juan

    2009-01-01

    Gravitational waves were copiously produced in the early Universe whenever the processes taking place were sufficiently violent. The spectra of several of these gravitational wave backgrounds on subhorizon scales have been extensively studied in the literature. In this paper we analyze the shape and amplitude of the gravitational wave spectrum on scales which are superhorizon at the time of production. Such gravitational waves are expected from the self ordering of randomly oriented scalar fields which can be present during a thermal phase transition or during preheating after hybrid inflation. We find that, if the gravitational wave source acts only during a small fraction of the Hubble time, the gravitational wave spectrum at frequencies lower than the expansion rate at the time of production behaves as Ω GW (f) ∝ f 3 with an amplitude much too small to be observable by gravitational wave observatories like LIGO, LISA or BBO. On the other hand, if the source is active for a much longer time, until a given mode which is initially superhorizon (kη * 1, we find that the gravitational wave energy density is frequency independent, i.e. scale invariant. Moreover, its amplitude for a GUT scale scenario turns out to be within the range and sensitivity of BBO and marginally detectable by LIGO and LISA. This new gravitational wave background can compete with the one generated during inflation, and distinguishing both may require extra information

  20. Inhibition of interleukin-6 decreases atrogene expression and ameliorates tail suspension-induced skeletal muscle atrophy

    Science.gov (United States)

    Yakabe, Mitsutaka; Ota, Hidetaka; Iijima, Katsuya; Eto, Masato; Ouchi, Yasuyoshi; Akishita, Masahiro

    2018-01-01

    Background Interleukin-6 (IL-6) is an inflammatory cytokine. Whether systemic IL-6 affects atrogene expression and disuse-induced skeletal muscle atrophy is unclear. Methods Tail-suspended mice were used as a disuse-induced muscle atrophy model. We administered anti-mouse IL-6 receptor antibody, beta-hydroxy-beta-methylbutyrate (HMB) and vitamin D to the mice and examined the effects on atrogene expression and muscle atrophy. Results Serum IL-6 levels were elevated in the mice. Inhibition of IL-6 receptor suppressed muscle RING finger 1 (MuRF1) expression and prevented muscle atrophy. HMB and vitamin D inhibited the serum IL-6 surge, downregulated the expression of MuRF1 and atrogin-1 in the soleus muscle, and ameliorated atrophy in the mice. Conclusion Systemic IL-6 affects MuRF1 expression and disuse-induced muscle atrophy. PMID:29351340

  1. Inhibition of interleukin-6 decreases atrogene expression and ameliorates tail suspension-induced skeletal muscle atrophy.

    Directory of Open Access Journals (Sweden)

    Mitsutaka Yakabe

    Full Text Available Interleukin-6 (IL-6 is an inflammatory cytokine. Whether systemic IL-6 affects atrogene expression and disuse-induced skeletal muscle atrophy is unclear.Tail-suspended mice were used as a disuse-induced muscle atrophy model. We administered anti-mouse IL-6 receptor antibody, beta-hydroxy-beta-methylbutyrate (HMB and vitamin D to the mice and examined the effects on atrogene expression and muscle atrophy.Serum IL-6 levels were elevated in the mice. Inhibition of IL-6 receptor suppressed muscle RING finger 1 (MuRF1 expression and prevented muscle atrophy. HMB and vitamin D inhibited the serum IL-6 surge, downregulated the expression of MuRF1 and atrogin-1 in the soleus muscle, and ameliorated atrophy in the mice.Systemic IL-6 affects MuRF1 expression and disuse-induced muscle atrophy.

  2. A new geometrical gravitational theory

    International Nuclear Information System (INIS)

    Obata, T.; Chiba, J.; Oshima, H.

    1981-01-01

    A geometrical gravitational theory is developed. The field equations are uniquely determined apart from one unknown dimensionless parameter ω 2 . It is based on an extension of the Weyl geometry, and by the extension the gravitational coupling constant and the gravitational mass are made to be dynamical and geometrical. The fundamental geometrical objects in the theory are a metric gsub(μν) and two gauge scalars phi and psi. The theory satisfies the weak equivalence principle, but breaks the strong one generally. u(phi, psi) = phi is found out on the assumption that the strong one keeps holding good at least for bosons of low spins. Thus there is the simple correspondence between the geometrical objects and the gravitational objects. Since the theory satisfies the weak one, the inertial mass is also dynamical and geometrical in the same way as is the gravitational mass. Moreover, the cosmological term in the theory is a coscalar of power -4 algebraically made of psi and u(phi, psi), so it is dynamical, too. Finally spherically symmetric exact solutions are given. The permissible range of the unknown parameter ω 2 is experimentally determined by applying the solutions to the solar system. (author)

  3. Gravitational waves from supernova matter

    International Nuclear Information System (INIS)

    Scheidegger, S; Whitehouse, S C; Kaeppeli, R; Liebendoerfer, M

    2010-01-01

    We have performed a set of 11 three-dimensional magnetohydrodynamical (MHD) core-collapse supernova simulations in order to investigate the dependences of the gravitational wave signal on the progenitor's initial conditions. We study the effects of the initial central angular velocity and different variants of neutrino transport. Our models are started up from a 15M o-dot progenitor and incorporate an effective general relativistic gravitational potential and a finite temperature nuclear equation of state. Furthermore, the electron flavour neutrino transport is tracked by efficient algorithms for the radiative transfer of massless fermions. We find that non- and slowly rotating models show gravitational wave emission due to prompt- and lepton driven convection that reveals details about the hydrodynamical state of the fluid inside the protoneutron stars. Furthermore we show that protoneutron stars can become dynamically unstable to rotational instabilities at T/|W| values as low as ∼2% at core bounce. We point out that the inclusion of deleptonization during the postbounce phase is very important for the quantitative gravitational wave (GW) prediction, as it enhances the absolute values of the gravitational wave trains up to a factor of ten with respect to a lepton-conserving treatment.

  4. Inflationary gravitational waves in collapse scheme models

    Energy Technology Data Exchange (ETDEWEB)

    Mariani, Mauro, E-mail: mariani@carina.fcaglp.unlp.edu.ar [Facultad de Ciencias Astronómicas y Geofísicas, Universidad Nacional de La Plata, Paseo del Bosque S/N, 1900 La Plata (Argentina); Bengochea, Gabriel R., E-mail: gabriel@iafe.uba.ar [Instituto de Astronomía y Física del Espacio (IAFE), UBA-CONICET, CC 67, Suc. 28, 1428 Buenos Aires (Argentina); León, Gabriel, E-mail: gleon@df.uba.ar [Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria – Pab. I, 1428 Buenos Aires (Argentina)

    2016-01-10

    The inflationary paradigm is an important cornerstone of the concordance cosmological model. However, standard inflation cannot fully address the transition from an early homogeneous and isotropic stage, to another one lacking such symmetries corresponding to our present universe. In previous works, a self-induced collapse of the wave function has been suggested as the missing ingredient of inflation. Most of the analysis regarding the collapse hypothesis has been solely focused on the characteristics of the spectrum associated to scalar perturbations, and within a semiclassical gravity framework. In this Letter, working in terms of a joint metric-matter quantization for inflation, we calculate, for the first time, the tensor power spectrum and the tensor-to-scalar ratio corresponding to the amplitude of primordial gravitational waves resulting from considering a generic self-induced collapse.

  5. Gravitational scattering of electromagnetic radiation

    Science.gov (United States)

    Brooker, J. T.; Janis, A. I.

    1980-01-01

    The scattering of electromagnetic radiation by linearized gravitational fields is studied to second order in a perturbation expansion. The incoming electromagnetic radiation can be of arbitrary multipole structure, and the gravitational fields are also taken to be advanced fields of arbitrary multipole structure. All electromagnetic multipole radiation is found to be scattered by gravitational monopole and time-varying dipole fields. No case has been found, however, in which any electromagnetic multipole radiation is scattered by gravitational fields of quadrupole or higher-order multipole structure. This lack of scattering is established for infinite classes of special cases, and is conjectured to hold in general. The results of the scattering analysis are applied to the case of electromagnetic radiation scattered by a moving mass. It is shown how the mass and velocity may be determined by a knowledge of the incident and scattered radiation.

  6. Bipolar outflows as a repulsive gravitational phenomenon - Azimuthally Symmetric Theory of Gravitation (II)

    International Nuclear Information System (INIS)

    Nyambuya, Golden Gadzirayi

    2010-01-01

    This paper is part of a series on the Azimuthally Symmetric Theory of Gravitation (ASTG). This theory is built on Laplace-Poisson's well known equation and it has been shown that the ASTG is capable of explaining, from a purely classical physics standpoint, the precession of the perihelion of solar planets as a consequence of the azimuthal symmetry emerging from the spin of the Sun. This symmetry has and must have an influence on the emergent gravitational field. We show herein that the emergent equations from the ASTG, under some critical conditions determined by the spin, do possess repulsive gravitational fields in the polar regions of the gravitating body in question. This places the ASTG on an interesting pedestal to infer the origins of outflows as a repulsive gravitational phenomenon. Outflows are a ubiquitous phenomenon found in star forming systems and their true origin is a question yet to be settled. Given the current thinking on their origin, the direction that the present paper takes is nothing short of an asymptotic break from conventional wisdom; at the very least, it is a complete paradigm shift because gravitation is not at all associated with this process, but rather it is thought to be an all-attractive force that only tries to squash matter together onto a single point. Additionally, we show that the emergent Azimuthally Symmetric Gravitational Field from the ASTG strongly suggests a solution to the supposed Radiation Problem that is thought to be faced by massive stars in their process of formation. That is, at ∼ 8-10 M sun , radiation from the nascent star is expected to halt the accretion of matter. We show that in-falling material will fall onto the equatorial disk and from there, this material will be channeled onto the forming star via the equatorial plane, thus accretion of mass continues well past the value of ∼ 8-10 M sun , albeit via the disk. Along the equatorial plane, the net force (with the radiation force included) on any

  7. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    International Nuclear Information System (INIS)

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang

    2015-01-01

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity

  8. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang, E-mail: lvguoqiangwuxivip@163.com

    2015-08-07

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity.

  9. (+)-Nootkatone inhibits tumor necrosis factor α/interferon γ-induced production of chemokines in HaCaT cells.

    Science.gov (United States)

    Choi, Hyeon-Jae; Lee, Jin-Hwee; Jung, Yi-Sook

    2014-05-02

    Chemokines are important mediators of cell migration, and thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) are well-known typical inflammatory chemokines involved in atopic dermatitis (AD). (+)-Nootkatone is the major component of Cyperus rotundus. (+)-Nootkatone has antiallergic, anti-inflammatory, and antiplatelet activities. The purpose of this study was to investigate the effect of (+)-nootkatone on tumor necrosis factor α (TNF-α)/interferon γ (IFN-γ)-induced expression of Th2 chemokines in HaCaT cells. We found that (+)-nootkatone inhibited the TNF-α/IFN-γ-induced expression of TARC/CCL17 and MDC/CCL22 mRNA in HaCaT cells. It also significantly inhibited TNF-α/IFN-γ-induced activation of nuclear factor kappa B (NF-κB), p38 mitogen-activated protein kinase (MAPK), and protein kinase Cζ (PKCζ). Furthermore, we showed that PKCζ and p38 MAPK contributed to the inhibition of TNF-α/IFN-γ-induced TARC/CCL17 and MDC/CCL22 expression by blocking IκBα degradation in HaCaT cells. Taken together, these results suggest that (+)-nootkatone may suppress TNF-α/IFN-γ-induced TARC/CCL17 and MDC/CCL22 expression in HaCaT cells by inhibiting of PKCζ and p38 MAPK signaling pathways that lead to activation of NF-κB. We propose that (+)-nootkatone may be a useful therapeutic candidate for inflammatory skin diseases such as AD. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Nec-1 Enhances Shikonin-Induced Apoptosis in Leukemia Cells by Inhibition of RIP-1 and ERK1/2

    Directory of Open Access Journals (Sweden)

    Hongming Pan

    2012-06-01

    Full Text Available Necrostatin-1 (Nec-1 inhibits necroptosis by allosterically inhibiting the kinase activity of receptor-interacting protein 1 (RIP1, which plays a critical role in necroptosis. RIP1 is a crucial adaptor kinase involved in the activation of NF-κB, production of reactive oxygen species (ROS and the phosphorylation of mitogen activated protein kinases (MAPKs. NF-κB, ROS and MAPKs all play important roles in apoptotic signaling. Nec-1 was regarded as having no effect on apoptosis. Here, we report that Nec-1 increased the rate of nuclear condensation and caspases activation induced by a low concentration of shikonin (SHK in HL60, K562 and primary leukemia cells. siRNA-mediated knockdown of RIP1 significantly enhanced shikonin-induced apoptosis in K562 and HL60 cells. Shikonin treatment alone could slightly inhibit the phosphorylation of ERK1/2 in leukemia cells, and the inhibitory effect on ERK1/2 was significantly augmented by Nec-1. We also found that Nec-1 could inhibit NF-κB p65 translocation to the nucleus at a later stage of SHK treatment. In conclusion, we found that Nec-1 can promote shikonin-induced apoptosis in leukemia cells. The mechanism by which Nec-1 sensitizes shikonin-induced apoptosis appears to be the inhibition of RIP1 kinase-dependent phosphorylation of ERK1/2. To our knowledge, this is the first study to document Nec-1 sensitizes cancer cells to apoptosis.

  11. Interaction of gravitational plane waves

    International Nuclear Information System (INIS)

    Ferrari, V.

    1988-01-01

    The mathematical theory of colliding, infinite-fronted, plane gravitational waves is presented. The process of focusing, the creation of singularities and horizons, due to the interaction, and the lens effect due to a beam-like gravitational wave are discussed

  12. Laboratory generation of gravitational waves

    International Nuclear Information System (INIS)

    Pinto, I.M.; Rotoli, G.

    1988-01-01

    The authors have performed calculations on the basic type of gravitational wave electromagnetic laboratory generators. Their results show that laboratory generations of gravitational wave is at limit of state-of-the-art of present-day giant electromagnetic field generation

  13. Inhibition of IRAK-4 activity for rescuing endotoxin LPS-induced septic mortality in mice by lonicerae flos extract

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sun Hong; Roh, Eunmiri [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Kim, Hyun Soo [Pharmaceutical R and D Center, Huons Co., Ltd., Anyang (Korea, Republic of); Baek, Seung-Il [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Choi, Nam Song [Pharmaceutical R and D Center, Huons Co., Ltd., Anyang (Korea, Republic of); Kim, Narae; Hwang, Bang Yeon; Han, Sang-Bae [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Kim, Youngsoo, E-mail: youngsoo@chungbuk.ac.kr [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of)

    2013-12-13

    Highlights: •Lonicerae flos extract (HS-23) is a clinical candidate, Phase I for sepsis treatment. •Here, HS-23 or its major constituents rescued LPS-induced septic mortality in mice. •As a mechanism, they directly inhibited IRAK-4-catalyzed kinase activity. •Thus, they suppressed LPS-induced expression of NF-κB/AP-1-target inflammatory genes. -- Abstract: Lonicerae flos extract (HS-23) is a clinical candidate currently undergoing Phase I trial in lipopolysaccharide (LPS)-injected healthy human volunteers, but its molecular basis remains to be defined. Here, we investigated protective effects of HS-23 or its major constituents on Escherichia coli LPS-induced septic mortality in mice. Intravenous treatment with HS-23 rescued LPS-intoxicated C57BL/6J mice under septic conditions, and decreased the levels of cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and high-mobility group box-1 (HMGB-1) in the blood. Chlorogenic acid (CGA) and its isomers were assigned as major constituents of HS-23 in the protection against endotoxemia. As a molecular mechanism, HS-23 or CGA isomers inhibited endotoxin LPS-induced autophosphorylation of the IL-1 receptor-associated kinase 4 (IRAK-4) in mouse peritoneal macrophages as well as the kinase activity of IRAK-4 in cell-free reactions. HS-23 consequently suppressed downstream pathways critical for LPS-induced activation of nuclear factor (NF)-κB or activating protein 1 (AP-1) in the peritoneal macrophages. HS-23 also inhibited various toll-like receptor agonists-induced nitric oxide (NO) production, and down-regulated LPS-induced expression of NF-κB/AP-1-target inflammatory genes in the cells. Taken together, HS-23 or CGA isomers exhibited anti-inflammatory therapy against LPS-induced septic mortality in mice, at least in part, mediated through the inhibition of IRAK-4.

  14. Essential oil from lemon peels inhibit key enzymes linked to neurodegenerative conditions and pro-oxidant induced lipid peroxidation.

    Science.gov (United States)

    Oboh, Ganiyu; Olasehinde, Tosin A; Ademosun, Ayokunle O

    2014-01-01

    This study sought to investigate the effects of essential oil from lemon (Citrus limoni) peels on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities in vitro. The essential oil was extracted by hydrodistillation, dried with anhydrous Na2SO4 and characterized using gas chromatography. Antioxidant properties of the oil and inhibition of pro-oxidant-induced lipid peroxidation in rats brain homogenate were also assessed. The essential oil inhibited AChE and BChE activities in a concentration-dependent manner. GC analysis revealed the presence of sabinene, limonene, α-pinene, β-pinene, neral, geranial, 1,8-cineole, linalool, borneol, α-terpineol, terpinen-4-ol, linalyl acetate and β-caryophyllene. Furthermore, the essential oil exhibited antioxidant activities as typified by ferric reducing property, Fe(2+)-chelation and radicals [DPPH, ABTS, OH, NO] scavenging abilities. The inhibition of AChE and BChE activities, inhibition of pro-oxidant induced lipid peroxidation and antioxidant activities could be possible mechanisms for the use of the essential oil in the management and prevention of oxidative stress-induced neurodegeneration.

  15. Glycogen synthase kinase-3 inhibition sensitizes human induced pluripotent stem cells to thiol-containing antioxidants induced apoptosis.

    Science.gov (United States)

    Tu, Chengyi; Xu, Robert; Koleti, Meghana; Zoldan, Janet

    2017-08-01

    Inhibition of glycogen synthase kinase 3 (GSK3) is an extensively used strategy to activate Wnt pathway for pluripotent stem cell (PSC) differentiation. However, the effects of such inhibition on PSCs, besides upregulating the Wnt pathway, have rarely been investigated despite that GSK3 is broadly involved in other cellular activities such as insulin signaling and cell growth/survival regulation. Here we describe a previously unknown synergistic effect between GSK3 inhibition (e.g., Chir99021 and LY2090314) and various normally non-toxic thiol-containing antioxidants (e.g., N-acetylcysteine, NAC) on the induction of apoptosis in human induced pluripotent stem cells (iPSCs). Neither Chir99021 nor the antioxidants individually induced significant apoptosis, whereas their combined treatment resulted in rapid and extensive apoptosis, with substantial caspase 3 activity observed within 3h and over 90% decrease in cell viability after 24h. We confirmed the generality of this phenomenon with multiple independent iPSCs lines, various thiol-based antioxidants and distinct GSK3 inhibitors. Mechanistically, we demonstrated that rapamycin treatment could substantially reduce cell death, suggesting the critical role of mammalian target of rapamycin (mTOR). Akt dysregulation was also found to partially contribute to cell apoptosis but was not the primary cause. Further, this coordinated proapoptotic effect was not detected in mouse ESCs but was present in another human cells line: a breast cancer cell line (MDA-MB-231). Given the wide use of GSK3 inhibition in biomedical research: from iPSC differentiation to cancer intervention and the treatment of neuronal diseases, researchers can potentially take advantage of or avoid this synergistic effect for improved experimental or clinical outcome. Copyright © 2017. Published by Elsevier B.V.

  16. Gravitationally coupled electroweak monopole

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Y.M., E-mail: ymcho7@konkuk.ac.kr [Administration Building 310-4, Konkuk University, Seoul 143-701 (Korea, Republic of); School of Physics and Astronomy, Seoul National University, Seoul 151-742 (Korea, Republic of); Kimm, Kyoungtae [Faculty of Liberal Education, Seoul National University, Seoul 151-747 (Korea, Republic of); Yoon, J.H. [Department of Physics, College of Natural Sciences, Konkuk University, Seoul 143-701 (Korea, Republic of)

    2016-10-10

    We present a family of gravitationally coupled electroweak monopole solutions in Einstein–Weinberg–Salam theory. Our result confirms the existence of globally regular gravitating electroweak monopole which changes to the magnetically charged black hole as the Higgs vacuum value approaches to the Planck scale. Moreover, our solutions could provide a more accurate description of the monopole stars and magnetically charged black holes.

  17. A radiometer for stochastic gravitational waves

    International Nuclear Information System (INIS)

    Ballmer, Stefan W

    2006-01-01

    The LIGO Scientific Collaboration recently reported a new upper limit on an isotropic stochastic background of gravitational waves obtained based on the data from the third LIGO science run (S3). Here I present a new method for obtaining directional upper limits on stochastic gravitational waves that essentially implements a gravitational wave radiometer. The LIGO Scientific Collaboration intends to use this method for future LIGO science runs

  18. Arctigenin Inhibits Adipogenesis by Inducing AMPK Activation and Reduces Weight Gain in High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Han, Yo-Han; Kee, Ji-Ye; Park, Jinbong; Kim, Hye-Lin; Jeong, Mi-Young; Kim, Dae-Seung; Jeon, Yong-Deok; Jung, Yunu; Youn, Dong-Hyun; Kang, JongWook; So, Hong-Seob; Park, Raekil; Lee, Jong-Hyun; Shin, Soyoung; Kim, Su-Jin; Um, Jae-Young; Hong, Seung-Heon

    2016-09-01

    Although arctigenin (ARC) has been reported to have some pharmacological effects such as anti-inflammation, anti-cancer, and antioxidant, there have been no reports on the anti-obesity effect of ARC. The aim of this study is to investigate whether ARC has an anti-obesity effect and mediates the AMP-activated protein kinase (AMPK) pathway. We investigated the anti-adipogenic effect of ARC using 3T3-L1 pre-adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs). In high-fat diet (HFD)-induced obese mice, whether ARC can inhibit weight gain was investigated. We found that ARC reduced weight gain, fat pad weight, and triglycerides in HFD-induced obese mice. ARC also inhibited the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) in in vitro and in vivo. Furthermore, ARC induced the AMPK activation resulting in down-modulation of adipogenesis-related factors including PPARγ, C/EBPα, fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase. This study demonstrates that ARC can reduce key adipogenic factors by activating the AMPK in vitro and in vivo and suggests a therapeutic implication of ARC for obesity treatment. J. Cell. Biochem. 117: 2067-2077, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Gravitational waves from rotating neutron stars and evaluation of fast chirp transform techniques

    CERN Document Server

    Strohmayer, T E

    2002-01-01

    X-ray observations suggest that neutron stars in low mass x-ray binaries (LMXB) are rotating with frequencies in the range 300-600 Hz. These spin rates are significantly less than the break-up rates for essentially all realistic neutron star equations of state, suggesting that some process may limit the spin frequencies of accreting neutron stars to this range. If the accretion-induced spin up torque is in equilibrium with gravitational radiation losses, these objects could be interesting sources of gravitational waves. I present a brief summary of current measurements of neutron star spins in LMXBs based on the observations of high-Q oscillations during thermonuclear bursts (so-called 'burst oscillations'). Further measurements of neutron star spins will be important in exploring the gravitational radiation hypothesis in more detail. To this end, I also present a study of fast chirp transform (FCT) techniques as described by Jenet and Prince (Prince T A and Jenet F A 2000 Phys. Rev. D 62 122001) in the conte...

  20. STOCHASTIC NATURE OF GRAVITATIONAL WAVES FROM SUPERNOVA EXPLOSIONS WITH STANDING ACCRETION SHOCK INSTABILITY

    International Nuclear Information System (INIS)

    Kotake, Kei; Iwakami, Wakana; Ohnishi, Naofumi; Yamada, Shoichi

    2009-01-01

    We study the properties of gravitational waves (GWs) based on three-dimensional (3D) simulations, which demonstrate neutrino-driven explosions aided by standing accretion shock instability (SASI). Pushed by evidence supporting slow rotation prior to core collapse, we focus on the asphericities in neutrino emissions and matter motions outside the protoneutron star. By performing a ray-tracing calculation in 3D, we estimate accurately the gravitational waveforms from anisotropic neutrino emissions. In contrast to the previous work assuming axisymmetry, we find that the gravitational waveforms vary much more stochastically because the explosion anisotropies depend sensitively on the growth of SASI which develops chaotically in all directions. Our results show that the GW spectrum has its peak near ∼100 Hz, reflecting SASI-induced matter overturns of ∼O(10) ms. We point out that the detection of such signals, possibly visible to the LIGO-class detectors for a Galactic supernova, could be an important probe into the long-veiled explosion mechanism.

  1. Detecting gravitational waves from accreting neutron stars

    NARCIS (Netherlands)

    Watts, A.L.; Krishnan, B.

    2009-01-01

    The gravitational waves emitted by neutron stars carry unique information about their structure and composition. Direct detection of these gravitational waves, however, is a formidable technical challenge. In a recent study we quantified the hurdles facing searches for gravitational waves from the

  2. The role of outcome inhibition in interference between outcomes: a contingency-learning analogue of retrieval-induced forgetting.

    Science.gov (United States)

    Vadillo, Miguel A; Orgaz, Cristina; Luque, David; Cobos, Pedro L; López, Francisco J; Matute, Helena

    2013-05-01

    Current associative theories of contingency learning assume that inhibitory learning plays a part in the interference between outcomes. However, it is unclear whether this inhibitory learning results in the inhibition of the outcome representation or whether it simply counteracts previous excitatory learning so that the outcome representation is neither activated nor inhibited. Additionally, these models tend to conceptualize inhibition as a relatively transient and cue-dependent state. However, research on retrieval-induced forgetting suggests that the inhibition of representations is a real process that can be relatively independent of the retrieval cue used to access the inhibited information. Consistent with this alternative view, we found that interference between outcomes reduces the retrievability of the target outcome even when the outcome is associated with a novel (non-inhibitory) cue. This result has important theoretical implications for associative models of interference and shows that the empirical facts and theories developed in studies of retrieval-induced forgetting might be relevant in contingency learning and vice versa. © 2012 The British Psychological Society.

  3. The Japanese space gravitational wave antenna; DECIGO

    OpenAIRE

    Kawamura, Seiji; Ando, Masaki; Nakamura, Takashi; Tsubono, Kimio; Tanaka, Takahiro; Funaki, Ikkoh; Seto, Naoki; Numata, Kenji; Sato, Shuichi; Ioka, Kunihito; Kanda, Nobuyuki; Takashima, Takeshi; Agatsuma, Kazuhiro; Akutsu, Tomotada; Akutsu, Tomomi

    2008-01-01

    DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. The goal of DECIGO is to detect gravitational waves from various kinds of sources mainly between 0.1 Hz and 10 Hz and thus to open a new window of observation for gravitational wave astronomy. DECIGO will consist of three drag-free spacecraft, 1000 km apart from each other, whose relative displacements are measured by a Fabry—Perot Michelson interferometer. We plan to lau...

  4. The Japanese space gravitational wave antenna - DECIGO

    OpenAIRE

    Kawamura, Seiji; Ando, Masaki; Nakamura, Takashi; Tsubono, Kimio; Tanaka, Takahiro; Funaki, Iklkoh; Seto, Naoki; Numata, Kenji; Sato, Shuichi; Ioka, Kunihito; Kanda, Nobuyuki; Takashima, Takeshi; Agatsuma, Kazuhiro; Akutsu, Tomotada; Akutsu, Tomomi

    2008-01-01

    DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. The goal of DECIGO is to detect gravitational waves from various kinds of sources mainly between 0.1 Hz and 10 Hz and thus to open a new window of observation for gravitational wave astronomy. DECIGO will consist of three drag-free spacecraft, 1000 km apart from each other, whose relative displacements are measured by a Fabry—Perot Michelson interferometer. We plan to lau...

  5. Gravitational waves from instabilities in relativistic stars

    International Nuclear Information System (INIS)

    Andersson, Nils

    2003-01-01

    This paper provides an overview of stellar instabilities as sources of gravitational waves. The aim is to put recent work on secular and dynamical instabilities in compact stars in context, and to summarize the current thinking about the detectability of gravitational waves from various scenarios. As a new generation of kilometre length interferometric detectors is now coming online this is a highly topical theme. The review is motivated by two key questions for future gravitational-wave astronomy: are the gravitational waves from various instabilities detectable? If so, what can these gravitational-wave signals teach us about neutron star physics? Even though we may not have clear answers to these questions, recent studies of the dynamical bar-mode instability and the secular r-mode instability have provided new insights into many of the difficult issues involved in modelling unstable stars as gravitational-wave sources. (topical review)

  6. Xijiao Dihuang Decoction combined with Yinqiao Powder reverses influenza virus-induced F-actin reorganization in PMVECs by inhibiting ERM phosphorylation

    Directory of Open Access Journals (Sweden)

    Zinan Xuan

    2016-01-01

    Conclusion: These results show that XDY-CS inhibited influenza-induced F-actin reorganization in PMVECs by down-regulating p-ERM expression via inhibition of the Rho/ROCK, p38 MAPK, and PKC pathways. In conclusion, XDY could reduce the damage to endothelial cytoskeleton induced by IV infection, thus protecting the barriers of PMVECs.

  7. Callose deposition during gravitropism of Zea mays and Pisum sativum and its inhibition by 2-deoxy-D-glucose

    Science.gov (United States)

    Jaffe, M. J.; Leopold, A. C.

    1984-01-01

    In etiolated corn (Zea mays L.) and etiolated pea (Pisum sativum L.) seedlings, a gravitropic stimulation induces the deposition of callose. In the corn coleoptiles this occurs within 5 min of gravity stimulation, and prior to the beginning of curvature. Both gravitropic curvature and callose deposition reach their maxima by 12 h. Within the first 2 h more callose is deposited on the upper (concave) side, but after 2-3 h, this deposition pattern is reversed. An inhibitor of protein glycosylation, 2-deoxy-D-glucose (DDG), inhibits callose production and considerably retards gravitropic bending in both species of plants. Mannose can relieve the inhibition of gravitropic bending by DDG. The pea mutant "Ageotropum", which does not respond to gravity when etiolated, also fails to produce callose in response to a gravitic stimulus. These correlations indicate that callose deposition may be a biochemical component of gravitropism in plant shoots.

  8. Andrographolide inhibits hypoxia-induced hypoxia-inducible factor 1α and endothelin 1 expression through the heme oxygenase 1/CO/cGMP/MKP-5 pathways in EA.hy926 cells.

    Science.gov (United States)

    Lin, Hung-Chih; Su, Shih-Li; Lin, Wan-Chun; Lin, Ai-Hsuan; Yang, Ya-Chen; Lii, Chong-Kuei; Chen, Haw-Wen

    2018-03-01

    Andrographolide is a potent anti-inflammatory agent found in Andrographis paniculata. Endothelin 1 (ET-1) is an endothelium-derived vasoconstrictor with pro-inflammatory properties secreted in response to hypoxia. Mitogen-activated protein kinase phosphatase 5 (MKP-5) is a dual-specificity phosphatase that dephosphorylates threonine and tyrosine residues of MAPKs. We showed previously that hypoxia-induced HIF-1α expression and ET-1 secretion are dependent on p38 MAPK in EA.hy926 cells. Here, we investigate what role MKP-5 plays in andrographolide's inhibition of hypoxia-induced expression of HIF-1α and ET-1. Hypoxic conditions were created using the hypoxia-mimetic agent CoCl 2 . Andrographolide enhanced HO-1 and MKP-5 expression and cellular cGMP content in addition to inhibiting hypoxia-induced ROS generation. Concomitantly, the HO-1 byproduct CO and the cGMP analogue 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) increased MKP-5 expression, and pretreatment with CO and 8-Br-cGMP inhibited hypoxia-induced HIF-1α and ET-1 expression. Transfection of HO-1 siRNA or pretreatment with the HO-1 inhibitor ZnPP-9 or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a specific inhibitor of soluble guanylate cyclase, reduced andrographolide-induced MKP-5 expression. Moreover, silencing MKP-5 or treatment with the phosphatase inhibitor vanadate abrogated andrographolide's suppressing hypoxia-induced p38 MAPK activation and HIF-1α expression. The inhibition of hypoxia-induced HIF-1α and ET-1 expression by andrographolide is likely associated with HO-1/CO/cGMP/MKP-5 pathways, which is involved in inhibiting hypoxia-induced p38 MAPK activation. © 2017 Wiley Periodicals, Inc.

  9. Endoglin inhibits ERK-induced c-Myc and cyclin D1 expression to impede endothelial cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Christopher C.; Bloodworth, Jeffrey C. [Division of Pharmacology, Columbus, OH 43210 (United States); Mythreye, Karthikeyan [Duke University, Department of Medicine, Durham, NC 27708 (United States); Lee, Nam Y., E-mail: lee.5064@osu.edu [Division of Pharmacology, Columbus, OH 43210 (United States); Davis Heart and Lung Research Institute, Columbus, OH 43210 (United States)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Endoglin inhibits ERK activation in endothelial cells. Black-Right-Pointing-Pointer Endoglin is a regulator of c-Myc and cyclin D1 expression. Black-Right-Pointing-Pointer {beta}-arrestin2 interaction with endoglin is required for ERK/c-Myc repression. Black-Right-Pointing-Pointer Endoglin impedes cellular proliferation by targeting ERK-induced mitogenic signaling. -- Abstract: Endoglin is an endothelial-specific transforming growth factor beta (TGF-{beta}) co-receptor essential for angiogenesis and vascular remodeling. Endoglin regulates a wide range of cellular processes, including cell adhesion, migration, and proliferation, through TGF-{beta} signaling to canonical Smad and Smad-independent pathways. Despite its overall pro-angiogenic role in the vasculature, the underlying mechanism of endoglin action is poorly characterized. We previously identified {beta}-arrestin2 as a binding partner that causes endoglin internalization from the plasma membrane and inhibits ERK signaling towards endothelial migration. In the present study, we examined the mechanistic role of endoglin and {beta}-arrestin2 in endothelial cell proliferation. We show that endoglin impedes cell growth through sustained inhibition of ERK-induced c-Myc and cyclin D1 expression in a TGF-{beta}-independent manner. The down-regulation of c-Myc and cyclin D1, along with growth-inhibition, are reversed when the endoglin/{beta}-arrestin2 interaction is disrupted. Given that TGF-{beta}-induced Smad signaling potently represses c-Myc in most cell types, our findings here show a novel mechanism by which endoglin augments growth-inhibition by targeting ERK and key downstream mitogenic substrates.

  10. Putting retrieval-induced forgetting in context: an inhibition-free, context-based account.

    Science.gov (United States)

    Jonker, Tanya R; Seli, Paul; MacLeod, Colin M

    2013-10-01

    We present a new theoretical account of retrieval-induced forgetting (RIF) together with new experimental evidence that fits this account and challenges the dominant inhibition account. RIF occurs when the retrieval of some material from memory produces later forgetting of related material. The inhibition account asserts that RIF is the result of an inhibition mechanism that acts during retrieval to suppress the representations of interfering competitors. This inhibition is enduring, such that the suppressed material is difficult to access on a later test and is, therefore, recalled more poorly than baseline material. Although the inhibition account is widely accepted, a growing body of research challenges its fundamental assumptions. Our alternative account of RIF instead emphasizes the role of context in remembering. According to this context account, both of 2 tenets must be met for RIF to occur: (a) A context change must occur between study and subsequent retrieval practice, and (b) the retrieval practice context must be the active context during the final test when testing practiced categories. The results of 3 experiments, which directly test the divergent predictions of the 2 accounts, support the context account but cannot be explained by the inhibition account. In an extensive discussion, we survey the literature on RIF and apply our context account to the key findings, demonstrating the explanatory power of context. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  11. Technetium-99 conjugated with methylene diphosphonate inhibits receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis.

    Science.gov (United States)

    Gong, Wei; Dou, Huan; Liu, Xianqin; Sun, Lingyun; Hou, Yayi

    2012-10-01

    1. In the present study, we investigated the effects of technetium-99 conjugated with methylene diphosphonate ((99)Tc-MDP), an agent used in radionuclide therapy, on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and explored the underlying mechanisms. 2. The murine macrophage cell line RAW264.7 and bone marrow-derived-macrophages from C57BL/6 mice (BMM) were used as models for osteoclastogenesis in vitro. The expression of some key factors in RANKL (50 ng/mL)-induced osteoclastogenesis in RAW264.7 cells was investigated by flow cytometry and real-time reverse transcription-polymerase chain reaction (RT-PCR). To detect multinucleated osteoclast formation, RAW264.7 cells were induced with RANKL for 4 days, whereas BMM were induced by 50 ng/mL RANKL and 20 ng/mL macrophage colony-stimulating factor for 7 days, before being stained with tartrate-resistant acid phosphatase. 3. Osteoclastogenesis was evaluated using the osteoclast markers CD51, matrix metalloproteinase (MMP)-9 and cathepsin K. At 0.01 μg/mL, (99)Tc-MDP significantly inhibited RANKL-induced osteoclastogenesis without any cytotoxicity. In addition, (99)Tc-MDP abolished the appearance of multinucleated osteoclasts. 4. Real-time RT-PCR analysis of transcription factor expression revealed that (99)Tc-MDP inhibited the expression of c-Fos and nuclear factor of activated T cells. In addition, (99)Tc-MDP inhibited the expression of the inflammatory factors interleukin (IL)-6, tumour necrosis factor-α and IL-1β. Finally, (99)Tc-MDP inhibited the activation of mitogen-activated protein kinases in RAW264.7 cells following RANKL stimulation. 5. In conclusion, (99)Tc-MDP possesses anti-osteoclastogenic activity against RANKL-induced osteoclast formation. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.

  12. The gravitational-wave memory effect

    International Nuclear Information System (INIS)

    Favata, Marc

    2010-01-01

    The nonlinear memory effect is a slowly growing, non-oscillatory contribution to the gravitational-wave amplitude. It originates from gravitational waves that are sourced by the previously emitted waves. In an ideal gravitational-wave interferometer a gravitational wave with memory causes a permanent displacement of the test masses that persists after the wave has passed. Surprisingly, the nonlinear memory affects the signal amplitude starting at leading (Newtonian-quadrupole) order. Despite this fact, the nonlinear memory is not easily extracted from current numerical relativity simulations. After reviewing the linear and nonlinear memory I summarize some recent work, including (1) computations of the memory contribution to the inspiral waveform amplitude (thus completing the waveform to third post-Newtonian order); (2) the first calculations of the nonlinear memory that include all phases of binary black hole coalescence (inspiral, merger, ringdown); and (3) realistic estimates of the detectability of the memory with LISA.

  13. Highlights in gravitation and cosmology

    International Nuclear Information System (INIS)

    Iyer, B.R.; Kembhavi, Ajit; Narlikar, J.V.; Vishveshwara, C.V.

    1988-01-01

    This book assesses research into gravitation and cosmology by examining the subject from various viewpoints: the classical and quantum pictures, along with the cosmological and astrophysical applications. There are 35 articles by experts of international standing. Each defines the state of the art and contains a concise summary of our present knowledge of a facet of gravitational physics. These edited papers are based on those first given at an international conference held in Goa, India at the end of 1987. The following broad areas are covered: classical relativity, quantum gravity, cosmology, black holes, compact objects, gravitational radiation and gravity experiments. In this volume there are also summaries of discussions on the following special topics: exact solutions of cosmological equations, mathematical aspects of general relativity, the early universe, and quantum gravity. For research workers in cosmology and gravitation this reference book provides a broad view of present achievements and current problems. (author)

  14. Advanced interferometric gravitational-wave detectors

    CERN Document Server

    Saulson, Peter R

    2019-01-01

    Gravitational waves are one of the most exciting and promising emerging areas of physics and astrophysics today. The detection of gravitational waves will rank among the most significant physics discoveries of the 21st century.Advanced Interferometric Gravitational-Wave Detectors brings together many of the world's top experts to deliver an authoritative and in-depth treatment on current and future detectors. Volume I is devoted to the essentials of gravitational-wave detectors, presenting the physical principles behind large-scale precision interferometry, the physics of the underlying noise sources that limit interferometer sensitivity, and an explanation of the key enabling technologies that are used in the detectors. Volume II provides an in-depth look at the Advanced LIGO and Advanced Virgo interferometers that have just finished construction, as well as examining future interferometric detector concepts. This two-volume set will provide students and researchers the comprehensive background needed to und...

  15. Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qiang [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen (China); The First Affiliated Hospital of Xiamen University, Xiamen (China); Jiang, Yuan; An, Yuan; Zhao, Na; Zhao, Yang [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen (China); Yu, Chundong, E-mail: cdyu@xmu.edu.cn [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen (China)

    2011-06-17

    Highlights: {yields} Soluble FGFR4 extracellular domain (FGFR4-ECD) was effectively expressed. {yields} FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling. {yields} FGFR4-ECD reduced palmitic acid-induced steatosis of HepG2 cells. {yields} FGFR4-ECD reduced tetracycline-induced fatty liver in mice. {yields} FGFR4-ECD partially restored tetracycline-repressed PPAR{alpha} expression. -- Abstract: Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane tyrosine kinase receptor that plays a crucial role in the regulation of hepatic bile acid and lipid metabolism. FGFR4 underlies high-fat diet-induced hepatic steatosis, suggesting that inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD). To determine whether neutralization of FGFR4 ligands by soluble FGFR4 extracellular domain (FGFR4-ECD) can inhibit the activation of FGFR4, we constructed FGFR4-ECD expression vector and showed that FGFR4-ECD was effectively expressed in cells and secreted into culture medium. FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling and reduced steatosis of HepG2 induced by palmitic acid in vitro. Furthermore, in a tetracycline-induced fatty liver model, expression of FGFR4-ECD in mouse liver reduced the accumulation of hepatic lipids and partially restored the expression of peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}), which promotes the mitochondrial fatty acid beta-oxidation but is repressed by tetracycline. Taken together, these results demonstrate that FGFR4-ECD can block FGFR4 signaling and prevent hepatic steatosis, highlighting the potential value of inhibition of FGFR4 signaling as a method for therapeutic intervention against NAFLD.

  16. Soluble FGFR4 extracellular domain inhibits FGF19-induced activation of FGFR4 signaling and prevents nonalcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Chen, Qiang; Jiang, Yuan; An, Yuan; Zhao, Na; Zhao, Yang; Yu, Chundong

    2011-01-01

    Highlights: → Soluble FGFR4 extracellular domain (FGFR4-ECD) was effectively expressed. → FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling. → FGFR4-ECD reduced palmitic acid-induced steatosis of HepG2 cells. → FGFR4-ECD reduced tetracycline-induced fatty liver in mice. → FGFR4-ECD partially restored tetracycline-repressed PPARα expression. -- Abstract: Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane tyrosine kinase receptor that plays a crucial role in the regulation of hepatic bile acid and lipid metabolism. FGFR4 underlies high-fat diet-induced hepatic steatosis, suggesting that inhibition of FGFR4 activation may be an effective way to prevent or treat nonalcoholic fatty liver disease (NAFLD). To determine whether neutralization of FGFR4 ligands by soluble FGFR4 extracellular domain (FGFR4-ECD) can inhibit the activation of FGFR4, we constructed FGFR4-ECD expression vector and showed that FGFR4-ECD was effectively expressed in cells and secreted into culture medium. FGFR4-ECD inhibited FGF19-induced activation of FGFR4 signaling and reduced steatosis of HepG2 induced by palmitic acid in vitro. Furthermore, in a tetracycline-induced fatty liver model, expression of FGFR4-ECD in mouse liver reduced the accumulation of hepatic lipids and partially restored the expression of peroxisome proliferator-activated receptor α (PPARα), which promotes the mitochondrial fatty acid beta-oxidation but is repressed by tetracycline. Taken together, these results demonstrate that FGFR4-ECD can block FGFR4 signaling and prevent hepatic steatosis, highlighting the potential value of inhibition of FGFR4 signaling as a method for therapeutic intervention against NAFLD.

  17. Sargahydroquinoic acid inhibits TNFα-induced AP-1 and NF-κB signaling in HaCaT cells through PPARα activation

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Youngsic; Jung, Yujung; Kim, Min Cheol; Kwon, Hak Cheol [Natural Medicine Center, KIST Gangneung Institute, Gangneung 210-340 (Korea, Republic of); Kang, Ki Sung [College of Korean Medicine, Gachon University, Seongnam 461-701 (Korea, Republic of); Kim, Yong Kee, E-mail: yksnbk@sm.ac.kr [College of Pharmacy, Sookmyung Women’s University, Seoul 140-742 (Korea, Republic of); Kim, Su-Nam, E-mail: snkim@kist.re.kr [Natural Medicine Center, KIST Gangneung Institute, Gangneung 210-340 (Korea, Republic of)

    2014-08-08

    Highlights: • SHQA increases PPARα/γ transactivation and inhibits MMP-2/-9 expression. • SHQA inhibits TNFα-induced AP-1 and MAPK signaling. • SHQA inhibits TNFα-induced p65 translocation and IκBα phosphorylation. • SHQA inhibits TNFα-induced AP-1 and NF-κB signaling via PPARα. - Abstract: Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors and expressed in various cell types in the skin, including keratinocytes, fibroblasts and infiltrating immune cells. Thus, their ligands are targets for the treatment of various skin disorders, such as photo-aging and chronological aging of skin. Intensive studies have revealed that PPARα/γ functions in photo-aging and age-related inflammation by regulating matrix metalloproteinases (MMPs) via activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). However, the detailed mechanism of PPARα/γ’s role in skin aging has not yet been elucidated. In this study, we confirmed that sargahydroquinoic acid (SHQA) as a PPARα/γ ligand significantly decreased Tumor Necrosis Factor-alpha (TNFα)-induced MMP-2/-9 expression by downregulating TNFα-induced transcription factors, subsequently reducing IκBα degradation and blocking NF-κB p65 nuclear translocation in HaCaT human epidermal keratinocyte cells. Treatment of cells with SHQA and GW6471 (PPARα antagonist) not bisphenol A diglycidyl ether (PPARγ antagonists), reversed the effect on TNFα-induced inflammatory signaling pathway activation. Taken together, our data suggest that SHQA inhibit TNFα-induced MMP-2/-9 expression and age-related inflammation by suppressing AP-1 and NF-κB pathway via PPARα.

  18. Gravitational waves from scalar field accretion

    International Nuclear Information System (INIS)

    Nunez, Dario; Degollado, Juan Carlos; Moreno, Claudia

    2011-01-01

    Our aim in this work is to outline some physical consequences of the interaction between black holes and scalar field halos in terms of gravitational waves. In doing so, the black hole is taken as a static and spherically symmetric gravitational source, i.e. the Schwarzschild black hole, and we work within the test field approximation, considering that the scalar field lives in the curved space-time outside the black hole. We focused on the emission of gravitational waves when the black hole is perturbed by the surrounding scalar field matter. The symmetries of the space-time and the simplicity of the matter source allow, by means of a spherical harmonic decomposition, to study the problem by means of a one-dimensional description. Some properties of such gravitational waves are discussed as a function of the parameters of the infalling scalar field, and allow us to make the conjecture that the gravitational waves carry information on the type of matter that generated them.

  19. Fundamentals of interferometric gravitational wave detectors

    CERN Document Server

    Saulson, Peter R

    2017-01-01

    LIGO's recent discovery of gravitational waves was headline news around the world. Many people will want to understand more about what a gravitational wave is, how LIGO works, and how LIGO functions as a detector of gravitational waves.This book aims to communicate the basic logic of interferometric gravitational wave detectors to students who are new to the field. It assumes that the reader has a basic knowledge of physics, but no special familiarity with gravitational waves, with general relativity, or with the special techniques of experimental physics. All of the necessary ideas are developed in the book.The first edition was published in 1994. Since the book is aimed at explaining the physical ideas behind the design of LIGO, it stands the test of time. For the second edition, an Epilogue has been added; it brings the treatment of technical details up to date, and provides references that would allow a student to become proficient with today's designs.

  20. Gravitational-Wave Astronomy

    Science.gov (United States)

    Kelly, Bernard J.

    2010-01-01

    Einstein's General Theory of Relativity is our best classical description of gravity, and informs modern astronomy and astrophysics at all scales: stellar, galactic, and cosmological. Among its surprising predictions is the existence of gravitational waves -- ripples in space-time that carry energy and momentum away from strongly interacting gravitating sources. In my talk, I will give an overview of the properties of this radiation, recent breakthroughs in computational physics allowing us to calculate the waveforms from galactic mergers, and the prospect of direct observation with interferometric detectors such as LIGO and LISA.

  1. Gravitational-wave detector realized by a superconductor

    International Nuclear Information System (INIS)

    Ishidoshiro, K.; Ando, M.; Takamori, A.; Okada, K.; Tsubono, K.

    2010-01-01

    In this article, we present a new gravitational-wave detector based on superconducting magnetic levitation and results of its prototype test. Our detector is composed of the suspended test mass that is rotated by gravitational waves. Gravitational wave signals are readout by monitoring its angular motion. Superconducting magnetic levitation is used for the suspension of the test mass, since it has many advantages, such as zero mechanical loss and resonant frequency around its suspension axis in an ideal situation. For the study of actual performance of such gravitational-wave detector, a prototype detector has been developed. Using the prototype detector, the actual loss factor and resonant frequency are measured as 1.2 x 10 -8 Nms/rad and 5 mHz respectively. A detector noise is also evaluated. The current noise level is determined by the magnetic coupling with external magnetic field and mechanical coupling between translation and angular motion. The prototype detector has already one of the lowest noise levels for gravitational waves at 0.1 Hz among current gravitational-wave detectors. We have succeeded at the demonstration of the advantages of our torsion gravitational-wave detector.

  2. Anti-ghrelin Spiegelmer inhibits exogenous ghrelin-induced increases in food intake, hoarding, and neural activation, but not food deprivation-induced increases

    Science.gov (United States)

    Teubner, Brett J. W.

    2013-01-01

    Circulating concentrations of the stomach-derived “hunger-peptide” ghrelin increase in direct proportion to the time since the last meal. Exogenous ghrelin also increases food intake in rodents and humans, suggesting ghrelin may increase post-fast ingestive behaviors. Food intake after food deprivation is increased by laboratory rats and mice, but not by humans (despite dogma to the contrary) or by Siberian hamsters; instead, humans and Siberian hamsters increase food hoarding, suggesting the latter as a model of fasting-induced changes in human ingestive behavior. Exogenous ghrelin markedly increases food hoarding by ad libitum-fed Siberian hamsters similarly to that after food deprivation, indicating sufficiency. Here, we tested the necessity of ghrelin to increase food foraging, food hoarding, and food intake, and neural activation [c-Fos immunoreactivity (c-Fos-ir)] using anti-ghrelin Spiegelmer NOX-B11–2 (SPM), an l-oligonucleotide that specifically binds active ghrelin, inhibiting peptide-receptor interaction. SPM blocked exogenous ghrelin-induced increases in food hoarding the first 2 days after injection, and foraging and food intake at 1–2 h and 2–4 h, respectively, and inhibited hypothalamic c-Fos-ir. SPM given every 24 h across 48-h food deprivation inconsistently inhibited food hoarding after refeeding and c-Fos-ir, similarly to inabilities to do so in laboratory rats and mice. These results suggest that ghrelin may not be necessary for food deprivation-induced foraging and hoarding and neural activation. A possible compensatory response, however, may underlie these findings because SPM treatment led to marked increases in circulating ghrelin concentrations. Collectively, these results show that SPM can block exogenous ghrelin-induced ingestive behaviors, but the necessity of ghrelin for food deprivation-induced ingestive behaviors remains unclear. PMID:23804279

  3. Exact piecewise flat gravitational waves

    NARCIS (Netherlands)

    van de Meent, M.

    2011-01-01

    We generalize our previous linear result (van de Meent 2011 Class. Quantum Grav 28 075005) in obtaining gravitational waves from our piecewise flat model for gravity in 3+1 dimensions to exact piecewise flat configurations describing exact planar gravitational waves. We show explicitly how to

  4. VCC-1 over-expression inhibits cisplatin-induced apoptosis in HepG2 cells

    International Nuclear Information System (INIS)

    Zhou, Zhitao; Lu, Xiao; Zhu, Ping; Zhu, Wei; Mu, Xia; Qu, Rongmei; Li, Ming

    2012-01-01

    Highlights: ► VCC-1 is hypothesized to be associated with carcinogenesis. ► Levels of VCC-1 are increased significantly in HCC. ► Over-expression of VCC-1 could promotes cellular proliferation rate. ► Over-expression of VCC-1 inhibit the cisplatin-provoked apoptosis in HepG2 cells. ► VCC-1 plays an important role in control the tumor growth and apoptosis. -- Abstract: Vascular endothelial growth factor-correlated chemokine 1 (VCC-1), a recently described chemokine, is hypothesized to be associated with carcinogenesis. However, the molecular mechanisms by which aberrant VCC-1 expression determines poor outcomes of cancers are unknown. In this study, we found that VCC-1 was highly expressed in hepatocellular carcinoma (HCC) tissue. It was also associated with proliferation of HepG2 cells, and inhibition of cisplatin-induced apoptosis of HepG2 cells. Conversely, down-regulation of VCC-1 in HepG2 cells increased cisplatin-induced apoptosis of HepG2 cells. In summary, these results suggest that VCC-1 is involved in cisplatin-induced apoptosis of HepG2 cells, and also provides some evidence for VCC-1 as a potential cellular target for chemotherapy.

  5. Experimental hint for gravitational CP violation

    Energy Technology Data Exchange (ETDEWEB)

    Gharibyan, Vahagn [Deutsches Elektronen-Synchrotron, Hamburg (Germany). MDI Group

    2016-01-15

    An equality of particle and antiparticle gravitational interactions holds in general relativity and is supported by indirect observations. Gravity dependence on rotation or spin direction is experimentally constrained only at low energies. Here a method based on high energy Compton scattering is developed to measure the gravitational interaction of accelerated charged particles. Within that formalism the Compton spectra measured at HERA rule out the positron's anti-gravity and hint for a gravitational CP violation around 13 GeV energies, at a maximal level of 1.3±0.2% for the charge and 0.68±0.09% for the space parity. A stronger gravitational coupling to left helicity electrons relative to right helicity positrons is detected.

  6. Experimental hint for gravitational CP violation

    International Nuclear Information System (INIS)

    Gharibyan, Vahagn

    2016-01-01

    An equality of particle and antiparticle gravitational interactions holds in general relativity and is supported by indirect observations. Gravity dependence on rotation or spin direction is experimentally constrained only at low energies. Here a method based on high energy Compton scattering is developed to measure the gravitational interaction of accelerated charged particles. Within that formalism the Compton spectra measured at HERA rule out the positron's anti-gravity and hint for a gravitational CP violation around 13 GeV energies, at a maximal level of 1.3±0.2% for the charge and 0.68±0.09% for the space parity. A stronger gravitational coupling to left helicity electrons relative to right helicity positrons is detected.

  7. Gravitation. [Book on general relativity

    Science.gov (United States)

    Misner, C. W.; Thorne, K. S.; Wheeler, J. A.

    1973-01-01

    This textbook on gravitation physics (Einstein's general relativity or geometrodynamics) is designed for a rigorous full-year course at the graduate level. The material is presented in two parallel tracks in an attempt to divide key physical ideas from more complex enrichment material to be selected at the discretion of the reader or teacher. The full book is intended to provide competence relative to the laws of physics in flat space-time, Einstein's geometric framework for physics, applications with pulsars and neutron stars, cosmology, the Schwarzschild geometry and gravitational collapse, gravitational waves, experimental tests of Einstein's theory, and mathematical concepts of differential geometry.

  8. Non-Euclidean Geometry and Gravitation

    Directory of Open Access Journals (Sweden)

    Stavroulakis N.

    2006-04-01

    Full Text Available A great deal of misunderstandings and mathematical errors are involved in the currently accepted theory of the gravitational field generated by an isotropic spherical mass. The purpose of the present paper is to provide a short account of the rigorous mathematical theory and exhibit a new formulation of the problem. The solution of the corresponding equations of gravitation points out several new and unusual features of the stationary gravitational field which are related to the non-Euclidean structure of the space. Moreover it precludes the black hole from being a mathematical and physical notion.

  9. Hydrodynamics, fields and constants in gravitational theory

    International Nuclear Information System (INIS)

    Stanyukovich, K.P.; Mel'nikov, V.N.

    1983-01-01

    Results of original inveatigations into problems of standard gravitation theory and its generalizations are presented. The main attention is paid to the application of methods of continuous media techniques in the gravitation theory; to the specification of the gravitation role in phenomena of macro- and microworld, accurate solutions in the case, when the medium is the matter, assigned by hydrodynamic energy-momentum tensor; and to accurate solutions for the case when the medium is the field. GRT generalizations are analyzed, such as the new cosmologic hypothesis which is based on the gravitation vacuum theory. Investigations are performed into the quantization of cosmological models, effects of spontaneous symmetry violation and particle production in cosmology. Graeity theory with fundamental Higgs field is suggested in the framework of which in the atomic unit number one can explain possible variations of the effective gravitational bonds, and in the gravitation bond, variations of masses of all particles

  10. Skin protective effect of guava leaves against UV-induced melanogenesis via inhibition of ORAI1 channel and tyrosinase activity.

    Science.gov (United States)

    Lee, Dong-Ung; Weon, Kwon Yeon; Nam, Da-Yeong; Nam, Joo Hyun; Kim, Woo Kyung

    2016-12-01

    Ultraviolet (UV) irradiation is a major environmental factor affecting photoageing, which is characterized by skin wrinkle formation and hyperpigmentation. Although many factors are involved in the photoageing process, UV irradiation is thought to play a major role in melanogenesis. Tyrosinase is the key enzyme in melanin synthesis; therefore, many whitening agents target tyrosinase through various mechanisms, such as direct interference of tyrosinase catalytic activity or inhibition of tyrosinase mRNA expression. Furthermore, the highly selective calcium channel ORAI1 has been shown to be associated with UV-induced melanogenesis. Thus, ORAI1 antagonists may have applications in the prevention of melanogenesis. Here, we aimed to identify the antimelanogenesis agents from methanolic extract of guava leaves (Psidium guajava) that can inhibit tyrosinase and ORAI1 channel. The n-butanol (47.47%±7.503% inhibition at 10 μg/mL) and hexane (57.88%±7.09% inhibition at 10 μg/mL) fractions were found to inhibit ORAI1 channel activity. In addition, both fractions showed effective tyrosinase inhibitory activity (68.3%±0.50% and 56.9%±1.53% inhibition, respectively). We also confirmed that the hexane fraction decreased the melanin content induced by UVB irradiation and the ET-1-induced melanogenesis in murine B16F10 melanoma cells. These results suggest that the leaves of P. guajava can be used to protect against direct and indirect UV-induced melanogenesis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Neutrino Oscillations within the Induced Gravitational Collapse Paradigm of Long Gamma-Ray Bursts

    Science.gov (United States)

    Becerra, L.; Guzzo, M. M.; Rossi-Torres, F.; Rueda, J. A.; Ruffini, R.; Uribe, J. D.

    2018-01-01

    The induced gravitational collapse paradigm of long gamma-ray bursts associated with supernovae (SNe) predicts a copious neutrino–antineutrino (ν \\bar{ν }) emission owing to the hypercritical accretion process of SN ejecta onto a neutron star (NS) binary companion. The neutrino emission can reach luminosities of up to 1057 MeV s‑1, mean neutrino energies of 20 MeV, and neutrino densities of 1031 cm‑3. Along their path from the vicinity of the NS surface outward, such neutrinos experience flavor transformations dictated by the neutrino-to-electron-density ratio. We determine the neutrino and electron on the accretion zone and use them to compute the neutrino flavor evolution. For normal and inverted neutrino mass hierarchies and within the two-flavor formalism ({ν }e{ν }x), we estimate the final electronic and nonelectronic neutrino content after two oscillation processes: (1) neutrino collective effects due to neutrino self-interactions where the neutrino density dominates, and (2) the Mikheyev–Smirnov–Wolfenstein effect, where the electron density dominates. We find that the final neutrino content is composed by ∼55% (∼62%) of electronic neutrinos, i.e., {ν }e+{\\bar{ν }}e, for the normal (inverted) neutrino mass hierarchy. The results of this work are the first step toward the characterization of a novel source of astrophysical MeV neutrinos in addition to core-collapse SNe and, as such, deserve further attention.

  12. Aromatic hydrocarbon receptor inhibits lysophosphatidic acid-induced vascular endothelial growth factor-A expression in PC-3 prostate cancer cells

    International Nuclear Information System (INIS)

    Wu, Pei-Yi; Lin, Yueh-Chien; Lan, Shun-Yan; Huang, Yuan-Li; Lee, Hsinyu

    2013-01-01

    Highlights: •LPA-induced VEGF-A expression was regulated by HIF-1α and ARNT. •PI3K mediated LPA-induced VEGF-A expression. •AHR signaling inhibited LPA-induced VEGF-A expression in PC-3 cells. -- Abstract: Lysophosphatidic acid (LPA) is a lipid growth factor with multiple biological functions and has been shown to stimulate cancer cell secretion of vascular endothelial growth factor-A (VEGF-A) and trigger angiogenesis. Hypoxia-inducible factor-1 (HIF-1), a heterodimer consisting of HIF-1α and HIF-1β (also known as aromatic hydrocarbon receptor nuclear translocator (ARNT)) subunits, is an important regulator of angiogenesis in prostate cancer (PC) through the enhancement of VEGF-A expression. In this study, we first confirmed the ability of LPA to induce VEGF-A expression in PC-3 cells and then validated that LPA-induced VEGF-A expression was regulated by HIF-1α and ARNT through phosphatidylinositol 3-kinase activation. Aromatic hydrocarbon receptor (AHR), a receptor for dioxin-like compounds, functions as a transcription factor through dimerization with ARNT and was found to inhibit prostate carcinogenesis and vanadate-induced VEGF-A production. Since ARNT is a common dimerization partner of AHR and HIF-1α, we hypothesized that AHR might suppress LPA-induced VEGF-A expression in PC-3 cells by competing with HIF-1α for ARNT. Here we demonstrated that overexpression and ligand activation of AHR inhibited HIF-1-mediated VEGF-A induction by LPA treatment of PC-3 cells. In conclusion, our results suggested that AHR activation may inhibit LPA-induced VEGF-A expression in PC-3 cells by attenuating HIF-1α signaling, and subsequently, suppressing angiogenesis and metastasis of PC. These results suggested that AHR presents a potential therapeutic target for the prevention of PC metastasis

  13. Phenylbutyrate inhibits homologous recombination induced by camptothecin and methyl methanesulfonate.

    Science.gov (United States)

    Kaiser, Gitte S; Germann, Susanne M; Westergaard, Tine; Lisby, Michael

    2011-08-01

    Homologous recombination is accompanied by extensive changes to chromatin organization at the site of DNA damage. Some of these changes are mediated through acetylation/deacetylation of histones. Here, we show that recombinational repair of DNA damage induced by the anti-cancer drug camptothecin (CPT) and the alkylating agent methyl methanesulfonate (MMS) is blocked by sodium phenylbutyrate (PBA) in the budding yeast Saccharomyces cerevisiae. In particular, PBA suppresses CPT- and MMS-induced genetic recombination as well as DNA double-strand break repair during mating-type interconversion. Treatment with PBA is accompanied by a dramatic reduction in histone H4 lysine 8 acetylation. Live cell imaging of homologous recombination proteins indicates that repair of CPT-induced DNA damage is redirected to a non-recombinogenic pathway in the presence of PBA without loss in cell viability. In contrast, the suppression of MMS-induced recombination by PBA is accompanied by a dramatic loss in cell viability. Taken together, our results demonstrate that PBA inhibits DNA damage-induced homologous recombination likely by mediating changes in chromatin acetylation. Moreover, the combination of PBA with genotoxic agents can lead to different cell fates depending on the type of DNA damage inflicted. 2011 Elsevier B.V. All rights reserved.

  14. Thermodynamics of gravitational clustering phenomena: N-body self-gravitating gas on the sphere {{{S}}^{3}}\\subset {{{R}}^{4}}

    Science.gov (United States)

    Tello-Ortiz, F.; Velazquez, L.

    2016-10-01

    This work is devoted to the thermodynamics of gravitational clustering, a collective phenomenon with a great relevance in the N-body cosmological problem. We study a classical self-gravitating gas of identical non-relativistic particles defined on the sphere {{{S}}3}\\subset {{{R}}4} by considering gravitational interaction that corresponds to this geometric space. The analysis is performed within microcanonical description of an isolated Hamiltonian system by combining continuum approximation and the steepest descend method. According to numerical solution of resulting equations, the gravitational clustering can be associated with two microcanonical phase transitions. A first phase transition with a continuous character is associated with breakdown of SO(4) symmetry of this model. The second one is the gravitational collapse, whose continuous or discontinuous character crucially depends on the regularization of short-range divergence of gravitation potential. We also derive the thermodynamic limit of this model system, the astrophysical counterpart of the Gibbs-Duhem relation, the order parameters that characterize its phase transitions and the equation of state. Other interesting behavior is the existence of states with negative heat capacities, which appear when the effects of gravitation turn dominant for energies sufficiently low. Finally, we comment on the relevance of some of these results in the study of astrophysical and cosmological situations. Special interest deserves the gravitational modification of the equation of state due to the local inhomogeneities of matter distribution. Although this feature is systematically neglected in studies about universe expansion, the same one is able to mimic an effect that is attributed to the dark energy: a negative pressure.

  15. Spinor approach to gravitational motion and precession

    International Nuclear Information System (INIS)

    Hestenes, D.

    1986-01-01

    The translational and rotational equations of motion for a small rigid body in a gravitational field are combined in a single spinor equation. Besides its computational advantages, this unifies the description of gravitational interaction in classical and quantum theory. Explicit expressions for gravitational precession rates are derived. (author)

  16. Selective inhibition by chloramphenicol of pregnenolone-16 α-carbonitrile-inducible rat liver cytochrome P-450 isozymes

    International Nuclear Information System (INIS)

    Graves, P.E.; Kaminsky, L.S.; Halpert, J.

    1986-01-01

    Pregnenolone-16 α-carbonitrile (PCN) has been shown to induce, in male rats, cytochrome P-450 isozymes responsible for the formation of R-10-hydroxywarfarin and R-dehydrowarfarin. Antibodies to the major PCN-inducible isozyme (PB/PCN-E) inhibit both activities in microsomal preparations. Recently the authors have shown that PCN treatment of female rats also induces the formation of both R-warfarin metabolites. However, in both sexes chloramphenicol (CAP) treatment selectively inhibits only the rate of formation of the R-dehydrowarfarin. A decrease in microsomal P-450 content occurs after in vivo administration of CAP to PCN-treated rats of both sexes. This is in contrast to the lack of effect of CAP on P-450 levels in phenobarbital-treated rats. Covalent binding of 14 C-CAP to microsomal protein in vitro was increased 3 to 4-fold following PCN treatment. Chromatographic evidences suggests the presence of at least two PCN-induced isozymes of similar molecular weights in both male and female rat liver microsomes. These data are consistent with the multiplicity of PCN-inducible P-450 in rat liver

  17. Physics, Astrophysics and Cosmology with Gravitational Waves.

    Science.gov (United States)

    Sathyaprakash, B S; Schutz, Bernard F

    2009-01-01

    Gravitational wave detectors are already operating at interesting sensitivity levels, and they have an upgrade path that should result in secure detections by 2014. We review the physics of gravitational waves, how they interact with detectors (bars and interferometers), and how these detectors operate. We study the most likely sources of gravitational waves and review the data analysis methods that are used to extract their signals from detector noise. Then we consider the consequences of gravitational wave detections and observations for physics, astrophysics, and cosmology.

  18. The confrontation between gravitation theory and experiment

    International Nuclear Information System (INIS)

    Will, C.M.

    1979-01-01

    After an introductory section, an analysis is given of the foundations of gravitation theory - principles of equivalence, the fundamental criteria for the viability of a gravitational theory, and the experiments that support those criteria. One of the principal conclusions is that the correct, viable theory of gravity must in all probability be a 'metric' theory. Attention is focussed on solar-system tests, using a 'theory of theories' known as the parametrized post-Newtonian formalism that encompasses most metric theories of gravity and that is ideally suited to the solar-system arena. Gravitational radiation is discussed as a possible tool for testing gravitational theory. The binary pulsar, a new , 'stellar-system' testing ground is studied. Tests of gravitation theory in a cosmic arena are described. (U.K.)

  19. A new theory of gravitation

    International Nuclear Information System (INIS)

    Logunov, A.A.

    1989-01-01

    The author believes that the General Relativity Theory (GRT) suffers from a substantial deficiency since it ignors the fundamental laws of conservation of energy. Einstein neglected the classical concept of the field due to his belief in the truth of the principle of equivalence between forces of inertid gravitation. This equivalence leads, as the author says, to nonequivalence of these forces, making GRT logically contradictory from the physical point of view. The author considers GRT as a certain stage in the course of the study of space-time and gravitation, and suggests a new theory called the Relativistic Theory of Gravitation (RTG) which obeys the fundamental laws of conservation, and which is justified in some of its aspects by astronomical observations. RTG does not suffer from some deficiencies met in Einsteins theory. One is nonunique predictions of gravitation effects within the boundaries of the solar system. Also, RTG refuses some hypothesis as that of black holes. 7 refs

  20. Academic Training: Gravitational Waves Astronomy

    CERN Multimedia

    2006-01-01

    2006-2007 ACADEMIC TRAINING PROGRAMME LECTURE SERIES 16, 17, 18 October from 11:00 to 12:00 - Main Auditorium, bldg. 500 Gravitational Waves Astronomy M. LANDRY, LIGO Hanford Observatory, Richland, USA Gravitational wave astronomy is expected to become an observational field within the next decade. First direct detection of gravitational waves is possible with existing terrestrial-based detectors, and highly probable with proposed upgrades. In this three-part lecture series, we give an overview of the field, including material on gravitional wave sources, detection methods, some details of interferometric detectors, data analysis methods, and current results from observational data-taking runs of the LIGO and GEO projects. ENSEIGNEMENT ACADEMIQUE ACADEMIC TRAINING Françoise Benz 73127 academic.training@cern.ch If you wish to participate in one of the following courses, please tell to your supervisor and apply electronically from the course description pages that can be found on the Web at: http://www...

  1. Academic Training: Gravitational Waves Astronomy

    CERN Multimedia

    2006-01-01

    2006-2007 ACADEMIC TRAINING PROGRAMME LECTURE SERIES 16, 17, 18 October from 11:00 to 12:00 - Main Auditorium, bldg. 500 Gravitational Waves Astronomy M. LANDRY, LIGO Hanford Observatory, Richland, USA Gravitational wave astronomy is expected to become an observational field within the next decade. First direct detection of gravitational waves is possible with existing terrestrial-based detectors, and highly probable with proposed upgrades. In this three-part lecture series, we give an overview of the field, including material on gravitional wave sources, detection methods, some details of interferometric detectors, data analysis methods, and current results from observational data-taking runs of the LIGO and GEO projects.ENSEIGNEMENT ACADEMIQUE ACADEMIC TRAINING Françoise Benz 73127 academic.training@cern.ch If you wish to participate in one of the following courses, please tell to your supervisor and apply electronically from the course description pages that can be found on the Web at: http://www.cern...

  2. Bunge on gravitational waves

    OpenAIRE

    Romero, Gustavo E.

    2017-01-01

    I discuss the recent claims made by Mario Bunge on the philosophical implications of the discovery of gravitational waves. I think that Bunge is right when he points out that the detection implies the materiality of spacetime, but I reject his identification of spacetime with the gravitational field. I show that Bunge's analysis of the spacetime inside a hollow sphere is defective, but this in no way affects his main claim.

  3. Inhibition of c-Jun N-terminal kinase sensitizes tumor cells to flavonoid-induced apoptosis through down-regulation of JunD

    International Nuclear Information System (INIS)

    Kook, Sung-Ho; Son, Young-Ok; Jang, Yong-Suk; Lee, Kyung-Yeol; Lee, Seung-Ah; Kim, Beom-Soo; Lee, Hyun-Jeong; Lee, Jeong-Chae

    2008-01-01

    Reduction of susceptibility to apoptosis signals is a crucial step in carcinogenesis. Therefore, sensitization of tumor cells to apoptosis is a promising therapeutic strategy. c-Jun NH 2 -terminal kinase (JNK) has been implicated in stress-induced apoptosis. However, many studies also emphasize the role of JNK on cell survival, although its mechanisms are not completely understood. Previously, we found that inhibition of JNK activity promotes flavonoid-mediated apoptosis of human osteosarcoma cells. We thus determined whether inhibition of JNK sensitizes tumor cells to a bioflavonoid-induced apoptosis, and whether this effect of JNK is a general effect. As the results, quercetin and genistein as well as a flavonoid fraction induced apoptosis of tumor cells, which was further accelerated by specific JNK inhibitor, SP600125 or by small interfering RNA specific to JNK1/2. This effect was specific to types of cells because it was further apparent in tumorigenic cell lines. Inhibition of JNK by SP600125 also reduced flavonoid-stimulated nuclear induction of JunD which was known to have protective role in apoptosis, whereas JNK inhibition alone had little effect on apoptosis. The flavonoid-induced apoptosis of tumor cells was significantly enhanced by transfecting them with antisense JunD oligonucleotides. These results suggest that inhibition of JNK facilitates flavonoid-induced apoptosis through down-regulation of JunD, which is further sensitive to tumor cells. Therefore, combination with a specific JNK inhibitor further enhances the anti-cancer and chemopreventive potential of bio-flavonoids

  4. Inhibition of PKR protects against H2O2-induced injury on neonatal cardiac myocytes by attenuating apoptosis and inflammation.

    Science.gov (United States)

    Wang, Yongyi; Men, Min; Xie, Bo; Shan, Jianggui; Wang, Chengxi; Liu, Jidong; Zheng, Hui; Yang, Wengang; Xue, Song; Guo, Changfa

    2016-12-08

    Reactive oxygenation species (ROS) generated from reperfusion results in cardiac injury through apoptosis and inflammation, while PKR has the ability to promote apoptosis and inflammation. The aim of the study was to investigate whether PKR is involved in hydrogen peroxide (H 2 O 2 ) induced neonatal cardiac myocytes (NCM) injury. In our study, NCM, when exposed to H 2 O 2 , resulted in persistent activation of PKR due to NCM endogenous RNA. Inhibition of PKR by 2-aminopurine (2-AP) or siRNA protected against H 2 O 2 induced apoptosis and injury. To elucidate the mechanism, we revealed that inhibition of PKR alleviated H 2 O 2 induced apoptosis companied by decreased caspase3/7 activity, BAX and caspase-3 expression. We also revealed that inhibition of PKR suppressed H 2 O 2 induced NFκB pathway and NLRP3 activation. Finally, we found ADAR1 mRNA and protein expression were both induced after H 2 O 2 treatment through STAT-2 dependent pathway. By gain and loss of ADAR1 expression, we confirmed ADAR1 modulated PKR activity. Therefore, we concluded inhibition of PKR protected against H 2 O 2 -induced injury by attenuating apoptosis and inflammation. A self-preservation mechanism existed in NCM that ADAR1 expression is induced by H 2 O 2 to limit PKR activation simultaneously. These findings identify a novel role for PKR/ADAR1 in myocardial reperfusion injury.

  5. Vitamin K3 attenuates cerulein-induced acute pancreatitis through inhibition of the autophagic pathway.

    Science.gov (United States)

    Chinzei, Ryo; Masuda, Atsuhiro; Nishiumi, Shin; Nishida, Masayuki; Onoyama, Mitsuko; Sanuki, Tsuyoshi; Fujita, Tsuyoshi; Moritoh, Satoshi; Itoh, Tomoo; Kutsumi, Hiromu; Mizuno, Shigeto; Azuma, Takeshi; Yoshida, Masaru

    2011-01-01

    The discovery of novel and effective treatment methods would be of great help to patients with acute pancreatitis. The aims of this study were to determine the inhibitory effects of vitamin K3 (VK3) against cerulein-induced acute pancreatitis in mice and to examine the mechanisms behind these effects. Acute pancreatitis in mice was induced by intraperitoneal injection of cerulein 6 times at hourly intervals. Vitamin K3 was administered once before the first injection of cerulein or twice before and after the first injection of cerulein. The degrees of inflammation and autophagy in the pancreatic tissue were estimated by histological examination, measurement of enzyme activity, confocal microscopy, and Western blotting. The inhibitory effects of VK3 against rapamycin-induced autophagy were also examined using HeLa cells stably expressing green fluorescent protein LC3. Cerulein-induced acute pancreatitis was markedly attenuated by the administration of VK3. In addition, VK3 led to the inhibition of cerulein-evoked autophagic changes and colocalization of autophagosomes and lysosomes in the pancreatic tissue. Vitamin K3 also reduced rapamycin-induced autophagy in HeLa/green fluorescent protein LC3 cells. Our data suggest that the administration of VK3 reduces pancreatic inflammation in acute pancreatitis through inhibition of the autophagic pathway. Vitamin K3 may be an effective therapeutic strategy against acute pancreatitis.

  6. Rapid Monte Carlo Simulation of Gravitational Wave Galaxies

    Science.gov (United States)

    Breivik, Katelyn; Larson, Shane L.

    2015-01-01

    With the detection of gravitational waves on the horizon, astrophysical catalogs produced by gravitational wave observatories can be used to characterize the populations of sources and validate different galactic population models. Efforts to simulate gravitational wave catalogs and source populations generally focus on population synthesis models that require extensive time and computational power to produce a single simulated galaxy. Monte Carlo simulations of gravitational wave source populations can also be used to generate observation catalogs from the gravitational wave source population. Monte Carlo simulations have the advantes of flexibility and speed, enabling rapid galactic realizations as a function of galactic binary parameters with less time and compuational resources required. We present a Monte Carlo method for rapid galactic simulations of gravitational wave binary populations.

  7. Chloride secretion induced by rotavirus is oxidative stress-dependent and inhibited by Saccharomyces boulardii in human enterocytes.

    Science.gov (United States)

    Buccigrossi, Vittoria; Laudiero, Gabriella; Russo, Carla; Miele, Erasmo; Sofia, Morena; Monini, Marina; Ruggeri, Franco Maria; Guarino, Alfredo

    2014-01-01

    Rotavirus (RV) infection causes watery diarrhea via multiple mechanisms, primarily chloride secretion in intestinal epithelial cell. The chloride secretion largely depends on non-structural protein 4 (NSP4) enterotoxic activity in human enterocytes through mechanisms that have not been defined. Redox imbalance is a common event in cells infected by viruses, but the role of oxidative stress in RV infection is unknown. RV SA11 induced chloride secretion in association with an increase in reactive oxygen species (ROS) in Caco-2 cells. The ratio between reduced (GSH) and oxidized (GSSG) glutathione was decreased by RV. The same effects were observed when purified NSP4 was added to Caco-2 cells. N-acetylcysteine (NAC), a potent antioxidant, strongly inhibited the increase in ROS and GSH imbalance. These results suggest a link between oxidative stress and RV-induced diarrhea. Because Saccharomyces boulardii (Sb) has been effectively used to treat RV diarrhea, we tested its effects on RV-infected cells. Sb supernatant prevented RV-induced oxidative stress and strongly inhibited chloride secretion in Caco-2 cells. These results were confirmed in an organ culture model using human intestinal biopsies, demonstrating that chloride secretion induced by RV-NSP4 is oxidative stress-dependent and is inhibited by Sb, which produces soluble metabolites that prevent oxidative stress. The results of this study provide novel insights into RV-induced diarrhea and the efficacy of probiotics.

  8. Physics, Astrophysics and Cosmology with Gravitational Waves

    Directory of Open Access Journals (Sweden)

    Sathyaprakash B. S.

    2009-03-01

    Full Text Available Gravitational wave detectors are already operating at interesting sensitivity levels, and they have an upgrade path that should result in secure detections by 2014. We review the physics of gravitational waves, how they interact with detectors (bars and interferometers, and how these detectors operate. We study the most likely sources of gravitational waves and review the data analysis methods that are used to extract their signals from detector noise. Then we consider the consequences of gravitational wave detections and observations for physics, astrophysics, and cosmology.

  9. Feasibility analysis of gravitational experiments in space

    Science.gov (United States)

    Everitt, C. W. F.

    1977-01-01

    Experiments on gravitation and general relativity suggested by different workers in the past ten or more years are reviewed, their feasibility examined, and the advantages of performing them in space were studied. The experiments include: (1) the gyro relativity experiment; (2) experiments to test the equivalence of gravitational and inertial mass; (3) an experiment to look for nongeodesic motion of spinning bodies in orbit around the earth; (4) experiments to look for changes of the gravitational constant G with time; (5) a variety of suggestions; laboratory tests of experimental gravity; and (6) gravitational wave experiments.

  10. Gravitational Wave Astrophysics: Opening the New Frontier

    Science.gov (United States)

    Centrella, Joan

    2012-01-01

    A new era in astronomy will begin when the gravitational wave window onto the universe opens in approx. 5 years, as ground-based detectors make the first detections in the high-frequency regime. Since the universe is nearly transparent to gravitational waves, these signals carry direct information about their sources - such as masses, spins, luminosity distances, and orbital parameters - through dense, obscured regions across cosmic time. This talk will explore gravitational waves as cosmic messengers, highlighting key sources and opportunities for multi-messenger astronomy across the gravitational wave spectrum.

  11. The gravitational properties of antimatter

    International Nuclear Information System (INIS)

    Goldman, T.; Hughes, R.J.; Nieto, M.M.

    1986-09-01

    It is argued that a determination of the gravitational acceleration of antimatter towards the earth is capable of imposing powerful constraints on modern quantum gravity theories. Theoretical reasons to expect non-Newtonian non-Einsteinian effects of gravitational strength and experimental suggestions of such effects are reviewed. 41 refs

  12. Exercise Inhibits the Effects of Smoke-Induced COPD Involving Modulation of STAT3

    Directory of Open Access Journals (Sweden)

    Maysa Alves Rodrigues Brandao-Rangel

    2017-01-01

    Full Text Available Purpose. Evaluate the participation of STAT3 in the effects of aerobic exercise (AE in a model of smoke-induced COPD. Methods. C57Bl/6 male mice were divided into control, Exe, COPD, and COPD+Exe groups. Smoke were administered during 90 days. Treadmill aerobic training begun on day 61 until day 90. Pulmonary inflammation, systemic inflammation, the level of lung emphysema, and the airway remodeling were evaluated. Analysis of integral and phosphorylated expression of STAT3 by airway epithelial cells, peribronchial leukocytes, and parenchymal leukocytes was performed. Results. AE inhibited smoke-induced accumulation of total cells (p<0.001, lymphocytes (p<0.001, and neutrophils (p<0.001 in BAL, as well as BAL levels of IL-1β (p<0.001, CXCL1 (p<0.001, IL-17 (p<0.001, and TNF-α (p<0.05, while increased the levels of IL-10 (p<0.001. AE also inhibited smoke-induced increases in total leukocytes (p<0.001, neutrophils (p<0.05, lymphocytes (p<0.001, and monocytes (p<0.01 in blood, as well as serum levels of IL-1β (p<0.01, CXCL1 (p<0.01, IL-17 (p<0.05, and TNF-α (p<0.01, while increased the levels of IL-10 (p<0.001. AE reduced smoke-induced emphysema (p<0.001 and collagen fiber accumulation in the airways (p<0.001. AE reduced smoke-induced STAT3 and phospho-STAT3 expression in airway epithelial cells (p<0.001, peribronchial leukocytes (p<0.001, and parenchymal leukocytes (p<0.001. Conclusions. AE reduces smoke-induced COPD phenotype involving STAT3.

  13. Gravitational Waves and Time Domain Astronomy

    Science.gov (United States)

    Centrella, Joan; Nissanke, Samaya; Williams, Roy

    2012-01-01

    The gravitational wave window onto the universe will open in roughly five years, when Advanced LIGO and Virgo achieve the first detections of high frequency gravitational waves, most likely coming from compact binary mergers. Electromagnetic follow-up of these triggers, using radio, optical, and high energy telescopes, promises exciting opportunities in multi-messenger time domain astronomy. In the decade, space-based observations of low frequency gravitational waves from massive black hole mergers, and their electromagnetic counterparts, will open up further vistas for discovery. This two-part workshop featured brief presentations and stimulating discussions on the challenges and opportunities presented by gravitational wave astronomy. Highlights from the workshop, with the emphasis on strategies for electromagnetic follow-up, are presented in this report.

  14. Vacuum polarization and non-Newtonian gravitation

    International Nuclear Information System (INIS)

    Long, D.R.

    1980-01-01

    Gell-Mann and Low have emphasized that, as first pointed out by Uehling and Serber, vacuum polarization effects produce a logarithmic modification to the Coulomb potential at small distances. Here, it is pointed out that, if these same considerations are applied to gravitation, the logarithmic term will have a sign opposite to that in the Coulomb case and in agreement with recent laboratory results on the gravitational ''constant''. Of considerable importance is the fact that such vacuum polarization effects cannot be observed in null experiments to test the gravitational inverse square law because the polarizing field is absent. It is a striking circumstance that the coefficient of the logarithm in QED is nearly the same as that found in gravitational experiments. (author)

  15. Gravitational Waves: A New Observational Window

    Science.gov (United States)

    Camp, Jordan B.

    2010-01-01

    The era of gravitational wave astronomy is rapidly approaching, with a likely start date around the middle of this decade ' Gravitational waves, emitted by accelerated motions of very massive objects, provide detailed information about strong-field gravity and its sources, including black holes and neutron stars, that electromagnetic probes cannot access. In this talk I will discuss the anticipated sources and the status of the extremely sensitive detectors (both ground and space based) that will make gravitational wave detections possible. As ground based detectors are now taking data, I will show some initial science results related to measured upper limits on gravitational wave signals. Finally Z will describe new directions including advanced detectors and joint efforts with other fields of astronomy.

  16. Thermal gravitational waves in accelerating universe

    Directory of Open Access Journals (Sweden)

    B Ghayour

    2013-10-01

    Full Text Available Gravitational waves are considered in thermal vacuum state. The amplitude and spectral energy density of gravitational waves are found enhanced in thermal vacuum state compared to its zero temperature counterpart. Therefore, the allowed amount of enhancement depends on the upper bound of WMAP-5 and WMAP-7 for the amplitude and spectral energy density of gravitational waves. The enhancement of amplitude and spectral energy density of the waves in thermal vacuum state is consistent with current accelerating phase of the universe. The enhancement feature of amplitude and spectral energy density of the waves is independent of the expansion model of the universe and hence the thermal effect accounts for it. Therefore, existence of thermal gravitational waves is not ruled out

  17. Hydrodynamical equations for spherical gravitational collapse in terms of a generalized theory of gravitation with higher derivatives

    International Nuclear Information System (INIS)

    Nariai, Hidekazu.

    1986-06-01

    In similar to Misner and Sharp's formalism in general relativity for a spherical gravitational collapse, a formalism for the spherical gravitational collapse is presented on the basis of a generalized theory of gravitation in the sense of Utiyama-DeWitt (which was later extended by Parker's school and Zel'dovich's one). The resulted formalism is somewhat similar to that developed by me in 1972 based on the scalar-tensor theory of gravity. (author)

  18. Trifluoperazine inhibits acetaminophen-induced hepatotoxicity and hepatic reactive nitrogen formation in mice and in freshly isolated hepatocytes

    Directory of Open Access Journals (Sweden)

    Sudip Banerjee

    Full Text Available The hepatotoxicity of acetaminophen (APAP occurs by initial metabolism to N-acetyl-p-benzoquinone imine which depletes GSH and forms APAP-protein adducts. Subsequently, the reactive nitrogen species peroxynitrite is formed from nitric oxide (NO and superoxide leading to 3-nitrotyrosine in proteins. Toxicity occurs with inhibited mitochondrial function. We previously reported that in hepatocytes the nNOS (NOS1 inhibitor NANT inhibited APAP toxicity, reactive nitrogen and oxygen species formation, and mitochondrial dysfunction. In this work we examined the effect of trifluoperazine (TFP, a calmodulin antagonist that inhibits calcium induced nNOS activation, on APAP hepatotoxicity and reactive nitrogen formation in murine hepatocytes and in vivo. In freshly isolated hepatocytes TFP inhibited APAP induced toxicity, reactive nitrogen formation (NO, GSNO, and 3-nitrotyrosine in protein, reactive oxygen formation (superoxide, loss of mitochondrial membrane potential, decreased ATP production, decreased oxygen consumption rate, and increased NADH accumulation. TFP did not alter APAP induced GSH depletion in the hepatocytes or the formation of APAP protein adducts which indicated that reactive metabolite formation was not inhibited. Since we previously reported that TFP inhibits the hepatotoxicity of APAP in mice without altering hepatic APAP-protein adduct formation, we examined the APAP treated mouse livers for evidence of reactive nitrogen formation. 3-Nitrotyrosine in hepatic proteins and GSNO were significantly increased in APAP treated mouse livers and decreased in the livers of mice treated with APAP plus TFP. These data are consistent with a hypothesis that APAP hepatotoxicity occurs with altered calcium metabolism, activation of nNOS leading to increased reactive nitrogen formation, and mitochondrial dysfunction. Keywords: Acetaminophen, Neuronal nitric oxide, Oxidative stress, Mitochondria

  19. Particle production in a gravitational wave background

    Science.gov (United States)

    Jones, Preston; McDougall, Patrick; Singleton, Douglas

    2017-03-01

    We study the possibility that massless particles, such as photons, are produced by a gravitational wave. That such a process should occur is implied by tree-level Feynman diagrams such as two gravitons turning into two photons, i.e., g +g →γ +γ . Here we calculate the rate at which a gravitational wave creates a massless scalar field. This is done by placing the scalar field in the background of a plane gravitational wave and calculating the 4-current of the scalar field. Even in the vacuum limit of the scalar field it has a nonzero vacuum expectation value (similar to what occurs in the Higgs mechanism) and a nonzero current. We associate this with the production of scalar field quanta by the gravitational field. This effect has potential consequences for the attenuation of gravitational waves since the massless field is being produced at the expense of the gravitational field. This is related to the time-dependent Schwinger effect, but with the electric field replaced by the gravitational wave background and the electron/positron field quanta replaced by massless scalar "photons." Since the produced scalar quanta are massless there is no exponential suppression, as occurs in the Schwinger effect due to the electron mass.

  20. Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-κB/GSDMD signal in mice adipose tissue.

    Science.gov (United States)

    Liu, Zhenjiang; Gan, Lu; Xu, Yatao; Luo, Dan; Ren, Qian; Wu, Song; Sun, Chao

    2017-08-01

    Pyroptosis is a proinflammatory form of cell death that is associated with pathogenesis of many chronic inflammatory diseases. Melatonin is substantially reported to possess anti-inflammatory properties by inhibiting inflammasome activation. However, the effects of melatonin on inflammasome-induced pyroptosis in adipocytes remain elusive. Here, we demonstrated that melatonin alleviated lipopolysaccharides (LPS)-induced inflammation and NLRP3 inflammasome formation in mice adipose tissue. The NLRP3 inflammasome-mediated pyroptosis was also inhibited by melatonin in adipocytes. Further analysis revealed that gasdermin D (GSDMD), the key executioner of pyroptosis, was the target for melatonin inhibition of adipocyte pyroptosis. Importantly, we determined that nuclear factor κB (NF-κB) signal was required for the GSDMD-mediated pyroptosis in adipocytes. We also confirmed that melatonin alleviated adipocyte pyroptosis by transcriptional suppression of GSDMD. Moreover, GSDMD physically interacted with interferon regulatory factor 7 (IRF7) and subsequently formed a complex to promote adipocyte pyroptosis. Melatonin also attenuated NLRP3 inflammasome activation and pyroptosis, which was induced by LPS or obesity. In summary, our results demonstrate that melatonin alleviates inflammasome-induced pyroptosis by blocking NF-κB/GSDMD signal in mice adipose tissue. Our data reveal a novel function of melatonin on adipocyte pyroptosis, suggesting a new potential therapy for melatonin to prevent and treat obesity caused systemic inflammatory response. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Resveratrol alleviates diabetes-induced testicular dysfunction by inhibiting oxidative stress and c-Jun N-terminal kinase signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Faid, Iman; Al-Hussaini, Heba; Kilarkaje, Narayana, E-mail: knarayana@hsc.edu.kw

    2015-12-15

    Diabetes adversely affects reproductive functions in humans and animals. The present study investigated the effects of Resveratrol on diabetes-induced alterations in oxidative stress, c-Jun N-terminal kinase (JNK) signaling and apoptosis in the testis. Adult male Wistar rats (13–15 weeks; n = 6/group) were segregated into 1) normal control, 2) Resveratrol-treated (5 mg/kg; ip; given during last 3 weeks), 3) Streptozotocin-induced diabetic and, 4) Resveratrol-treated diabetic groups, and euthanized on day 42 after the confirmation of diabetes. Resveratrol did not normalize blood glucose levels in diabetic rats. Resveratrol supplementation recovered diabetes-induced decreases in reproductive organ weights, sperm count and motility, intra-testicular levels of superoxide dismutase, catalase, and glutathione peroxidase and an increase in 4-hydroxynonenal activities (P < 0.05). Resveratrol also recovered diabetes-induced increases in JNK signaling pathway proteins, namely, ASK1 (apoptosis signal-regulating kinase 1), JNKs (46 and 54 kDa isoforms) and p-JNK to normal control levels (P < 0.05). Interestingly, the expression of a down-stream target of ASK1, MKK4 (mitogen-activated protein kinase kinase 4) and its phosphorylated form (p-MKK4) did not change in experimental groups. Resveratrol inhibited diabetes-induced increases in AP-1 (activator protein-1) components, c-Jun and ATF2 (activating transcription factor 2), but not their phosphorylated forms, to normal control levels (P < 0.05). Further, Resveratrol inhibited diabetes-induced increase in cleaved-caspase-3 to normal control levels. In conclusion, Resveratrol alleviates diabetes-induced apoptosis in testis by modulating oxidative stress, JNK signaling pathway and caspase-3 activities, but not by inhibiting hyperglycemia, in rats. These results suggest that Resveratrol supplementation may be a useful strategy to treat diabetes-induced testicular dysfunction. - Highlights: • Resveratrol up-regulates glutathione

  2. Resveratrol alleviates diabetes-induced testicular dysfunction by inhibiting oxidative stress and c-Jun N-terminal kinase signaling in rats

    International Nuclear Information System (INIS)

    Faid, Iman; Al-Hussaini, Heba; Kilarkaje, Narayana

    2015-01-01

    Diabetes adversely affects reproductive functions in humans and animals. The present study investigated the effects of Resveratrol on diabetes-induced alterations in oxidative stress, c-Jun N-terminal kinase (JNK) signaling and apoptosis in the testis. Adult male Wistar rats (13–15 weeks; n = 6/group) were segregated into 1) normal control, 2) Resveratrol-treated (5 mg/kg; ip; given during last 3 weeks), 3) Streptozotocin-induced diabetic and, 4) Resveratrol-treated diabetic groups, and euthanized on day 42 after the confirmation of diabetes. Resveratrol did not normalize blood glucose levels in diabetic rats. Resveratrol supplementation recovered diabetes-induced decreases in reproductive organ weights, sperm count and motility, intra-testicular levels of superoxide dismutase, catalase, and glutathione peroxidase and an increase in 4-hydroxynonenal activities (P < 0.05). Resveratrol also recovered diabetes-induced increases in JNK signaling pathway proteins, namely, ASK1 (apoptosis signal-regulating kinase 1), JNKs (46 and 54 kDa isoforms) and p-JNK to normal control levels (P < 0.05). Interestingly, the expression of a down-stream target of ASK1, MKK4 (mitogen-activated protein kinase kinase 4) and its phosphorylated form (p-MKK4) did not change in experimental groups. Resveratrol inhibited diabetes-induced increases in AP-1 (activator protein-1) components, c-Jun and ATF2 (activating transcription factor 2), but not their phosphorylated forms, to normal control levels (P < 0.05). Further, Resveratrol inhibited diabetes-induced increase in cleaved-caspase-3 to normal control levels. In conclusion, Resveratrol alleviates diabetes-induced apoptosis in testis by modulating oxidative stress, JNK signaling pathway and caspase-3 activities, but not by inhibiting hyperglycemia, in rats. These results suggest that Resveratrol supplementation may be a useful strategy to treat diabetes-induced testicular dysfunction. - Highlights: • Resveratrol up-regulates glutathione

  3. Production of Purely Gravitational Dark Matter

    OpenAIRE

    Ema, Yohei; Nakayama, Kazunori; Tang, Yong

    2018-01-01

    In the purely gravitational dark matter scenario, the dark matter particle does not have any interaction except for gravitational one. We study the gravitational particle production of dark matter particle in such a minimal setup and show that correct amount of dark matter can be produced depending on the inflation model and the dark matter mass. In particular, we carefully evaluate the particle production rate from the transition epoch to the inflaton oscillation epoch in a realistic inflati...

  4. Merging Black Holes and Gravitational Waves

    Science.gov (United States)

    Centrella, Joan

    2009-01-01

    This talk will focus on simulations of binary black hole mergers and the gravitational wave signals they produce. Applications to gravitational wave detection with LISA, and electronagnetic counterparts, will be highlighted.

  5. Phenformin-Induced Mitochondrial Dysfunction Sensitizes Hepatocellular Carcinoma for Dual Inhibition of mTOR.

    Science.gov (United States)

    Veiga, Sonia Rosa; Ge, Xuemei; Mercer, Carol A; Hernández-Alvarez, María Isabel; Thomas, Hala Elnakat; Hernández-Losa, Javier; Ramón Y Cajal, Santiago; Zorzano, Antonio; Thomas, George; Kozma, Sara C

    2018-04-24

    Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited therapeutic options. We recently described the synergistic effect of allosteric and ATP-site competitive inhibitors against the mammalian target of rapamycin (mTOR) for the treatment of HCC. However, such inhibitors induce glycemia and increase mitochondrial efficiency. Here we determined whether the mitochondrial complex I inhibitor Phenformin could reverse both side effects, impose an energetic-stress on cancer cells and suppress the growth of HCC. Human HCC cell lines were used in vitro to access the signaling and energetic impact of mTOR inhibitors and Phenformin, either alone or in combination. Next, the therapeutic utility of these drugs alone or in combination was investigated pre-clinically in human orthotopic tumors implanted in mice, by analyzing their impact on the tumor burden and overall survival. We found Phenformin caused mitochondrial dysfunction and fragmentation, inducing a compensatory shift to glycolysis. In contrast, dual inhibition of mTOR impaired cell growth and glycolysis, while increasing mitochondrial fusion and efficiency. In a mouse model of human HCC, dual inhibition of mTOR, together with Phenformin, was highly efficacious in controlling tumor burden. However, more striking, pretreatment with Phenformin sensitized tumors to dual inhibition of mTOR, leading to a dramatic improvement in survival. Treatment of HCC cells in vitro with the biguanide Phenformin causes a metabolic shift to glycolysis, mitochondrial dysfunction and fragmentation, and dramatically sensitizes orthotopic liver tumors to dual inhibition of mTOR. We therefore propose this therapeutic approach should be tested clinically in HCC. Copyright ©2018, American Association for Cancer Research.

  6. Diclofenac inhibits tumor necrosis factor-α-induced nuclear factor-κB activation causing synergistic hepatocyte apoptosis.

    Science.gov (United States)

    Fredriksson, Lisa; Herpers, Bram; Benedetti, Giulia; Matadin, Quraisha; Puigvert, Jordi C; de Bont, Hans; Dragovic, Sanja; Vermeulen, Nico P E; Commandeur, Jan N M; Danen, Erik; de Graauw, Marjo; van de Water, Bob

    2011-06-01

    Drug-induced liver injury (DILI) is an important clinical problem. It involves crosstalk between drug toxicity and the immune system, but the exact mechanism at the cellular hepatocyte level is not well understood. Here we studied the mechanism of crosstalk in hepatocyte apoptosis caused by diclofenac and the proinflammatory cytokine tumor necrosis factor α (TNF-α). HepG2 cells were treated with diclofenac followed by TNF-α challenge and subsequent evaluation of necrosis and apoptosis. Diclofenac caused a mild apoptosis of HepG2 cells, which was strongly potentiated by TNF-α. A focused apoptosis machinery short interference RNA (siRNA) library screen identified that this TNF-α-mediated enhancement involved activation of caspase-3 through a caspase-8/Bid/APAF1 pathway. Diclofenac itself induced sustained activation of c-Jun N-terminal kinase (JNK) and inhibition of JNK decreased both diclofenac and diclofenac/TNF-α-induced apoptosis. Live cell imaging of GFPp65/RelA showed that diclofenac dampened the TNF-α-mediated nuclear factor kappaB (NF-κB) translocation oscillation in association with reduced NF-κB transcriptional activity. This was associated with inhibition by diclofenac of the TNF-α-induced phosphorylation of the inhibitor of NF-κB alpha (IκBα). Finally, inhibition of IκB kinase β (IKKβ) with BMS-345541 as well as stable lentiviral short hairpin RNA (shRNA)-based knockdown of p65/RelA sensitized hepatocytes towards diclofenac/TNF-α-induced cytotoxicity. Together, our data suggest a model whereby diclofenac-mediated stress signaling suppresses TNF-α-induced survival signaling routes and sensitizes cells to apoptosis. Copyright © 2011 American Association for the Study of Liver Diseases.

  7. EVA1A inhibits GBM cell proliferation by inducing autophagy and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Xue; Kan, Shifeng; Liu, Zhen [Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Lu, Guang [Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597 (Singapore); Zhang, Xiaoyan [Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Chen, Yingyu [Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Peking University Center for Human Disease Genomics, Beijing 100191 (China); Bai, Yun, E-mail: baiyun@bjmu.edu.cn [Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China)

    2017-03-01

    Eva-1 homolog A (EVA1A) is a novel lysosome and endoplasmic reticulum-associated protein involved in autophagy and apoptosis. In this study, we constructed a recombinant adenovirus 5-EVA1A vector (Ad5-EVA1A) to overexpress EVA1A in glioblastoma (GBM) cell lines and evaluated its anti-tumor activities in vitro and in vivo. We found that overexpression of EVA1A in three GBM cell lines (U251, U87 and SHG44) resulted in a suppression of tumor cell growth via activation of autophagy and induction of cell apoptosis in a dose- and time-dependent manner. EVA1A-mediated autophagy was associated with inactivation of the mTOR/RPS6KB1 signaling pathway. Furthermore in vivo, overexpression of EVA1A successfully inhibited tumor growth in NOD/SCID mice. Our data suggest that EVA1A-induced autophagy and apoptosis play a role in suppressing the development of GBM and their up-regulation may be an effective method for treating this form of cancer. - Highlights: • Overexpression of EVA1A suppresses GBM cell growth. • EVA1A induces autophagy through the mTOR/RPS6KB1 pathway. • EVA1A induces GBM cell apoptosis. • EVA1A inhibits the development of GBM in vivo.

  8. Gravitational Wave Experiments - Proceedings of the First Edoardo Amaldi Conference

    Science.gov (United States)

    Coccia, E.; Pizzella, G.; Ronga, F.

    1995-07-01

    The Table of Contents for the full book PDF is as follows: * Foreword * Notes on Edoardo Amaldi's Life and Activity * PART I. INVITED LECTURES * Sources and Telescopes * Sources of Gravitational Radiation for Detectors of the 21st Century * Neutrino Telescopes * γ-Ray Bursts * Space Detectors * LISA — Laser Interferometer Space Antenna for Gravitational Wave Measurements * Search for Massive Coalescing Binaries with the Spacecraft ULYSSES * Interferometers * The LIGO Project: Progress and Prospects * The VIRGO Experiment: Status of the Art * GEO 600 — A 600-m Laser Interferometric Gravitational Wave Antenna * 300-m Laser Interferometer Gravitational Wave Detector (TAMA300) in Japan * Resonant Detectors * Search for Continuous Gravitational Wave from Pulsars with Resonant Detector * Operation of the ALLEGRO Detector at LSU * Preliminary Results of the New Run of Measurements with the Resonant Antenna EXPLORER * Operation of the Perth Cryogenic Resonant-Bar Gravitational Wave Detector * The NAUTILUS Experiment * Status of the AURIGA Gravitational Wave Antenna and Perspectives for the Gravitational Waves Search with Ultracryogenic Resonant Detectors * Ultralow Temperature Resonant-Mass Gravitational Radiation Detectors: Current Status of the Stanford Program * Electromechanical Transducers and Bandwidth of Resonant-Mass Gravitational-Wave Detectors * Fully Numerical Data Analysis for Resonant Gravitational Wave Detectors: Optimal Filter and Available Information * PART II. CONTRIBUTED PAPERS * Sources and Telescopes * The Local Supernova Production * Periodic Gravitational Signals from Galactic Pulsars * On a Possibility of Scalar Gravitational Wave Detection from the Binary Pulsars PSR 1913+16 * Kazan Gravitational Wave Detector “Dulkyn”: General Concept and Prospects of Construction * Hierarchical Approach to the Theory of Detection of Periodic Gravitational Radiation * Application of Gravitational Antennae for Fundamental Geophysical Problems * On

  9. Osthol attenuates neutrophilic oxidative stress and hemorrhagic shock-induced lung injury via inhibition of phosphodiesterase 4.

    Science.gov (United States)

    Tsai, Yung-Fong; Yu, Huang-Ping; Chung, Pei-Jen; Leu, Yann-Lii; Kuo, Liang-Mou; Chen, Chun-Yu; Hwang, Tsong-Long

    2015-12-01

    Oxidative stress caused by neutrophils is an important pathogenic factor in trauma/hemorrhagic (T/H)-induced acute lung injury (ALI). Osthol, a natural coumarin found in traditional medicinal plants, has therapeutic potential in various diseases. However, the pharmacological effects of osthol in human neutrophils and its molecular mechanism of action remain elusive. In this study, our data showed that osthol potently inhibited the production of superoxide anion (O2(•-)) and reactive oxidants derived therefrom as well as expression of CD11b in N-formylmethionylleucylphenylalanine (FMLP)-activated human neutrophils. However, osthol inhibited neutrophil degranulation only slightly and it failed to inhibit the activity of subcellular NADPH oxidase. FMLP-induced phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) was inhibited by osthol. Notably, osthol increased the cAMP concentration and protein kinase A (PKA) activity in activated neutrophils. PKA inhibitors reversed the inhibitory effects of osthol, suggesting that these are mediated through cAMP/PKA-dependent inhibition of ERK and Akt activation. Furthermore, the activity of cAMP-specific phosphodiesterase (PDE) 4, but not PDE3 or PDE7, was significantly reduced by osthol. In addition, osthol reduced myeloperoxidase activity and pulmonary edema in rats subjected to T/H shock. In conclusion, our data suggest that osthol has effective anti-inflammatory activity in human neutrophils through the suppression of PDE4 and protects significantly against T/H shock-induced ALI in rats. Osthol may have potential for future clinical application as a novel adjunct therapy to treat lung inflammation caused by adverse circulatory conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Emodin attenuates high glucose-induced TGF-β1 and fibronectin expression in mesangial cells through inhibition of NF-κB pathway

    International Nuclear Information System (INIS)

    Yang, Jie; Zeng, Zhi; Wu, Teng; Yang, Zhicheng; Liu, Bing; Lan, Tian

    2013-01-01

    The activation of nuclear factor-κB (NF-κB) and the subsequent overexpression of its downstream targets transforming growth factor-β1 (TGF-β1) and fibronectin (FN) are among the hallmarks for the progressive diabetic nephropathy. Our previous studies demonstrated that emodin ameliorated renal injury and inhibited extracellular matrix accumulation in kidney and mesangial cells under diabetic condition. However, the molecular mechanism has not been fully elucidated. Here, we showed that emodin significantly attenuated high glucose-induced NF-κB nuclear translocation in mesangial cells. Interestingly, emodin also inhibited the DNA-binding activity and transcriptional activity of NF-κB. Furthermore, NF-κB-mediated TGF-β1 and FN expression was significantly decreased by emodin. These results demonstrated that emodin suppressed TGF-β1 and FN overexpression through inhibition of NF-κB activation, suggesting that emodin-mediated inhibition of the NF-κB pathway could protect against diabetic nephropathy. - Highlights: • Emodin decreased high glucose-induced p65 phosphorylation in MCs. • Emodin decreased high glucose-induced IκB-α degradation in MCs. • Emodin decreased high glucose-induced p65 translocation in MCs. • Emodin blocked high glucose-induced NF-κB activity. • Emodin blocked high glucose-induced the expression of TGF-β1 and FN

  11. Joint immobilization inhibits spontaneous hyaline cartilage regeneration induced by a novel double-network gel implantation.

    Science.gov (United States)

    Arakaki, Kazunobu; Kitamura, Nobuto; Kurokawa, Takayuki; Onodera, Shin; Kanaya, Fuminori; Gong, Jian-Ping; Yasuda, Kazunori

    2011-02-01

    We have recently discovered that spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect in the rabbit, when we implant a novel double-network (DN) gel plug at the bottom of the defect. To clarify whether joint immobilization inhibits the spontaneous hyaline cartilage regeneration, we conducted this study with 20 rabbits. At 4 or 12 weeks after surgery, the defect in the mobile knees was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type-2 collagen, while no cartilage tissues were observed in the defect in the immobilized knees. Type-2 collagen, Aggrecan, and SOX9 mRNAs were expressed only in the mobile knees at each period. This study demonstrated that joint immobilization significantly inhibits the spontaneous hyaline cartilage regeneration induced by the DN gel implantation. This fact suggested that the mechanical environment is one of the significant factors to induce this phenomenon.

  12. Self-gravitation in Saturn's rings

    International Nuclear Information System (INIS)

    Salo, H.; Lukkari, J.

    1982-01-01

    In a ring-shaped collisional system self-gravitation reduces the equilibrium values of the geometric and optical thickness. In Saturn's rings both effects are appreciable. The previously found discrepancy between the calculated profile and the observed profile of the rings is chiefly caused by the omission of self-gravitation. (Auth.)

  13. Salinomycin inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cell in vitro and suppresses tumor growth in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Danxin; Zhang, Yu; Huang, Jie; Fan, Zirong; Shi, Fengrong; Wang, Senming, E-mail: wsenming@126.com

    2014-01-10

    Highlight: •We first evaluated the effect of salinomycin on nasopharyngeal carcinoma (NPC). •Salinomycin could inhibit Wnt/β-catenin signaling and induce apoptosis in NPC. •So salinomycin may be a good potential candidate for the chemotherapy of NPC. -- Abstract: Salinomycin (Sal) is a polyether ionophore antibiotic that has recently been shown to induce cell death in various human cancer cells. However, whether salinomycin plays a functional role in nasopharyngeal carcinoma (NPC) has not been determined to date. The present study investigated the chemotherapeutic efficacy of salinomycin and its molecular mechanisms of action in NPC cells. Salinomycin efficiently inhibited proliferation and invasion of 3 NPC cell lines (CNE-1, CNE-2, and CNE-2/DDP) and activated a extensive apoptotic process that is accompanied by activation of caspase-3 and caspase-9, and decreased mitochondrial membrane potential. Meanwhile, the protein expression level of the Wnt coreceptor lipoprotein receptor related protein 6 (LRP6) and β-catenin was down-regulated, which showed that the Wnt/β-catenin signaling was involved in salinomycin-induced apoptosis of NPC cells. In a nude mouse NPC xenograft model, the anti-tumor effect of salinomycin was associated with the downregulation of β-catenin expression. The present study demonstrated that salinomycin can effectively inhibit proliferation and invasion, and induce apoptosis of NPC cells in vitro and inhibit tumor growth in vivo, probably via the inhibition of Wnt/β-catenin signaling, suggesting salinomycin as a potential candidate for the chemotherapy of NPC.

  14. Overexpression of ERβ is sufficient to inhibit hypoxia-inducible factor-1 transactivation

    International Nuclear Information System (INIS)

    Park, Choa; Lee, YoungJoo

    2014-01-01

    Highlights: • We examined the effect of ERβ specific ligand on HIF-1 inhibition. • DPN down-regulates the ARNT protein levels in PC3 cells. • DPN did not show additional effect in ERβ transfected MCF-7 cells. • Our study shows that unliganded ERβ is sufficient to inhibit HIF-1 in systems of overexpression. - Abstract: Estrogen receptor (ER) β is predicted to play an important role in the prevention of breast cancer development and progression. We have previously shown that ERβ suppresses hypoxia inducible factor (HIF)-1-mediated transcription through aryl hydrocarbon receptor nuclear translocator (ARNT) degradation via ubiquitination processes. In this study, we attempted to examine the effect of ERβ specific ligand on HIF-1 inhibition in ERβ positive PC3 cells and ERβ transfected MCF-7 cells. ERβ specific agonist diarylpropionitrile (DPN) stimulated estrogen response element (ERE)-luciferase activity in a similar fashion to estradiol in PC3 cells. We observed that DPN down-regulates the ARNT protein levels leading to an attenuation of hypoxia-induced hypoxia response element (HRE)-driven luciferase reporter gene activation in PC3 cells. Treatment of DPN reduced vascular endothelial growth factor (VEGF) expression and co-treatment with ERβ specific antagonist PHTPP abrogated the effect in PC3 cells. We then examined the effect of DPN in ERβ transfected MCF-7 cells. HIF-1 transcriptional activity repression by ERβ was not further reduced by DPN, as examined by HRE-driven luciferase assays. Expression of ERβ significantly decreased VEGF secretion and ARNT expression under hypoxic conditions. However, DPN did not additionally affect this suppression in MCF-7 cells transfected with ERβ. This result shows that unliganded ERβ is sufficient to inhibit HIF-1 in systems of overexpression

  15. Overexpression of ERβ is sufficient to inhibit hypoxia-inducible factor-1 transactivation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Choa; Lee, YoungJoo, E-mail: yjlee@sejong.ac.kr

    2014-07-18

    Highlights: • We examined the effect of ERβ specific ligand on HIF-1 inhibition. • DPN down-regulates the ARNT protein levels in PC3 cells. • DPN did not show additional effect in ERβ transfected MCF-7 cells. • Our study shows that unliganded ERβ is sufficient to inhibit HIF-1 in systems of overexpression. - Abstract: Estrogen receptor (ER) β is predicted to play an important role in the prevention of breast cancer development and progression. We have previously shown that ERβ suppresses hypoxia inducible factor (HIF)-1-mediated transcription through aryl hydrocarbon receptor nuclear translocator (ARNT) degradation via ubiquitination processes. In this study, we attempted to examine the effect of ERβ specific ligand on HIF-1 inhibition in ERβ positive PC3 cells and ERβ transfected MCF-7 cells. ERβ specific agonist diarylpropionitrile (DPN) stimulated estrogen response element (ERE)-luciferase activity in a similar fashion to estradiol in PC3 cells. We observed that DPN down-regulates the ARNT protein levels leading to an attenuation of hypoxia-induced hypoxia response element (HRE)-driven luciferase reporter gene activation in PC3 cells. Treatment of DPN reduced vascular endothelial growth factor (VEGF) expression and co-treatment with ERβ specific antagonist PHTPP abrogated the effect in PC3 cells. We then examined the effect of DPN in ERβ transfected MCF-7 cells. HIF-1 transcriptional activity repression by ERβ was not further reduced by DPN, as examined by HRE-driven luciferase assays. Expression of ERβ significantly decreased VEGF secretion and ARNT expression under hypoxic conditions. However, DPN did not additionally affect this suppression in MCF-7 cells transfected with ERβ. This result shows that unliganded ERβ is sufficient to inhibit HIF-1 in systems of overexpression.

  16. Method to measure a relative transverse velocity of a source-lens-observer system using gravitational lensing of gravitational waves

    International Nuclear Information System (INIS)

    Itoh, Yousuke; Futamase, Toshifumi; Hattori, Makoto

    2009-01-01

    Gravitational waves propagate along null geodesics like light rays in the geometrical optics approximation, and they may have a chance to suffer from gravitational lensing by intervening objects, as is the case for electromagnetic waves. Long wavelengths of gravitational waves and compactness of possible sources may enable us to extract information in the interference among the lensed images. We point out that the interference term contains information of relative transverse velocity of the source-lens-observer system, which may be obtained by possible future space-borne gravitational wave detectors such as BBO/DECIGO.

  17. Inhibition of Methylglyoxal-Induced AGEs/RAGE Expression Contributes to Dermal Protection by N-Acetyl-L-Cysteine

    Directory of Open Access Journals (Sweden)

    Chun-tao Yang

    2017-02-01

    Full Text Available Background/Aim: Accumulation of advanced glycation end products (AGEs is a major cause of diabetes mellitus (DM skin complications. Methylglyoxal (MGO, a reactive dicarbonyl compound, is a crucial intermediate of AGEs generation. N-acetyl-L-cysteine (NAC, an active ingredient of some medicines, can induce endogenous GSH and hydrogen sulfide generation, and set off a condensation reaction with MGO. However, there is rare evidence to show NAC can alleviate DM-induced skin injury through inhibition of AGEs generation or toxicity. The present study aimed to observe the effects of NAC on MGO-induced inflammatory injury and investigate the roles of AGEs and its receptor (RAGE in NAC’s dermal protection in human HaCaT keratinocytes. Methods: The cells were exposed to MGO to simulate a high MGO status in diabetic blood or tissues. The content of AGEs in serum or cell medium was measured with ELISA. The protective effects of NAC against MGO-induce injury were evaluated by administration before MGO one hour, in virtue of cell viability, mitochondrial membrane potential, inflammation reaction, nuclear factor (NF-κB activation, matrix metalloproteinase (MMP-9 expression, as well as cellular behavioral function. Results: We found the AGEs levels of patients with DM were elevated comparing with healthy volunteers. The in vitro AGEs generation was also able to be enhanced by the exposure of HaCaT cells to MGO, which reduced dose-dependently cellular viability, damaged mitochondrial function, triggered secretion of interleukin (IL-6 and IL-8, activated NF-κB and upregulated MMP-9 expression. Furthermore, the exposure caused cellular adhesion and migration dysfunction, as well as collagen type I inhibition. Importantly, before the exposure to MGO, the preconditioning with NAC significantly attenuated MGO-induced AGEs generation, improved cellular viability and mitochondrial function, partially reversed the overexpression of proinflammatory factors and MMP-9

  18. MFGE8 inhibits inflammasome-induced IL-1β production and limits postischemic cerebral injury.

    Science.gov (United States)

    Deroide, Nicolas; Li, Xuan; Lerouet, Dominique; Van Vré, Emily; Baker, Lauren; Harrison, James; Poittevin, Marine; Masters, Leanne; Nih, Lina; Margaill, Isabelle; Iwakura, Yoichiro; Ryffel, Bernhard; Pocard, Marc; Tedgui, Alain; Kubis, Nathalie; Mallat, Ziad

    2013-03-01

    Milk fat globule-EGF 8 (MFGE8) plays important, nonredundant roles in several biological processes, including apoptotic cell clearance, angiogenesis, and adaptive immunity. Several recent studies have reported a potential role for MFGE8 in regulation of the innate immune response; however, the precise mechanisms underlying this role are poorly understood. Here, we show that MFGE8 is an endogenous inhibitor of inflammasome-induced IL-1β production. MFGE8 inhibited necrotic cell-induced and ATP-dependent IL-1β production by macrophages through mediation of integrin β(3) and P2X7 receptor interactions in primed cells. Itgb3 deficiency in macrophages abrogated the inhibitory effect of MFGE8 on ATP-induced IL-1β production. In a setting of postischemic cerebral injury in mice, MFGE8 deficiency was associated with enhanced IL-1β production and larger infarct size; the latter was abolished after treatment with IL-1 receptor antagonist. MFGE8 supplementation significantly dampened caspase-1 activation and IL-1β production and reduced infarct size in wild-type mice, but did not limit cerebral necrosis in Il1b-, Itgb3-, or P2rx7-deficient animals. In conclusion, we demonstrated that MFGE8 regulates innate immunity through inhibition of inflammasome-induced IL-1β production.

  19. Inducible Inhibition of Gβγ Reveals Localization-dependent Functions at the Plasma Membrane and Golgi*

    Science.gov (United States)

    Klayman, Lauren M.; Wedegaertner, Philip B.

    2017-01-01

    Heterotrimeric G proteins signal at a variety of endomembrane locations, in addition to their canonical function at the cytoplasmic surface of the plasma membrane (PM), where they are activated by cell surface G protein-coupled receptors. Here we focus on βγ signaling at the Golgi, where βγ activates a signaling cascade, ultimately resulting in vesicle fission from the trans-Golgi network (TGN). To develop a novel molecular tool for inhibiting endogenous βγ in a spatial-temporal manner, we take advantage of a lipid association mutant of the widely used βγ inhibitor GRK2ct (GRK2ct-KERE) and the FRB/FKBP heterodimerization system. We show that GRK2ct-KERE cannot inhibit βγ function when expressed in cells, but recruitment to a specific membrane location recovers the ability of GRK2ct-KERE to inhibit βγ signaling. PM-recruited GRK2ct-KERE inhibits lysophosphatidic acid-induced phosphorylation of Akt, whereas Golgi-recruited GRK2ct-KERE inhibits cargo transport from the TGN to the PM. Moreover, we show that Golgi-recruited GRK2ct-KERE inhibits model basolaterally targeted but not apically targeted cargo delivery, for both PM-destined and secretory cargo, providing the first evidence of selectivity in terms of cargo transport regulated by βγ. Last, we show that Golgi fragmentation induced by ilimaquinone and nocodazole is blocked by βγ inhibition, demonstrating that βγ is a key regulator of multiple pathways that impact Golgi morphology. Thus, we have developed a new molecular tool, recruitable GRK2ct-KERE, to modulate βγ signaling at specific subcellular locations, and we demonstrate novel cargo selectivity for βγ regulation of TGN to PM transport and a novel role for βγ in mediating Golgi fragmentation. PMID:27994056

  20. Inducible Inhibition of Gβγ Reveals Localization-dependent Functions at the Plasma Membrane and Golgi.

    Science.gov (United States)

    Klayman, Lauren M; Wedegaertner, Philip B

    2017-02-03

    Heterotrimeric G proteins signal at a variety of endomembrane locations, in addition to their canonical function at the cytoplasmic surface of the plasma membrane (PM), where they are activated by cell surface G protein-coupled receptors. Here we focus on βγ signaling at the Golgi, where βγ activates a signaling cascade, ultimately resulting in vesicle fission from the trans-Golgi network (TGN). To develop a novel molecular tool for inhibiting endogenous βγ in a spatial-temporal manner, we take advantage of a lipid association mutant of the widely used βγ inhibitor GRK2ct (GRK2ct-KERE) and the FRB/FKBP heterodimerization system. We show that GRK2ct-KERE cannot inhibit βγ function when expressed in cells, but recruitment to a specific membrane location recovers the ability of GRK2ct-KERE to inhibit βγ signaling. PM-recruited GRK2ct-KERE inhibits lysophosphatidic acid-induced phosphorylation of Akt, whereas Golgi-recruited GRK2ct-KERE inhibits cargo transport from the TGN to the PM. Moreover, we show that Golgi-recruited GRK2ct-KERE inhibits model basolaterally targeted but not apically targeted cargo delivery, for both PM-destined and secretory cargo, providing the first evidence of selectivity in terms of cargo transport regulated by βγ. Last, we show that Golgi fragmentation induced by ilimaquinone and nocodazole is blocked by βγ inhibition, demonstrating that βγ is a key regulator of multiple pathways that impact Golgi morphology. Thus, we have developed a new molecular tool, recruitable GRK2ct-KERE, to modulate βγ signaling at specific subcellular locations, and we demonstrate novel cargo selectivity for βγ regulation of TGN to PM transport and a novel role for βγ in mediating Golgi fragmentation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Cyanidin-3-glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signaling pathways in SKH-1 hairless mice skin

    International Nuclear Information System (INIS)

    Pratheeshkumar, Poyil; Son, Young-Ok; Wang, Xin; Divya, Sasidharan Padmaja; Joseph, Binoy; Hitron, John Andrew; Wang, Lei; Kim, Donghern; Yin, Yuanqin; Roy, Ram Vinod; Lu, Jian; Zhang, Zhuo; Wang, Yitao

    2014-01-01

    Skin cancer is one of the most commonly diagnosed cancers in the United States. Exposure to ultraviolet-B (UVB) radiation induces inflammation and photocarcinogenesis in mammalian skin. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is present in various vegetables and fruits especially in edible berries, and displays potent antioxidant and anticarcinogenic properties. In this study, we have assessed the in vivo effects of C3G on UVB irradiation induced chronic inflammatory responses in SKH-1 hairless mice, a well-established model for UVB-induced skin carcinogenesis. Here, we show that C3G inhibited UVB-induced skin damage and inflammation in SKH-1 hairless mice. Our results indicate that C3G inhibited glutathione depletion, lipid peroxidation and myeloperoxidation in mouse skin by chronic UVB exposure. C3G significantly decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-6 and TNF-α, associated with cutaneous inflammation. Likewise, UVB-induced inflammatory responses were diminished by C3G as observed by a remarkable reduction in the levels of phosphorylated MAP kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, C3G also decreased UVB-induced cyclooxygenase-2 (COX-2), PGE 2 and iNOS levels, which are well-known key mediators of inflammation and cancer. Treatment with C3G inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mice skin. Immunofluorescence assay revealed that topical application of C3G inhibited the expression of 8-hydroxy-2′-deoxyguanosine, proliferating cell nuclear antigen, and cyclin D1 in chronic UVB exposed mouse skin. Collectively, these data indicates that C3G can provide substantial protection against the adverse effects of UVB radiation by modulating UVB-induced MAP kinase and NF-κB signaling pathways. - Highlights: • C3G inhibited UVB-induced oxidative damage and inflammation. • C3G inhibited UVB-induced COX-2, iNOS and PGE 2 production. • C3G inhibited

  2. Cyanidin-3-glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signaling pathways in SKH-1 hairless mice skin

    Energy Technology Data Exchange (ETDEWEB)

    Pratheeshkumar, Poyil; Son, Young-Ok; Wang, Xin; Divya, Sasidharan Padmaja [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Joseph, Binoy [Spinal Cord and Brain Injury Research Center and Department of Physiology, University of Kentucky, Lexington, KY 40536-0509 (United States); Hitron, John Andrew; Wang, Lei [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Kim, Donghern [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Yin, Yuanqin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Cancer Institute, The First Affiliated Hospital, China Medical University, Shenyang (China); Roy, Ram Vinod [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Lu, Jian [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013 (China); Zhang, Zhuo [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Wang, Yitao [State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau (China); and others

    2014-10-01

    Skin cancer is one of the most commonly diagnosed cancers in the United States. Exposure to ultraviolet-B (UVB) radiation induces inflammation and photocarcinogenesis in mammalian skin. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is present in various vegetables and fruits especially in edible berries, and displays potent antioxidant and anticarcinogenic properties. In this study, we have assessed the in vivo effects of C3G on UVB irradiation induced chronic inflammatory responses in SKH-1 hairless mice, a well-established model for UVB-induced skin carcinogenesis. Here, we show that C3G inhibited UVB-induced skin damage and inflammation in SKH-1 hairless mice. Our results indicate that C3G inhibited glutathione depletion, lipid peroxidation and myeloperoxidation in mouse skin by chronic UVB exposure. C3G significantly decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-6 and TNF-α, associated with cutaneous inflammation. Likewise, UVB-induced inflammatory responses were diminished by C3G as observed by a remarkable reduction in the levels of phosphorylated MAP kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, C3G also decreased UVB-induced cyclooxygenase-2 (COX-2), PGE{sub 2} and iNOS levels, which are well-known key mediators of inflammation and cancer. Treatment with C3G inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mice skin. Immunofluorescence assay revealed that topical application of C3G inhibited the expression of 8-hydroxy-2′-deoxyguanosine, proliferating cell nuclear antigen, and cyclin D1 in chronic UVB exposed mouse skin. Collectively, these data indicates that C3G can provide substantial protection against the adverse effects of UVB radiation by modulating UVB-induced MAP kinase and NF-κB signaling pathways. - Highlights: • C3G inhibited UVB-induced oxidative damage and inflammation. • C3G inhibited UVB-induced COX-2, iNOS and PGE{sub 2} production. • C3G

  3. [Arginase inhibitor nor-NOHA induces apoptosis and inhibits invasion and migration of HepG2 cells].

    Science.gov (United States)

    Li, Xiangnan; Zhu, Fangyu; He, Yongsong; Luo, Fang

    2017-04-01

    Objective To investigate the cell inhibitory effect of arginase inhibitor nor-NOHA on HepG2 hepatocellular carcinoma cells and related mechanism. Methods CCK-8 assay was used to detect the cell proliferation and flow cytometry to detect the apoptosis of HepG2 cells treated with (0, 0.5, 1.0, 2.0, 3.0) ng/μL nor-NOHA. The protein levels of arginase 1 (Arg1), P53, matrix metalloproteinase-2 (MMP-2), E-cadherin (ECD) were determined by Western blotting. Real time quantitative PCR was employed to examine the changes in the mRNA level of inducible nitric oxide synthase (iNOS). Griess assay was used to measure the concentration of nitric oxide (NO) in HepG2 cells. Transwell TM assay and wound-healing assay were performed to evaluate the changes of the cell invasion and migration ability, respectively. Results nor-NOHA inhibited the proliferation and induced the apoptosis of HepG2 cells. It also decreased the expression levels of Arg1 and MMP-2, increased the expression levels of P53 and ECD as well as the production of NO; in addition, nor-NOHA inhibited the invasion and migration of HepG2 cells. Conclusion Nor-NOHA can induce cell apoptosis and inhibit the ability of invasion and migration of HepG2 cells by inhibiting Arg1, which is related with the increase of iNOS expression and the high concentration of NO.

  4. Ginger extract inhibits LPS induced macrophage activation and function

    Directory of Open Access Journals (Sweden)

    Bruch David

    2008-01-01

    Full Text Available Abstract Background Macrophages play a dual role in host defence. They act as the first line of defence by mounting an inflammatory response to antigen exposure and also act as antigen presenting cells and initiate the adaptive immune response. They are also the primary infiltrating cells at the site of inflammation. Inhibition of macrophage activation is one of the possible approaches towards modulating inflammation. Both conventional and alternative approaches are being studied in this regard. Ginger, an herbal product with broad anti inflammatory actions, is used as an alternative medicine in a number of inflammatory conditions like rheumatic disorders. In the present study we examined the effect of ginger extract on macrophage activation in the presence of LPS stimulation. Methods Murine peritoneal macrophages were stimulated by LPS in presence or absence of ginger extract and production of proinflammatory cytokines and chemokines were observed. We also studied the effect of ginger extract on the LPS induced expression of MHC II, B7.1, B7.2 and CD40 molecules. We also studied the antigen presenting function of ginger extract treated macrophages by primary mixed lymphocyte reaction. Results We observed that ginger extract inhibited IL-12, TNF-α, IL-1β (pro inflammatory cytokines and RANTES, MCP-1 (pro inflammatory chemokines production in LPS stimulated macrophages. Ginger extract also down regulated the expression of B7.1, B7.2 and MHC class II molecules. In addition ginger extract negatively affected the antigen presenting function of macrophages and we observed a significant reduction in T cell proliferation in response to allostimulation, when ginger extract treated macrophages were used as APCs. A significant decrease in IFN-γ and IL-2 production by T cells in response to allostimulation was also observed. Conclusion In conclusion ginger extract inhibits macrophage activation and APC function and indirectly inhibits T cell activation.

  5. Rho-Kinase Inhibition Ameliorates Dasatinib-Induced Endothelial Dysfunction and Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Csilla Fazakas

    2018-05-01

    Full Text Available The multi-kinase inhibitor dasatinib is used for treatment of imatinib-resistant chronic myeloid leukemia, but is prone to induce microvascular dysfunction. In lung this can manifest as capillary leakage with pleural effusion, pulmonary edema or even pulmonary arterial hypertension. To understand how dasatinib causes endothelial dysfunction we examined the effects of clinically relevant concentrations of dasatinib on both human pulmonary arterial macro- and microvascular endothelial cells (ECs. The effects of dasatinib was compared to imatinib and nilotinib, two other clinically used BCR/Abl kinase inhibitors that do not inhibit Src. Real three-dimensional morphology and high resolution stiffness mapping revealed softening of both macro- and microvascular ECs upon dasatinib treatment, which was not observed in response to imatinib. In a dose-dependent manner, dasatinib decreased transendothelial electrical resistance/impedance and caused a permeability increase as well as disruption of tight adherens junctions in both cell types. In isolated perfused and ventilated rat lungs, dasatinib increased mean pulmonary arterial pressure, which was accompanied by a gain in lung weight. The Rho-kinase inhibitor Y27632 partly reversed the dasatinib-induced changes in vitro and ex vivo, presumably by acting downstream of Src. Co-administration of the Rho-kinase inhibitor Y27632 completely blunted the increased pulmonary pressure in response to dasatinib. In conclusion, a dasatinib-induced permeability increase in human pulmonary arterial macro- and microvascular ECs might explain many of the adverse effects of dasatinib in patients. Rho-kinase inhibition might be suitable to ameliorate these effects.

  6. Progress in gravitational wave detection: Interferometers

    International Nuclear Information System (INIS)

    Kuroda, Kazuaki

    2002-01-01

    A gravitational wave (GW) is a physical entity of space-time derived from Einstein's theory of general relativity. Challenging projects to observe gravitational waves are being conducted throughout the world. A Japanese project involving a 300 m baseline laser interferometer, TAMA, achieved 1000 hr of continuous observation with the best sensitivity in the world during the summer of 2001. After achieving promising results, the realization of LCGT (Large-scale Cryogenic Gravitational wave Telescope) will become possible in the near future

  7. L-cysteine reversibly inhibits glucose-induced biphasic insulin secretion and ATP production by inactivating PKM2.

    Science.gov (United States)

    Nakatsu, Daiki; Horiuchi, Yuta; Kano, Fumi; Noguchi, Yoshiyuki; Sugawara, Taichi; Takamoto, Iseki; Kubota, Naoto; Kadowaki, Takashi; Murata, Masayuki

    2015-03-10

    Increase in the concentration of plasma L-cysteine is closely associated with defective insulin secretion from pancreatic β-cells, which results in type 2 diabetes (T2D). In this study, we investigated the effects of prolonged L-cysteine treatment on glucose-stimulated insulin secretion (GSIS) from mouse insulinoma 6 (MIN6) cells and from mouse pancreatic islets, and found that the treatment reversibly inhibited glucose-induced ATP production and resulting GSIS without affecting proinsulin and insulin synthesis. Comprehensive metabolic analyses using capillary electrophoresis time-of-flight mass spectrometry showed that prolonged L-cysteine treatment decreased the levels of pyruvate and its downstream metabolites. In addition, methyl pyruvate, a membrane-permeable form of pyruvate, rescued L-cysteine-induced inhibition of GSIS. Based on these results, we found that both in vitro and in MIN6 cells, L-cysteine specifically inhibited the activity of pyruvate kinase muscle isoform 2 (PKM2), an isoform of pyruvate kinases that catalyze the conversion of phosphoenolpyruvate to pyruvate. L-cysteine also induced PKM2 subunit dissociation (tetramers to dimers/monomers) in cells, which resulted in impaired glucose-induced ATP production for GSIS. DASA-10 (NCGC00181061, a substituted N,N'-diarylsulfonamide), a specific activator for PKM2, restored the tetramer formation and the activity of PKM2, glucose-induced ATP production, and biphasic insulin secretion in L-cysteine-treated cells. Collectively, our results demonstrate that impaired insulin secretion due to exposure to L-cysteine resulted from its direct binding and inactivation of PKM2 and suggest that PKM2 is a potential therapeutic target for T2D.

  8. To theory of gravitational interaction

    OpenAIRE

    Minkevich, A. V.

    2008-01-01

    Some principal problems of general relativity theory and attempts of their solution are discussed. The Poincare gauge theory of gravity as natural generalization of Einsteinian gravitation theory is considered. The changes of gravitational interaction in the frame of this theory leading to the solution of principal problems of general relativity theory are analyzed.

  9. Inhibition of X-ray-induced protection of Escherichia coli K-12 cells against the lethal effects of ultra-violet light by nitrofurantoin

    Energy Technology Data Exchange (ETDEWEB)

    Martignoni, K D [Muenchen Univ. (Germany, F.R.). Strahlenbiologisches Inst.

    1978-06-01

    Wild-type cells of E.coli K-12 showed increasing U.V. resistance if they were X-irradiated and incubated at 37/sup 0/C in growth medium before the U.V. exposure. Development of higher U.V. resistance could be inhibited by incubating the X-irradiated cells either at temperatures below 15/sup 0/C, or in the presence of 0.01 M KCN. Nitrofurantoin (NF), which was recently found specifically to inhibit inducible enzyme synthesis, had only a transient inhibitory effect on X-ray-induced U.V. resistance. Cells grown in glucose medium showed less inhibition by NF of X-radiation-induced resistance to U.V.-radiation than did cells grown in glycerol, or in glucose medium with added cyclic AMP. It is suggested that X-ray-induced U.V. resistance requires active cellular metabolism, but it is not subject to catabolite repression. The following hypothesis is offered to explain the action of NF : Under de-repressed conditions (without catabolite repression by glucose) nitrofurantoin could counteract the radiation-induced inhibition of a repair inhibitor (such as post-irradiation DNA degradation).

  10. Possible role of torsion in gravitational theories

    International Nuclear Information System (INIS)

    Nieh, H.T.

    1983-01-01

    Torsion is of interest in an indirect way, in that it has the potential of being an important ingredient in a future successful quantum theory of gravitation. Einstein's theory of gravitation, despite its simplicity and elegance, and its successes in large-scale gravitational phenomena, can only be regarded as a macroscopic classical theory. It is a non-renormalizable quantum field theory, and, therefore, lacks the status of a good microscopic theory. It is the search for a successful quantum field theory of gravitation that poses as one of the great challenges to theoretical physics today. (Auth.)

  11. The Japanese space gravitational wave antenna-DECIGO

    International Nuclear Information System (INIS)

    Kawamura, Seiji; Nakamura, Takashi; Ando, Masaki

    2006-01-01

    DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. It aims at detecting various kinds of gravitational waves between 1 mHz and 100 Hz frequently enough to open a new window of observation for gravitational wave astronomy. The pre-conceptual design of DECIGO consists of three drag-free satellites, 1000 km apart from each other, whose relative displacements are measured by a Fabry-Perot Michelson interferometer. We plan to launch DECIGO in 2024 after a long and intense development phase, including two pathfinder missions for verification of required technologies

  12. Konishi anomaly approach to gravitational F-terms

    International Nuclear Information System (INIS)

    David, Justin R.; Gava, Edi; Narain, K.S.

    2003-04-01

    We study gravitational corrections to the effective superpotential in theories with a single adjoint chiral multiplet, using the generalized Konishi anomaly and the gravitationally deformed chiral ring. We show that the genus one correction to the loop equation in the corresponding matrix model agrees with the gravitational corrected anomaly equations in the gauge theory. An important ingredient in the proof is the lack of factorization of chiral gauge invariant operators in presence of a supergravity background. We also find a genus zero gravitational correction to the superpotential, which can be removed by a field redefinition. (author)

  13. Actuality of the Einstein theory of gravitation

    International Nuclear Information System (INIS)

    Ivanenko, D.D.

    1982-01-01

    Problems of actuality of the Einstein theory of gravitation are lightened. The great Einstein theory of gravitation is shown to remain a reliable base of understanding of modern physical world pattern and its inevitable further inexhaustible precising. The main GRT difficulties are enumirated: determination of reference systems, presence of singularities in the theory, absence of consistent determination of the gravity energy, impossibility of accounting the relations between atomic, gravitational and cosmological characteristics. The attention is paid to gauge, twistor problems and to unified interaction theory. The great contribution of the soviet science in the theory of gravitation is stressed

  14. Essay on gravitation: The cosmological constant problem in brane-worlds and gravitational Lorentz violations

    International Nuclear Information System (INIS)

    Csaki, Csaba; Erlich, Joshua; Grojean, Christophe

    2001-01-01

    Brane worlds are theories with extra spatial dimensions in which ordinary matter is localized on a (3+1) dimensional submanifold. Such theories could have interesting consequences for particle physics and gravitational physics. In this essay we concentrate on the cosmological constant (CC) problem in the context of brane worlds. We show how extra-dimensional scenarios may violate Lorentz invariance in the gravity sector of the effective 4D theory, while particle physics remains unaffected. In such theories the usual no-go theorems for adjustment of the CC do not apply, and we indicate a possible explanation of the smallness of the CC. Lorentz violating effects would manifest themselves in gravitational waves travelling with a speed different from light, which can be searched for in gravitational wave experiments

  15. Gravitational Waves from Oscillons after Inflation.

    Science.gov (United States)

    Antusch, Stefan; Cefalà, Francesco; Orani, Stefano

    2017-01-06

    We investigate the production of gravitational waves during preheating after inflation in the common case of field potentials that are asymmetric around the minimum. In particular, we study the impact of oscillons, comparatively long lived and spatially localized regions where a scalar field (e.g., the inflaton) oscillates with large amplitude. Contrary to a previous study, which considered a symmetric potential, we find that oscillons in asymmetric potentials associated with a phase transition can generate a pronounced peak in the spectrum of gravitational waves that largely exceeds the linear preheating spectrum. We discuss the possible implications of this enhanced amplitude of gravitational waves. For instance, for low scale inflation models, the contribution from the oscillons can strongly enhance the observation prospects at current and future gravitational wave detectors.

  16. Gravitational perturbation theory and synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Breuer, R A [Max-Planck-Institut fuer Physik und Astrophysik, Muenchen (F.R. Germany). Inst. fuer Astrophysik

    1975-01-01

    This article presents methods and results for a gravitational perturbation theory which treats massless fields as linearized perturbations of an arbitrary gravitational vacuum background spacetime. The formalism is outlined for perturbations of type (22) spacetimes. As an application, high-frequency radiation emitted by particles moving approximately on relativistic circular geodesic orbits is computed. More precisely, the test particle assumption is made; throughout it is therefore assumed that the reaction of the radiation on the particle motion is negligible. In particular, these orbits are studied in the gravitational field of a spherically symmetric (Schwarzschild-) black hole as well as of a rotating (Kerr-) black hole. In this model, the outgoing radiation is highly focussed and of much higher fequency than the orbital frequency, i.e. one is dealing with 'gravitational synchrotron radiation'.

  17. Leishmania donovani isolates with antimony-resistant but not -sensitive phenotype inhibit sodium antimony gluconate-induced dendritic cell activation.

    Directory of Open Access Journals (Sweden)

    Arun Kumar Haldar

    2010-05-01

    Full Text Available The inability of sodium antimony gluconate (SAG-unresponsive kala-azar patients to clear Leishmania donovani (LD infection despite SAG therapy is partly due to an ill-defined immune-dysfunction. Since dendritic cells (DCs typically initiate anti-leishmanial immunity, a role for DCs in aberrant LD clearance was investigated. Accordingly, regulation of SAG-induced activation of murine DCs following infection with LD isolates exhibiting two distinct phenotypes such as antimony-resistant (Sb(RLD and antimony-sensitive (Sb(SLD was compared in vitro. Unlike Sb(SLD, infection of DCs with Sb(RLD induced more IL-10 production and inhibited SAG-induced secretion of proinflammatory cytokines, up-regulation of co-stimulatory molecules and leishmanicidal effects. Sb(RLD inhibited these effects of SAG by blocking activation of PI3K/AKT and NF-kappaB pathways. In contrast, Sb(SLD failed to block activation of SAG (20 microg/ml-induced PI3K/AKT pathway; which continued to stimulate NF-kappaB signaling, induce leishmanicidal effects and promote DC activation. Notably, prolonged incubation of DCs with Sb(SLD also inhibited SAG (20 microg/ml-induced activation of PI3K/AKT and NF-kappaB pathways and leishmanicidal effects, which was restored by increasing the dose of SAG to 40 microg/ml. In contrast, Sb(RLD inhibited these SAG-induced events regardless of duration of DC exposure to Sb(RLD or dose of SAG. Interestingly, the inhibitory effects of isogenic Sb(SLD expressing ATP-binding cassette (ABC transporter MRPA on SAG-induced leishmanicidal effects mimicked that of Sb(RLD to some extent, although antimony resistance in clinical LD isolates is known to be multifactorial. Furthermore, NF-kappaB was found to transcriptionally regulate expression of murine gammaglutamylcysteine synthetase heavy-chain (mgammaGCS(hc gene, presumably an important regulator of antimony resistance. Importantly, Sb(RLD but not Sb(SLD blocked SAG-induced mgammaGCS expression in DCs by

  18. Gravitation

    International Nuclear Information System (INIS)

    Fennelly, A.J.

    1978-01-01

    Investigations of several problems of gravitation are discussed. The question of the existence of black holes is considered. While black holes like those in Einstein's theory may not exist in other gravity theories, trapped surfaces implying such black holes certainly do. The theories include those of Brans-Dicke, Lightman-Lee, Rosen, and Yang. A similar two-tensor theory of Yilmaz is investigated and found inconsistent and nonviable. The Newman-Penrose formalism for Riemannian geometries is adapted to general gravity theories and used to implement a search for twisting solutions of the gravity theories for empty and nonempty spaces. The method can be used to find the gravitational fields for all viable gravity theories. The rotating solutions are of particular importance for strong field interpretation of the Stanford/Marshall gyroscope experiment. Inhomogeneous cosmologies are examined in Einstein's theory as generalizations of homogeneous ones by raising the dimension of the invariance groups by one more parameter. The nine Bianchi classifications are extended to Rosen's theory of gravity for homogeneous cosmological models

  19. Mifepristone inhibits MPA-and FGF2-induced mammary tumor growth but not FGF2-induced mammary hyperplasia

    Directory of Open Access Journals (Sweden)

    Juan P. Cerliani

    2010-12-01

    Full Text Available We have previously demonstrated a crosstalk between fibroblast growth factor 2 (FGF2 and progestins inducing experimental breast cancer growth. The aim of the present study was to compare the effects of FGF2 and of medroxyprogesterone acetate (MPA on the mouse mammary glands and to investigate whether the antiprogestin RU486 was able to reverse the MPA- or FGF2-induced effects on both, mammary gland and tumor growth. We demonstrate that FGF2 administered locally induced an intraductal hyperplasia that was not reverted by RU486, suggesting that FGF2-induced effects are progesterone receptor (PR-independent. However, MPA-induced paraductal hyperplasia was reverted by RU486 and a partial agonistic effect was observed in RU486-treated glands. Using C4-HD tumors which only grow in the presence of MPA, we showed that FGF2 administered intratumorally was able to stimulate tumor growth as MPA. The histology of FGF2-treated tumors showed different degrees of gland differentiation. RU486 inhibited both, MPA or FGF2 induced tumor growth. However, only complete regression was observed in MPA-treated tumors. Our results support the hypothesis that stromal FGF2 activates PR inducing hormone independent tumor growth.

  20. Dopamine inhibits lipopolysaccharide-induced nitric oxide production through the formation of dopamine quinone in murine microglia BV-2 cells

    Directory of Open Access Journals (Sweden)

    Yasuhiro Yoshioka

    2016-02-01

    Full Text Available Dopamine (DA has been suggested to modulate functions of glial cells including microglial cells. To reveal the regulatory role of DA in microglial function, in the present study, we investigated the effect of DA on lipopolysaccharide (LPS-induced nitric oxide (NO production in murine microglial cell line BV-2. Pretreatment with DA for 24 h concentration-dependently attenuated LPS-induced NO production in BV-2 cells. The inhibitory effect of DA on LPS-induced NO production was not inhibited by SCH-23390 and sulpiride, D1-like and D2-like DA receptor antagonists, respectively. In addition, pretreatment with (−-(6aR,12bR-4,6,6a,7,8,12b-Hexahydro-7-methylindolo[4,3-a]phenanthridin (CY 208–243 and bromocriptine, D1-like and D2-like DA receptor agonists, respectively, did not affect the LPS-induced NO production. N-Acetylcysteine, which inhibits DA oxidation, completely inhibited the effect of DA. Tyrosinase, which catalyzes the oxidation of DA to DA quionone (DAQ, accelerated the inhibitory effect of DA on LPS-induced NO production. These results suggest that DA attenuates LPS-induced NO production through the formation of DAQ in BV-2 cells.