Super Heavy-Duty Door Hardware.

ERIC Educational Resources Information Center

Fickes, Michael

2000-01-01

Discusses the new generation of durable school-door hardware and innovations that can resist everyday abuse. Concluding comments address cross-corridor door innovations that can help doorways more easily accommodate the passage of oversized items, and classroom door locking systems. (GR)

Experimental Characterization of Aluminum-Based Hybrid Composites Obtained Through Powder Metallurgy

NASA Astrophysics Data System (ADS)

Marcu, D. F.; Buzatu, M.; Ghica, V. G.; Petrescu, M. I.; Popescu, G.; Niculescu, F.; Iacob, G.

2018-06-01

The paper presents some experimental results concerning fabrication through powder metallurgy (P/M) of aluminum-based hybrid composites - Al/Al2O3/Gr. In order to understand the mechanisms that occur during the P/M processes of obtaining Al/Al2O3/Gr composite, we correlated the physical characteristics with their micro-structural characteristics. The characterization was performed using analysis techniques specific for P/M process, SEM-EDS and XRD analyses. Micro-structural characterization of the composites has revealed fairly uniform distribution this resulting in good properties of the final composite material.

Are You Ready for Y2K?

ERIC Educational Resources Information Center

Day, C. William

1999-01-01

Examines the planning process to identify equipment or systems within an educational facility that could be Y2K sensitive. Discusses developing a contingency plan to prevent operational shutdown. Concluding comments describe a simple Y2K equipment-testing procedure. (GR)

Electrochemical performance of 2D polyaniline anchored CuS/Graphene nano-active composite as anode material for lithium-ion battery.

PubMed

Iqbal, Shahid; Bahadur, Ali; Saeed, Aamer; Zhou, Kebin; Shoaib, Muhammad; Waqas, Muhammad

2017-09-15

Lithium-ion battery (LIB) is a revolutionary step in the electric energy storage technology for making green environment. In the present communication, a LIB anode material was constructed by using graphene/polyaniline/CuS nanocomposite (GR/PANI/CuS NC) as a high-performance electrode. Initially, pure covellite CuS nanoplates (NPs) of the hexagonal structure were synthesized by hydrothermal route and then GR/PANI/CuS NC was fabricated by in-situ polymerization of aniline in the presence of CuS NPs and graphene nanosheets (GR NSs) as host matrix. GR/PANI/CuS NC-based LIB has shown the superior reversible current capacity of 1255mAhg -1 , a high cycling stability with more than 99% coulombic efficiency over 250 cycles even at a high current density of 5Ag -1 , low volume expansion, and excellent power capabilities. Galvanostatic charge/discharge tests and cyclic voltammetry analysis were used to investigate electrochemical properties. The electrochemical test proves that GR/PANI/CuS NC is promising anode material for LIB. The crystal phases and purity of the GR/PANI/CuS NC were confirmed by X-ray diffraction (XRD). Scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray (EDX) and X-ray photoelectron spectroscopy (XPS) were employed to examine the morphology, size, chemical composition, and phase structure of the synthesized GR/PANI/CuS NC. Copyright © 2017. Published by Elsevier Inc.

Reduction of infarct size by gentle reperfusion without activation of reperfusion injury salvage kinases in pigs.

PubMed

Musiolik, Judith; van Caster, Patrick; Skyschally, Andreas; Boengler, Kerstin; Gres, Petra; Schulz, Rainer; Heusch, Gerd

2010-01-01

Reperfusion is mandatory to salvage ischaemic myocardium from infarction, but also induces additional reperfusion injury and contributes to infarct size (IS). Gentle reperfusion (GR) has been proposed to attenuate reperfusion injury, but this remains contentious. We now investigated whether (i) GR reduces IS and (ii) GR is associated with the activation of reperfusion injury salvage kinases (RISK). Anaesthetized pigs were subjected to 90 min left anterior descending coronary artery hypoperfusion and 120 min reperfusion. GR was induced by slowly increasing coronary inflow back to baseline over 30 min, using an exponential algorithm [F(t) = F(i)+e(-(0.1)(t)((min)-3)).(F(b)-F(i)); F(b), coronary inflow at baseline; F(i), coronary inflow during ischaemia; n = 12]. Pigs subjected to immediate full reperfusion (IFR; n = 13) served as controls. IS was determined by triphenyl tetrazolium chloride staining. The expression level of phosphorylated RISK proteins was determined by western blot analysis in myocardial biopsies taken at baseline, after 80-85 min ischaemia and at 10, 30, and 120 min reperfusion. In additional experiments with IFR (n = 3) and GR (n = 3), the PI3-AKT and MEK1/2-ERK1/2 pathways were pharmacologically blocked (BL). IS was 37 +/- 2% (mean +/- SEM) of the area at risk with IFR and 29 +/- 1% (P < 0.05) with GR. RISK phosphorylation was similar between GR and IFR at baseline and 85 min ischaemia. At 10 min reperfusion, RISK phosphorylation was increased with IFR, but not with GR. At 30 and 120 min reperfusion, RISK phosphorylation was still greater with IFR than GR. RISK blockade did not abolish the IS reduction by GR (BL-IFR: 27 +/- 4% of the area at risk; BL-GR: 42 +/- 5%; P < 0.05). Gentle reperfusion reduces infarct size in pigs, but RISK activation is not causally involved in this infarct size reduction.

What Energy Deregulation Means for Your District.

ERIC Educational Resources Information Center

Costello, Richard J.

1999-01-01

Provides advice on how school districts might reduce energy costs in an era of electric industry deregulation. The competitive environment is described along with suggestions about joining purchasing groups to achieve pricing discounts. Final comments reveal the importance of energy contract negotiation. (GR)

One step electrochemical synthesis of bimetallic PdAu supported on nafion–graphene ribbon film for ethanol electrooxidation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shendage, Suresh S., E-mail: sureshsshendage@gmail.com; Singh, Abilash S.; Nagarkar, Jayashree M., E-mail: jm.nagarkar@ictmumbai.edu.in

2015-10-15

Highlights: • Electrochemical deposition of bimetallic PdAu NPs. • Highly loaded PdAu NPs are obtained. • Nafion–graphene supported PdAu NPs shows good activity for ethanol electrooxidation. - Abstract: A nafion–graphene ribbon (Nf–GR) supported bimetallic PdAu nanoparticles (PdAu/Nf–GR) catalyst was prepared by electrochemical codeposition of Pd and Au at constant potential. The prepared catalyst was characterized by scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDAX), transmission electron microscopy (TEM) and X-ray diffraction analysis (XRD). The average particle size of PdAu nanoparticles (NPs) determined from XRD was 3.5 nm. The electrocatalytic activity of the PdAu/Nf–GR catalyst was examined by cyclic voltametry.more » It was observed that the as prepared catalyst showed efficient activity and good stability for ethanol electrooxidation in alkaline medium.« less

Bye Bye Cafeteria, Hello Restaurant-Style Dining.

ERIC Educational Resources Information Center

Milshtein, Amy

1999-01-01

Examines how the university cafeteria is being transformed into restaurant-style dining to attract and retain sophisticated student customers. Harvard's and Seattle Pacific University's dining facilities are briefly highlighted. Concluding comments address planning tips for converting the old cafeteria into a better dining experience. (GR)

Wired vs. Wireless.

ERIC Educational Resources Information Center

Fielding, Randall

2000-01-01

Presents a debate on which technology will be in tomorrow's classrooms and the pros and cons of wiring classrooms and using a wireless network. Concluding comments address the likelihood, and desirability, of placing computers throughout the entire educational process and what types of computers and capabilities are needed. (GR)

Locker-Room Talk.

ERIC Educational Resources Information Center

Lowe, Jason; Noyes, Brad

1999-01-01

Explains how proper athletic facility locker-room design can save time and money. Design factors that address who will be using the facility are discussed as are user requirements, such as preparation areas, total storage area per user, grooming area, and security areas. Final comments address maintenance and operations issues. (GR)

Locker Room Talk.

ERIC Educational Resources Information Center

Fickes, Michael

1999-01-01

Examines the trends in college and university sports and recreation center locker rooms as envisioned by a specialist. Features of the modern locker room and the different levels of locker room design are explained. Final comments discuss whether college and university facility managers are inclined to move to high-end locker rooms. (GR)

Innovation & Risk Management Result in Energy and Life-Cycle Savings.

ERIC Educational Resources Information Center

Anstrand, David E.; Singh, J. B.

1999-01-01

Examines a Pennsylvania school's successful planning, design, and bidding process for acquiring a geothermal heat pump (GHP)system whose subsequent efficiency became award-winning for environmental excellence. Charts and statistical tables describe the GHP's energy savings. Concluding comments review the lessons learned from the process. (GR)

A facile method for synthesis of graphene-coated hexagonal ZnO photocatalyst with enhanced photodegradation activity

NASA Astrophysics Data System (ADS)

Zhang, Yunlong; Zhang, Yuzhi

2017-12-01

A kind of hexagonal ZnO (HZO) was synthesized in N-methyl-2-pyrrolidone (NMP)/H2O mixed solvent for a high exposure of polar ±(0001) facets to get a high-efficiency photocatalyst. The amine-functionalized HZO particles were coated with graphene oxide (GO) by electrostatic force-induced self-assemby and thermal reduction to form HZO@Gr core/shell structure. The as-prepared HZO and HZO@Gr were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman spectroscopy and UV-visible diffuse reflectance spectroscopy (UV-vis/DRS). The results indicate that the graphene on HZO@Gr remains high quality and the optical properties of the composite change a lot with sunlight absorption improving, bandgap and photoluminescence (PL) intensity decreasing. The obtained HZO photocatalyst shows good photocatalytic activity for methylene blue (MB) under UV-visible irradiation. Furthermore, the HZO@Gr photocatalyst exhibits the best photodegradation rate of MB reaching up to 98.2% within 50 minutes. The graphene-coated HZO structure could offer new directions which would further extend the scope for synthesis of various ZnO/graphene composites with improved properties useful for various applications.

Highly selective colorimetric and electrochemical sensing of iron (III) using Nile red functionalized graphene film.

PubMed

Sadak, Omer; Sundramoorthy, Ashok K; Gunasekaran, Sundaram

2017-03-15

We report a highly selective method for identification and detection of iron (III) (ferric iron, Fe 3+ ) using Nile red (NR) as a complexing agent. Fe 3+ preferentially binds with NR in dimethylformamide (DMF)/water (1:1) solution over other cations such as Fe 2+ , Cu 2+ , Pb 2+ , Hg 2+ , Mn 2+ , Ni 2+ , Zn 2+ , Co 2+ and Cd 2+ at room temperature. In the presence of Fe 3+ , the color of NR solution changes from purple to dark brown, which is detectable with bare eyes. Using UV-vis spectroscopy, we could measure the amount of Fe 3+ in the sample solution by monitoring changes in absorption from 540 to 580nm; the linear range and the limit of detection are 30-1000µM and 24.9µM, respectively. Taking advantage of the NR selectivity, we treated partially oxidized graphene sheets (po-Gr) with NR to obtain po-Gr-NR dispersion by ultrasonication. The NR-treated po-Gr flakes (po-Gr-NR) were characterized by UV-vis, FT-IR, and Raman spectroscopies and FE-SEM, which indicated attachment of NR on po-Gr sheets. The po-Gr-NR hybrid film deposited glassy carbon electrode (po-Gr-NR/GCE) served as the Fe 3+ sensor. Differential pulse voltammetry was used to investigate the detection of Fe 3+ in 0.05M HCl+0.05M KCl solution. The linear range and the limit of detection of Fe 3+ were from 37.5nM to 21.53µM and 18.7nM, respectively. Furthermore, this sensor was successfully used to measure Fe 3+ content in red wine samples. Copyright © 2016 Elsevier B.V. All rights reserved.

The Relationship between Mean Square Differences and Standard Error of Measurement: Comment on Barchard (2012)

ERIC Educational Resources Information Center

Pan, Tianshu; Yin, Yue

2012-01-01

In the discussion of mean square difference (MSD) and standard error of measurement (SEM), Barchard (2012) concluded that the MSD between 2 sets of test scores is greater than 2(SEM)[superscript 2] and SEM underestimates the score difference between 2 tests when the 2 tests are not parallel. This conclusion has limitations for 2 reasons. First,…

Simultaneous determination of ascorbic acid, dopamine and uric acid based on tryptophan functionalized graphene.

PubMed

Lian, Qianwen; He, Zhifang; He, Qian; Luo, Ai; Yan, Kaiwang; Zhang, Dongxia; Lu, Xiaoquan; Zhou, Xibin

2014-05-01

A new type of tryptophan-functionalized graphene nanocomposite (Trp-GR) was synthesized by utilizing a facile ultrasonic method via π-π conjugate action between graphene (GR) and tryptophan (Trp) molecule. The material as prepared had well dispersivity in water and better conductivity than pure GR. The surface morphology of Trp-GR was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Raman spectroscopy. The electrochemical behaviors of ascorbic acid (AA), dopamine (DA), and uric acid (UA) were investigated by cyclic voltammetry (CV) on the surface of Trp-GR. The separation of the oxidation peak potentials for AA-DA, DA-UA and UA-AA was about 182 mV, 125 mV and 307 mV, which allowed simultaneously determining AA, DA, and UA. Differential pulse voltammetery (DPV) was used for the determination of AA, DA, and UA in their mixture. Under optimum conditions, the linear response ranges for the determination of AA, DA, and UA were 0.2-12.9 mM, 0.5-110 μM, and 10-1000 μM, with the detection limits (S/N=3) of 10.09 μM, 0.29 μM and 1.24 μM, respectively. Furthermore, the modified electrode was investigated for real sample analysis. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Auger Electrons as Probes for Composite Micro- and Nano- structured Materials: Application to Solid Electrolyte Interphases in Graphite and Silicon-Graphite Electrodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalaga, Kaushik; Shkrob, Ilya A.; Haasch, Richard T.

In this study, Auger electron spectroscopy (AES) combined with ion sputtering profilometry, Xray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM) have been used in a complementary fashion to examine chemical and microstructural changes in graphite (Gr) and silicon/graphite (Si/Gr) blends contained in the negative electrodes of lithium-ion cells. We demonstrate how AES can be used to characterize morphology of the solid-electrolyte interphase (SEI) deposits in such heterogeneous media, complementing well-established methods, such as XPS and SEM. In this way we demonstrate that the SEI does not consist of uniformly thick layers on the graphite and silicon; the thickness ofmore » the SEI layers in cycle-life aged electrodes follows an exponential distribution with a mean of ca. 13 nm for the graphite and ca. 20-25 nm for the silicon nanoparticles (with a crystalline core of 50-70 nm in diameter). Furthermore, a “sticky-sphere” model, in which Si nanoparticles are covered with a layer of polymer binder (that is replaced by the SEI during cycling) of variable thickness is introduced to account for the features observed.« less

Auger Electrons as Probes for Composite Micro- and Nano- structured Materials: Application to Solid Electrolyte Interphases in Graphite and Silicon-Graphite Electrodes

DOE PAGES

Kalaga, Kaushik; Shkrob, Ilya A.; Haasch, Richard T.; ...

2017-10-05

In this study, Auger electron spectroscopy (AES) combined with ion sputtering profilometry, Xray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM) have been used in a complementary fashion to examine chemical and microstructural changes in graphite (Gr) and silicon/graphite (Si/Gr) blends contained in the negative electrodes of lithium-ion cells. We demonstrate how AES can be used to characterize morphology of the solid-electrolyte interphase (SEI) deposits in such heterogeneous media, complementing well-established methods, such as XPS and SEM. In this way we demonstrate that the SEI does not consist of uniformly thick layers on the graphite and silicon; the thickness ofmore » the SEI layers in cycle-life aged electrodes follows an exponential distribution with a mean of ca. 13 nm for the graphite and ca. 20-25 nm for the silicon nanoparticles (with a crystalline core of 50-70 nm in diameter). Furthermore, a “sticky-sphere” model, in which Si nanoparticles are covered with a layer of polymer binder (that is replaced by the SEI during cycling) of variable thickness is introduced to account for the features observed.« less

Quantum Cosmology

NASA Astrophysics Data System (ADS)

Bojowald, Martin

The universe, ultimately, is to be described by quantum theory. Quantum aspects of all there is, including space and time, may not be significant for many purposes, but are crucial for some. And so a quantum description of cosmology is required for a complete and consistent worldview. At any rate, even if we were not directly interested in regimes where quantum cosmology plays a role, a complete physical description could not stop at a stage before the whole universe is reached. Quantum theory is essential in the microphysics of particles, atoms, molecules, solids, white dwarfs and neutron stars. Why should one expect this ladder of scales to end at a certain size? If regimes are sufficiently violent and energetic, quantum effects are non-negligible even on scales of the whole cosmos; this is realized at least once in the history of the universe: at the big bang where the classical theory of general relativity would make energy densities diverge. 1.Lachieze-Rey, M., Luminet, J.P.: Phys. Rept. 254,135 (1995), gr-qc/9605010 2.BSDeWitt1967Phys. Rev.160511131967PhRv..160.1113D0158.4650410.1103/PhysRev.160.1113DeWitt, B.S.: Phys. Rev. 160(5), 1113 (1967) 3.Wiltshire, D.L.: In: Robson B., Visvanathan N., Woolcock W.S. (eds.) Cosmology: The Physics of the Universe, pp. 473-531. World Scientific, Singapore (1996). gr-qc/0101003 4.Isham C.J.: In: DeWitt, B.S., Stora, R. (eds.) Relativity, Groups and Topology II. Lectures Given at the 1983 Les Houches Summer School on Relativity, Groups and Topology, Elsevier Science Publishing Company (1986) 5.Klauder, J.: Int. J. Mod. Phys. D 12, 1769 (2003), gr-qc/0305067 6.Klauder, J.: Int. J. Geom. Meth. Mod. Phys. 3, 81 (2006), gr-qc/0507113 7.DGiulini1995Phys. Rev. D5110563013381161995PhRvD..51.5630G10.1103/PhysRevD.51.5630Giulini, D.: Phys. Rev. D 51(10), 5630 (1995) 8.Kiefer, C., Zeh, H.D.: Phys. Rev. D 51, 4145 (1995), gr-qc/9402036 9.WFBlythCJIsham1975Phys. Rev. D117684086991975PhRvD..11..768B10.1103/PhysRevD.11.768Blyth, W.F., Isham, C.J.: Phys. Rev. D 11, 768 (1975) 10.JDBrownKVKuchař1995Phys. Rev. D51560013381151995PhRvD..51.5600B10.1103/PhysRevD.51.5600Brown, J.D., Kuchař, K.V.: Phys. Rev. D 51, 5600 (1995) 11.Alvarenga, F.G., Fabris, J.C., Lemos, N.A., Monerat, G.A.: Gen. Rel. Grav. 34, 651 (2002), gr-qc/0106051 12.JAcaciode BarrosNPinto-NetoMASagiaro-Leal1998Phys. Lett. A.2412291998PhLA..241..229D10.1016/S0375-9601(98)00169-8Acacio de Barros, J., Pinto-Neto, N., Sagiaro-Leal, M.A.: Phys. Lett. A. 241, 229 (1998), gr-qc/9710084 13.DBohm1952Phys. Rev.85166462871952PhRv...85..166B0046.2100410.1103/PhysRev.85.166Bohm, D.: Phys. Rev. 85, 166 (1952) 14.DBohm1952Phys. Rev.85180462881952PhRv...85..180B10.1103/PhysRev.85.180Bohm, D.: Phys. Rev. 85, 180 (1952) 15.DBohm1953Phys. Rev.89458669531953PhRv...89..458B0051.2050210.1103/PhysRev.89.458Bohm, D.: Phys. Rev. 89, 458 (1953) 16.Goldstein, S.: Stanford Encyclopedia of Philosophy. http://plato.stanford.edu/entries/qm-bohm/ 17.RColisteteJrJCFabrisNPinto-Neto2000Phys. Rev. D620835072000PhRvD..62h3507C10.1103/PhysRevD.62.083507Colistete, R. Jr, Fabris, J.C., Pinto-Neto, N.: Phys. Rev. D 62, 083507 (2000), gr-qc/0005013 18.FTFalcianoNPinto-NetoESSantini2007Phys. Rev. D760835212007PhRvD..76h3521F10.1103/PhysRevD.76.083521Falciano, F.T., Pinto-Neto, N., Santini, E.S.: Phys. Rev. D 76, 083521 (2007), arXiv:0707.1088 19.FTFalcianoNPinto-Neto2009Phys. Rev. D7902350724911632009PhRvD..79b3507F10.1103/PhysRevD.79.023507Falciano, F.T., Pinto-Neto, N.: Phys. Rev. D 79, 023507 (2009), arXiv:0810.3542 20.AShojaiFShojai2005Europhys. Lett.718862005EL.....71..886S10.1209/epl/i2005-10186-yShojai, A., Shojai, F.: Europhys. Lett. 71, 886 (2005), gr-qc/0409020 21.RBGriffiths1993Phys. Rev. Lett.70220112145601993PhRvL..70.2201G1051.8150610.1103/PhysRevLett.70.2201Griffiths, R.B.: Phys. Rev. Lett. 70, 2201 (1993) 22.ROmnés1992Rev. Mod. Phys.643391992RvMP...64..339O10.1103/RevModPhys.64.339Omnés, R.: Rev. Mod. Phys. 64, 339 (1992) 23.MGell-MannJBHartle1993Phys. Rev. D47334512188231993PhRvD..47.3345G10.1103/PhysRevD.47.3345Gell-Mann, M., Hartle, J.B.: Phys. Rev. D 47, 3345 (1993), gr-qc/9210010 24.FDowkerAKent1996J. Statist. Phys.82157513749291996JSP....82.1575D1042.8150710.1007/BF02183396Dowker, F., Kent, A.: J. Statist. Phys. 82, 1575 (1996), gr-qc/9412067 25.Dias, N.C., Mikovic, A, Prata, J.N.: J. Math. Phys. 47, 082101 (2006), hep-th/0507255 26.MBojowaldASkirzewski2006Rev. Math. Phys.1871322671131124.8201010.1142/S0129055X06002772Bojowald, M., Skirzewski, A.: Rev. Math. Phys. 18, 713 (2006), math-ph/0511043 27.MBojowaldBSandhöferASkirzewskiATsobanjan2009Rev. Math. Phys.2111124931141167.8102510.1142/S0129055X09003591Bojowald, M., Sandhöfer, B., Skirzewski, A., Tsobanjan, A.: Rev. Math. Phys. 21, 111 (2009), arXiv:0804.3365 28.JJHalliwellSWHawking1985Phys. Rev. D31817777877481985PhRvD..31.1777H10.1103/PhysRevD.31.1777Halliwell, J.J., Hawking, S.W.: Phys. Rev. D 31(8), 1777 (1985) 29.PDD'Eath2005Supersymmetric Quantum CosmologyCambridge University PressCambridgeD'Eath, P.D.: Supersymmetric Quantum Cosmology. Cambridge University Press, Cambridge (2005) 30.PVMoniz2010Quantum Cosmology - The Supersymmetric PerspectiveSpringerBerlinMoniz, P.V.: Quantum Cosmology—The Supersymmetric Perspective. Springer, Berlin(2010) 31.PDD'EathJJHalliwell1987Phys. Rev. D3511008785261987PhRvD..35.1100D10.1103/PhysRevD.35.1100D'Eath, P.D., Halliwell, J.J.: Phys. Rev. D 35, 1100 (1987) 32.TGold1962Am. J. Phys.304031962AmJPh..30..403G0105.2250110.1119/1.1942052Gold, T.: Am. J. Phys. 30, 403 (1962) 33.SWHawking1985Phys. Rev. D3224898114021985PhRvD..32.2489H10.1103/PhysRevD.32.2489Hawking, S.W.: Phys. Rev. D 32, 2489 (1985) 24.DNPage1985Phys. Rev. D3224968114031985PhRvD..32.2496P10.1103/PhysRevD.32.2496Page, D.N.: Phys. Rev. D 32, 2496 (1985) 35.BCarr2007Universe or Multiverse?Cambridge University PressCambridgeCarr, B.(ed.): Universe or Multiverse? Cambridge University Press, Cambridge (2007) 1.D.GiuliniCKieferE.JoosJKupschI.O.StamatescuH.D.Zeh1996Decoherence and the Appearance of a Classical World in Quantum TheorySpringerBerlin0855.0000310.1007/978-3-662-03263-3Giulini, D., Kiefer, C., Joos, E., Kupsch, J., Stamatescu, I.O., Zeh, H.D.: Decoherence and the Appearance of a Classical World in Quantum Theory. Springer, Berlin (1996) 2.Bojowald, M., Brizuela, D., Hernandez, H.H., Koop, M.J., Morales-Técotl, H.A.:arXiv:1011.3022 3.J.P.GazeauJ.Klauder1999J. Phys. A: Math. Gen.3212316685761999JPhA...32..123G0919.4706110.1088/0305-4470/32/1/013arXiv:1011.3022Gazeau, J.P., Klauder, J.: J. Phys. A: Math. Gen. 32, 123 (1999) 4.M.NovelloS.E.P.Bergliaffa2008Phys. Rep.46312724370502008PhR...463..127N10.1016/j.physrep.2008.04.006Novello, M., Bergliaffa, S.E.P.: Phys. Rep. 463, 127 (2008) 5.M.Bojowald2010Canonical Gravity and Applications: Cosmology, Black Holes, and Quantum GravityCambridge University PressCambridge10.1017/CBO9780511921759Bojowald, M.: Canonical Gravity and Applications: Cosmology, Black Holes, and Quantum Gravity. Cambridge University Press, Cambridge (2010) 6.A.Ashtekar1987Phys. Rev. D36615879096671987PhRvD..36.1587A10.1103/PhysRevD.36.1587Ashtekar, A.: Phys. Rev. D 36(6), 1587 (1987) 7.Barbero G.J.F., (1995) Phys. Rev. D 51(10): 5507 8.G.Immirzi1997Class. Quantum Grav.14L 17714765391997CQGra..14L.177I10.1088/0264-9381/14/10/002Immirzi, G.: Class. Quantum Grav. 14, L 177 (1997) 9.J.LewandowskiE.T.NewmanC.Rovelli1993J. Math. Phys.34464612359631993JMP....34.4646L0790.5305710.1063/1.530362Lewandowski, J., Newman, E.T., Rovelli, C.: J. Math. Phys. 34, 4646 (1993) 10.C.RovelliL.Smolin1990Nucl. Phys. B3318010444931990NuPhB.331...80R10.1016/0550-3213(90)90019-ARovelli, C., Smolin, L.: Nucl. Phys. B 331, 80 (1990) 11.A.CorichiK.Krasnov1998Mod. Phys. Lett. A13133916358811998MPLA...13.1339C10.1142/S0217732398001406hep-th/9703177Corichi, A., Krasnov, K.: Mod. Phys. Lett. A 13, 1339 (1998). hep-th/9703177 12.A.AshtekarJ.LewandowskiD.MarolfJ.Mour aoT.Thiemann1995J. Math. Phys.3611645613559161995JMP....36.6456A0856.5800610.1063/1.531252gr-qc/9504018Ashtekar, A., Lewandowski, J., Marolf, D., Mour ao, J., Thiemann, T.: J. Math. Phys. 36(11), 6456 (1995). gr-qc/9504018 13.A.AshtekarJ.Lewandowski1995J. Math. Phys.365217013292511995JMP....36.2170A0844.5800910.1063/1.531037Ashtekar, A., Lewandowski, J.: J. Math. Phys. 36(5), 2170 (1995) 14.C.RovelliL.Smolin1995Phys. Rev. D5210574313604271995PhRvD..52.5743R10.1103/PhysRevD.52.5743Rovelli, C., Smolin, L.: Phys. Rev. D 52(10), 5743 (1995) 15.C.RovelliL.Smolin1995Nucl. Phys. B44259313327051995NuPhB.442..593R0925.8301310.1016/0550-3213(95)00150-Qgr-qc/9411005, Erratum: Nucl. Phys. B 456 (1995) 753Rovelli, C., Smolin, L.: Nucl. Phys. B 442, 593 (1995). gr-qc/9411005 16.A.AshtekarJ.Lewandowski1997Class Quantum Grav.14A 5516918871997CQGra..14A..55Agr-qc/9602046Ashtekar, A., Lewandowski, J.: Class Quantum Grav. 14, A 55 (1997). gr-qc/9602046 17.A.AshtekarJ.Lewandowski1998Adv. Theor. Math. Phys.13881605640gr-qc/9711031Ashtekar, A., Lewandowski, J.: Adv. Theor. Math. Phys. 1, 388 (1998). gr-qc/9711031 18.R.De PietriC.Rovelli1996Phys. Rev. D544266414069701996PhRvD..54.2664D10.1103/PhysRevD.54.2664De Pietri, R., Rovelli, C.: Phys. Rev. D 54(4), 2664 (1996) 19.J.BrunnemannT.Thiemann2006Class Quantum Grav.23128922054852006CQGra..23.1289B1089.8301310.1088/0264-9381/23/4/014gr-qc/0405060Brunnemann, J., Thiemann, T.: Class Quantum Grav. 23, 1289 (2006). gr-qc/0405060 20.J..BrunnemannD.Rideout2008Class. Quant. Grav.2506500123987022008CQGra..25f5001B10.1088/0264-9381/25/6/065001arXiv:0706.0469Brunnemann, J.., Rideout, D.: Class. Quant. Grav. 25, 065001 (2008). arXiv:0706.0469 21.J.BrunnemannD.Rideout2008Class. Quant. Grav.2506500223987032008CQGra..25f5002B10.1088/0264-9381/25/6/065002arXiv:0706.0382Brunnemann, J., Rideout, D.: Class. Quant. Grav. 25, 065002 (2008). arXiv:0706.0382 22.M.Bojowald2008Living Rev. Relativity1142008LRR....11....4B10.12942/lrr-2008-4gr-qc/0601085, http://www.livingreviews.org/lrr-2008-4Bojowald, M.: Living Rev. Relativity 11, 4 (2008). gr-qc/0601085 23.M.Bojowald2000Class. Quantum Grav.17148917526492000CQGra..17.1489B0969.8303510.1088/0264-9381/17/6/312gr-qc/9910103Bojowald, M.: Class. Quantum Grav. 17, 1489 (2000). gr-qc/9910103 24.M.Bojowald2002Class. Quantum Grav.19271719081252002CQGra..19.2717B1008.8303710.1088/0264-9381/19/10/313gr-qc/0202077Bojowald, M.: Class. Quantum Grav. 19, 2717 (2002). gr-qc/0202077 25.C.FewsterH.Sahlmann2008Class Quantum Grav2522501524533882008CQGra..25v5015F10.1088/0264-9381/25/22/225015arXiv:0804.2541Fewster, C., Sahlmann, H.: Class Quantum Grav 25, 225015 (2008). arXiv:0804.2541 26.J.M.Velhinho2007Class. Quantum Grav.24374523394202007CQGra..24.3745V1129.8332410.1088/0264-9381/24/14/013arXiv:0704.2397.Velhinho, J.M.: Class. Quantum Grav. 24, 3745 (2007). arXiv:0704.2397. 27.TThiemann1998Class Quantum Grav1583916202091998CQGra..15..839T0956.8301310.1088/0264-9381/15/4/011gr-qc/9606089Thiemann, T.: Class Quantum Grav 15, 839 (1998). gr-qc/9606089 28.T.Thiemann1998Class. Quantum Grav.15128116230751998CQGra..15.1281T0945.8301610.1088/0264-9381/15/5/012gr-qc/9705019Thiemann, T.: Class. Quantum Grav. 15, 1281 (1998). gr-qc/9705019 29.M.Bojowald2001Phys. Rev. D6408401818587272001PhRvD..64h4018B10.1103/PhysRevD.64.084018gr-qc/0105067Bojowald, M.: Phys. Rev. D 64, 084018 (2001). gr-qc/0105067 30.J.BrunnemannT.Thiemann2006Class. Quantum Grav.23139522046892006CQGra..23.1395B1097.8301310.1088/0264-9381/23/5/001gr-qc/0505032Brunnemann, J., Thiemann, T.: Class. Quantum Grav. 23, 1395 (2006). gr-qc/0505032 31.M.Bojowald2006Class. Quantum Grav.2398722029402006CQGra..23..987B1087.8302710.1088/0264-9381/23/3/023gr-qc/0508118Bojowald, M.: Class. Quantum Grav. 23, 987 (2006). gr-qc/0508118 32.J.BrunnemannT.Thiemann2006Class. Quantum Grav.23142922046902006CQGra..23.1429B1089.8301410.1088/0264-9381/23/5/002gr-qc/0505033Brunnemann, J., Thiemann, T.: Class. Quantum Grav. 23, 1429 (2006). gr-qc/0505033 1.W.Unruh1997Time, Gravity, and Quantum MechanicsCambridge University PressCambridge2394Unruh, W.: Time, Gravity, and Quantum Mechanics pp. 23-94. Cambridge University Press, Cambridge (1997) 2.N.Weiss1985Phys Rev D3232288150791985PhRvD..32.3228W10.1103/PhysRevD.32.3228Weiss, N.: Phys. Rev. D 32, 3228 (1985) 3.Jacobson, T.: (2000). hep-th/0001085 4.M.BojowaldP.SinghA.Skirzewski2004Phys. Rev. D7012402221247062004PhRvD..70l4022B10.1103/PhysRevD.70.124022gr-qc/0408094Bojowald, M., Singh, P., Skirzewski, A.: Phys. Rev. D 70, 124022 (2004). gr-qc/0408094 5.C.RovelliL.Smolin1994Phys. Rev. Lett.7244612569161994PhRvL..72..446R0973.8352310.1103/PhysRevLett.72.446gr-qc/9308002Rovelli, C., Smolin, L.: Phys. Rev. Lett. 72, 446 (1994). gr-qc/9308002 6.K.GieselT.Thiemann2007Class Quantum Grav.24246523194272007CQGra..24.2465G1117.8304510.1088/0264-9381/24/10/003gr-qc/0607099Giesel, K., Thiemann, T.: Class Quantum Grav. 24, 2465 (2007). gr-qc/0607099 7.T.Thiemann1998Class Quantum Grav.1583916202091998CQGra..15..839T0956.8301310.1088/0264-9381/15/4/011gr-qc/9606089Thiemann, T.: Class Quantum Grav. 15, 839 (1998). gr-qc/9606089 8.T.Thiemann1998Class Quantum Grav.15128116230751998CQGra..15.1281T0945.8301610.1088/0264-9381/15/5/012gr-qc/9705019Thiemann, T.: Class Quantum Grav. 15, 1281 (1998). gr-qc/9705019 9.T.Thiemann1998Class Quantum Grav.1587516202131998CQGra..15..875T10.1088/0264-9381/15/4/012gr-qc/9606090Thiemann, T.: Class Quantum Grav. 15, 875 (1998). gr-qc/9606090 10.T.Thiemann1996Phys. Lett. B38025713983881996PhLB..380..257T0945.8301310.1016/0370-2693(96)00532-1gr-qc/9606088Thiemann, T.: Phys. Lett. B 380, 257 (1996). gr-qc/9606088 11.J.LewandowskiD.Marolf1998Int. J. Mod. Phys. D729916357561998IJMPD...7..299L0936.8302210.1142/S0218271898000231gr-qc/9710016Lewandowski, J., Marolf, D.: Int. J Mod. Phys. D 7, 299 (1998). gr-qc/9710016 12.R.GambiniJ.LewandowskiD.MarolfJ.Pullin1998Int. J Mod. Phys. D79716250591998IJMPD...7...97G0936.8302110.1142/S0218271898000103gr-qc/9710018Gambini, R., Lewandowski, J., Marolf, D., Pullin, J.: Int. J Mod. Phys. D 7, 97 (1998).gr-qc/9710018 13.A.AshtekarJ.LewandowskiH.Sahlmann2003Class Quantum Grav.20L1119557752003CQGra..20L..11A1025.8350110.1088/0264-9381/20/1/103gr-qc/0211012Ashtekar, A., Lewandowski, J., Sahlmann, H.: Class Quantum Grav. 20, L11 (2003). gr-qc/0211012 14.H.SahlmannT.Thiemann2006Class Quantum Grav.2386722029362006CQGra..23..867S1098.8301410.1088/0264-9381/23/3/019gr-qc/0207030Sahlmann, H., Thiemann, T.: Class Quantum Grav. 23, 867 (2006). gr-qc/0207030 15.M.Bojowald2009

Investigation on the properties of nano copper matrix composite via vacuum arc melting method

NASA Astrophysics Data System (ADS)

Liu, Yi; Leng, Jinfeng; Wu, Qirui; Zhang, Shaochen; Teng, Xinying

2017-10-01

Copper and copper matrix composites (CMCs) are widely used as electrical contact materials in electrical switch systems due to their excellent electrical properties. Graphene has great mechanical, physical and electrical properties, which is competent as an attractive reinforcing material for fabricating CMCs. Therefore, graphene was added to CMCs to improve the mechanical properties. In this study, graphene-reinforced copper matrix composites (Gr/Cu composites) were obtained. The xGr/Cu (x  =  0, 0.1, 0.3 and 0.5 wt.%) composites were fabricated via the vacuum arc melting method and compared the performance of them. The mechanical properties and electrical properties were obtained by measuring the hardness and conductivity. The microstructure of Gr/Cu composites was observed by optical microscopy (OM) and scanning electron microscopy (SEM). With the addition of graphene from 0 wt.% to 0.5 wt.%, the densities of materials decreased from 97.0% to 95.7%. With the increasing of graphene content, the hardness of composites increased at beginning and then decreased. In this range of adding amount, the hardness of 0.3Gr/Cu composite was up to 66.8 HB and increased by 15.4% compared to Al2O3/Cu composites without graphene. With the addition of graphene powder, the international annealing copper standard IACS% of Gr/Cu composites decreased from 86.16 to 69.86. The range of decline and the percentage of decline range are middle and 18.9%, respectively.

The Great War and Remembrance in Jose Leon Machado's "Memoria das Estrelas sem Brilho"

ERIC Educational Resources Information Center

Azevedo, Milton M.

2011-01-01

This article analyzes Jose Leon Machado's novel, "Memoria das Estrelas sem Brilho," as a multilayered historical novel in which a war story provides a background for comments on aspects of early twentieth-century Portuguese society, such as male bonding, religion, sexual mores, and social stratification. (Contains 11 notes.)

Electrochemical DNA biosensor based on a glassy carbon electrode modified with gold nanoparticles and graphene for sensitive determination of Klebsiella pneumoniae carbapenemase.

PubMed

Pan, Hong-zhi; Yu, Hong-wei; Wang, Na; Zhang, Ze; Wan, Guang-cai; Liu, Hao; Guan, Xue; Chang, Dong

2015-11-20

We describe the fabrication of a sensitive electrochemical DNA biosensor for determination of Klebsiella pneumoniae carbapenemase (KPC). The highly sensitive and selective electrochemical biosensor for DNA detection was constructed based on a glassy carbon electrode (GCE) modified with gold nanoparticles (Au-NPs) and graphene (Gr). Then Au-NPs/Gr/GCE was characterized by scanning electro microscope (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The hybridization detection was measured by diffierential pulse voltammetry (DPV) using methylene blue (MB) as the hybridization indicator. The dynamic range of detection of the sensor for the target DNA sequences was from 1 × 10(-12) to 1 × 10(-7)mol/L, with a detection limit of 2 × 10(-13)mol/L. The DNA biosensor had excellent specificity for distinguishing complementary DNA sequence in the presence of non-complementary and mismatched DNA sequence. The results demonstrated that the Au-NPs/Gr nanocomposite was a promising substrate for the development of high-performance electrocatalysts for determination of KPC. Copyright © 2015 Elsevier B.V. All rights reserved.

78 FR 50079 - Information Collection Activities: Safety and Environmental Management Systems (SEMS); Proposed...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-16

... DEPARTMENT OF THE INTERIOR Bureau of Safety and Environmental Enforcement [Docket ID BSEE-2013-0005; OMB Control Number 1014-0017: 134E1700D2 EEEE500000 ET1SF0000.DAQ000] Information Collection Activities: Safety and Environmental Management Systems (SEMS); Proposed Collection; Comment Request Correction In notice document 2013-19416 appearing o...

Reliability, validity and minimal detectable change of the Mini-BESTest in Greek participants with chronic stroke.

PubMed

Lampropoulou, Sofia I; Billis, Evdokia; Gedikoglou, Ingrid A; Michailidou, Christina; Nowicky, Alexander V; Skrinou, Dimitra; Michailidi, Fotini; Chandrinou, Danae; Meligkoni, Margarita

2018-02-23

This study aimed to investigate the psychometric characteristics of reliability, validity and ability to detect change of a newly developed balance assessment tool, the Mini-BESTest, in Greek patients with stroke. A prospective, observational design study with test-retest measures was conducted. A convenience sample of 21 Greek patients with chronic stroke (14 male, 7 female; age of 63 ± 16 years) was recruited. Two independent examiners administered the scale, for the inter-rater reliability, twice within 10 days for the test-retest reliability. Bland Altman Analysis for repeated measures assessed the absolute reliability and the Standard Error of Measurement (SEM) and the Minimum Detectable Change at 95% confidence interval (MDC 95% ) were established. The Greek Mini-BESTest (Mini-BESTest GR ) was correlated with the Greek Berg Balance Scale (BBS GR ) for assessing the concurrent validity and with the Timed Up and Go (TUG), the Functional Reach Test (FRT) and the Greek Falls Efficacy Scale-International (FES-I GR ) for the convergent validity. The Mini-BESTestGR demonstrated excellent inter-rater reliability (ICC (95%CI) = 0.997 (0.995-0.999, SEM = 0.46) with the scores of two raters within the limits of agreement (mean dif  = -0.143 ± 0.727, p > 0.05) and test-retest reliability (ICC (95%CI) = 0.966 (0.926-0.988), SEM = 1.53). Additionally, the Mini-BESTest GR yielded very strong to moderate correlations with BBS GR (r = 0.924, p < 0.001), TUG (r = -0.823, p < 0.001), FES-I GR (r = -0.734, p < 0.001) and FRT (r = 0.689, p < 0.001). MDC 95 was 4.25 points. The exceptionally high reliability and the equally good validity of the Mini-BESTest GR , strongly support its utility in Greek people with chronic stroke. Its ability to identify clinically meaningful changes and falls risk need further investigation.

Dissolution kinetics as a function of the Gibbs free energy of reaction: An experimental study based on albite feldspar

NASA Astrophysics Data System (ADS)

Hellmann, Roland; Tisserand, Delphine

2006-01-01

Here we report on an experimental investigation of the relation between the dissolution rate of albite feldspar and the Gibbs free energy of reaction, Δ Gr. The experiments were carried out in a continuously stirred flow-through reactor at 150 °C and pH (150 °C) 9.2. The dissolution rates R are based on steady-state Si and Al concentrations and sample mass loss. The overall relation between Δ Gr and R was determined over a free energy range of -150 < Δ Gr < -15.6 kJ mol -1. The data define a continuous and highly non-linear, sigmoidal relation between R and Δ Gr that is characterized by three distinct free energy regions. The region furthest from equilibrium, delimited by -150 < Δ Gr < -70 kJ mol -1, represents an extensive dissolution rate plateau with an average rate R¯=1.0×10-8molm-2s-1. In this free energy range the rates of dissolution are constant and independent of Δ Gr, as well as [Si] and [Al]. The free energy range delimited by -70 ⩽ Δ Gr ⩽ -25 kJ mol -1, referred to as the 'transition equilibrium' region, is characterized by a sharp decrease in dissolution rates with increasing Δ Gr, indicating a very strong inverse dependence of the rates on free energy. Dissolution nearest equilibrium, defined by Δ Gr > -25 kJ mol -1, represents the 'near equilibrium' region where the rates decrease as chemical equilibrium is approached, but with a much weaker dependence on Δ Gr. The lowest rate measured in this study, R = 6.2 × 10 -11 mol m -2 s -1 at Δ Gr = -16.3 kJ mol -1, is more than two orders of magnitude slower than the plateau rate. The data have been fitted to a rate equation (adapted from Burch et al. [Burch, T. E., Nagy, K. L., Lasaga, A. C., 1993. Free energy dependence of albite dissolution kinetics at 80 °C and pH 8.8. Chem. Geol.105, 137-162]) that represents the sum of two parallel reactions R=k1[1-exp(-ng)]+k2[1-exp(-g)], where k1 and k2 are rate constants that have been determined by regression, with values 1.02 × 10 -8 and 1.80 × 10 -10 mol m -2 s -1, g ≡ |Δ Gr|/R T is a dimensionless number, and n, m1, and m2 are adjustable fitted parameters ( n = 7.98 × 10 -5, m1 = 3.81 and m2 = 1.17). Based on measurements of the temporal evolution of RSi and RAl for each experiment, steady-state dissolution rates appear to be congruent at all Δ Gr. In contrast, non-steady-state dissolution is incongruent, and is related to Δ Gr. Scanning electron microscopy (SEM) images of post-reaction grain surfaces indicate that dissolution close to equilibrium (Δ Gr > -25 kJ mol -1) resulted in the precipitation of a secondary crystalline phase, but there are no indications that this altered the measured R-Δ Gr relation.

Synthesis and characterization of a new high entropy composite matrix

NASA Astrophysics Data System (ADS)

Popescu, G.; Matara, M. A.; Csaki, I.; Popescu, C. A.; Truşcă, R.

2016-06-01

Even if high entropy alloys were not reported in a scientific journal till 2003, these new alloys have been investigated since 1995 due to their high temperature properties. In the last years the synthesis of these alloys has been widely investigated. Thus, the present work has been carried out to produce a high entropy composite using an equiatomic AlCrFeMnNi high entropy alloy (HEA) matrix and graphite particles (Gr) as reinforcing material. The high entropy composite was obtained by powder metallurgy route using a planetary ball mill. The mechanically alloyed mixture was investigated by scanning electron microscopy (SEM). Microstructural investigation realized by SEM revealed the homogenous structure of the composite, with multiple phases and decreasing particles size, mostly reaching nanometric scale.

Facile one-pot synthesis of platinum nanoparticles decorated nitrogen-graphene with high electrocatalytic performance for oxygen reduction and anodic fuels oxidation

NASA Astrophysics Data System (ADS)

Navaee, Aso; Salimi, Abdollah; Soltanian, Saeid; Servati, Peyman

2015-03-01

Due to exceptional electronic properties of graphene (Gr) and nitrogen doped graphene (N-Gr), they are considered as superior supporting platforms for novel metal nanoparticle decorations. Here, we report, a novel one-step electrochemical method for synthesis of Nitrogen-doped graphene sheets uniformly decorated with platinum nanoparticles (Pt/N-Gr). A graphite rod and platinum wire are respectively used for graphene and platinum nanoparticles production. The potential is cycled from -3V to +3V in acetonitrile solution as a nitrogen dopant source. By increasing the number of cycles the nitrogen-doped graphene/platinum nanoparticles composite is generated. After heat-treating the composite is characterized with various techniques such as FTIR, Raman, XPS, SEM and TEM. The electrocatalytic activity of the prepared composite toward the reduction of O2 and the oxidation of usual anodic fuels such as methanol, ethanol, hydrazine and formic acid is investigated using cyclic voltammetry technique. In comparison to commercial platinum/carbon, the onset potentials and the current densities for both O2 reduction and fuels oxidation are remarkably improved. Furthermore, the modified electrode by this composite shows good long-term stability and poisoning tolerance.

Comparative performances of a bare graphite-polyurethane composite electrode unmodified and modified with graphene and carbon nanotubes in the electrochemical determination of escitalopram.

PubMed

Baccarin, Marina; Cervini, Priscila; Cavalheiro, Eder Tadeu Gomes

2018-02-01

A bare composite graphite-polyurethane electrode (EGPU) and two other modified with graphene (EGPU-GR) and functionalized multi-walled carbon nanotubes (EGPU-CNTs) were prepared and compared regarding their voltammetric response to escitalopran (EST). The modifiers were characterized by Raman spectroscopy and the resulting electrode materials by contact angle measurements with a hydrophilicity character in the ascending order for the composites: GPU > GPU-GR > GPU-CNTs and scanning electron microscopy (SEM). The electroactive areas of the EGPU, EGPU-GR, and EGPU-CNTs were 0.065, 0.080, and 0.092cm 2 , respectively, calculated from the chronocoulometry using K 3 [Fe(CN) 6 ] as a probe and the Cottrell equation. The cyclic voltammograms obtained for EST indicated irreversible electrochemical behavior, with an anodic peak at ca. +0.80V (νs. SCE). These measurements were carried out with the three electrodes, and comparison of the analytical responses led to the EGPU-GR electrode being selected for use in the subsequent experiments. Under optimal conditions, square wave and differential pulse voltammetry at EGPU-GR presented linear dynamic ranges between 1.5 × 10 -6 and 1.2 × 10 -5 mol L -1 , with a detection limit of 2.5 × 10 -7 molL -1 (SWV) and 1.5 × 10 -6 and 1.2 × 10 -5 molL -1 , with a detection limit of 3.2 × 10 -7 molL -1 (DPV) for EST. The proposed method was applied for the quantification of EST in synthetic urine and cerebrospinal fluid samples, offering advantages including simplicity of fabrication, no requirement for analyte preconcentration and surface renewal, fast response, and selectivity. Copyright © 2017 Elsevier B.V. All rights reserved.

A novel nitromethane biosensor based on biocompatible conductive redox graphene-chitosan/hemoglobin/graphene/room temperature ionic liquid matrix.

PubMed

Wang, Lu; Zhang, Xiuhua; Xiong, Huayu; Wang, Shengfu

2010-11-15

A novel amperometric biosensor for nitromethane (CH(3)NO(2)) based on immobilization of graphene (GR), chitosan (CS), hemoglobin (Hb) and room temperature ionic liquid (IL) on a glassy carbon electrode (GCE) was developed for the first time. The surface morphologies of a set of representative membranes were characterized by means of scanning electron microscopy (SEM). The electrochemical performance of the biosensor was evaluated by cyclic voltammetry (CV) and chronoamperometry. A pair of stable and well-defined redox peaks of Hb with a formal potential of -0.240 V was observed at the GR-CS/Hb/GR/IL/GCE. The effects of phosphate buffer pH, scan rate, and temperature on the biosensor were investigated to provide optimum analytical performance. Moreover, several electrochemical parameters, e.g., the heterogeneous electron transfer rate constant (k(s)), were calculated in detail. The presence of both GR and IL not only dramatically facilitated the electron transfer of Hb, but also greatly enhanced electrocatalytic activity towards CH(3)NO(2). The apparent Michaelis-Menten constant was down to 0.16 μM, indicating that the biosensor possessed high affinity to CH(3)NO(2). Besides this, the proposed biosensor exhibited fast amperometric response (<5s), low detection limit (6.0 × 10(-10)M), and excellent long-time storage stability for the determination of CH(3)NO(2). Copyright © 2010 Elsevier B.V. All rights reserved.

Laser sintered thin layer graphene and cubic boron nitride reinforced nickel matrix nanocomposites

NASA Astrophysics Data System (ADS)

Hu, Zengrong; Tong, Guoquan

2015-10-01

Laser sintered thin layer graphene (Gr)-cubic boron nitride (CBN)-Ni nanocomposites were fabricated on AISI 4140 plate substrate. The composites fabricating process, composites microstructure and mechanical properties were studied. Scanning electron microscopy (SEM), X-ray diffraction (XRD) and Raman spectroscopy were employed to study the micro structures and composition of the composites. XRD and Raman tests proved that graphene and CBN were dispersed in the nanocomposites. Nanoindentation test results indicate the significant improvements were achieved in the composites mechanical properties.

Effect of coarse grinding, overglazing, and 2 polishing systems on the flexural strength, surface roughness, and phase transformation of yttrium-stabilized tetragonal zirconia.

PubMed

Mohammadi-Bassir, Mahshid; Babasafari, Mansoure; Rezvani, Mohammad Bagher; Jamshidian, Mahdieh

2017-11-01

Limited information is available for the best polishing systems and methods to obtain minimally abrasive monolithic zirconia surfaces after contouring and occlusal adjustment. The purpose of this in vitro study was to evaluate the effect of grinding and polishing procedures on the flexural strength, quality and quantity of surface roughness, topography, and phase transformation of a zirconia-based ceramic system. Fifty bar-shaped yttrium-stabilized zirconium oxide specimens (20×4×2 mm) were cut from presintered zirconia blanks. The specimens were wet-polished and divided into 5 groups (n=10): standard polishing without any surface treatment (group SP); grinding with a diamond rotary instrument (group Gr); grinding with a diamond rotary instrument (DRI) and over-glazing (group Gl); grinding with a DRI and polishing with an intraoral zirconia polishing kit in a 2-step procedure (group BP); and grinding with a DRI and polishing with an intraoral polishing kit (group MP). The Ra and Rz surface roughness values (μm) were measured with a profilometer. One specimen of each group was subjected to x-ray diffraction (XRD) to estimate the monoclinic phase and evaluated using scanning electron microscopy (SEM) for surface topography. The 3-point flexural strength of the bars was measured in a universal testing machine at a crosshead speed of 0.5 mm/min. The mean flexural strength (MPa) and surface roughness values were calculated, and the results were analyzed using 1-way ANOVA and Tukey honest significant difference tests (α=.05). Statistically significant differences were noted among the experimental groups for Ra, Rz (P<.001), and flexural strength values (P<.001). The highest Ra and Rz values were found in group Gr (P<.001) and the lowest in group Gl, which were significantly lower than the values in group Gr (P<.001). The 2 polishing systems (BP and MP) were not significantly different in terms of Ra and Rz values (P=.755 for Ra and P=.319 for Rz). The highest flexural strength was found in group Gr (283.35 ±49.85 MPa) without significant differences from those of MP and BP (P=.958 for BP and P=.404 for MP). The lowest flexural strength was found in Gl, which had no significant differences from those of the control group (P=1.000). In XRD the monoclinic phase was observed in Gr (26%), BP (24%), and MP (23%) groups. However, groups Gl and SP did not have any monoclinic phase. SEM showed deep unidirectional scratches after grinding that were smoothened by glazing and polishing. Roughness increased significantly after grinding, but polishing and glazing similarly diminished it. Glazing after grinding significantly decreased the flexural strength values, but polishing did not. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

An exact solution for a rotating black hole in modified gravity

NASA Astrophysics Data System (ADS)

Filippini, Francesco; Tasinato, Gianmassimo

2018-01-01

Exact solutions describing rotating black holes can offer important tests for alternative theories of gravity, motivated by the dark energy and dark matter problems. We present an analytic rotating black hole solution for a class of vector-tensor theories of modified gravity, valid for arbitrary values of the rotation parameter. The new configuration is characterised by parametrically large deviations from the Kerr-Newman geometry, controlled by non-minimal couplings between vectors and gravity. It has an oblate horizon in Boyer-Lindquist coordinates, and it can rotate more rapidly and have a larger ergosphere than black holes in General Relativity (GR) with the same asymptotic properties. We analytically investigate the features of the innermost stable circular orbits for massive objects on the equatorial plane, and show that stable orbits lie further away from the black hole horizon with respect to rotating black holes in GR. We also comment on possible applications of our findings for the extraction of rotational energy from the black hole.

How automatic is the musical stroop effect? Commentary on “the musical stroop effect: opening a new avenue to research on automatisms” by l. Grégoire, P. Perruchet, and B. Poulin-Charronnat (Experimental Psychology, 2013, vol. 60, pp. 269–278).

PubMed

Moeller, Birte; Frings, Christian

2014-01-01

Grégoire, Perruchet, and Poulin-Charronnat (2013) investigated a musical variant of the reversed Stroop effect. According to the authors, one big advantage of this variant is that the automaticity of note naming can be better controlled than in other Stroop variants as musicians are very practiced in note reading whereas non-musicians are not. In this comment we argue that at present the exact impact of automaticity in this Stroop variant remains somewhat unclear for at least three reasons, namely due to the type of information that is automatically retrieved when notes are encountered, due to the possible influence of object-based attention, and finally due to the fact that the exact influence of expertise on interference cannot be pinpointed with an extreme group design.

A novel lable-free electrochemical immunosensor for carcinoembryonic antigen based on gold nanoparticles-thionine-reduced graphene oxide nanocomposite film modified glassy carbon electrode.

PubMed

Kong, Fen-Ying; Xu, Mao-Tian; Xu, Jing-Juan; Chen, Hong-Yuan

2011-10-15

In this paper, gold nanoparticle-thionine-reduced graphene oxide (GNP-THi-GR) nanocomposites were prepared to design a label-free immunosensor for the sensitive detection of carcinoembryonic antigen (CEA). The nanocomposites with good biocompatibility, excellent redox electrochemical activity and large surface area were coated onto the glassy carbon electrode (GCE) surface and then CEA antibody (anti-CEA) was immobilized on the electrode to construct the immunosensor. The morphologies and electrochemistry of the formed nanocomposites were investigated by using scanning electron microscopy (SEM), ultraviolet-visible (UV-vis) spectrometry, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). CV and differential pulse voltammetry (DPV) studies demonstrated that the formation of antibody-antigen complexes decreased the peak current of THi in the GNP-THi-GR nanocomposites. The decreased currents were proportional to the CEA concentration in the range of 10-500 pg/mL with a detection limit of 4 pg/mL. The proposed method was simple, fast and inexpensive for the determination of CEA at very low levels. Copyright © 2011 Elsevier B.V. All rights reserved.

Electrochemical sensor based on gold nanoparticles fabricated molecularly imprinted polymer film at chitosan-platinum nanoparticles/graphene-gold nanoparticles double nanocomposites modified electrode for detection of erythromycin.

PubMed

Lian, Wenjing; Liu, Su; Yu, Jinghua; Xing, Xianrong; Li, Jie; Cui, Min; Huang, Jiadong

2012-01-01

A molecularly imprinted electrochemical sensor was fabricated based on gold electrode decorated by chitosan-platinum nanoparticles (CS-PtNPs) and graphene-gold nanoparticles (GR-AuNPs) nanocomposites for convenient and sensitive determination of erythromycin. The synergistic effects of CS-PtNPs and GR-AuNPs nanocomposites improved the electrochemical response and the sensitivity of the sensor. The molecularly imprinted polymers (MIPs) were prepared by HAuCl(4), 2-mercaptonicotinic acid (MNA) and erythromycin. Erythromycin and MNA were used as template molecule and functional monomer, respectively. They were first assembled on the surface of GR-AuNPs/CS-PtNPs/gold electrode by the formation of Au-S bonds and hydrogen-bonding interactions. Then the MIPs were formed by electropolymerization of HAuCl(4), MNA and erythromycin. The sensor was characterized by cyclic voltammetry (CV), scanning electron microscope (SEM), UV-visible (UV-vis) absorption speactra and amperometry. The linear range of the sensor was from 7.0 × 10(-8)mol/L-9.0 × 10(-5)mol/L, with the limit of detection (LOD) of 2.3 × 10(-8)mol/L (S/N=3). The sensor showed high selectivity, excellent stability and good reproducibility for the determination of erythromycin, and it was successfully applied to the detection of erythromycin in real spiked samples. Copyright © 2012 Elsevier B.V. All rights reserved.

PAMAM dendrimers and graphene: Materials for removing aromatic contaminants from water

DOE Office of Scientific and Technical Information (OSTI.GOV)

DeFever, Ryan S.; Geitner, Nicholas K.; Bhattacharya, Priyanka

2015-04-07

We present results from experiments and atomistic molecular dynamics simulations on the association of naphthalene with polyamidoamine (PAMAM) dendrimers and graphene oxide (GrO). Specifically, we investigate 3rd-6th generation (G3-G6) PAMAM dendrimers and GrO with different levels of oxidation. The work is motivated by the potential applications of these materials in removing polycyclic aromatic hydrocarbon contaminants from water. Our experimental results indicate that graphene oxide outperforms dendrimers in removing naphthalene from water. Molecular dynamics simulations suggest that the prominent factors driving naphthalene association to these seemingly disparate materials are similar. Interestingly, we find that cooperative interactions between the naphthalene molecules playmore » a significant role in enhancing their association to the dendrimers and graphene oxide. Our findings highlight that while selection of appropriate materials is important, the interactions between the contaminants themselves can also be important in governing the effectiveness of a given material. The combined use of experiments and molecular dynamics simulations allows us to comment on the possible factors resulting in better performance of graphene oxide in removing naphthalene from water.« less

Filter feeding mechanics of Hypophthalmichthys molitrix regarding porous gill rakers

NASA Astrophysics Data System (ADS)

Palumbo, David; Bulusu, Kartik V.; Cohen, Karly; Hernandez, Particia; Leftwich, Megan C.; Plesniak, Michael W.

2017-11-01

The silver carp (Hypophthalmichthys molitrix) is a filter-feeding fish known to feed upon algal-growth in lakes, rivers, and aquacultures. The filter-feeding process centers on sponge-like membranes located in the carp's pharynx supported by fused gill rakers (GRs), which can efficiently strain suspended food particles as small as 4 µm without clogging. Guided by the anatomy of the silver carp, scanning electron microscope (SEM) images of GRs, and video of the silver carp feeding, we have hypothesized that the filtration mechanism involves a pump-based biological function to capture food particles within the GRs. Dye visualization experiments were performed on a silver carp cadaver head, an excised GR sample, and on a scaled GR in vitro model - the Artificial Gill Raker (AGR). Measurements are performed for the AGR using laser Doppler velocimetry (LDV) and penetration pressure monitoring with a biologically-inspired pumping mechanism. The role of mucus in the retention and capture of food particles has also been explored through rheological measurements, and further experimentation is planned. Our motivation stems from the potential to develop bioinspired industrial-scale filtration technologies ranging from wastewater treatment to filtration in the food industry. supported by GW Center for Biomimetics and Bioinspired Engineering.

Silica-polyethylene glycol hybrids synthesized by sol-gel: Biocompatibility improvement of titanium implants by coating.

PubMed

Catauro, M; Bollino, F; Papale, F; Ferrara, C; Mustarelli, P

2015-10-01

Although metallic implants are the most used in dental and orthopaedic fields, they can early fail due to low tissue tolerance or osseointegration ability. To overcome this drawback, functional coatings can be applied on the metallic surface to provide a firm fixation of the implants. The objective of the present study was twofold: to synthesize and to characterize silica/polyethylene glycol (PEG) hybrid materials using sol-gel technique and to investigate their capability to dip-coat titanium grade 4 (Ti-gr4) substrates to improve their biological properties. Various hybrid systems have been synthesized by changing the ratio between the organic and inorganic phases in order to study the influence of the polymer amount on the structure and, thus, on the properties of the coatings. Fourier transform infrared (FTIR) spectroscopy and solid state Nuclear Magnetic Resonance (NMR) allowed us to detect the formation of hydrogen bonds between the inorganic sol-gel matrix and the organic component. SEM analysis showed that high PEG content enables to obtain crack free-coating. Moreover, the effective improvement in biological properties of Ti-gr4 implants has been evaluated by performing in vitro tests. The bioactivity of the hybrid coatings has been showed by the hydroxyapatite formation on the surface of SiO2/PEG coated Ti-gr4 substrates after soaking in a simulated body fluid and the lack of cytotoxicity by the WST-8 Assay. The results showed that the coated substrates are more bioactive and biocompatible than the uncoated ones and that the bioactivity is not significantly affected by PEG amount whereas its addition makes the films more biocompatible. Copyright © 2015. Published by Elsevier B.V.

Bonding to CAD-CAM Composites: An Interfacial Fracture Toughness Approach.

PubMed

Eldafrawy, M; Ebroin, M G; Gailly, P A; Nguyen, J-F; Sadoun, M J; Mainjot, A K

2018-01-01

The objective of this study was to evaluate the interfacial fracture toughness (IFT) of composite cement with dispersed filler (DF) versus polymer-infiltrated ceramic network (PICN) computer-aided design and computer-aided manufacturing (CAD-CAM) composite blocks after 2 different surface pretreatments using the notchless triangular prism (NTP) test. Two DFs (Cerasmart [CRT] and Lava Ultimate [LVA]), 2 PICNs (Enamic [ENA] and experimental PICN [EXP]), and e.max CAD lithium disilicate glass-ceramic (EMX, control) prism samples were bonded to their counterparts with Variolink Esthetic DC composite cement after either hydrofluoric acid etching (HF) or gritblasting (GR). Both procedures were followed by silanization. All samples ( n = 30 per group) were thermocycled (10,000 cycles) and tested for their IFT in a water bath at 36°C. Moreover, representative samples from each group were subjected to a developed interfacial area ratio (Sdr) measurement by profilometry and scanning electron microscopy (SEM) characterization. EXP-HF gave the highest IFT (1.85 ± 0.39 MPa·m 1/2 ), followed by EMX-HF and ENA-HF, while CRT-HF gave the lowest (0.15 ± 0.22 MPa·m 1/2 ). PICNs gave significantly better results with HF, and DF showed better results with GR. A 2-way analysis of variance indicated that there were significantly higher IFT and Sdr for PICNs than for DF. A positive correlation ( r² = 0.872) was found between IFT and Sdr. SEM characterization showed the specific microstructure of the surface of etched PICNs, indicating the presence of a retentive polymer-based honeycomb structure. Etching of the typical double-network microstructure of PICNs causes an important increase in the Sdr and IFT, while DF should be gritblasted. DF exhibited significantly lower Sdr and IFT values than PICNs. The present results show the important influence of the material class and surface texture, and consequently the micromechanical bond, on the adhesive interface performance of CAD-CAM composites.

Reliability, minimal detectable change and responsiveness to change: Indicators to select the best method to measure sedentary behaviour in older adults in different study designs.

PubMed

Dontje, Manon L; Dall, Philippa M; Skelton, Dawn A; Gill, Jason M R; Chastin, Sebastien F M

2018-01-01

Prolonged sedentary behaviour (SB) is associated with poor health. It is unclear which SB measure is most appropriate for interventions and population surveillance to measure and interpret change in behaviour in older adults. The aims of this study: to examine the relative and absolute reliability, Minimal Detectable Change (MDC) and responsiveness to change of subjective and objective methods of measuring SB in older adults and give recommendations of use for different study designs. SB of 18 older adults (aged 71 (IQR 7) years) was assessed using a systematic set of six subjective tools, derived from the TAxonomy of Self report Sedentary behaviour Tools (TASST), and one objective tool (activPAL3c), over 14 days. Relative reliability (Intra Class Correlation coefficients-ICC), absolute reliability (SEM), MDC, and the relative responsiveness (Cohen's d effect size (ES) and Guyatt's Responsiveness coefficient (GR)) were calculated for each of the different tools and ranked for different study designs. ICC ranged from 0.414 to 0.946, SEM from 36.03 to 137.01 min, MDC from 1.66 to 8.42 hours, ES from 0.017 to 0.259 and GR from 0.024 to 0.485. Objective average day per week measurement ranked as most responsive in a clinical practice setting, whereas a one day measurement ranked highest in quasi-experimental, longitudinal and controlled trial study designs. TV viewing-Previous Week Recall (PWR) ranked as most responsive subjective measure in all study designs. The reliability, Minimal Detectable Change and responsiveness to change of subjective and objective methods of measuring SB is context dependent. Although TV viewing-PWR is the more reliable and responsive subjective method in most situations, it may have limitations as a reliable measure of total SB. Results of this study can be used to guide choice of tools for detecting change in sedentary behaviour in older adults in the contexts of population surveillance, intervention evaluation and individual care.

Supporting Uncertainty Reasoning in SIMulated Operators for Networks (SIMON) (Le support du raisonnement dans l’incertitude pour des operateurs simules dans un reseau)

DTIC Science & Technology

2005-12-01

moteur de simulation de l’Environnement Intégré de Modélisation de la Performance est utilisé de pair avec l’approche pour démontrer comment des...d’être utilisé dans les forces générées par ordinateur. Le travail ultérieur inclura plus d’essais, l’intégration avec les moteurs de simulateurs et...Aspects are reasoning units relevant to simulated tasks. Each Aspect schema is a 4-tuple: AspectSchema = <MA, WM, LM, CL>, where MA refers to meta

Comments on gravitoelectromagnetism of Ummarino and Gallerati in "Superconductor in a weak static gravitational field" vs other versions

NASA Astrophysics Data System (ADS)

Behera, Harihar

2017-12-01

Recently reported [Eur. Phys. J. C., 77, 549 (2017). https://doi.org/10.1140/epjc/s10052-017-5116-y] gravitoelectromagnetic equations of Ummarino and Gallerati (UG) in their linearized version of general relativity (GR) are shown to match with (a) our previously reported special relativistic Maxwellian Gravity equations in the non-relativistic limit and with (b) the non-relativistic equations derived here, when the speed of gravity c_g (an undetermined parameter of the theory here) is set equal to c (the speed of light in vacuum). Seen in the light of our new results, the UG equations satisfy the Correspondence Principle (cp), while many other versions of linearized GR equations that are being (or may be) used to interpret the experimental data defy the cp. Such new findings assume significance and relevance in the contexts of recent detection of gravitational waves and the gravitomagnetic field of the spinning earth and their interpretations. Being well-founded and self-consistent, the equations may be of interest and useful to researchers exploring the phenomenology of gravitomagnetism, gravitational waves and the novel interplay of gravity with different states of matter in flat space-time like UG's interesting work on superconductors in weak gravitational fields.

Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses

NASA Astrophysics Data System (ADS)

Bansal, Sandeep Kumar; Jaiswal, Deepika; Gupta, Nishi; Singh, Kiran; Dada, Rima; Sankhwar, Satya Narayan; Gupta, Gopal; Rajender, Singh

2016-02-01

We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions (gr/gr, b1/b3, b2/b3) in 822 infertile and 225 proven fertile men. We observed complete AZFc deletions in 0.97% and partial deletions in 6.20% of the cases. Among partial deletions, the frequency of gr/gr deletions was the highest (5.84%). The comparison of partial deletion data between cases and controls suggested a significant association of the gr/gr deletions with infertility (P = 0.0004); however, the other partial deletions did not correlate with infertility. In cohort analysis, men with gr/gr deletions had a relatively poor sperm count (54.20 ± 57.45 million/ml) in comparison to those without deletions (72.49 ± 60.06), though the difference was not statistically significant (p = 0.071). Meta-analysis also suggested that gr/gr deletions are significantly associated with male infertility risk (OR = 1.821, 95% CI = 1.39-2.37, p = 0.000). We also performed trial sequential analyses that strengthened the evidence for an overall significant association of gr/gr deletions with the risk of male infertility. Another meta-analysis suggested a significant association of the gr/gr deletions with low sperm count. In conclusion, the gr/gr deletions show a strong correlation with male infertility risk and low sperm count, particularly in the Caucasian populations.

Impact of the maze operation combined with left-sided valve surgery on the change in tricuspid regurgitation over time.

PubMed

Kim, Hyung-Kwan; Kim, Yong-Jin; Kim, Kwang-Il; Jo, Sang-Ho; Kim, Ki-Bong; Ahn, Hyuk; Sohn, Dae-Won; Oh, Byung-Hee; Lee, Myoung-Mook; Park, Young-Bae; Choi, Yun-Shik

2005-08-30

Atrial fibrillation (AF) has been reported to be a predisposing factor for the progression of TR in patients with previous mitral or combined mitral/aortic valve surgery. We hypothesized that the maze operation (MAZE) can prevent the progression of tricuspid regurgitation (TR) in these patients. We analyzed 170 patients (age, 45.5+/-10.9 years) who had undergone mitral or combined mitral/aortic valve surgery. On the basis of preoperative rhythm, patients were divided into 3 groups; GrI was composed of 44 patients with sinus rhythm, GrII of 48 who had undergone MAZE, and GrIII of 78 with AF who had not undergone MAZE. Echocardiographic examinations were performed before, immediately after, and 92.2+/-17.2 (range, 50 to 131) months after surgery. Preoperative and immediate postoperative clinical and echocardiographic parameters were similar among the groups. Insignificant TR at the immediate postoperative examination worsened with time in 7.3% of GrI (3 of 41), 12.8% of GrII (6 of 47), and 38.8% of GrIII (26 of 67) patients at the final examination (P=0.63 for GrI versus GrII, P=0.001 for GrI versus GrIII, P=0.005 for GrII versus GrIII). The incidence of significant TR at the final echocardiographic examination was higher in GrIII (39.7%) compared with GrI (9.1%) and GrII (14.6%) (P=0.001 for GrI versus GrIII, P=0.005 for GrII versus GrIII), whereas GrI and GrII did not show any difference (P=0.63). By multivariate analysis, the only factor identified to prevent TR progression was the group factor (GrI and GrII versus GrIII, P=0.002 and P=0.005, respectively). In a subgroup analysis of GrII according to the presence or absence of atrial mechanical activity, the absence of atrial mechanical activity was identified as an independent parameter for the progression of TR (P=0.001). AF predisposes patients undergoing mitral valve surgery to the progression of TR, which can be prevented by MAZE. This additional benefit of MAZE is largely dependent on the restoration and maintenance of atrial mechanical function.

Hydroxyapatite grafted carbon nanotubes and graphene nanosheets: Promising bone implant materials

NASA Astrophysics Data System (ADS)

Oyefusi, Adebola; Olanipekun, Opeyemi; Neelgund, Gururaj M.; Peterson, Deforest; Stone, Julia M.; Williams, Ebonee; Carson, Laura; Regisford, Gloria; Oki, Aderemi

2014-11-01

In the present study, hydroxyapatite (HA) was successfully grafted to carboxylated carbon nanotubes (CNTs) and graphene nanosheets. The HA grafted CNTs and HA-graphene nanosheets were characterized using FT-IR, TGA, SEM and X-ray diffraction. The HA grafted CNTs and graphene nanosheets (CNTs-HA and Gr-HA) were further used to examine the proliferation and differentiation rate of temperature-sensitive human fetal osteoblastic cell line (hFOB 1.19). Total protein assays and western blot analysis of osteocalcin expression were used as indicators of cell proliferation and differentiation. Results indicated that hFOB 1.19 cells proliferate and differentiate well in treatment media containing CNTs-HA and graphene-HA. Both CNTs-HA and graphene-HA could be promising nanomaterials for use as scaffolds in bone tissue engineering.

Synthesis of one-dimensional gold nanostructures and the electrochemical application of the nanohybrid containing functionalized graphene oxide for cholesterol biosensing.

PubMed

Nandini, Seetharamaiah; Nalini, Seetharamaiah; Reddy, M B Madhusudana; Suresh, Gurukar Shivappa; Melo, Jose Savio; Niranjana, Pathappa; Sanetuntikul, Jakkid; Shanmugam, Sangaraju

2016-08-01

This manuscript reports a new approach for the synthesis of one dimensional gold nanostructure (AuNs) and its application in the development of cholesterol biosensor. Au nanostructures have been synthesized by exploiting β-diphenylalanine (β-FF) as an sacrificial template, whereas the Au nanoparticles (AuNPs) were synthesized by ultrasound irradiation. X-ray diffractometer (XRD), scanning electron microscope (SEM) and energy dispersive analysis of X-rays (EDAX) have been employed to characterize the morphology and composition of the prepared samples. With the aim to develop a highly sensitive cholesterol biosensor, cholesterol oxidase (ChOx) was immobilized on AuNs which were appended on the graphite (Gr) electrode via chemisorption onto thiol-functionalized graphene oxide (GO-SH). This Gr/GO-SH/AuNs/ChOx biosensor has been characterized using cyclic voltammetry (CV), electrochemical impedance spectroscopy and chronoamperometry. CV results indicated a direct electron transfer between the enzyme and the electrode surface. A new potentiostat intermitant titration technique (PITT) has been studied to determine the diffusion coefficient and maxima potential value. The proposed biosensor showed rapid response, high sensitivity, wide linear range and low detection limit. Furthermore, our AuNs modified electrode showed excellent selectivity, repeatability, reproducibility and long term stability. The proposed electrode has also been used successfully to determine cholesterol in serum samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of carbamate pesticides on perforin, granzymes A-B-3/K, and granulysin in human natural killer cells.

PubMed

Li, Qing; Kobayashi, Maiko; Kawada, Tomoyuki

2015-09-01

We previously found that ziram, a carbamate pesticide, significantly reduced perforin, granzyme A (GrA), granzyme B (GrB), granzyme 3/K (Gr3/K), and granulysin (GRN) levels in NK-92MI cells, a human natural killer (NK) cell line. To investigate whether other carbamate pesticides also show similar toxicity on human NK cells, we conducted further experiments with NK-92CI cells, a human NK cell line, using a more sensitive assay. We previously confirmed that NK-92CI cells express CD56, perforin, GrA, GrB, Gr3/K, and GRN and are highly cytotoxic to K562 cells in a chromium release assay, which are more sensitive to organophosphorus pesticides and ziram than the NK-92MI cell line. NK-92CI cells were treated with ziram, thiram, maneb, or carbaryl at various concentrations for 4-24 h at 37°C in vitro. Thereafter, intracellular levels of perforin, GrA, GrB, Gr3/K, and GRN were determined by flow cytometry. It was found that all carbamate pesticides significantly reduced the intracellular levels of perforin, GrA, GrB, Gr3/K, and GRN in NK-92CI cells in a dose-dependent manner. However, the strength of the effect differed among the pesticides, and the order was thiram > ziram > maneb > carbaryl. In addition, it was also found that the degree of the reductions differed among the five proteins, with perforin more sensitive to pesticides than GRN, GrA, GrB, and Gr3/K, and the order was perforin > GRN > Gr3/K ≒ GrA ≒ GrB. © The Author(s) 2015.

Highly-stable and -flexible graphene/(CF3SO2)2NH/graphene transparent conductive electrodes for organic solar cells

NASA Astrophysics Data System (ADS)

Seo, Sang Woo; Lee, Ha Seung; Shin, Dong Hee; Kim, Ju Hwan; Jang, Chan Wook; Kim, Jong Min; Kim, Sung; Choi, Suk-Ho

2017-10-01

We first employ highly-stable and -flexible (CF3SO2)2NH-doped graphene (TFSA/GR) and GR-encapsulated TFSA/GR (GR/TFSA/GR) transparent conductive electrodes (TCEs) prepared on polyethylene terephthalate substrates for flexible organic solar cells (OSCs). Compared to conventional indium tin oxide (ITO) TCEs, the TFSA-doped-GR TCEs show higher optical transmittance and larger sheet resistance. The TFSA/GR and GR/TFSA/GR TCEs show work functions of 4.89 ± 0.16 and 4.97 ± 0.18 eV, respectively, which are not only larger than those of the ITO TCEs but also indicate p-type doping of GR, and are therefore more suitable for anode TCEs of OSCs. In addition, typical GR/TFSA/GR-TCE OSCs are much more mechanically flexible than the ITO-TCE ones with their photovoltaic parameters being similar, as proved by bending tests as functions of cycle and curvature.

Effect of Grinding and Resintering on the Fatigue Limit and Surface Characterization of a Y-TZP Ceramic.

PubMed

Polli, Gabriela Scatimburgo; Hatanaka, Gabriel Rodrigues; Abi-Rached, Filipe de Oliveira; Pinelli, Lígia Antunes Pereira; Góes, Márcio de Sousa; Cesar, Paulo Francisco; Reis, José Maurício Dos Santos Nunes

2016-01-01

This study evaluated the effect of grinding protocols and resintering on flexural fatigue limit and surface characterization of LavaTM Y-TZP. Bar-shaped specimens (20×4.0×1.2 mm, n=40; 20×4.0×1.5 mm, n=80) were obtained. Half of the thinner specimens (1.2 mm) constituted the as-sintered group (AS), while the thicker ones (1.5 mm) were ground with diamond burs under irrigation (WG) or not (G). The other half of thinner and half of ground specimens were resintered (1000 ºC, 30 min), forming the groups ASR, WGR and GR. Fatigue limit (500,000 cycles, 10 Hz) was evaluated by staircase method in a 4-point flexural fixture. Data were analyzed by 2-way ANOVA and Tukey's test (α=0.05). Surface topography (n=3) and fracture area (n=3) were evaluated by SEM. X-ray diffraction data (n=1) was analyzed by Rietveld refinement. ANOVA revealed significant differences (p<0.001) for the grinding protocol, resintering and their interaction. Grinding increased the fatigue limit of non-resintered groups. There was no significant difference among the resintered groups. Resintering significantly increased the fatigue limit of the AS group only. Both protocols created evident grooves on zirconia surface. The failures initiated at the tensile side of all specimens. The percentages (wt%) of monoclinic phase were AS (8.6), ASR (1.2), G (1.8), GR (0.0), WG (8.2), WGR (0.0) before, and AS (7.4), ASR (6.5), G (3.2), GR (0.2), WG (4.6), WGR (1.1) after cyclic loading. Grinding increased the fatigue limit of non-resintered Y-TZP and formed evident grooves on its surface. Resintering provided significant increase in the fatigue limit of as-sintered specimens. In general, grinding and resintering decreased or zeroed the monoclinic phase.

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

DTIC Science & Technology

2010-10-01

count < 15,000 > 7 days or need for > 3 plt transfusions in 30 days • Gr 4 neutropenia > 7 days • Febrile neutropenia • Attributable Gr > 3...11% No febrile neutropenia (no growth factor use) • Transaminitis Transient Gr 1 AST 29% (1 Gr 2) Need for transfusions 6 pts...No pts had significant bleeding; 2 received plt transfusions (cohort 6) • Neutropenia Gr 0 = 40%; Gr 1-2 = 32%; Gr 3 = 29%; Gr 4

Electrochemical sensors and biosensors based on less aggregated graphene.

PubMed

Bo, Xiangjie; Zhou, Ming; Guo, Liping

2017-03-15

As a novel single-atom-thick sheet of sp 2 hybridized carbon atoms, graphene (GR) has attracted extensive attention in recent years because of its unique and remarkable properties, such as excellent electrical conductivity, large theoretical specific surface area, and strong mechanical strength. However, due to the π-π interaction, GR sheets are inclined to stack together, which may seriously degrade the performance of GR with the unique single-atom layer. In recent years, an increasing number of GR-based electrochemical sensors and biosensors are reported, which may reflect that GR has been considered as a kind of hot and promising electrode material for electrochemical sensor and biosensor construction. However, the active sites on GR surface induced by the irreversible GR aggregations would be deeply secluded inside the stacked GR sheets and therefore are not available for the electrocatalysis. So the alleviation or the minimization of the aggregation level for GR sheets would facilitate the exposure of active sites on GR and effectively upgrade the performance of GR-based electrochemical sensors and biosensors. Less aggregated GR with low aggregation and high dispersed structure can be used in improving the electrochemical activity of GR-based electrochemical sensors or biosensors. In this review, we summarize recent advances and new progress for the development of electrochemical sensors based on less aggregated GR. To achieve such goal, many strategies (such as the intercalation of carbon materials, surface modification, and structural engineering) have been applied to alleviate the aggregation level of GR in order to enhance the performance of GR-based electrochemical sensors and biosensors. Finally, the challenges associated with less aggregated GR-based electrochemical sensors and biosensors as well as related future research directions are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Arbitrary conditional discriminative functions of meaningful stimuli and enhanced equivalence class formation.

PubMed

Nedelcu, Roxana I; Fields, Lanny; Arntzen, Erik

2015-03-01

Equivalence class formation by college students was influenced through the prior acquisition of conditional discriminative functions by one of the abstract stimuli (C) in the to-be-formed classes. Participants in the GR-0, GR-1, and GR-5 groups attempted to form classes under the simultaneous protocol, after mastering 0, 1, or 5 conditional relations between C and other abstract stimuli (V, W, X, Y, Z) that were not included in the to-be-formed classes (ABCDE). Participants in the GR-many group attempted to form classes that contained four abstract stimuli and one meaningful picture as the C stimulus. In the GR-0, GR-1, GR-5, and GR-many groups, classes were formed by 17, 25, 58, and 67% of participants, respectively. Thus, likelihood of class formation was enhanced by the prior formation of five C-based conditional relations (the GR-5 vs. GR-0 condition), or the inclusion of a meaningful stimulus as a class member (the GR-many vs. GR-0 condition). The GR-5 and GR-many conditions produced very similar yields, indicating that class formation was enhanced to a similar degree by including a meaningful stimulus or an abstract stimulus that had become a member of five conditional relations prior to equivalence class formation. Finally, the low and high yields produced by the GR-1 and GR-5 conditions showed that the class enhancement effect of the GR-5 condition was due to the number of conditional relations established during preliminary training and not to the sheer amount of reinforcement provided while learning these conditional relations. Class enhancement produced by meaningful stimuli, then, can be attributed to their acquired conditional discriminative functions as well as their discriminative, connotative, and denotative properties. © Society for the Experimental Analysis of Behavior.

Alternative splicing: a novel mechanism of regulation identified in the chorismate mutase gene of the potato cyst nematode Globodera rostochiensis.

PubMed

Lu, Shun-Wen; Tian, Duanhua; Borchardt-Wier, Harmony B; Wang, Xiaohong

2008-11-01

Chorismate mutase (CM) secreted from the stylet of plant-parasitic nematodes plays an important role in plant parasitism. We isolated and characterized a new nematode CM gene (Gr-cm-1) from the potato cyst nematode, Globodera rostochiensis. The Gr-cm-1 gene was found to exist in the nematode genome as a single-copy gene that has two different alleles, Gr-cm-1A and Gr-cm-1B, both of which could give rise to two different mRNA transcripts of Gr-cm-1 and Gr-cm-1-IRII. In situ mRNA hybridization showed that the Gr-cm-1 gene was exclusively expressed within the subventral oesophageal gland cells of the nematode. Gr-cm-1 was demonstrated to encode a functional CM (GR-CM-1) potentially having a dimeric structure as the secreted bacterial *AroQ CMs. Gr-cm-1-IRII, generated by retention of intron 2 of the Gr-cm-1 pre-mRNA through alternative splicing (AS), would encode a truncated protein (GR-CM-1t) lacking the CM domain with no CM activity. The quantitative real-time reverse transcription-PCR assay revealed that splicing of the Gr-cm-1 gene was developmentally regulated; Gr-cm-1 was up-regulated whereas Gr-cm-1-IRII was down-regulated in early nematode parasitic stages compared to the preparasitic juvenile stage. Low-temperature SDS-PAGE analysis revealed that GR-CM-1 could form homodimers when expressed in Escherichia coli and the dimerization domain was retained in the truncated GR-CM-1t protein. The specific interaction between the two proteins was demonstrated in yeast. Our data suggested that the novel splice variant might function as a dominant negative isoform through heterodimerization with the full-length GR-CM-1 protein and that AS may represent an important mechanism for regulating CM activity during nematode parasitism.

A Glycine-Rich RNA-Binding Protein, CsGR-RBP3, Is Involved in Defense Responses Against Cold Stress in Harvested Cucumber (Cucumis sativus L.) Fruit

PubMed Central

Wang, Bin; Wang, Guang; Shen, Fei; Zhu, Shijiang

2018-01-01

Plant glycine-rich RNA-binding proteins (GR-RBPs) have been shown to play important roles in response to abiotic stresses in actively proliferating organs such as young plants, root tips, and flowers, but their roles in chilling responses of harvested fruit remains largely unknown. Here, we investigated the role of CsGR-RBP3 in the chilling response of cucumber fruit. Pre-storage cold acclimation at 10°C (PsCA) for 3 days significantly enhanced chilling tolerance of cucumber fruit compared with the control fruit that were stored at 5°C. In the control fruit, only one of the six cucumber CsGR-RBP genes, CsGR-RBP2, was enhanced whereas the other five, i.e., CsGR-RBP3, CsGR-RBP4, CsGR-RBP5, CsGR-RBP-blt801, and CsGR-RBP-RZ1A were not. However, in the fruit exposed to PsCA before storage at 5°C, CsGR-RBP2 transcript levels were not obviously different from those in the controls, whereas the other five were highly upregulated, with CsGR-RBP3 the most significantly induced. Treatment with endogenous ABA and NO biosynthesis inhibitors, tungstate and L-nitro-arginine methyl ester, respectively, prior to PsCA treatment, clearly downregulated CsGR-RBP3 expression and significantly aggravated chilling injury. These results suggest a strong connection between CsGR-RBP3 expression and chilling tolerance in cucumber fruit. Transient expression in tobacco suggests CsGR-RBP3 was located in the mitochondria, implying a role for CsGR-RBP3 in maintaining mitochondria-related functions under low temperature. Arabidopsis lines overexpressing CsGR-RBP3 displayed faster growth at 23°C, lower electrolyte leakage and higher Fv/Fm ratio at 0°C, and higher survival rate at -20°C, than wild-type plants. Under cold stress conditions, Arabidopsis plants overexpressing CsGR-RBP3 displayed lower reactive oxygen species levels, and higher catalase and superoxide dismutase expression and activities, compared with the wild-type plants. In addition, overexpression of CsGR-RBP3 significantly upregulated nine Arabidopsis genes involved in defense responses to various stresses, including chilling. These results strongly suggest CsGR-RBP3 plays a positive role in defense against chilling stress. PMID:29740470

Hydroxyapatite grafted carbon nanotubes and graphene nanosheets: promising bone implant materials.

PubMed

Oyefusi, Adebola; Olanipekun, Opeyemi; Neelgund, Gururaj M; Peterson, Deforest; Stone, Julia M; Williams, Ebonee; Carson, Laura; Regisford, Gloria; Oki, Aderemi

2014-11-11

In the present study, hydroxyapatite (HA) was successfully grafted to carboxylated carbon nanotubes (CNTs) and graphene nanosheets. The HA grafted CNTs and HA-graphene nanosheets were characterized using FT-IR, TGA, SEM and X-ray diffraction. The HA grafted CNTs and graphene nanosheets (CNTs-HA and Gr-HA) were further used to examine the proliferation and differentiation rate of temperature-sensitive human fetal osteoblastic cell line (hFOB 1.19). Total protein assays and western blot analysis of osteocalcin expression were used as indicators of cell proliferation and differentiation. Results indicated that hFOB 1.19 cells proliferate and differentiate well in treatment media containing CNTs-HA and graphene-HA. Both CNTs-HA and graphene-HA could be promising nanomaterials for use as scaffolds in bone tissue engineering. Copyright © 2014 Elsevier B.V. All rights reserved.

Addition of Lubiprostone to polyethylene glycol(PEG) enhances the quality & efficacy of colonoscopy preparation: a randomized, double-blind, placebo controlled trial.

PubMed

Banerjee, Rupa; Chaudhari, Hrushikesh; Shah, Nirish; Saravanan, Arjunan; Tandan, Manu; Reddy, D Nageshwar

2016-10-13

Adequate bowel preparation is an essential prerequisite for complete mucosal visualization during colonoscopy. Polyethylene glycol (PEG) solutions are commonly used. However the large volume of the solution is often poorly tolerated. Addition of Lubiprostone (LB) could improve the adequacy of standard PEG preparation & reduce requirement. The aims to assess adequacy of PEG preparation with addition of single dose LB (24mcg) vs placebo and efficacy of reduced dose PEG + LB compared with full dose PEG + LB. Single center prospective double blind randomized controlled trial. Part I: 442 patients for colonoscopy randomized to receive placebo (GrA) or single dose of LB (GrB) prior to PEG preparation. Quality of bowel preparation graded 0-9 according to Boston Bowel Preparation Scale (BBPS). BBPS-9: excellent and BBPS 0-4: repeat procedure. Part II: 146 patients randomized to receive LB + 1.5 L PEG (GrC; 75) or LB + 1 L PEG (GrD; 71). BBPS score compared with GrB (2 L PEG). Part I: 442 patients (221 GrA & 221 Gr B). LB resulted in significant improvement in total BBPS (7.44 + 0.14 vs. 6.36 + 0.16, p < 0.0001). 66.5 % Gr B vs 38 % Gr A had excellent prep; 42.5 % GrB vs 24 % GrA had adequate prep. Repeat procedure needed 9.5 % Gr B vs 16.7 % Gr A (P < 0.01). Part II: No difference in BBPS scores with lower doses (Gr C&D) compared to standard (GrB) (Mean BBPS 7.44 + 0.14 GrA,7.30 + 0.25 GrC;7.25 + 0.26 GrD;p >0.05). Single dose LB prior to PEG significantly enhanced bowel preparation compared to PEG alone. There was no significant difference in quality of preparation with lower doses of PEG when combined with LB. The study protocol was approved by institutional review board and the trial was registered on March 22, 2011 with clinicaltrials.gov ( NCT01324284 ).

Long-Term Use of Probiotic-Containing Yogurts Is a Safe Way to Prevent Helicobacter pylori: Based on a Mongolian Gerbil's Model

PubMed Central

Kuo, Chao-Hung; Wang, Sophie S. W.; Lu, Chien-Yu; Hu, Huang-Ming; Kuo, Fu-Chen; Weng, Bi-Chuang; Wu, Chun-Chieh; Liu, Chung-Jung; Tsai, Pei-Yun; Lee, Tsung-Cheng; Chen, Li-Wei; Cheng, Kuang-Hung; Chang, Lin-Li; Wu, Deng-Chyang

2013-01-01

Background. The suppression of Helicobacter pylori (H. pylori) decreases H. pylori-related diseases. The probiotics have an inhibitory effect on H. pylori. Aim. We investigated the effects of long-term use of yogurt on H. pylori based on Mongolian gerbils' model. Materials and Methods. Yogurt (containing a supplement of Lactobacillus acidophilus, Bifidobacterium lactis, etc.) was used. Forty-six gerbils were divided into five groups. All groups were inoculated with H. pylori for 5 to 8 weeks. The yogurt was given as follows: Group (Gr.) A: from 1st to 4th week; Gr. B from 5th to 8th week; Gr. C: from 17th week to sacrifice; Gr. D: from 5th week to sacrifice. Gerbils were sacrificed on the 52nd week. Histology was evaluated according to the Sydney system. Results. The positive rates of H. pylori were 60% (Gr. A), 75% (Gr. B), 67% (Gr. C), 44% (Gr. D), and 100% (Gr. E). Gr. D showed lower inflammatory score. Only Gr. E (60%) had intestinal metaplasia. Gr. D showed higher IL-10 and lower TNF-α expression than Gr. E. Conclusion. Long-term intake of yogurt could decrease H. pylori infection. The long-term use of yogurt would be an alternative strategy to manage H. pylori infection. PMID:24349780

Biogenic hydroxysulfate green rust, a potential electron acceptor for SRB activity

NASA Astrophysics Data System (ADS)

Zegeye, Asfaw; Huguet, Lucie; Abdelmoula, Mustapha; Carteret, Cédric; Mullet, Martine; Jorand, Frédéric

2007-11-01

Microbiological reduction of a biogenic sulfated green rust (GR2(SO42-)), was examined using a sulfate reducing bacterium ( Desulfovibrio alaskensis). Experiments investigated whether GR2(SO42-) could serve as a sulfate source for D. alaskensis anaerobic respiration by analyzing mineral transformation. Batch experiments were conducted using lactate as the electron donor and biogenic GR2(SO42-) as the electron acceptor, at circumneutral pH in unbuffered medium. GR2(SO42-) transformation was monitored with time by X-ray diffraction (XRD), Transmission Mössbauer Spectroscopy (TMS), Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS), Transmission Electron Microscopy (TEM) and X-ray Photoelectron Spectroscopy (XPS). The reduction of sulfate anions and the formation of iron sulfur mineral were clearly identified by XPS analyses. TMS showed the formation of additional mineral as green rust (GR) and vivianite. XRD analyses discriminated the type of the newly formed GR as GR1. The formed GR1 was GR1(CO32-) as indicated by DRIFTS analysis. Thus, the results presented in this study indicate that D. alaskensis cells were able to use GR2(SO42-) as an electron acceptor. GR1(CO32-), vivianite and an iron sulfur compound were formed as a result of GR2(SO42-) reduction by D. alaskensis. Hence, in environments where geochemical conditions promote biogenic GR2(SO42-) formation, this mineral could stimulate the anaerobic respiration of sulfate reducing bacteria.

Brain-Derived Neurotrophic Factor Signaling Rewrites the Glucocorticoid Transcriptome via Glucocorticoid Receptor Phosphorylation

PubMed Central

Lambert, W. Marcus; Xu, Chong-Feng; Neubert, Thomas A.; Chao, Moses V.

2013-01-01

Abnormal glucocorticoid and neurotrophin signaling has been implicated in numerous psychiatric disorders. However, the impact of neurotrophic signaling on glucocorticoid receptor (GR)-dependent gene expression is not understood. We therefore examined the impact of brain-derived neurotrophic factor (BDNF) signaling on GR transcriptional regulatory function by gene expression profiling in primary rat cortical neurons stimulated with the selective GR agonist dexamethasone (Dex) and BDNF, alone or in combination. Simultaneous treatment with BDNF and Dex elicited a unique set of GR-responsive genes associated with neuronal growth and differentiation and also enhanced the induction of a large number of Dex-sensitive genes. BDNF via its receptor TrkB enhanced the transcriptional activity of a synthetic GR reporter, suggesting a direct effect of BDNF signaling on GR function. Indeed, BDNF treatment induces the phosphorylation of GR at serine 155 (S155) and serine 287 (S287). Expression of a nonphosphorylatable mutant (GR S155A/S287A) impaired the induction of a subset of BDNF- and Dex-regulated genes. Mechanistically, BDNF-induced GR phosphorylation increased GR occupancy and cofactor recruitment at the promoter of a BDNF-enhanced gene. GR phosphorylation in vivo is sensitive to changes in the levels of BDNF and TrkB as well as stress. Therefore, BDNF signaling specifies and amplifies the GR transcriptome through a coordinated GR phosphorylation-dependent detection mechanism. PMID:23878391

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Qun-Yi; Zhang, Meng; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai

Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K{sub i} = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids formore » the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.« less

The enhanced efficiency of graphene-silicon solar cells by electric field doping.

PubMed

Yu, Xuegong; Yang, Lifei; Lv, Qingmin; Xu, Mingsheng; Chen, Hongzheng; Yang, Deren

2015-04-28

The graphene-silicon (Gr-Si) Schottky junction solar cell has been recognized as one of the most low-cost candidates in photovoltaics due to its simple fabrication process. However, the low Gr-Si Schottky barrier height largely limits the power conversion efficiency of Gr-Si solar cells. Here, we demonstrate that electric field doping can be used to tune the work function of a Gr film and therefore improve the photovoltaic performance of the Gr-Si solar cell effectively. The electric field doping effects can be achieved either by connecting the Gr-Si solar cell to an external power supply or by polarizing a ferroelectric polymer layer integrated in the Gr-Si solar cell. Exploration of both of the device architecture designs showed that the power conversion efficiency of Gr-Si solar cells is more than twice of the control Gr-Si solar cells. Our study opens a new avenue for improving the performance of Gr-Si solar cells.

The Microtubule-Associated Protein Doublecortin-Like Regulates the Transport of the Glucocorticoid Receptor in Neuronal Progenitor Cells

PubMed Central

Fitzsimons, Carlos P.; Ahmed, Suaad; Wittevrongel, Christiaan F. W.; Schouten, Theo G.; Dijkmans, Thomas F.; Scheenen, Wim J. J. M.; Schaaf, Marcel J. M.; Ronald de Kloet, E.; Vreugdenhil, Erno

2008-01-01

In neuronal cells, activated glucocorticoid receptor (GR) translocates to the nucleus guided by the cytoskeleton. However, the detailed mechanisms underlying GR translocation remain unclear. Using gain and loss of function studies, we report here for the first time that the microtubule-associated protein doublecortin-like (DCL) controls GR translocation to the nucleus. DCL overexpression in COS-1 cells, neuroblastoma cells, and rat hippocampus organotypic slice cultures impaired GR translocation and decreased GR-dependent transcriptional activity, measured by a specific reporter gene assay, in COS-1 cells. Moreover, DCL and GR directly interact on microtubule bundles formed by DCL overexpression. A C-terminal truncated DCL with conserved microtubule-bundling activity did not influence GR translocation. In N1E-115 mouse neuroblastoma cells and neuronal progenitor cells in rat hippocampus organotypic slice cultures, laser-scanning confocal microscopy showed colabeling of endogenously expressed DCL and GR. In these systems, RNA-interference-mediated DCL knockdown hampered GR translocation. Thus, we conclude that DCL expression is tightly regulated to adequately control GR transport. Because DCL is primarily expressed in neuronal progenitor cells, our results introduce this microtubule-associated protein as a new modulator of GR signaling in this cell type and suggest the existence of cell-specific mechanisms regulating GR translocation to the nucleus. PMID:17975023

The effect of various concentration of tilapia (Oreochromis sp.) surimi for edible coating on the shelf-life of Pangasius sp. fillets

NASA Astrophysics Data System (ADS)

Purnama, M. A. P.; Agustono; Sahidu, A. M.

2018-04-01

Pangasius sp. fillets prone to deterioration the quality that will affect the appearance and the shelf life of fillets. The effort to extend the shelf life of fish fillet that is by using an edible coating. Surimi can be used as a protein-based edible coating because they have superior inhibitory and mechanical properties compared to the polysaccharides based material. Surimi can be made from freshwater tilapia (Oreochromis sp.) fish. The experimental design used was Completely Randomized Design (CRD) with five treatments of surimi (0 gr, 2 gr, 4 gr, 6 gr, 8 gr) with four replications. The results showed that Pangasius sp. fillets with an edible coating 8 gr surimi have the highest value in the organoleptic test. The pH testing on Pangasius sp. fillets with edible coating 2 gr, 4 gr, 6 gr, and 8 gr surimi from the 0th hour to 18th hour have increased but slower than Pangasius sp. fillets without edible coating surimi. The best value of Total Plate Count (TPC) test is in edible coating 6 gr and 8 gr surimi as it is in accordance with SNI 2696:2013 at room temperature storage until the 18th hours.

Complete Genome Sequence of the Alfalfa Symbiont Sinorhizobium/Ensifer meliloti Strain GR4.

PubMed

Martínez-Abarca, Francisco; Martínez-Rodríguez, Laura; López-Contreras, José Antonio; Jiménez-Zurdo, José Ignacio; Toro, Nicolás

2013-01-01

We present the complete nucleotide sequence of the multipartite genome of Sinorhizobium/Ensifer meliloti GR4, a predominant rhizobial strain in an agricultural field site. The genome (total size, 7.14 Mb) consists of five replicons: one chromosome, two expected symbiotic megaplasmids (pRmeGR4c and pRmeGR4d), and two accessory plasmids (pRmeGR4a and pRmeGR4b).

DOE Office of Scientific and Technical Information (OSTI.GOV)

Togi, Sumihito; Nakasuji, Misa; Muromoto, Ryuta

Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA), which interacts with cellular proteins, plays a central role in modification of viral and/or cellular gene expression. Here, we show that LANA associates with glucocorticoid receptor (GR), and that LANA enhances the transcriptional activity of GR. Co-immunoprecipitation revealed a physical interaction between LANA and GR in transiently transfected 293T and HeLa cells. In human B-lymphoma cells, LANA overexpression enhanced GR activity and cell growth suppression following glucocorticoid stimulation. Furthermore, confocal microscopy showed that activated GR was bound to LANA and accumulated in the nucleus, leading to an increase in binding of activatedmore » GR to the glucocorticoid response element of target genes. Taken together, KSHV-derived LANA acts as a transcriptional co-activator of GR. Our results might suggest a careful use of glucocorticoids in the treatment of patients with KSHV-related malignancies such as Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman disease. - Highlights: • KSHV-LANA enhances the transcriptional activity of GR in 293T and HeLa cells. • KSHV-LANA physically associates with GR. • KSHV-LANA enhances GR activation and cell growth suppression in human B-lymphocytes. • KSHV-LANA influences the nuclear retention and DNA binding activity of GR.« less

Purification and properties of glutathione reductase from liver of the anoxia-tolerant turtle, Trachemys scripta elegans.

PubMed

Willmore, William G; Storey, Kenneth B

2007-03-01

Glutathione reductase (GR) is a homodimeric flavoprotein that catalyzes the reduction of oxidized glutathione (GSSG) using NADPH as a cofactor. The enzyme is a major component of cellular defense mechanisms against oxidative injury. In this study, GR was purified from the liver of the anoxia-tolerant turtle, Trachemys scripta elegans. The overall fold purifications were 13.3- and 12.1-fold with final specific activities of 5.5 and 1.44 U/mg of protein for control and anoxic turtle GR, respectively. SDS-PAGE of purified turtle liver GR showed a single protein band at approximately 55 kDa. Reverse phase HPLC of turtle GR revealed a single peak that had the same retention time as yeast GR. No new isoform of GR was detected in liver of T. s. elegans during anoxia. The K (m) values of turtle GR for GSSG and NADPH was 44.6 and 6.82 microM, respectively, suggesting a substantially higher affinity of turtle GR toward GSSG than most other vertebrates. Unlike other human GR, NADP(+ )did not inhibit turtle GR activity. The activation energy of turtle GR, calculated from the slope of the Arrhenius plot, was 32.2 +/- 2.64 kJ/mol. Turtle GR had high activity under a broad pH range (having activity between pHs 4 and 10; optimal activity at pH 6.5) and the enzyme maintains activity under the pH drop that occurs under anoxic conditions. The high affinity of turtle GR suggests that turtles have high redox buffering capacity of tissues to protect against oxidative stress encountered during anoxia/reoxygenation.

Intracellular Serine Protease Inhibitor SERPINB4 Inhibits Granzyme M-Induced Cell Death

PubMed Central

de Koning, Pieter J. A.; Kummer, J. Alain; de Poot, Stefanie A. H.; Quadir, Razi; Broekhuizen, Roel; McGettrick, Anne F.; Higgins, Wayne J.; Devreese, Bart; Worrall, D. Margaret; Bovenschen, Niels

2011-01-01

Granzyme-mediated cell death is the major pathway for cytotoxic lymphocytes to kill virus-infected and tumor cells. In humans, five different granzymes (i.e. GrA, GrB, GrH, GrK, and GrM) are known that all induce cell death. Expression of intracellular serine protease inhibitors (serpins) is one of the mechanisms by which tumor cells evade cytotoxic lymphocyte-mediated killing. Intracellular expression of SERPINB9 by tumor cells renders them resistant to GrB-induced apoptosis. In contrast to GrB, however, no physiological intracellular inhibitors are known for the other four human granzymes. In the present study, we show that SERPINB4 formed a typical serpin-protease SDS-stable complex with both recombinant and native human GrM. Mutation of the P2-P1-P1′ triplet in the SERPINB4 reactive center loop completely abolished complex formation with GrM and N-terminal sequencing revealed that GrM cleaves SERPINB4 after P1-Leu. SERPINB4 inhibited GrM activity with a stoichiometry of inhibition of 1.6 and an apparent second order rate constant of 1.3×104 M−1s−1. SERPINB4 abolished cleavage of the macromolecular GrM substrates α-tubulin and nucleophosmin. Overexpression of SERPINB4 in tumor cells inhibited recombinant GrM-induced as well as NK cell-mediated cell death and this inhibition depended on the reactive center loop of the serpin. As SERPINB4 is highly expressed by squamous cell carcinomas, our results may represent a novel mechanism by which these tumor cells evade cytotoxic lymphocyte-induced GrM-mediated cell death. PMID:21857942

Engineering the unique 2D mat of graphene to achieve graphene-TiO2 nanocomposite for photocatalytic selective transformation: what advantage does graphene have over its forebear carbon nanotube?

PubMed

Zhang, Yanhui; Tang, Zi-Rong; Fu, Xianzhi; Xu, Yi-Jun

2011-09-27

Increasing interest has been devoted to synthesizing graphene (GR)-semiconductor nanocomposites as photocatalysts for potential applications, which is very similar to its forebear carbon nanotube (CNT)-semiconductor photocatalysts. Unfortunately, a thoughtful and inevitable comparison between GR- and CNT-semiconductors as photocatalysts is often neglected in literature. This situation may give incomplete or exaggerated information on the contribution role of GR to enhance the semiconductor photocatalytic activity, as compared to CNT. Thus, our knowledge regarding the specific advantage of GR over CNT on how to design more efficient GR-semiconductor nanocomposites and understanding the origin of their enhanced photocatalytic performance is far from satisfactory. By taking the TiO(2) semiconductor as an example, we conceptually demonstrate how to synthesize a more efficient GR-TiO(2) nanocomposite as a visible light photocatalyst toward selective oxidation of alcohols under mild conditions. Comparison between GR-TiO(2) and CNT-TiO(2) discloses the prominent advantage of GR over CNT on both controlling the morphology of GR-TiO(2) nanocomposite and enhancing the photocatalytic activity of TiO(2). This work clearly highlights the importance and necessity for a comparison investigation between GR- and CNT-semiconductors as photocatalysts, which will promote our in-depth fundamental understanding on the analogy and difference between GR and CNT on controlling the morphology of GR (or CNT)-semiconductor nanocomposites and enhancing the photocatalytic performance. Therefore, we appeal the photocatalysis community to pay attention to this respect rather than separately imposing hype on the miracle of GR in much the same way as its carbon forebears, which could significantly advance our rational fabrication of smart GR-semiconductor nanocomposites for artificial photosynthesis. © 2011 American Chemical Society

Complete Genome Sequence of the Alfalfa Symbiont Sinorhizobium/Ensifer meliloti Strain GR4

PubMed Central

Martínez-Abarca, Francisco; Martínez-Rodríguez, Laura; López-Contreras, José Antonio; Jiménez-Zurdo, José Ignacio

2013-01-01

We present the complete nucleotide sequence of the multipartite genome of Sinorhizobium/Ensifer meliloti GR4, a predominant rhizobial strain in an agricultural field site. The genome (total size, 7.14 Mb) consists of five replicons: one chromosome, two expected symbiotic megaplasmids (pRmeGR4c and pRmeGR4d), and two accessory plasmids (pRmeGR4a and pRmeGR4b). PMID:23409262

Investigation of thermal energy transport interface of hybrid graphene-carbon nanotube/polyethylene nanocomposites.

PubMed

Liu, Feng; Liu, Xuyang; Hu, Ning; Ning, Huiming; Atobe, Satoshi; Yan, Cheng; Mo, Fuhao; Fu, Shaoyun; Zhang, Jianyu; Wang, Yu; Mu, Xiaojing

2017-10-31

It is well known the thermal properties of three-dimensional (3-D) hybrid graphene (GR)-carbon nanotube (CNT) structures are not superior to that of the individual GR and CNT, however, the 3-D hybrid GR-CNT structures can effectively improve the thermal properties of polymer matrix. Therefore, understanding the thermal energy transport in the interface between polymer matrix and 3-D hybrid GR-CNT structure is essential. Here, the enhancement mechanism of interfacial thermal transport of hybrid GR-CNT structure was explored by applying non-equilibrium molecular dynamics (NEMD) simulations. Three different types of hybrid GR-CNT structures were built. The influences of CNT radius and CNT type for the hybrid GR-CNT on the interfacial thermal properties were also analyzed. Computational results show that among the three different types of hybrid GR-CNT structures, the Model-I, i.e., the covalent bond hybrid GR-CNT structures are of the best interfacial thermal properties. Meanwhile, the CNT radius of hybrid GR-CNT structure has a great influence on the interfacial thermal properties.

Glyphosate Effects on Plant Mineral Nutrition, Crop Rhizosphere Microbiota, and Plant Disease in Glyphosate-Resistant Crops

PubMed Central

2012-01-01

Claims have been made recently that glyphosate-resistant (GR) crops sometimes have mineral deficiencies and increased plant disease. This review evaluates the literature that is germane to these claims. Our conclusions are: (1) although there is conflicting literature on the effects of glyphosate on mineral nutrition on GR crops, most of the literature indicates that mineral nutrition in GR crops is not affected by either the GR trait or by application of glyphosate; (2) most of the available data support the view that neither the GR transgenes nor glyphosate use in GR crops increases crop disease; and (3) yield data on GR crops do not support the hypotheses that there are substantive mineral nutrition or disease problems that are specific to GR crops. PMID:23013354

Convergence of glycogen synthase kinase 3β and GR signaling in response to fluoxetine treatment in chronically stressed female and male rats.

PubMed

Mitic, Milos; Brkic, Zeljka; Lukic, Iva; Adzic, Miroslav

2017-08-30

Accumulating evidence strongly suggest that impaired glucocorticoid receptor (GR) signaling is involved in stress-related mood disorders, and nominate GR as a potential target for antidepressants (ADs). It is known that different classes of ADs affects the GR action via modifying its phosphorylation, while the mechanism through which ADs alter GR phosphorylation targeted by GSK3β, a kinase modulated via serotonin neurotransmission, are unclear. On this basis, we investigated whether GSK3β-GR signaling could be a convergence point of fluoxetine action on brain function and behavior, by examining its effect on GSK3β targeted-GR phosphorylation on threonine 171 (pGR171), and expression of GR-regulated genes in the hippocampus of female and male rats exposed to chronic isolation stress. Stress induced sex-specific GSK3β-targeted phosphorylation of pGR171 in the nucleus of the hippocampus of stressed animals. Namely, while in females stress triggered coupled action of GSK3β-pGR171 signaling, in males changes in pGR171 levels did not correspond to GSK3β activity. On the other hand, fluoxetine managed to up-regulate this pathway in sex-unbiased manner. Furthermore, fluoxetine reverted stress-induced changes in most of the analyzed genes in males, CRH, 5-HT1a and p11, while in females its effect was limited to CRH. These data further suggest that pGR171 signaling affects cellular localization of GR in response to chronic stress and fluoxetine in both sexes. Collectively, our results describe a novel convergence point between GR signaling and GSK3β pathway in rat hippocampus in response to stress and fluoxetine in both sexes and its involvement in fluoxetine-regulated brain function in males. Copyright © 2017 Elsevier B.V. All rights reserved.

Negative Correlation between the Diffusion Coefficient and Transcriptional Activity of the Glucocorticoid Receptor.

PubMed

Mikuni, Shintaro; Yamamoto, Johtaro; Horio, Takashi; Kinjo, Masataka

2017-08-25

The glucocorticoid receptor (GR) is a transcription factor, which interacts with DNA and other cofactors to regulate gene transcription. Binding to other partners in the cell nucleus alters the diffusion properties of GR. Raster image correlation spectroscopy (RICS) was applied to quantitatively characterize the diffusion properties of EGFP labeled human GR (EGFP-hGR) and its mutants in the cell nucleus. RICS is an image correlation technique that evaluates the spatial distribution of the diffusion coefficient as a diffusion map. Interestingly, we observed that the averaged diffusion coefficient of EGFP-hGR strongly and negatively correlated with its transcriptional activities in comparison to that of EGFP-hGR wild type and mutants with various transcriptional activities. This result suggests that the decreasing of the diffusion coefficient of hGR was reflected in the high-affinity binding to DNA. Moreover, the hyper-phosphorylation of hGR can enhance the transcriptional activity by reduction of the interaction between the hGR and the nuclear corepressors.

Ray-tracing in pseudo-complex General Relativity

NASA Astrophysics Data System (ADS)

Schönenbach, T.; Caspar, G.; Hess, P. O.; Boller, T.; Müller, A.; Schäfer, M.; Greiner, W.

2014-07-01

Motivated by possible observations of the black hole candidate in the centre of our Galaxy and the galaxy M87, ray-tracing methods are applied to both standard General Relativity (GR) and a recently proposed extension, the pseudo-complex GR (pc-GR). The correction terms due to the investigated pc-GR model lead to slower orbital motions close to massive objects. Also the concept of an innermost stable circular orbit is modified for the pc-GR model, allowing particles to get closer to the central object for most values of the spin parameter a than in GR. Thus, the accretion disc, surrounding a massive object, is brighter in pc-GR than in GR. Iron Kα emission-line profiles are also calculated as those are good observables for regions of strong gravity. Differences between the two theories are pointed out.

Autoregulation of human relaxin-2 gene expression critically involves relaxin and glucocorticoid receptor binding to glucocorticoid response half-sites in the relaxin-2 promoter.

PubMed

Dschietzig, Thomas; Bartsch, Cornelia; Wessler, Silja; Baumann, Gert; Stangl, Karl

2009-06-05

Relaxin peptides act in brain, reproductive and cardiovascular systems, kidneys, and connective tissue through different G protein-coupled receptors. We reported that human relaxin-2 and porcine relaxin are both agonists at the human glucocorticoid receptor (GR). Here, we investigated the possible auto-regulation of relaxin-2 gene expression via recently discovered GR-binding sites in the relaxin-2 promoter. We found that porcine relaxin increased the secretion of human relaxin-like immunoreactivity in HeLa and THP-1 cells. Silencing of GR gene expression completely abolished this effect whereas transfection of wild-type GR into naturally GR-devoid HT-29 cells established relaxin sensitivity. Relaxin was shown to stimulate CAT expression driven by different deletion constructs of the 5'-flanking region of the relaxin-2 promoter. In chromatin immunoprecipitation assays, we detected both GR and relaxin binding to the relaxin-2 promoter. Gel shift assays indicated binding of relaxin-activated GR to half-GREs located between 160 and 200 bp upstream of transcription start but not to the GRE at -900 bp. Relaxin bound to human GR and displaced established GR agonists. Immunofluorescence experiments visualized nuclear co-localization of relaxin and GR in response to relaxin. In conclusion, we have identified a positive auto-regulatory loop of human relaxin-2 expression which involves GR and relaxin/GR binding to half-GREs in the relaxin-2 promoter.

Carbon dioxide receptor genes in cotton bollworm Helicoverpa armigera

NASA Astrophysics Data System (ADS)

Xu, Wei; Anderson, Alisha

2015-04-01

Carbon dioxide (CO2) is important in insect ecology, eliciting a range of behaviours across different species. Interestingly, the numbers of CO2 gustatory receptors (GRs) vary among insect species. In the model organism Drosophila melanogaster, two GRs (DmelGR21a and DmelGR63a) have been shown to detect CO2. In the butterfly, moth, beetle and mosquito species studied so far, three CO2 GR genes have been identified, while in tsetse flies, four CO2 GR genes have been identified. In other species including honeybees, pea aphids, ants, locusts and wasps, no CO2 GR genes have been identified from the genome. These genomic differences may suggest different mechanisms for CO2 detection exist in different insects but, with the exception of Drosophila and mosquitoes, limited attention has been paid to the CO2 GRs in insects. Here, we cloned three putative CO2 GR genes from the cotton bollworm Helicoverpa armigera and performed phylogenetic and expression analysis. All three H. armigera CO2 GRs (HarmGR1, HarmGR2 and HarmGR3) are specifically expressed in labial palps, the CO2-sensing tissue of this moth. HarmGR3 is significantly activated by NaHCO3 when expressed in insect Sf9 cells but HarmGR1 and HarmGR2 are not. This is the first report characterizing the function of lepidopteran CO2 receptors, which contributes to our general understanding of the molecular mechanisms of insect CO2 gustatory receptors.

Improving the photocatalytic performance of graphene-TiO2 nanocomposites via a combined strategy of decreasing defects of graphene and increasing interfacial contact.

PubMed

Zhang, Yanhui; Zhang, Nan; Tang, Zi-Rong; Xu, Yi-Jun

2012-07-07

Incessant interest has been shown in the synthesis of graphene (GR)-semiconductor nanocomposites as photocatalysts aiming to utilize the excellent electron conductivity of GR to lengthen the lifetime of photoexcited charge carriers in the semiconductor and, hence, improve the photoactivity. However, research works focused on investigating how to make sufficient use of the unique electron conductivity of GR to design a more efficient GR-semiconductor photocatalyst have been quite lacking. Here, we show a proof-of-concept study on improving the photocatalytic performance of GR-TiO(2) nanocomposites via a combined strategy of decreasing defects of GR and improving the interfacial contact between GR and the semiconductor TiO(2). The GR-TiO(2) nanocomposite fabricated by this approach is able to make more sufficient use of the electron conductivity of GR, by which the lifetime and transfer of photoexcited charge carriers of GR-TiO(2) upon visible light irradiation will be improved more efficiently. This in turn leads to the enhancement of visible-light-driven photoactivity of GR-TiO(2) toward selective transformation of alcohols to corresponding aldehydes using molecular oxygen as a benign oxidant under ambient conditions. It is anticipated that our current work would inform ongoing efforts to exploit the rational design of smart, more efficient GR-semiconductor photocatalysts for conversion of solar to chemical energy by heterogeneous photocatalysis.

Differential effects of the new glucocorticoid receptor antagonist ORG 34517 and RU486 (mifepristone) on glucocorticoid receptor nuclear translocation in the AtT20 cell line.

PubMed

Peeters, B W M M; Ruigt, G S F; Craighead, M; Kitchener, P

2008-12-01

Glucocorticoid agonists bind to cytoplasmic glucocorticoid receptors (GRs) and subsequently translocate as an agonist-GR complex into the nucleus. In the nucleus the complex regulates the transcription of target genes. A number of GR antagonists (RU486, progesterone, RU40555) have also been shown to induce receptor translocation. These compounds should be regarded as partial agonists. For the nonselective progesterone receptor antagonists, RTI3021-012 and RTI3021-022, it was shown that GR antagonism is possible without the induction of GR translocation. In the present studies, the new GR antagonist, ORG 34517, was investigated for its potential to induce GR translocation and to antagonize corticosterone-induced GR translocation in the AtT20 (mouse pituitary) cell line. ORG 34517 was compared to RU486. In contrast to RU486, ORG 34517 (at doses up to 3 x 10(-7) M) did not induce GR translocation, but was able to block corticosterone (3 x 10(-8) M) induced GR translocation. ORG 34517 can be regarded as a true competitive GR antagonist without partial agonistic activities.

Xenobiotics and the Glucocorticoid Receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gulliver, Linda S M, E-mail: linda.gulliver@otago.

Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmunemore » processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid Receptor. • Involvement of Glucocorticoid Receptor in multiple pathologies. • Novel xenobiotic ligands for Glucocorticoid Receptor. • Potential for multifaceted Glucocorticoid Receptor-targeted pharmacological interventions.« less

Low serum albumin may predict the need for gastric resection in patients with perforated peptic ulcer.

PubMed

Seow, J G; Lim, Y R; Shelat, V G

2017-06-01

Perforated peptic ulcer (PPU) is a common surgical emergency and treatment involves omental patch repair (PR). Gastric resection (GR) is reserved for difficult pathologies. We audit the outcomes of GR at our institution and evaluate the pre-operative factors predicting the need for GR. This is a single-institution, retrospective study of patients with PPU who underwent surgery from 2004 to 2012. Demographics, clinical presentation and intra-operative findings were studied to identify factors predicting the need for GR in PPU. An audit of clinical outcomes and mortality for all patients with GR is reported. 537 (89.6 %) patients underwent PR and 62 (10.4 %) patients GR. Old age (p < 0.0001), female sex (p = 0.0123), non-steroidal anti-inflammatory drugs (NSAIDs) usage (p = 0.0008), previous history of peptic ulcer disease (PUD) (p = 0.0159), low hemoglobin (p < 0.0001), low serum albumin (p < 0.0001), high serum creatinine (p = 0.0030), high urea (p = 0.0006) and large ulcer size (p < 0.0001) predict the need for GR. On multivariate analysis only low serum albumin (OR 5.57, 95 % CI 1.56-19.84, p = 0.008) predicted the need for GR. The presence of Helicobacter pylori infection was protective against GR (OR 0.25, 95 %CI 0.14-0.44, p < 0.0001). Morbidity and mortality of GR was 27.7 and 24.2 %, respectively. GR is needed in one in ten cases of PPU. Low serum albumin predicted the need for GR on multivariate analysis. Morbidity and mortality of GR remains high.

Pattern of heat shock factor and heat shock protein expression in lymphocytes of bipolar patients: increased HSP70-glucocorticoid receptor heterocomplex.

PubMed

Bei, E S; Salpeas, V; Alevizos, B; Anagnostara, C; Pappa, D; Moutsatsou, P

2013-11-01

Bipolar disorder (BD), a stress-related disease, is characterized by altered glucocorticoid receptor (GR) signalling. Stress response includes activation of heat shock factor (HSF) and subsequent heat shock protein (HSP) synthesis which regulate GR folding and function. The objective of this study was to investigate the possible role of HSFs, HSPs and their interaction with GR in BD. We applied immunoprecipitation, SDS-PAGE/Western blot analysis and electrophoretic mobility shift assay (EMSA) in lymphocytes (whole cell or nuclear extracts) from BD patients and healthy subjects and determined the HSPs (HSP90 and HSP70), the heterocomplexes HSP90-GR and HSP70-GR, the HSFs (HSF1 and HSF4) as well as the HSF-DNA binding. The HSP70-GR heterocomplex was elevated (p < 0.05) in BD patients vs healthy subjects, and nuclear HSP70 was reduced (p ≤ 0.01) in bipolar manic patients. Protein levels of HSF1, HSF4, HSP90, HSP90-GR heterocomplex, and HSF-DNA binding remained unaltered in BD patients vs healthy subjects. The corresponding effect sizes (ES) indicated a large ES for HSP70-GR, HSP70, HSF-DNA binding and HSF4, and a medium ES for HSP90, HSF1 and HSP90-GR between healthy subjects and bipolar patients. Significant correlations among HSFs, HSPs, GR and HSP70-GR heterocomplex were observed in healthy subjects, which were abrogated in bipolar patients. The higher interaction between GR and HSP70 and the disturbances in the relations among heat shock response parameters and GR as observed in our BD patients may provide novel insights into the contribution of these factors in BD aetiopathogenesis. Copyright © 2013. Published by Elsevier Ltd.

Simultaneous determination of dopamine and uric acid using layer-by-layer graphene and chitosan assembled multilayer films.

PubMed

Weng, Xuexiang; Cao, Qingxue; Liang, Lixin; Chen, Jianrong; You, Chunping; Ruan, Yongmin; Lin, Hongjun; Wu, Lanju

2013-12-15

Multilayer films containing graphene (Gr) and chitosan (CS) were prepared on glassy carbon electrodes with layer-by-layer (LBL) assembly technique. After being characterized with cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM), the electrochemical sensor based on the resulted films was developed to simultaneously determine dopamine (DA) and uric acid (UA). The LBL assembled electrode showed excellent electrocatalytic activity towards the oxidation of DA and UA. In addition, the self-assembly electrode possessed an excellent sensing performance for detection of DA and UA with a linear range from 0.1 μM to 140 µM and from 1.0 µM to 125 µM with the detection limit as low as 0.05 µM and 0.1 µM based on S/N=3, respectively. © 2013 Elsevier B.V. All rights reserved.

Improvement of efficiency in graphene/gallium nitride nanowire on Silicon photoelectrode for overall water splitting

NASA Astrophysics Data System (ADS)

Bae, Hyojung; Rho, Hokyun; Min, Jung-Wook; Lee, Yong-Tak; Lee, Sang Hyun; Fujii, Katsushi; Lee, Hyo-Jong; Ha, Jun-Seok

2017-11-01

Gallium nitride (GaN) nanowires are one of the most promising photoelectrode materials due to their high stability in acidic and basic electrolytes, and tunable band edge potentials. In this study, GaN nanowire arrays (GaN NWs) were prepared by molecular beam epitaxy (MBE); their large surface area enhanced the solar to hydrogen conversion efficiency. More significantly, graphene was grown by chemical vapor deposition (CVD), which enhanced the electron transfer between NWs for water splitting and protected the GaN NW surface. Structural characterizations of the prepared composite were performed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The photocurrent density of Gr/GaN NWs exhibited a two-fold increase over pristine GaN NWs and sustained water splitting up to 70 min. These improvements may accelerate possible applications for hydrogen generation with high solar to hydrogen conversion efficiency.

Crystalline Bacterial Surface Layer (S-Layer) Opens Golden Opportunities for Nanobiotechnology in Textiles.

PubMed

Asadi, Narges; Chand, Nima; Rassa, Mehdi

2015-12-01

This study focuses on the successful recrystallization of bacterial S-layer arrays of the Lactobacillus acidophilus ATCC 4356 at textile surfaces to create a novel method and material. Optimum bacterial growth was obtained at approximately 45 °C, pH 5.0, and 14 h pi. The cells were resuspended in guanidine hydrochloride and the 43 kDa S-protein was dialyzed and purified. The optimum reassembly on the polypropylene fabric surface in terms of scanning electron microscopy (SEM), reflectance, and uniformity (spectrophotometry) was obtained at 30 °C, pH 5.0 for 30 minutes in the presence of 2 gr/l (liquor ratio; 1:40) of the S-protein. Overall, our data showed that the functional aspects and specialty applications of the fabric would be very attractive for the textile and related sciences, and result in advanced technical textiles.

Comparison of Notch Strength between Gr/PEEK (APC-1 and APC-2) and Gr/Epoxy Composite Materials at Elevated Temperature.

DTIC Science & Technology

1985-12-01

J ub. we Jr. Captain, USARt Z712 AFIT/GAE/AA/85D- 12 Iv COMPARISON OF NOTCH STRENGTH BETWEEN GR/PEEK (APC-1 AND APC-2) AND GR/EPOXY COMPOSITE ...85D-12 COMPARISON OF NOTCH STRENGTH BETWEEN GR/PEEK _ (APC-1 AND APC-2) AND GR/EPOXY COMPOSITE MATERIAL AT ELEVATED TEMPERATURE THESIS Presented to the...unlimited Preface In this experimental investigation, the reduction of strength for notched composite laminates of Aromatic Polymer Composite , APC-2

Cobalt nanoparticles/nitrogen-doped graphene with high nitrogen doping efficiency as noble metal-free electrocatalysts for oxygen reduction reaction.

PubMed

Liang, Jingwen; Hassan, Mehboob; Zhu, Dongsheng; Guo, Liping; Bo, Xiangjie

2017-03-15

Nitrogen-doped graphene (N/GR) has been considered as active metal-free electrocatalysts for oxygen reduction reaction (ORR). However, the nitrogen (N) doping efficiency is very low and only few N atoms are doped into the framework of GR. To boost the N doping efficiency, in this work, a confined pyrolysis method with high N doping efficiency is used for the preparation of cobalt nanoparticles/nitrogen-doped GR (Co/N/GR). Under the protection of SiO 2 , the inorganic ligand NH 3 in cobalt amine complex ([Co(NH 3 ) 6 ] 3+ ) is trapped in the confined space and then can be effectively doped into the framework of GR without the introduction of any carbon residues. Meanwhile, due to the redox reaction between the cobalt ions and carbon atoms of GR, Co nanoparticles are supported into the framework of N/GR. Due to prevention of GR layer aggregation with SiO 2 , the Co/N/GR with high dispersion provides sufficient surface area and maximum opportunity for the exposure of Co nanoparticles and active sites of N dopant. By combination of enhanced N doping efficiency, Co nanoparticles and high dispersion of GR sheets, the Co/N/GR is remarkably active, cheap and selective noble-metal free catalysts for ORR. Copyright © 2016 Elsevier Inc. All rights reserved.

Selected physico-mechanical characteristics of cryogenic and ambient ground turmeric

NASA Astrophysics Data System (ADS)

Barnwal, Pradyuman; Mohite, Ashish M.; Singh, Krishna K.; Kumar, Pankaj

2014-03-01

In this communication, selected physicomechanical characteristics of ground turmeric (cv. Prabha) were investigated for cryogenic and ambient grinding conditions of turmeric at different moisture contents (4, 6, 8 and 10% w.b.). A cryogenic grinder (Model: 100 UPZ, Hosokawa Alpine, Germany) and a micro pulverizer (hammer mill) were used for cryogenic and ambient grinding, respectively. The ground turmeric was graded in three grades viz. Gr-I, Gr-II and Gr-III with a sieve shaker using BSS Nos. 40, 85 and pan, respectively. Tap densities for cryogenic and ambient ground turmeric decreased from 678.7 (Gr-I) to 546.7 kgm-3 (Gr-III) and from 642.3 (Gr-I) to 468.6 kgm-3 (Gr-III), respectively, with the moisture increase. The angle of repose for cryogenic and ambient ground turmeric increased linearly from 26.85 (Gr-I) to 34.0° (Gr-III) and from 23.10 (Gr-I) to 28.06° (Gr-III), respectively with the increase in moisture content. The static coefficient of friction was the highest on plywood surface followed by mild steel sheet and galvanized iron sheet. The cryoground samples were found better in colour. Thermal conductivity of cryo-ground samples was higher than that of ambient ground samples. These physico-mechanical characteristics of cryogenic and ambient ground turmeric will be helpful for packaging, handling, and storage.

Corticosteroid receptor gene expression is related to sex and social behaviour in a social fish.

PubMed

O'Connor, Constance M; Rodela, Tammy M; Mileva, Viktoria R; Balshine, Sigal; Gilmour, Kathleen M

2013-03-01

Circulating corticosteroids have been related to social status in a variety of species. However, our understanding of corticosteroid receptor expression and its relationship with sociality is still in its infancy. Knowledge of variation in receptor expression is critical to understand the physiological relevance of differences in circulating corticosteroid concentrations. In this study, we examined corticosteroid receptor gene expression in relation to dominance rank, sex, and social behaviour in the highly social cichlid fish, Neolamprologus pulcher. We examined the relative gene expression of the three known teleost corticosteroid receptors: glucocorticoid receptor 1 (GR1), glucocorticoid receptor 2 (GR2), and the mineralocorticoid receptor (MR) in liver and brain tissue of dominant and subordinate N. pulcher males and females. Phylogenetic analysis revealed the N. pulcher gene originally described as GR2, clustered with other teleost GR1 genes, while the originally-described N. pulcher GR1 gene clustered with the GR2 genes of other teleosts. Therefore we propose a change in the original nomenclature of the N. pulcher GRs: GR1 (formerly GR2) and GR2 (formerly GR1) and adopt this new nomenclature throughout this manuscript. Liver MR transcript levels were higher in males than females, and positively related to submissive behaviour. Liver GR2 (formerly GR1) transcript levels were also higher in males than females. Collectively, the results demonstrate sex differences in corticosteroid receptor abundance, and suggest tissue- and receptor-specific roles for corticosteroid receptors in mediating aspects of social behaviour. Copyright © 2012. Published by Elsevier Inc.

Pseudo and true visible light photocatalytic activity of nanotube titanic acid/graphene composites

NASA Astrophysics Data System (ADS)

Wang, Xiaodong; Liu, Xiaogang; Xue, Xiaoxiao; Pan, Hui; Zhang, Min; Li, Qiuye; Yu, Laigui; Yang, Jianjun; Zhang, Zhijun

2013-09-01

Nanotube titanic acid/graphene (NTA/Gr) composites were prepared by an easy hydrothermal treatment of graphene oxide (GO) and NTA in a mixed solvent of ethanol-water. As-prepared NTA/Gr composites and GO were characterized by means of Fourier transform infrared spectrometry, X-ray diffraction, diffuse-reflection spectrometry, thermal analysis, and transmission electron microscopy. Besides, the photocatalytic activities of as-prepared NTA/Gr composites were evaluated by monitoring the degradation of methyl orange (MO) under visible light irradiation. It has been found that extending hydrothermal reaction time (24 h instead of 3 h) leads to great changes in the morphology and crystal structure of as-prepared composites. Namely, the orthorhombic NTA (ca. 10 nm in diameter) in the composite transformed to anatase TiO2 particle (ca. 20-30 nm in diameter) while the Gr sheets (with micrometers-long wrinkles) in it transformed to a few Gr fragments (ca. 50 nm in diameter). Correspondingly, the NTA/Gr composite transformed to titanium dioxide/graphene (TiO2/Gr) composite. In the meantime, pure GO only has adsorption effect but it has no photocatalytic activity in the visible light region. Nevertheless, increasing Gr ratio results in enhanced visible light absorption capability and photocatalytic activity of NTA/Gr composites as well as the TiO2/Gr composites. This demonstrates that the true visible light photocatalytic activity of NTA/Gr composites as well as the TiO2/Gr composites for the degradation of MO is not as excellent as expected, and their high apparent activity is attributed to the strong adsorption of MO on the composites.

Controls of soil hydraulic characteristics on modeling groundwater recharge under different climatic conditions

NASA Astrophysics Data System (ADS)

Wang, Tiejun; Franz, Trenton E.; Zlotnik, Vitaly A.

2015-02-01

To meet the challenge of estimating spatially varying groundwater recharge (GR), increasing attention has been given to the use of vadose zone models (VZMs). However, the application of this approach is usually constrained by the lack of field soil hydraulic characteristics (SHCs) required by VZMs. To tackle this issue, SHCs based on the van Genuchten or Brooks-Corey model are generally estimated by pedotransfer functions or taken from texture based class averages. With the increasing use of this method, it is important to elucidate the controls of SHCs on computing GR mostly due to the high nonlinearity of the models. In this study, it is hypothesized that the nonlinear controls of SHCs on computing GR would vary with climatic conditions. To test this hypothesis, a widely used VZM along with two SHCs datasets for sand and loamy sand is used to compute GR at four sites in the continental Unites States with a significant gradient of precipitation (P). The simulation results show that the distribution patterns of mean annual GR ratios (GR ‾ / P ‾ , where GR ‾ and P ‾ are mean annual GR and P, respectively) vary considerably across the sites, largely depending on soil texture and climatic conditions at each site. It is found that GR ‾ / P ‾ is mainly controlled by the shape factor n in the van Genuchten model and the nonlinear effect of n on GR ‾ / P ‾ varies with climatic conditions. Specifically, for both soil textures, the variability in GR ‾ / P ‾ is smallest at the Andrews Forest with the highest P ‾ (191.3 cm/year) and GR ‾ / P ‾ is least sensitive to n; whereas, the variability in GR ‾ / P ‾ at the Konza Prairie (P ‾ = 84.2 cm/year) is the largest and GR ‾ / P ‾ is most sensitive to n. With further decreasing P ‾ , the nonlinear effect of n weakens at the Barta Brothers (P ‾ = 57.3 cm/year) and Sevilleta (P ‾ = 20.3 cm/year), leading to smaller GR ‾ / P ‾ variability at those two sites than at the Konza Prairie. The results also reveal that GR ‾ / P ‾ in finer soils with smaller n values decreases more rapidly with decreasing P ‾ .

Meat quality, proximate composition and muscle fatty acid profile of young llamas (Lama glama) supplemented with hay or concentrate during the dry season.

PubMed

Mamani-Linares, L W; Gallo, C B

2014-01-01

Thirty llamas were used to study the effect of a 90 day feed supplementation on meat quality, chemical composition and muscle fatty acid profile. Treatments were: GR=llama on native pasture until slaughter; GR+SH=like GR, but with overnight free access to barley/alfalfa hay; and GR+SC=like GR, but with overnight free access to a wheat bran/sorghum grain concentrate. The supplementation had no effect on postmortem pH and temperature decline in the Longissimus lumborum muscle (LLM), cooking losses nor Warner-Bratzler shear force values (P>0.05). Meat from GR+SC llama had higher fat content in LLM (P<0.05) compared to GR and GR+SH llama. Intramuscular fat from GR+SH llama showed higher (P<0.01) proportions of polyunsaturated fatty acids, higher (P<0.05) polyunsaturated fatty acids/saturated fatty acids and desirable fatty acids ratio, lower (P<0.05) omega-6/omega-3 (n-6/n-3) ratio, and higher (P<0.01) conjugated linoleic acid. © 2013.

Global Precipitation Measurement (GPM) Validation Network

NASA Technical Reports Server (NTRS)

Schwaller, Mathew; Moris, K. Robert

2010-01-01

The method averages the minimum TRMM PR and Ground Radar (GR) sample volumes needed to match-up spatially/temporally coincident PR and GR data types. PR and GR averages are calculated at the geometric intersection of the PR rays with the individual Ground Radar(GR)sweeps. Along-ray PR data are averaged only in the vertical, GR data are averaged only in the horizontal. Small difference in PR & GR reflectivity high in the atmosphere, relatively larger differences. Version 6 TRMM PR underestimates rainfall in the case of convective rain in the lower part of the atmosphere by 30 to 40 percent.

Structure of Greyhound hemoglobin: origin of high oxygen affinity.

PubMed

Bhatt, Veer S; Zaldívar-López, Sara; Harris, David R; Couto, C Guillermo; Wang, Peng G; Palmer, Andre F

2011-05-01

This study presents the crystal structure of Greyhound hemoglobin (GrHb) determined to 1.9 Å resolution. GrHb was found to crystallize with an α₁β₁ dimer in the asymmetric unit and belongs to the R2 state. Oxygen-affinity measurements combined with the fact that GrHb crystallizes in the R2 state despite the high-salt conditions used for crystallization strongly indicate that GrHb can serve as a model high-oxygen-affinity hemoglobin (Hb) for higher mammals, especially humans. Structural analysis of GrHb and its comparison with the R2-state of human Hb revealed several regions that can potentially contribute to the high oxygen affinity of GrHb and serve to rationalize the additional stability of the R2-state of GrHb. A previously well studied hydrophobic cluster of bar-headed goose Hb near α119 was also incorporated in the comparison between GrHb and human Hb. Finally, a structural comparison with generic dog Hb and maned wolf Hb was conducted, revealing that in contrast to GrHb these structures belong to the R state of Hb and raising the intriguing possibility of an additional allosteric factor co-purifying with GrHb that can modulate its quaternary structure.

Role of the chromatin landscape and sequence in determining cell type-specific genomic glucocorticoid receptor binding and gene regulation

PubMed Central

Huska, Matthew R.; Jurk, Marcel; Schöpflin, Robert; Starick, Stephan R.; Schwahn, Kevin; Cooper, Samantha B.; Yamamoto, Keith R.; Thomas-Chollier, Morgane; Vingron, Martin

2017-01-01

Abstract The genomic loci bound by the glucocorticoid receptor (GR), a hormone-activated transcription factor, show little overlap between cell types. To study the role of chromatin and sequence in specifying where GR binds, we used Bayesian modeling within the universe of accessible chromatin. Taken together, our results uncovered that although GR preferentially binds accessible chromatin, its binding is biased against accessible chromatin located at promoter regions. This bias can only be explained partially by the presence of fewer GR recognition sequences, arguing for the existence of additional mechanisms that interfere with GR binding at promoters. Therefore, we tested the role of H3K9ac, the chromatin feature with the strongest negative association with GR binding, but found that this correlation does not reflect a causative link. Finally, we find a higher percentage of promoter–proximal GR binding for genes regulated by GR across cell types than for cell type-specific target genes. Given that GR almost exclusively binds accessible chromatin, we propose that cell type-specific regulation by GR preferentially occurs via distal enhancers, whose chromatin accessibility is typically cell type-specific, whereas ubiquitous target gene regulation is more likely to result from binding to promoter regions, which are often accessible regardless of cell type examined. PMID:27903902

Single Nucleotide Variations of the Human GR Gene Manifested as Pathologic Mutations or Polymorphisms.

PubMed

Kino, Tomoshige

2018-05-11

The human genome contains numerous single nucleotide variations (SNVs), and the human GR gene harbors ∼450 of these genetic changes. Among them, extremely rare non-synonymous variants known as pathologic GR gene mutations develop a characteristic pathologic condition, familial/sporadic generalized glucocorticoid resistance syndrome, by replacing the amino acids critical for GR protein structure and functions, whereas others known as pathologic polymorphisms develop mild manifestations recognized mainly at population bases by changing the GR activities slightly. Recent progress on the structural analysis to the GR protein and subsequent computer-based structural simulation revealed details of the molecular defects caused by such pathologic GR gene mutations, including their impact on the receptor interaction to ligands, nuclear receptor coactivators (NCoAs) or DNA glucocorticoid response elements (GREs). Indeed, those found in the GR ligand-binding domain significantly damage protein structure of the ligand-binding pocket and/or the activation function-2 transactivation domain and change their molecular interaction to glucocorticoids or the LxxLL signature motif of NCoAs. Two mutations found in GR DBD also affect interaction of the mutant receptors to GRE DNA by affecting the critical amino acid for the interaction or changing local hydrophobic circumstance. In this review, we discuss recent findings on the structural simulation of the pathologic GR mutants in connection to their functional and clinical impacts along with brief explanation to recent research achievement on the GR polymorphisms.

Central glucocorticoid receptors regulate the upregulation of spinal cannabinoid-1 receptors after peripheral nerve injury in rats.

PubMed

Wang, Shuxing; Lim, Grewo; Mao, Ji; Sung, Backil; Yang, Liling; Mao, Jianren

2007-09-01

Previous studies have shown that peripheral nerve injury upregulated both glucocorticoid receptors (GR) and cannabinoid-1 receptors (CB1R) within the spinal cord dorsal horn in rats. However, the relationship between the expression of spinal GR and CB1R after nerve injury remains unclear. Here, we examined the hypothesis that the upregulation of spinal CB1R induced by chronic constriction nerve injury (CCI) in rats would be regulated by spinal GR. CCI induced the upregulation of spinal CB1R primarily within the ipsilateral spinal cord dorsal horn as revealed by Western blot and immunohistochemistry. The expression of CB1R in CCI rats was substantially attenuated by intrathecal treatment with either the GR antagonist RU38486 or a GR antisense oligonucleotide given twice daily for postoperative day 1-6, whereas the expression of spinal CB1R was enhanced following intrathecal administration of a GR sense oligonucleotide twice daily for postoperative day 1-6. Furthermore, the upregulation of spinal CB1R after nerve injury was prevented in adrenalectomized rats, which was at least partially restored with the intrathecal administration of an exogenous GR agonist dexamethasone, indicating that corticosteroids (endogenous GR agonists) were critical to spinal GR actions. Since the development of neuropathic pain behaviors in CCI rats was attenuated by either RU38486 or a GR antisense oligonucleotide, these results suggest that CB1R is a downstream target for spinal GR actions contributory to the mechanisms of neuropathic pain.

Microfacies and biofabric of nummulite accumulations (Bank) from the Eocene deposits of Western Alborz (NW Iran)

NASA Astrophysics Data System (ADS)

Hadi, Mehdi; Mosaddegh, Hossein; Abbassi, Nasrollah

2016-12-01

The nummulite bank from the Eocene Ziarat Formation is described for the first time from Alborz, Iran, enhancing the record of these nummulite-rich accumulations in the Eocene of the circum-Tethyan carbonate platform. Five microfacies types have been defined within the shallow-water carbonate deposits of the Ziarat formation located in the western Alborz zone. Microfacies type 1 contains the most diverse Alveolina species associated with predominance of Nummulites A-forms. Microfacies type 2 is characterized by the presence of bivalve (oysters) fragments. Microfacies type 3 is supported by the high abundance of nummulitids. Microfacies type 4 is dominated by the occurrence of encrusting foraminifera-algal with flat growth forms that are mainly formed within the acervulinids assemblage. Finally, there is the presence of orthophragminids and nummuitids represented by microfacies type 5. Microfacies data obtained from the investigation area show that nummulite banks were formed within the back, core and fore-bank palaeoenvironments. The classification method of this paper is based on use biometric, biofabric, taphonomic and palaeoecological characteristics of larger benthic foraminifera. In addition, the calculated intraskeletal porosity by the use of numerous sections and FE-SEM images of Nummulites tests were displacement of tests in order to achieve a better understanding of paleo-conditions that occurred during sedimentation. We conclude that differences among bank frameworks suggest that small biconvex A-forms of Nummulites tests along with alveolinids were living in shallow, euphotic waters, whereas robust and ovate nummulitid tests thrived and concentrated in the intermediate (40-80 m) water with biofabrics in the min-scales, which indicates the influence of waves and currents in combination with wave-winnowing processes. More distal accumulations, the fore-bank were characterized by orthophragminid and nummulitid tests in the deeper part of the photic zone. The larger benthic foraminifera, as confirmed by Discocyclina javana (VERBEEK), D. cf. dispansa (SOWERBY), Assilina ex. gr. exponens (SOWERBY), Nummulites ex. gr. globulus)SCHAUB(, Alveolina ellipsoidalis (SCHWAGER), A. subpyrenaica (LEYMERIE), A. pisiformis (HOTTINGER), A. tumida (HOTTINGER), A. cemali (SIREL et ACAR), A. laxa (HOTTINGER), A. ex. gr. cremae)CHECCHIA-RISPOLI(, suggest the early Ilerdian-Middle Eocene age of these sediments.

Glucocorticoid receptor gene expression and promoter CpG modifications throughout the human brain.

PubMed

Cao-Lei, Lei; Suwansirikul, Songkiet; Jutavijittum, Prapan; Mériaux, Sophie B; Turner, Jonathan D; Muller, Claude P

2013-11-01

Glucocorticoids and the glucocorticoid (GR) and mineralocorticoid (MR) receptors have been implicated in many processes, particularly in negative feedback regulation of the hypothalamic-pituitary-adrenal axis. Epigenetically programmed GR alternative promoter usage underlies transcriptional control of GR levels, generation of GR 3' splice variants, and the overall GC response in the brain. No detailed analysis of GR first exons or GR transcript variants throughout the human brain has been reported. Therefore we investigated post mortem tissues from 28 brain regions of 5 individuals. GR first exons were expressed throughout the healthy human brain with no region-specific usage patterns. First exon levels were highly inter-correlated suggesting that they are co-regulated. GR 3' splice variants (GRα and GR-P) were equally distributed in all regions, and GRβ expression was always low. GR/MR ratios showed significant differences between the 28 tissues with the highest ratio in the pituitary gland. Modification levels of individual CpG dinucleotides, including 5-mC and 5-hmC, in promoters 1D, 1E, 1F, and 1H were low, and diffusely clustered; despite significant heterogeneity between the donors. In agreement with this clustering, sum modification levels rather than individual CpG modifications correlated with GR expression. Two-way ANOVA showed that this sum modification was both promoter and brain region specific, but that there was however no promoter*tissue interaction. The heterogeneity between donors may however hide such an interaction. In both promoters 1F and 1H modification levels correlated with GRα expression suggesting that 5-mC and 5-hmC play an important role in fine tuning GR expression levels throughout the brain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sequence family variant loss from the AZFc interval of the human Y chromosome, but not gene copy loss, is strongly associated with male infertility

PubMed Central

Machev, N; Saut, N; Longepied, G; Terriou, P; Navarro, A; Levy, N; Guichaoua, M; Metzler-Guillemai..., C; Collignon, P; Frances, A; Belougne, J; Clemente, E; Chiaroni, J; Chevillard, C; Durand, C; Ducourneau, A; Pech, N; McElreavey, K; Mattei, M; Mitchell, M

2004-01-01

Background: Complete deletion of the complete AZFc interval of the Y chromosome is the most common known genetic cause of human male infertility. Two partial AZFc deletions (gr/gr and b1/b3) that remove some copies of all AZFc genes have recently been identified in infertile and fertile populations, and an association study indicates that the resulting gene dose reduction represents a risk factor for spermatogenic failure. Methods: To determine the incidence of various partial AZFc deletions and their effect on fertility, we combined quantitative and qualitative analyses of the AZFc interval at the DAZ and CDY1 loci in 300 infertile men and 399 control men. Results: We detected 34 partial AZFc deletions (32 gr/gr deletions), arising from at least 19 independent deletion events, and found gr/gr deletion in 6% of infertile and 3.5% of control men (p>0.05). Our data provide evidence for two large AZFc inversion polymorphisms, and for relative hot and cold spots of unequal crossing over within the blocks of homology that mediate gr/gr deletion. Using SFVs (sequence family variants), we discriminate DAZ1/2, DAZ3/4, CDY1a (proximal), and CDY1b (distal) and define four types of DAZ-CDY1 gr/gr deletion. Conclusions: The only deletion type to show an association with infertility was DAZ3/4-CDY1a (p = 0.042), suggesting that most gr/gr deletions are neutral variants. We see a stronger association, however, between loss of the CDY1a SFV and infertility (p = 0.002). Thus, loss of this SFV through deletion or gene conversion could be a major risk factor for male infertility. PMID:15520406

High-fat diet-induced hepatic steatosis reduces glucagon receptor content in rat hepatocytes: potential interaction with acute exercise

PubMed Central

Charbonneau, Alexandre; Unson, Cecilia G; Lavoie, Jean-Marc

2007-01-01

Studies have revealed that high-fat (HF) diets promote hyperglycaemia, whole-body insulin resistance and non-alcoholic fatty liver disease (NAFLD). Recently, hepatic glucagon resistance has been shown to occur in rats fed a HF diet. More precisely, diet-induced obesity (DIO) reduces the number of hepatic plasma membrane glucagon receptors (GR), which results in a diminished response to glucagon during a hyperglucagonaemic clamp. The present study was undertaken to test the hypothesis that a HF-DIO is associated with a desensitization and destruction of the hepatic GR. We also hypothesized that a single bout of endurance exercise would modify the GR cellular distribution under our DIO model. Male rats were either fed a standard (sd) or a HF diet for two weeks. Each group was subdivided into a non-exercised (Rest) and an acute exercised (EX) group. The HF diet resulted in a reduction of total hepatic GR (55%) and hepatic plasma membrane GR protein content (20%). These changes were accompanied by a significant increase in endosomal and lysosomal GR content with the feeding of a HF diet. The reduction of GR plasma membrane as well as the increase in endosomal GR was strongly correlated with an increase of PKC-α, suggesting a role of PKC-α in GR desensitization. EX increased significantly PKC-α protein content in both diets, suggesting a role of PKC-α in EX-induced GR desensitization. The present results suggest that liver lipid infiltration plays a role in reducing glucagon action in the liver through a reduction in total cellular and plasma membrane GR content. Furthermore, the GR desensitization observed in our in vivo model of HF diet-induced hepatic steatosis and in EX individuals may be regulated by PKC-α. PMID:17053032

Glyphosate-Resistant and Conventional Canola (Brassica napus L.) Responses to Glyphosate and Aminomethylphosphonic Acid (AMPA) Treatment.

PubMed

Corrêa, Elza Alves; Dayan, Franck E; Owens, Daniel K; Rimando, Agnes M; Duke, Stephen O

2016-05-11

Glyphosate-resistant (GR) canola contains two transgenes that impart resistance to the herbicide glyphosate: (1) the microbial glyphosate oxidase gene (gox) encoding the glyphosate oxidase enzyme (GOX) that metabolizes glyphosate to aminomethylphosphonic acid (AMPA) and (2) cp4 that encodes a GR form of the glyphosate target enzyme 5-enolpyruvylshikimic acid-3-phosphate synthase. The objectives of this research were to determine the phytotoxicity of AMPA to canola, the relative metabolism of glyphosate to AMPA in GR and conventional non-GR (NGR) canola, and AMPA pool sizes in glyphosate-treated GR canola. AMPA applied at 1.0 kg ha(-1) was not phytotoxic to GR or NGR. At this AMPA application rate, NGR canola accumulated a higher concentration of AMPA in its tissues than GR canola. At rates of 1 and 3.33 kg ae ha(-1) of glyphosate, GR canola growth was stimulated. This stimulatory effect is similar to that of much lower doses of glyphosate on NGR canola. Both shikimate and AMPA accumulated in tissues of these glyphosate-treated plants. In a separate experiment in which young GR and NGR canola plants were treated with non-phytotoxic levels of [(14)C]-glyphosate, very little glyphosate was metabolized in NGR plants, whereas most of the glyphosate was metabolized to AMPA in GR plants at 7 days after application. Untreated leaves of GR plants accumulated only metabolites (mostly AMPA) of glyphosate, indicating that GOX activity is very high in the youngest leaves. These data indicate that more glyphosate is transformed to AMPA rapidly in GR canola and that the accumulated AMPA is not toxic to the canola plant.

Monoclonal antibodies against the rat liver glucocorticoid receptor.

PubMed Central

Okret, S; Wikström, A C; Wrange, O; Andersson, B; Gustafsson, J A

1984-01-01

Splenic cells from one BALB/c mouse and one C57/BL mouse, immunized with purified rat liver glucocorticoid receptor (GR), were fused with the mouse myeloma cell line Sp 2/0-Ag 14. Screening for production of anti-GR-antibodies by the hybridomas was carried out with an enzyme-linked immunosorbent assay, using partially purified rat liver GR as antigen. Further screening was by a second-antibody immunoprecipitation assay using [3H]triamcinolone acetonide-GR complex from rat liver cytosol as tracer. Hybridomas from 10 different microplate wells, positive in both assays, were successfully cloned by the limiting dilution method to monoclonality. The different origins of the monoclonal antibodies were confirmed by their various isoelectric points when analyzed by isoelectric focusing. Four of the monoclonal hybridoma cell lines secreted IgM antibodies; two, IgG1; three, IgG2a; and one, IgG2b. The GR-antibody complex was identified in glycerol density gradients by a shift of the 4S GR to an 8.5S or 19S GR-antibody complex when incubated with monoclonal IgG or IgM antibody, respectively. The 10 monoclonal antibodies recognized different determinants on the GR, all situated on that domain of the receptor that is separate from the ligand and DNA-binding domains. Also, the cross-reactivity to the mouse liver GR varied among the monoclonal antibodies. No cross-reactivity was observed to the human lymphocytic GR. NaDodSO4 electrophoresis of a 0.5% pure GR preparation followed by immunoblotting using one of the monoclonal antibodies identified a single peptide with a molecular weight of 94,000, identical to the purified rat liver GR. Images PMID:6200880

SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice

PubMed Central

Percopo, Caroline M.; Brenner, Todd A.; Ma, Michelle; Kraemer, Laura S.; Hakeem, Reem M. A.; Lee, James J.; Rosenberg, Helene F.

2017-01-01

Although eosinophils as a group are readily identified by their unique morphology and staining properties, flow cytometry provides an important means for identification of subgroups based on differential expression of distinct surface Ags. Here, we characterize an eosinophil subpopulation defined by high levels of expression of the neutrophil Ag Gr1 (CD45+CD11c−SiglecF+Gr1hi). SiglecF+Gr1hi eosinophils, distinct from the canonical SiglecF+Gr1− eosinophil population, were detected in allergen-challenged wild-type and granule protein-deficient (EPX−/− and MBP-1−/−) mice, but not in the eosinophil-deficient ΔdblGATA strain. In contrast to Gr1+ neutrophils, which express both cross-reacting Ags Ly6C and Ly6G, SiglecF+Gr1hi eosinophils from allergen-challenged lung tissue are uniquely Ly6G+. Although indistinguishable from the more-numerous SiglecF+Gr1− eosinophils under light microscopy, FACS-isolated populations revealed prominent differences in cytokine contents. The lymphocyte-targeting cytokines CXCL13 and IL-27 were identified only in the SiglecF+Gr1hi eosinophil population (at 3.9 and 4.8 pg/106 cells, respectively), as was the prominent proinflammatory mediator IL-13 (72 pg/106 cells). Interestingly, bone marrow-derived (SiglecF+), cultured eosinophils include a more substantial Gr1+ subpopulation (∼50%); Gr1+ bmEos includes primarily a single Ly6C+ and a smaller, double-positive (Ly6C+Ly6G+) population. Taken together, our findings characterize a distinct SiglecF+Gr1hi eosinophil subset in lungs of allergen-challenged, wild-type and granule protein-deficient mice. SiglecF+Gr1hi eosinophils from wild-type mice maintain a distinct subset of cytokines, including those active on B and T lymphocytes. These cytokines may facilitate eosinophil-mediated immunomodulatory responses in the allergen-challenged lung as well as in other distinct microenvironments. PMID:27531929

SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice.

PubMed

Percopo, Caroline M; Brenner, Todd A; Ma, Michelle; Kraemer, Laura S; Hakeem, Reem M A; Lee, James J; Rosenberg, Helene F

2017-01-01

Although eosinophils as a group are readily identified by their unique morphology and staining properties, flow cytometry provides an important means for identification of subgroups based on differential expression of distinct surface Ags. Here, we characterize an eosinophil subpopulation defined by high levels of expression of the neutrophil Ag Gr1 (CD45 + CD11c - SiglecF + Gr1 hi ). SiglecF + Gr1 hi eosinophils, distinct from the canonical SiglecF + Gr1 - eosinophil population, were detected in allergen-challenged wild-type and granule protein-deficient (EPX -/- and MBP-1 -/- ) mice, but not in the eosinophil-deficient ΔdblGATA strain. In contrast to Gr1 + neutrophils, which express both cross-reacting Ags Ly6C and Ly6G, SiglecF + Gr1 hi eosinophils from allergen-challenged lung tissue are uniquely Ly6G + Although indistinguishable from the more-numerous SiglecF + Gr1 - eosinophils under light microscopy, FACS-isolated populations revealed prominent differences in cytokine contents. The lymphocyte-targeting cytokines CXCL13 and IL-27 were identified only in the SiglecF + Gr1 hi eosinophil population (at 3.9 and 4.8 pg/10 6 cells, respectively), as was the prominent proinflammatory mediator IL-13 (72 pg/10 6 cells). Interestingly, bone marrow-derived (SiglecF + ), cultured eosinophils include a more substantial Gr1 + subpopulation (∼50%); Gr1 + bmEos includes primarily a single Ly6C + and a smaller, double-positive (Ly6C + Ly6G + ) population. Taken together, our findings characterize a distinct SiglecF + Gr1 hi eosinophil subset in lungs of allergen-challenged, wild-type and granule protein-deficient mice. SiglecF + Gr1 hi eosinophils from wild-type mice maintain a distinct subset of cytokines, including those active on B and T lymphocytes. These cytokines may facilitate eosinophil-mediated immunomodulatory responses in the allergen-challenged lung as well as in other distinct microenvironments. © Society for Leukocyte Biology.

Age related differences of selected Hatha yoga practices on anthropometric characteristics, muscular strength and flexibility of healthy individuals

PubMed Central

Halder, Kaushik; Chatterjee, Abhirup; Pal, Rameshwar; Tomer, Omveer S; Saha, Mantu

2015-01-01

Background: Physiological benefits of yoga on volunteers of a particular age group are available. However, reports on efficacy of a specific yoga package on the populace of different age groups from similar occupational background is still very limited. Therefore, the present study was conducted to appraise the effect of a specific Hatha yoga package on anthropometric characteristics, flexibility and muscular strength of healthy individuals of different age groups from similar occupational trade. Materials and Methods: A total of 71 participants (Group All) from Indian Air Force ground personnel volunteered and age wise divided into 3 groups - (i) Group I (Gr. - I) (n1 = 27, 20-29 years), (ii) Group II (Gr. - II) (n2 = 21, 30-39 years) and (iii) Group III (Gr. - III) (n3 = 23, 40-49 years). All the participants undergone selected Hatha yoga training for 1 h daily for a period of 12 weeks. Parameters were recorded before and after the training. Pre and post training differences were assessed by Student's t-test. Results: Body weight (All, Gr. - II and Gr. - III [all P < 0.05]), body mass index (Gr. - II and Gr. - III [both P < 0.01]) and fat% (Gr. - II and III [both P < 0.05]) were decreased significantly. Neck circumference was increased significantly in Gr. - I (P < 0.05) but decreased significantly in Gr. - III (P < 0.05). Chest circumference (All (P < 0.001), in Gr. - I and II [both P < 0.05]), grip strength (All [left: P < 0.01 and right: P < 0.05], in Gr. - I [left: P < 0.05 and right: P < 0.01], in Gr. - II [right: P < 0.05] and in Gr. - III [left: P < 0.05 and right: P < 0.01]), back leg strength (group wise P < 0.001, P < 0.05, P < 0.01 and P < 0.05 respectively) and flexibility (all P < 0.001) were increased significantly. Summary and Conclusion: Hatha yoga can improve anthropometric characteristics, muscular strength and flexibility among volunteers of different age group and can also be helpful in preventing and attenuating age related deterioration of these parameters. PMID:25558132

Role of Pro-637 and Gln-642 in human glucocorticoid receptors and Ser-843 and Leu-848 in mineralocorticoid receptors in their differential responses to cortisol and aldosterone.

PubMed

Mani, Orlando; Nashev, Lyubomir G; Livelo, Christopher; Baker, Michael E; Odermatt, Alex

2016-05-01

Mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) are descended from a common ancestral corticoid receptor. The basis for specificities of human MR for aldosterone and human GR for glucocorticoids, such as cortisol, bearing 17α-hydroxyl-groups, is incompletely understood. Differences in MR at S843 and L848 and GR at the corresponding P637 and Q642 have been proposed as important in their different responses to glucocorticoids with 17α-hydroxyl-groups. We investigated the impact of these residues on binding affinity (Ki) and transcriptional activation (EC50) of mutants MR-S843P, MR-L848Q and MR-S843P/L848Q and mutants GR-P637S, GR-Q642L and GR-P637S/Q642L in the presence of different corticosteroids. Aldosterone, cortisol and corticosterone had similar affinities for wild-type MR and all mutants, while dexamethasone had increased affinity for the three mutants. However, transactivation of MR-S843P and MR-S843P/L848Q by all four steroids was significantly lower than for wild-type MR. In contrast, transactivation of MR-L848Q tended to be 3-fold higher for cortisol and corticosterone and increased 7-fold for dexamethasone, indicating that MR-L848Q has an increased response to glucocorticoids, while retaining a strong response to aldosterone. Compared to wild-type GR, GR-P637S and GR-Q642L had increased affinities and significantly increased transcriptional activity with aldosterone and corticosterone, and GR-P637S had similar transcriptional activity with cortisol and dexamethasone, while GR-Q642L and GR-P637S/Q642L had a significant decrease in transcriptional activity with cortisol and dexamethasone. 3D-models of these MR and GR mutants revealed that dexamethasone and aldosterone, respectively, fit nicely into the steroid-binding pocket, consistent with the affinity of dexamethasone for MR mutants and aldosterone for GR mutants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Slip Activity in Single Grains Extracted from Polycrystalline Specimen by X-Ray Line Broadening (Preprint)

DTIC Science & Technology

2010-01-01

4 6 8 0.005 0.010 -101-3 -110-2 1-10-2F W H M [ 1 /n m ] K [ 1/nm ] Gr #44 Gr #50 Gr #72 -101-1 1-101 (a...0 2 4 6 0.000 0.005 0.010 (b) K2Ccalc [ 1/nm ] FW H M [ 1 /n m ] Gr #44 Gr #50 Gr #72 17 Figure 5. The FWHM (in 1/nm scales) in...Preprint 01 January 2010 – 01 January 2010 4 . TITLE AND SUBTITLE SLIP ACTIVITY IN SINGLE GRAINS EXTRACTED FROM POLYCRYSTALLINE SPECIMEN BY X-RAY

Development of glyphosate-resistant alfalfa (Medicago sativa L.) upon transformation with the GR79Ms gene encoding 5-enolpyruvylshikimate-3-phosphate synthase.

PubMed

Yi, Dengxia; Ma, Lin; Lin, Min; Li, Cong

2018-07-01

The glyphosate-resistant gene, GR79Ms, was successfully introduced into the genome of alfalfa. The transgenic events may serve as novel germplasm resources in alfalfa breeding. Weed competition can reduce the alfalfa yield, generating new alfalfa germplasm with herbicide resistance is essential. To obtain transgenic alfalfa lines with glyphosate resistance, a new synthetic glyphosate-resistant gene GR79Ms encoding 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) was introduced into alfalfa germplasm by Agrobacterium tumefaciens-mediated transformation. In total, 67 transformants were obtained. PCR and Southern blot analyses confirmed that GR79Ms was successfully inserted into the genome of alfalfa. Reverse transcription-PCR and western blot analyses further demonstrated the expression of GR79Ms and its product, GR79Ms EPSPS. Moreover, two homozygous transgenic lines were developed in the T 2 generation by means of molecular-assisted selection. Herbicide tolerance spray tests showed that the transgenic plants T 0 -GR1, T 0 -GR2, T 0 -GR3 and two homozygous lines were able to tolerate fourfold higher commercial usage of glyphosate than non-transgenic plants.

An 8.68% efficiency chemically-doped-free graphene-silicon solar cell using silver nanowires network buried contacts.

PubMed

Yang, Lifei; Yu, Xuegong; Hu, Weidan; Wu, Xiaolei; Zhao, Yan; Yang, Deren

2015-02-25

Graphene-silicon (Gr-Si) heterojunction solar cells have been recognized as one of the most low-cost candidates in photovoltaics due to its simple fabrication process. However, the high sheet resistance of chemical vapor deposited (CVD) Gr films is still the most important limiting factor for the improvement of the power conversion efficiency of Gr-Si solar cells, especially in the case of large device-active area. In this work, we have fabricated a novel transparent conductive film by hybriding a monolayer Gr film with silver nanowires (AgNWs) network soldered by the graphene oxide (GO) flakes. This Gr-AgNWs hybrid film exhibits low sheet resistance and larger direct-current to optical conductivity ratio, quite suitable for solar cell fabrication. An efficiency of 8.68% has been achieved for the Gr-AgNWs-Si solar cell, in which the AgNWs network acts as buried contacts. Meanwhile, the Gr-AgNWs-Si solar cells have much better stability than the chemically doped Gr-Si solar cells. These results show a new route for the fabrication of high efficient and stable Gr-Si solar cells.

Evaluation of pulmonary and systemic toxicity following lung exposure to graphite nanoplates: a member of the graphene-based nanomaterial family.

PubMed

Roberts, Jenny R; Mercer, Robert R; Stefaniak, Aleksandr B; Seehra, Mohindar S; Geddam, Usha K; Chaudhuri, Ishrat S; Kyrlidis, Angelos; Kodali, Vamsi K; Sager, Tina; Kenyon, Allison; Bilgesu, Suzan A; Eye, Tracy; Scabilloni, James F; Leonard, Stephen S; Fix, Natalie R; Schwegler-Berry, Diane; Farris, Breanne Y; Wolfarth, Michael G; Porter, Dale W; Castranova, Vincent; Erdely, Aaron

2016-06-21

Graphene, a monolayer of carbon, is an engineered nanomaterial (ENM) with physical and chemical properties that may offer application advantages over other carbonaceous ENMs, such as carbon nanotubes (CNT). The goal of this study was to comparatively assess pulmonary and systemic toxicity of graphite nanoplates, a member of the graphene-based nanomaterial family, with respect to nanoplate size. Three sizes of graphite nanoplates [20 μm lateral (Gr20), 5 μm lateral (Gr5), and <2 μm lateral (Gr1)] ranging from 8-25 nm in thickness were characterized for difference in surface area, structure,, zeta potential, and agglomeration in dispersion medium, the vehicle for in vivo studies. Mice were exposed by pharyngeal aspiration to these 3 sizes of graphite nanoplates at doses of 4 or 40 μg/mouse, or to carbon black (CB) as a carbonaceous control material. At 4 h, 1 day, 7 days, 1 month, and 2 months post-exposure, bronchoalveolar lavage was performed to collect fluid and cells for analysis of lung injury and inflammation. Particle clearance, histopathology and gene expression in lung tissue were evaluated. In addition, protein levels and gene expression were measured in blood, heart, aorta and liver to assess systemic responses. All Gr samples were found to be similarly composed of two graphite structures and agglomerated to varying degrees in DM in proportion to the lateral dimension. Surface area for Gr1 was approximately 7-fold greater than Gr5 and Gr20, but was less reactive reactive per m(2). At the low dose, none of the Gr materials induced toxicity. At the high dose, Gr20 and Gr5 exposure increased indices of lung inflammation and injury in lavage fluid and tissue gene expression to a greater degree and duration than Gr1 and CB. Gr5 and Gr20 showed no or minimal lung epithelial hypertrophy and hyperplasia, and no development of fibrosis by 2 months post-exposure. In addition, the aorta and liver inflammatory and acute phase genes were transiently elevated in Gr5 and Gr20, relative to Gr1. Pulmonary and systemic toxicity of graphite nanoplates may be dependent on lateral size and/or surface reactivity, with the graphite nanoplates > 5 μm laterally inducing greater toxicity which peaked at the early time points post-exposure relative to the 1-2 μm graphite nanoplate.

Recruitment of Gr-1+ monocytes is essential for control of acute toxoplasmosis

PubMed Central

Robben, Paul M.; LaRegina, Marie; Kuziel, William A.; Sibley, L. David

2005-01-01

Circulating murine monocytes comprise two largely exclusive subpopulations that are responsible for seeding normal tissues (Gr-1−/CCR2−/CX3CR1high) or responding to sites of inflammation (Gr-1+/CCR2+/CX3CR1lo). Gr-1+ monocytes are recruited to the site of infection during the early stages of immune response to the intracellular pathogen Toxoplasma gondii. A murine model of toxoplasmosis was thus used to examine the importance of Gr-1+ monocytes in the control of disseminated parasitic infection in vivo. The recruitment of Gr-1+ monocytes was intimately associated with the ability to suppress early parasite replication at the site of inoculation. Infection of CCR2−/− and MCP-1−/− mice with typically nonlethal, low doses of T. gondii resulted in the abrogated recruitment of Gr-1+ monocytes. The failure to recruit Gr-1+ monocytes resulted in greatly enhanced mortality despite the induction of normal Th1 cell responses leading to high levels of IL-12, TNF-α, and IFN-γ. The profound susceptibility of CCR2−/− mice establishes Gr-1+ monocytes as necessary effector cells in the resistance to acute toxoplasmosis and suggests that the CCR2-dependent recruitment of Gr-1+ monocytes may be an important general mechanism for resistance to intracellular pathogens. PMID:15928200

Ultrasound assisted simultaneous reduction and direct functionalization of graphene oxide with thermal and cytotoxicity profile.

PubMed

Maktedar, Shrikant S; Avashthi, Gopal; Singh, Man

2017-01-01

The new sonochemical approach for simultaneous reduction and direct functionalization of graphene oxide (GrO) has been developed. The GrO was functionalized with 2-Aminobenzoxazole (2-ABOZ) in twenty min with complete deletion of hazardous steps. The significance of ultrasound was exemplified with the comparative conventional methods. The newly prepared f-(2-ABOZ)GrO was extensively characterized with near edge X-ray absorption fine structure (NEXAFS) spectroscopy, 13 C solid state NMR, XPS, XRD, HRTEM, SAED, AFM, Raman, UV-vis, FTIR and TGA. The thermal stability of f-(2-ABOZ)GrO was confirmed with total percentage weight loss in TGA. The biological activity of f-(2-ABOZ)GrO was explored with MCF-7 and Vero cell lines. The inherent cytotoxicity was evaluated with SRB assay at 10, 20, 40 and 80μgmL -1 . The estimated cell viabilities were >78% with f-(2-ABOZ) GrO. A high cytocompatibility of f-(2-ABOZ)GrO was ensured with in vitro evaluation on living cell lines, and low toxicity of f-(2-ABOZ)GrO was confirmed its excellent biocompatibility. The morphological effect on Vero cell line evidently supports the formation of biocompatible f-(2-ABOZ)GrO. Therefore, f-(2-ABOZ)GrO was emerged as an advanced functional material for thermally stable biocompatible coatings. Copyright © 2016 Elsevier B.V. All rights reserved.

Neonatal growth restriction-related leptin deficiency enhances leptin-triggered sympathetic activation and central angiotensin II receptor-dependent stress-evoked hypertension.

PubMed

Peotta, Veronica; Rahmouni, Kamal; Segar, Jeffrey L; Morgan, Donald A; Pitz, Kate M; Rice, Olivia M; Roghair, Robert D

2016-08-01

Neonatal growth restriction (nGR) leads to leptin deficiency and increases the risk of hypertension. Previous studies have shown nGR-related hypertension is normalized by neonatal leptin (nLep) and exacerbated by psychological stress. With recent studies linking leptin and angiotensin signaling, we hypothesized that nGR-induced nLep deficiency increases adult leptin sensitivity; leading to leptin- or stress-induced hypertension, through a pathway involving central angiotensin II type 1 receptors. We randomized mice with incipient nGR, by virtue of their presence in large litters, to vehicle or physiologic nLep supplementation (80 ng/g/d). Adult caloric intake and arterial pressure were monitored at baseline, during intracerebroventricular losartan infusion and during systemic leptin administration. nGR increased leptin-triggered renal sympathetic activation and hypertension with increased leptin receptor expression in the arcuate nucleus of the hypothalamus; all of those nGR-associated phenotypes were normalized by nLep. nGR mice also had stress-related hyperphagia and hypertension, but only the stress hypertension was blocked by central losartan infusion. nGR leads to stress hypertension through a pathway that involves central angiotensin II receptors, and nGR-associated leptin deficiency increases leptin-triggered hypertension in adulthood. These data suggest potential roles for preservation of neonatal growth and nLep supplementation in the prevention of nGR-related hypertension.

Role of the chromatin landscape and sequence in determining cell type-specific genomic glucocorticoid receptor binding and gene regulation.

PubMed

Love, Michael I; Huska, Matthew R; Jurk, Marcel; Schöpflin, Robert; Starick, Stephan R; Schwahn, Kevin; Cooper, Samantha B; Yamamoto, Keith R; Thomas-Chollier, Morgane; Vingron, Martin; Meijsing, Sebastiaan H

2017-02-28

The genomic loci bound by the glucocorticoid receptor (GR), a hormone-activated transcription factor, show little overlap between cell types. To study the role of chromatin and sequence in specifying where GR binds, we used Bayesian modeling within the universe of accessible chromatin. Taken together, our results uncovered that although GR preferentially binds accessible chromatin, its binding is biased against accessible chromatin located at promoter regions. This bias can only be explained partially by the presence of fewer GR recognition sequences, arguing for the existence of additional mechanisms that interfere with GR binding at promoters. Therefore, we tested the role of H3K9ac, the chromatin feature with the strongest negative association with GR binding, but found that this correlation does not reflect a causative link. Finally, we find a higher percentage of promoter-proximal GR binding for genes regulated by GR across cell types than for cell type-specific target genes. Given that GR almost exclusively binds accessible chromatin, we propose that cell type-specific regulation by GR preferentially occurs via distal enhancers, whose chromatin accessibility is typically cell type-specific, whereas ubiquitous target gene regulation is more likely to result from binding to promoter regions, which are often accessible regardless of cell type examined. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Electrochemical Co-Reduction Synthesis of AuPt Bimetallic Nanoparticles-Graphene Nanocomposites for Selective Detection of Dopamine in the Presence of Ascorbic Acid and Uric Acid

PubMed Central

Zhao, Zongya; Zhang, Mingming; Chen, Xiang; Li, Youjun; Wang, Jue

2015-01-01

In this paper, AuPt bimetallic nanoparticles-graphene nanocomposites were obtained by electrochemical co-reduction of graphene oxide (GO), HAuCl4 and H2PtCl6. The as-prepared AuPt bimetallic nanoparticles-graphene nanocomposites were characterized by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and other electrochemical methods. The morphology and composition of the nanocomposite could be easily controlled by adjusting the HAuCl4/H2PtCl6 concentration ratio. The electrochemical experiments showed that when the concentration ratio of HAuCl4/H2PtCl6 was 1:1, the obtained AuPt bimetallic nanoparticles-graphene nanocomposite (denoted as Au1Pt1NPs-GR) possessed the highest electrocatalytic activity toward dopamine (DA). As such, Au1Pt1NPs-GR nanocomposites were used to detect DA in the presence of ascorbic acid (AA) and uric acid (UA) using the differential pulse voltammetry (DPV) technique and on the modified electrode, there were three separate DPV oxidation peaks with the peak potential separations of 177 mV, 130 mV and 307 mV for DA and AA, DA and UA, AA and UA, respectively. The linear range of the constructed DA sensor was from 1.6 μM to 39.7 μM with a detection limit of 0.1 μM (S/N = 3). The obtained DA sensor with good stability, high reproducibility and excellent selectivity made it possible to detect DA in human urine samples. PMID:26184200

Electrochemical Co-Reduction Synthesis of AuPt Bimetallic Nanoparticles-Graphene Nanocomposites for Selective Detection of Dopamine in the Presence of Ascorbic Acid and Uric Acid.

PubMed

Zhao, Zongya; Zhang, Mingming; Chen, Xiang; Li, Youjun; Wang, Jue

2015-07-09

In this paper, AuPt bimetallic nanoparticles-graphene nanocomposites were obtained by electrochemical co-reduction of graphene oxide (GO), HAuCl4 and H2PtCl6. The as-prepared AuPt bimetallic nanoparticles-graphene nanocomposites were characterized by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and other electrochemical methods. The morphology and composition of the nanocomposite could be easily controlled by adjusting the HAuCl4/H2PtCl6 concentration ratio. The electrochemical experiments showed that when the concentration ratio of HAuCl4/H2PtCl6 was 1:1, the obtained AuPt bimetallic nanoparticles-graphene nanocomposite (denoted as Au1Pt1NPs-GR) possessed the highest electrocatalytic activity toward dopamine (DA). As such, Au1Pt1NPs-GR nanocomposites were used to detect DA in the presence of ascorbic acid (AA) and uric acid (UA) using the differential pulse voltammetry (DPV) technique and on the modified electrode, there were three separate DPV oxidation peaks with the peak potential separations of 177 mV, 130 mV and 307 mV for DA and AA, DA and UA, AA and UA, respectively. The linear range of the constructed DA sensor was from 1.6 μM to 39.7 μM with a detection limit of 0.1 μM (S/N = 3). The obtained DA sensor with good stability, high reproducibility and excellent selectivity made it possible to detect DA in human urine samples.

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

DTIC Science & Technology

2008-10-01

for > 3 platelet transfusion in 30 days • Gr 4 neutropenia • Febrile neutropenia • Attributable Gr > 3 non-hematologic toxicity (excluding infusion...0% No febrile neutropenia (no growth factor use) • Transaminitis (n=12 evaluable) Transient Gr 1 17% (no Gr > 1) Figure-1...therapies and 36% progressed on 1-4 lines of chemotherapy including docetaxel. No DLT’s have been seen. 2 pts experienced reversible Gr 3 neutropenia

[4 years of Microbiología SEM (1994-1997)].

PubMed

Mas-Castellà, J

1997-12-01

Different aspects of Microbiología SEM editorial process over the years 1994-1997 are analyzed: number of originals received, the process leading to their publication, rates of accepted and refused papers, time needed for each step of the editorial process--which comprises scientific, language editing, if needed--, as well as some characteristics that can define the patterns of the articles, such as number of authors, institutions where the authors work and mean number of references. The contents of the different sections (editorial, research and review articles, perspectives, opinion, books review) are commented on, as well as the role played by some of them as forums for the discussion of topics of current scientific interest, especially the editorials focusing on the state-of-the-art of microbiological research in Latin American countries. Characteristics and frequency of monographic issues are also presented. The information is complemented with data about the circulation and distribution of the journal, its inclusion in international indexes and its current electronic publication on the world wide web.

Granzyme M and K release in human experimental endotoxemia.

PubMed

Wensink, Annette C; Wiewel, Maryse A; Jongeneel, Lieneke H; Boes, Marianne; van der Poll, Tom; Hack, C Erik; Bovenschen, Niels

2016-07-01

Granzymes are serine proteases involved in killing of tumor cells and virally infected cells. However, granzymes are also upregulated in blood under inflammatory conditions and contribute to cytokine release and processing. Here, we show that granzyme M (GrM) and to a lesser extent GrK are transiently elevated in the circulation following LPS administration in humans. GrM is released upon stimulation of whole blood with LPS or the gram-negative bacteria Escherichia coli BL21, Pseudomonas aeruginosa, and Neisseria meningitidis. GrK is only released upon stimulation with P. aeruginosa. Thus, GrM and GrK are differentially released in response to LPS and gram-negative bacteria. Copyright © 2016 Elsevier GmbH. All rights reserved.

Regulation of the glucocorticoid receptor via a BET-dependent enhancer drives antiandrogen resistance in prostate cancer.

PubMed

Shah, Neel; Wang, Ping; Wongvipat, John; Karthaus, Wouter R; Abida, Wassim; Armenia, Joshua; Rockowitz, Shira; Drier, Yotam; Bernstein, Bradley E; Long, Henry W; Freedman, Matthew L; Arora, Vivek K; Zheng, Deyou; Sawyers, Charles L

2017-09-11

In prostate cancer, resistance to the antiandrogen enzalutamide (Enz) can occur through bypass of androgen receptor (AR) blockade by the glucocorticoid receptor (GR). In contrast to fixed genomic alterations, here we show that GR-mediated antiandrogen resistance is adaptive and reversible due to regulation of GR expression by a tissue-specific enhancer. GR expression is silenced in prostate cancer by a combination of AR binding and EZH2-mediated repression at the GR locus, but is restored in advanced prostate cancers upon reversion of both repressive signals. Remarkably, BET bromodomain inhibition resensitizes drug-resistant tumors to Enz by selectively impairing the GR signaling axis via this enhancer. In addition to revealing an underlying molecular mechanism of GR-driven drug resistance, these data suggest that inhibitors of broadly active chromatin-readers could have utility in nuanced clinical contexts of acquired drug resistance with a more favorable therapeutic index.

Coregulator profiling of the glucocorticoid receptor in lymphoid malignancies

PubMed Central

Clarisse, Dorien; Thommis, Jonathan; Van Wesemael, Karlien; Houtman, René; Ratman, Dariusz; Tavernier, Jan; Offner, Fritz; Beck, Ilse; De Bosscher, Karolien

2017-01-01

Coregulators cooperate with nuclear receptors, such as the glucocorticoid receptor (GR), to enhance or repress transcription. These regulatory proteins are implicated in cancer, yet, their role in lymphoid malignancies, including multiple myeloma (MM) and acute lymphoblastic leukemia (ALL), is largely unknown. Here, we report the use and extension of the microarray assay for real-time nuclear receptor coregulator interactions (MARCoNI) technology to detect coregulator associations with endogenous GR in cell lysates. We use MARCoNI to determine the GR coregulator profile of glucocorticoid-sensitive (MM and ALL) and glucocorticoid-resistant (ALL) cells, and identify common and unique coregulators for different cell line comparisons. Overall, we identify SRC-1/2/3, PGC-1α, RIP140 and DAX-1 as the strongest interacting coregulators of GR in MM and ALL cells and show that the interaction strength does not correlate with GR protein levels. Lastly, as a step towards patient samples, we determine the GR coregulator profile of peripheral blood mononuclear cells. We profile the interactions between GR and coregulators in MM and ALL cells and suggest to further explore the GR coregulator profile in hematological patient samples. PMID:29312638

Coregulator profiling of the glucocorticoid receptor in lymphoid malignancies.

PubMed

Clarisse, Dorien; Thommis, Jonathan; Van Wesemael, Karlien; Houtman, René; Ratman, Dariusz; Tavernier, Jan; Offner, Fritz; Beck, Ilse; De Bosscher, Karolien

2017-12-12

Coregulators cooperate with nuclear receptors, such as the glucocorticoid receptor (GR), to enhance or repress transcription. These regulatory proteins are implicated in cancer, yet, their role in lymphoid malignancies, including multiple myeloma (MM) and acute lymphoblastic leukemia (ALL), is largely unknown. Here, we report the use and extension of the microarray assay for real-time nuclear receptor coregulator interactions (MARCoNI) technology to detect coregulator associations with endogenous GR in cell lysates. We use MARCoNI to determine the GR coregulator profile of glucocorticoid-sensitive (MM and ALL) and glucocorticoid-resistant (ALL) cells, and identify common and unique coregulators for different cell line comparisons. Overall, we identify SRC-1/2/3, PGC-1α, RIP140 and DAX-1 as the strongest interacting coregulators of GR in MM and ALL cells and show that the interaction strength does not correlate with GR protein levels. Lastly, as a step towards patient samples, we determine the GR coregulator profile of peripheral blood mononuclear cells. We profile the interactions between GR and coregulators in MM and ALL cells and suggest to further explore the GR coregulator profile in hematological patient samples.

A sugar gustatory receptor identified from the foregut of cotton bollworm Helicoverpa armigera.

PubMed

Xu, Wei; Zhang, Hui-Jie; Anderson, Alisha

2012-12-01

Helicoverpa armigera (Hübner) is one of the most polyphagous and cosmopolitan pest species, the larvae of which feed on numerous important crops. The gustatory system is critical in guiding insect feeding behavior. Here, we identified a gustatory receptor from H. armigera, HaGR9, which shows high levels of identity to DmGR43a from Drosophila melanogaster and BmGR9 from Bombyx mori. Reverse transcriptase PCR (RT-PCR) revealed HaGR9 is highly expressed in larval foregut, with little or no expression in other chemosensory tissues. Membrane topology studies indicated that, like two previously studied B. mori GRs, BmGR8 and BmGR53, HaGR9 has an inverted topology relative to G protein-coupled receptors (GPCRs), an intracellular N-terminus and an extracellular C-terminus. Calcium imaging studies confirmed HaGR9 is a sugar receptor showing dose-dependent responses to D-galactose, D-maltose, and D-fructose. This highly-expressed foregut-specific gustatory receptor may contribute to the regulation of larval feeding behavior.

Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription.

PubMed

Stavreva, Diana A; Wiench, Malgorzata; John, Sam; Conway-Campbell, Becky L; McKenna, Mervyn A; Pooley, John R; Johnson, Thomas A; Voss, Ty C; Lightman, Stafford L; Hager, Gordon L

2009-09-01

Studies on glucocorticoid receptor (GR) action typically assess gene responses by long-term stimulation with synthetic hormones. As corticosteroids are released from adrenal glands in a circadian and high-frequency (ultradian) mode, such treatments may not provide an accurate assessment of physiological hormone action. Here we demonstrate that ultradian hormone stimulation induces cyclic GR-mediated transcriptional regulation, or gene pulsing, both in cultured cells and in animal models. Equilibrium receptor-occupancy of regulatory elements precisely tracks the ligand pulses. Nascent RNA transcripts from GR-regulated genes are released in distinct quanta, demonstrating a profound difference between the transcriptional programs induced by ultradian and constant stimulation. Gene pulsing is driven by rapid GR exchange with response elements and by GR recycling through the chaperone machinery, which promotes GR activation and reactivation in response to the ultradian hormone release, thus coupling promoter activity to the naturally occurring fluctuations in hormone levels. The GR signalling pathway has been optimized for a prompt and timely response to fluctuations in hormone levels, indicating that biologically accurate regulation of gene targets by GR requires an ultradian mode of hormone stimulation.

Glyphosate resistance in Ambrosia trifida: Part 1. Novel rapid cell death response to glyphosate.

PubMed

Van Horn, Christopher R; Moretti, Marcelo L; Robertson, Renae R; Segobye, Kabelo; Weller, Stephen C; Young, Bryan G; Johnson, William G; Schulz, Burkhard; Green, Amanda C; Jeffery, Taylor; Lespérance, Mackenzie A; Tardif, François J; Sikkema, Peter H; Hall, J Christopher; McLean, Michael D; Lawton, Mark B; Sammons, R Douglas; Wang, Dafu; Westra, Philip; Gaines, Todd A

2018-05-01

Glyphosate-resistant (GR) Ambrosia trifida is now present in the midwestern United States and in southwestern Ontario, Canada. Two distinct GR phenotypes are known, including a rapid response (GR RR) phenotype, which exhibits cell death within hours after treatment, and a non-rapid response (GR NRR) phenotype. The mechanisms of resistance in both GR RR and GR NRR remain unknown. Here, we present a description of the RR phenotype and an investigation of target-site mechanisms on multiple A. trifida accessions. Glyphosate resistance was confirmed in several accessions, and whole-plant levels of resistance ranged from 2.3- to 7.5-fold compared with glyphosate-susceptible (GS) accessions. The two GR phenotypes displayed similar levels of resistance, despite having dramatically different phenotypic responses to glyphosate. Glyphosate resistance was not associated with mutations in EPSPS sequence, increased EPSPS copy number, EPSPS quantity, or EPSPS activity. These encompassing results suggest that resistance to glyphosate in these GR RR A. trifida accessions is not conferred by a target-site resistance mechanism. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Targeting the FKBP51/GR/Hsp90 Complex to Identify Functionally Relevant Treatments for Depression and PTSD.

PubMed

Sabbagh, Jonathan J; Cordova, Ricardo A; Zheng, Dali; Criado-Marrero, Marangelie; Lemus, Andrea; Li, Pengfei; Baker, Jeremy D; Nordhues, Bryce A; Darling, April L; Martinez-Licha, Carlos; Rutz, Daniel A; Patel, Shreya; Buchner, Johannes; Leahy, James W; Koren, John; Dickey, Chad A; Blair, Laura J

2018-06-19

Genetic and epigenetic alterations in FK506-binding protein 5 ( FKBP5) have been associated with increased risk for psychiatric disorders, including post-traumatic stress disorder (PTSD). Some of these common variants can increase the expression of FKBP5, the gene that encodes FKBP51. Excess FKBP51 promotes hypothalamic-pituitary-adrenal (HPA) axis dysregulation through altered glucocorticoid receptor (GR) signaling. Thus, we hypothesized that GR activity could be restored by perturbing FKBP51. Here, we screened 1280 pharmacologically active compounds and identified three compounds that rescued FKBP51-mediated suppression of GR activity without directly activating GR. One of the three compounds, benztropine mesylate, disrupted the association of FKBP51 with the GR/Hsp90 complex in vitro. Moreover, we show that removal of FKBP51 from this complex by benztropine restored GR localization in ex vivo brain slices and primary neurons from mice. In conclusion, we have identified a novel disruptor of the FKBP51/GR/Hsp90 complex. Targeting this complex may be a viable approach to developing treatments for disorders related to aberrant FKBP51 expression.

Graphene transforms wide band gap ZnS to a visible light photocatalyst. The new role of graphene as a macromolecular photosensitizer.

PubMed

Zhang, Yanhui; Zhang, Nan; Tang, Zi-Rong; Xu, Yi-Jun

2012-11-27

We report the assembly of nanosized ZnS particles on the 2D platform of a graphene oxide (GO) sheet by a facile two-step wet chemistry process, during which the reduced graphene oxide (RGO, also called GR) and the intimate interfacial contact between ZnS nanoparticles and the GR sheet are achieved simultaneously. The ZnS-GR nanocomposites exhibit visible light photoactivity toward aerobic selective oxidation of alcohols and epoxidation of alkenes under ambient conditions. In terms of structure-photoactivity correlation analysis, we for the first time propose a new photocatalytic mechanism where the role of GR in the ZnS-GR nanocomposites acts as an organic dye-like macromolecular "photosensitizer" for ZnS instead of an electron reservoir. This novel photocatalytic mechanism is distinctly different from all previous research on GR-semiconductor photocatalysts, for which GR is claimed to behave as an electron reservoir to capture/shuttle the electrons photogenerated from the semiconductor. This new concept of the reaction mechanism in graphene-semiconductor photocatalysts could provide a new train of thought on designing GR-based composite photocatalysts for targeting applications in solar energy conversion, promoting our in-depth thinking on the microscopic charge carrier transfer pathway connected to the interface between the GR and the semiconductor.

The novel GrCEP12 peptide from the plant-parasitic nematode Globodera rostochiensis suppresses flg22-mediated PTI.

PubMed

Chen, Shiyan; Chronis, Demosthenis; Wang, Xiaohong

2013-09-01

The potato cyst nematode Globodera rostochiensis is a biotrophic pathogen that secretes effector proteins into host root cells to promote successful plant parasitism. In addition to the role in generating within root tissue the feeding cells essential for nematode development, (1) nematode secreted effectors are becoming recognized as suppressors of plant immunity. (2)(-) (4) Recently we reported that the effector ubiquitin carboxyl extension protein (GrUBCEP12) from G. rostochiensis is processed into free ubiquitin and a 12-amino acid GrCEP12 peptide in planta. Transgenic potato lines overexpressing the derived GrCEP12 peptide showed increased susceptibility to G. rostochiensis and to an unrelated bacterial pathogen Streptomyces scabies, suggesting that GrCEP12 has a role in suppressing host basal defense or possibly pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) during the parasitic interaction. (3) To determine if GrCEP12 functions as a PTI suppressor we evaluated whether GrCEP12 suppresses flg22-induced PTI responses in Nicotiana benthamiana. Interestingly, we found that transient expression of GrCEP12 in N. benthamiana leaves suppressed reactive oxygen species (ROS) production and the induction of two PTI marker genes triggered by the bacterial PAMP flg22, providing direct evidence that GrCEP12 indeed has an activity in PTI suppression.

Baicalin promotes hippocampal neurogenesis via SGK1- and FKBP5-mediated glucocorticoid receptor phosphorylation in a neuroendocrine mouse model of anxiety/depression

PubMed Central

Zhang, Kuo; Pan, Xing; Wang, Fang; Ma, Jie; Su, Guangyue; Dong, Yingxu; Yang, Jingyu; Wu, Chunfu

2016-01-01

Antidepressants increase hippocampal neurogenesis by activating the glucocorticoid receptor (GR), but excessive GR activation impairs hippocampal neurogenesis, suggesting that normal GR function is crucial for hippocampal neurogenesis. Baicalin was reported to regulate the expression of GR and facilitate hippocampal neurogenesis, but the underlying molecular mechanisms are still unknown. In this study, we used the chronic corticosterone (CORT)-induced mouse model of anxiety/depression to assess antidepressant-like effects of baicalin and illuminate possible molecular mechanisms by which baicalin affects GR-mediated hippocampal neurogenesis. We found that oral administration of baicalin (40, 80 or 160 mg/kg) for 4 weeks alleviated several chronic CORT-induced anxiety/depression-like behaviors. Baicalin also increased Ki-67- and DCX-positive cells to restore chronic CORT-induced suppression of hippocampal neurogenesis. Moreover, baicalin normalized the chronic CORT-induced decrease in GR protein levels, the increase in GR nuclear translocation and the increase in GR phosphorylation at Ser203 and Ser211. Finally, chronic CORT exposure increased the level of FK506-binding protein 51 (FKBP5) and of phosphorylated serum- and glucocorticoid-inducible kinase 1 (SGK1) at Ser422 and Thr256, whereas baicalin normalized these changes. Together, our findings suggest that baicalin improves anxiety/depression-like behaviors and promotes hippocampal neurogenesis. We propose that baicalin may normalize GR function through SGK1- and FKBP5-mediated GR phosphorylation. PMID:27502757

Increased antidepressant sensitivity after prefrontal cortex glucocorticoid receptor gene deletion in mice.

PubMed

Hussain, Rifat J; Jacobson, Lauren

2015-01-01

Our laboratory has previously shown that antidepressants regulate glucocorticoid receptor (GR) expression in the prefrontal cortex (PFC). To determine if PFC GR are involved in antidepressant effects on behavior or hypothalamic-pituitary-adrenocortical (HPA) axis activity, we treated floxed GR male mice with saline or 15 or 30 mg/kg/d imipramine after PFC injection of adeno-associated virus 2/9 vectors transducing expression of Cre recombinase, to knock-down GR (PFC-GRKD), or green fluorescent protein (PFC-GFP), to serve as a control. The pattern of virally transduced GR deletion, common to all imipramine treatment groups, included the infralimbic, prelimbic, and medial anterior cingulate cortex at its largest extent, but was confined to the prelimbic and anterior cingulate cortex at its smallest extent. PFC GR knock-down increased behavioral sensitivity to imipramine, with imipramine-treated PFC-GRKD but not PFC-GFP mice exhibiting significant decreases in depression-like immobility during forced swim. PFC GR deletion did not alter general locomotor activity. The 30 mg/kg dose of imipramine increased plasma corticosterone levels immediately after a 5-min forced swim, but PFC GR knock-down had no significant effect on plasma corticosterone under these experimental conditions. We conclude that PFC GR knock-down, likely limited to the medial prelimbic and anterior cingulate cortices, can increase behavioral sensitivity to antidepressants. These findings indicate a novel role for PFC GR in influencing antidepressant response. Copyright © 2014 Elsevier Inc. All rights reserved.

Bacillus amyloliquefaciens subsp. plantarum GR53, a potent biocontrol agent resists Rhizoctonia disease on Chinese cabbage through hormonal and antioxidants regulation.

PubMed

Kang, Sang-Mo; Radhakrishnan, Ramalingam; Lee, In-Jung

2015-10-01

The fungus Rhizoctonia solani is one of the causal agents of numerous diseases that affect crop growth and yield. The aim of this present investigation was to identify a biocontrol agent that acts against R. solani and to determine the agent's protective effect through phytohormones and antioxidant regulation in experimentally infected Chinese cabbage plants. Four rhizospheric soil bacterial isolates GR53, GR169, GR786, and GR320 were tested for their antagonistic activity against R. solani. Among these isolates, GR53 significantly suppressed fungal growth. GR53 was identified as Bacillus amyloliquefaciens subsp. plantarum by phylogenetic analysis of the 16S rDNA sequence. The biocontrol activity of B. amyloliquefaciens subsp. plantarum GR53 was tested in Chinese cabbage plants under controlled conditions. Results showed that R. solani inhibited plant growth (length, width, fresh and dry weight of leaves) by reducing chlorophyll and total phenolic content, as well as by increasing the levels of salicylic acid, jasmonic acid, abscisic acid, and DPPH scavenging activity. By regulating the levels of these compounds, the co-inoculation of B. amyloliquefaciens subsp. plantarum GR53 heightened induced systemic resistance in infected Chinese cabbage, effectively mitigating R. solani-induced damaging effects and improving plant growth. The results obtained from this study suggest that B. amyloliquefaciens subsp. plantarum GR53 is an effective biocontrol agent to prevent the damage caused by R. solani in Chinese cabbage plants.

Correlation of Serum and Salivary Cytokines Level With Clinical Parameters in Metabolic Syndrome With Periodontitis.

PubMed

Chauhan, Abhishek; Yadav, Suraj Singh; Dwivedi, Pradeep; Lal, Nand; Usman, Kauser; Khattri, Sanjay

2016-09-01

Metabolic Syndrome (MS) and chronic oral condition (periodontitis [PD]) are state of inflammation. The study was conducted to determine alterations in serum and salivary cytokines level in MS and/or chronic PD in the North Indian population. This cross-sectional study carried out in northern part of India. The study subjects of similar ethnicity were recruited according to International Diabetes Federation (IDF) criteria for MS, while chronic PD was diagnosed on the basis of packet depth and clinical attachment level. ELISA method was employed to assess cytokine level. All subjects were divided in four groups Gr A (MS + PD), B (MS), C (PD), and a control Gr D. The serum and salivary tumor necrosis factor alpha (TNF-α) level in Gr A, B, and C was significantly higher than Gr D (P < 0.05). Serum interleukin-10 (IL-10) level in Gr A, B, and C was lower than Gr D (P < 0.05), but this difference was not significant between Gr C and Gr D. Serum IL-10 level in Gr A was significantly lower than Gr C (P < 0.05). Salivary IL-10 level was not significantly altered in any group. Proinflammatory marker TNF-α has correlation with clinical parameters in patients of MS having PD. The study suggests level of salivary TNF-α may be utilized as a surrogate marker of MS and PD. © 2016 Wiley Periodicals, Inc.

EGFR-targeted granzyme B expressed in NK cells enhances natural cytotoxicity and mediates specific killing of tumor cells.

PubMed

Oberoi, Pranav; Jabulowsky, Robert A; Bähr-Mahmud, Hayat; Wels, Winfried S

2013-01-01

Natural killer (NK) cells are highly specialized effectors of the innate immune system that hold promise for adoptive cancer immunotherapy. Their cell killing activity is primarily mediated by the pro-apoptotic serine protease granzyme B (GrB), which enters targets cells with the help of the pore-forming protein perforin. We investigated expression of a chimeric GrB fusion protein in NK cells as a means to augment their antitumoral activity. For selective targeting to tumor cells, we fused the epidermal growth factor receptor (EGFR) peptide ligand transforming growth factor α (TGFα) to human pre-pro-GrB. Established human NKL natural killer cells transduced with a lentiviral vector expressed this GrB-TGFα (GrB-T) molecule in amounts comparable to endogenous wildtype GrB. Activation of the genetically modified NK cells by cognate target cells resulted in the release of GrB-T together with endogenous granzymes and perforin, which augmented the effector cells' natural cytotoxicity against NK-sensitive tumor cells. Likewise, GrB-T was released into the extracellular space upon induction of degranulation with PMA and ionomycin. Secreted GrB-T fusion protein displayed specific binding to EGFR-overexpressing tumor cells, enzymatic activity, and selective target cell killing in the presence of an endosomolytic activity. Our data demonstrate that ectopic expression of a targeted GrB fusion protein in NK cells is feasible and can enhance antitumoral activity of the effector cells.

Discrimination between NL1- and NL2-Mediated Nuclear Localization of the Glucocorticoid Receptor

PubMed Central

Savory, Joanne G. A.; Hsu, Brian; Laquian, Ian R.; Giffin, Ward; Reich, Terry; Haché, Robert J. G.; Lefebvre, Yvonne A.

1999-01-01

Glucocorticoid receptor (GR) cycles between a free liganded form that is localized to the nucleus and a heat shock protein (hsp)-immunophilin-complexed, unliganded form that is usually localized to the cytoplasm but that can also be nuclear. In addition, rapid nucleocytoplasmic exchange or shuttling of the receptor underlies its localization. Nuclear import of liganded GR is mediated through a well-characterized sequence, NL1, adjacent to the receptor DNA binding domain and a second, uncharacterized motif, NL2, that overlaps with the ligand binding domain. In this study we report that rapid nuclear import (half-life [t1/2] of 4 to 6 min) of agonist- and antagonist-treated GR and the localization of unliganded, hsp-associated GRs to the nucleus in G0 are mediated through NL1 and correlate with the binding of GR to pendulin/importin α. By contrast, NL2-mediated nuclear transfer of GR occurred more slowly (t1/2 = 45 min to 1 h), was agonist specific, and appeared to be independent of binding to importin α. Together, these results suggest that NL2 mediates the nuclear import of GR through an alternative nuclear import pathway. Nuclear export of GR was inhibited by leptomycin B, suggesting that the transfer of GR to the cytoplasm is mediated through the CRM1-dependent pathway. Inhibition of GR nuclear export by leptomycin B enhanced the nuclear localization of both unliganded, wild-type GR and hormone-treated NL1− GR. These results highlight that the subcellular localization of both liganded and unliganded GRs is determined, at least in part, by a flexible equilibrium between the rates of nuclear import and export. PMID:9891038

Growth restriction, leptin, and the programming of adult behavior in mice.

PubMed

Meyer, Lauritz R; Zhu, Vivian; Miller, Alise; Roghair, Robert D

2014-12-15

Prematurity and neonatal growth restriction (GR) are risk factors for autism and attention deficit hyperactivity disorder (ADHD). Leptin production is suppressed during periods of undernutrition, and we have shown that isolated neonatal leptin deficiency leads to adult hyperactivity while neonatal leptin supplementation normalizes the brain morphology of GR mice. We hypothesized that neonatal leptin would prevent the development of GR-associated behavioral abnormalities. From postnatal day 4-14, C57BL/6 mice were randomized to daily injections of saline or leptin (80ng/g), and GR was identified by a weanling weight below the tenth percentile. The behavioral phenotypes of GR and control mice were assessed beginning at 4 months. Within the tripartite chamber, GR mice had significantly impaired social interaction. Baseline escape times from the Barnes maze were faster for GR mice (65+/-6s vs 87+/-7s for controls, p<0.05), but GR mice exhibited regression in their escape times on days 2 and 3 (56% regressed vs 22% of control saline mice, p<0.05). Compared to controls, GR mice entered the open arms of the elevated plus maze more often and stayed there longer (72+/-10s vs 36+/-5s, p<0.01). Neonatal leptin supplementation normalized the behavior of GR mice across all behavioral assays. In conclusion, GR alters the social interactions, learning and activity of mice, and supplementation with the neurotrophic hormone leptin mitigates these effects. We speculate neonatal leptin deficiency may contribute to the adverse neurodevelopmental outcomes associated with postnatal growth restriction, and postnatal leptin therapy may be protective. Copyright © 2014 Elsevier B.V. All rights reserved.

Maternal betaine supplementation during gestation modifies hippocampal expression of GR and its regulatory miRNAs in neonatal piglets

PubMed Central

SUN, Qinwei; LI, Xi; JIA, Yimin; PAN, Shifeng; LI, Runsheng; YANG, Xiaojing; ZHAO, Ruqian

2016-01-01

Methyl donor nutrients are critical for embryonic development of brain. Hippocampus is the most susceptible brain region to various factors including prenatal supply of methyl donors. Glucocorticoid receptor (GR) expressed in hippocampus is involved in the regulation of energy homeostasis and stress sensitivity. Hippocampal GR expression is highly susceptible to epigenetic regulation, yet the effect of maternal methyl donor supplementation on epigenetic regulation of GR transcription in offspring hippocampus remains unclear. In this study, we fed sows with betaine (3 g/kg) throughout the gestation and analyzed the hippocampal expression of GR mRNA and its variants, as well as the CpG methylation status of the promoter and the microRNAs predicted to target 3’ UTR of porcine GR gene in neonatal piglets. Total GR mRNA (P<0.01) and its variants GR 1-4 (P<0.05) and 1-9,10 (P<0.01), were significantly higher in the hippocampus of betaine-treated piglets, while the content of GR protein was not significantly changed. The CpGs located in the –1650 ~ –1515 segment of GR gene were hypermethylated (P<0.05). The hippocampal expression of miR-130b (P<0.05), miR-181a (P<0.05) and miR-181d (P<0.01) was significantly up-regulated. The targeting efficacy of miR-130b and miR-181d was validated in vitro using dual-luciferase reporter assay system. Our results demonstrate that maternal betaine supplementation during gestation enhances GR mRNA expression in offspring hippocampus, which involves alterations in miRNAs expression. PMID:26875838

Three-dimensional fusion of spaceborne and ground radar reflectivity data using a neural network-based approach

NASA Astrophysics Data System (ADS)

Kou, Leilei; Wang, Zhuihui; Xu, Fen

2018-03-01

The spaceborne precipitation radar onboard the Tropical Rainfall Measuring Mission satellite (TRMM PR) can provide good measurement of the vertical structure of reflectivity, while ground radar (GR) has a relatively high horizontal resolution and greater sensitivity. Fusion of TRMM PR and GR reflectivity data may maximize the advantages from both instruments. In this paper, TRMM PR and GR reflectivity data are fused using a neural network (NN)-based approach. The main steps included are: quality control of TRMM PR and GR reflectivity data; spatiotemporal matchup; GR calibration bias correction; conversion of TRMM PR data from Ku to S band; fusion of TRMM PR and GR reflectivity data with an NN method; interpolation of reflectivity data that are below PR's sensitivity; blind areas compensation with a distance weighting-based merging approach; combination of three types of data: data with the NN method, data below PR's sensitivity and data within compensated blind areas. During the NN fusion step, the TRMM PR data are taken as targets of the training NNs, and gridded GR data after horizontal downsampling at different heights are used as the input. The trained NNs are then used to obtain 3D high-resolution reflectivity from the original GR gridded data. After 3D fusion of the TRMM PR and GR reflectivity data, a more complete and finer-scale 3D radar reflectivity dataset incorporating characteristics from both the TRMM PR and GR observations can be obtained. The fused reflectivity data are evaluated based on a convective precipitation event through comparison with the high resolution TRMM PR and GR data with an interpolation algorithm.

In situ sonochemical reduction and direct functionalization of graphene oxide: A robust approach with thermal and biomedical applications.

PubMed

Maktedar, Shrikant S; Mehetre, Shantilal S; Avashthi, Gopal; Singh, Man

2017-01-01

The rapid, robust, scalable and non-hazardous sonochemical approach for in situ reduction and direct functionalization of graphene oxide has been developed for non-toxic biomedical applications. The graphene oxide (GrO) was directly functionalized with tryptamine (TA) without using any hazardous acylating and coupling reagents. The reaction was completed within 20min. An impact of ultrasound was inferred for a direct functionalization with other conventional methods. The evolved electronic states were confirmed with near edge X-ray absorption fine structure (NEXAFS). The direct covalent functionalization and formation of f-(TA) GrO was proven with FTIR, 13 C solid state NMR, XPS, XRD, Raman' HRTEM, AFM and TGA. The total percentage weight loss in TGA confirms an enhanced thermal stability of f-(TA) GrO. The f-(TA) GrO was further explored for an investigation of in vitro antimicrobial activity to ensure the health and environmental safety. An outstanding antibacterial activity of f-(TA) GrO was found against gram positive Staphylococcus aureus at MIC 128mgmL -1 . It confirms a suitability of f-(TA) GrO for thermally stable antibacterial coating. The f-(TA) GrO showed 39.14-48.9% antioxidant activities, evaluated with 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical assay. The inherent cytotoxicity of f-(TA) GrO was evaluated with SRB assay to living cells, MCF-7 and Vero. The estimated cell viabilities were >80% upon addition of f-(TA) GrO over a wide concentration range of 10-80μgmL -1 . The high cytocompatibility of f-(TA) GrO confirms the low toxicity and an excellent biocompatibility. The morphological effect on Vero cell line, evidently confirmed the biocompatibility of f-(TA) GrO. Therefore, f-(TA) GrO was emerged as an advanced functional biomaterial for thermal and biomedical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular regulation of urea cycle function by the liver glucocorticoid receptor.

PubMed

Okun, Jürgen G; Conway, Sean; Schmidt, Kathrin V; Schumacher, Jonas; Wang, Xiaoyue; de Guia, Roldan; Zota, Annika; Klement, Johanna; Seibert, Oksana; Peters, Achim; Maida, Adriano; Herzig, Stephan; Rose, Adam J

2015-10-01

One of the major side effects of glucocorticoid (GC) treatment is lean tissue wasting, indicating a prominent role in systemic amino acid metabolism. In order to uncover a novel aspect of GCs and their intracellular-receptor, the glucocorticoid receptor (GR), on metabolic control, we conducted amino acid and acylcarnitine profiling in human and mouse models of GC/GR gain- and loss-of-function. Blood serum and tissue metabolite levels were determined in Human Addison's disease (AD) patients as well as in mouse models of systemic and liver-specific GR loss-of-function (AAV-miR-GR) with or without dexamethasone (DEX) treatments. Body composition and neuromuscular and metabolic function tests were conducted in vivo and ex vivo, the latter using precision cut liver slices. A serum metabolite signature of impaired urea cycle function (i.e. higher [ARG]:[ORN + CIT]) was observed in human (CTRL: 0.45 ± 0.03, AD: 1.29 ± 0.04; p < 0.001) and mouse (AAV-miR-NC: 0.97 ± 0.13, AAV-miR-GR: 2.20 ± 0.19; p < 0.001) GC/GR loss-of-function, with similar patterns also observed in liver. Serum urea levels were consistently affected by GC/GR gain- (∼+32%) and loss (∼-30%) -of-function. Combined liver-specific GR loss-of-function with DEX treatment revealed a tissue-autonomous role for the GR to coordinate an upregulation of liver urea production rate in vivo and ex vivo, and prevent hyperammonaemia and associated neuromuscular dysfunction in vivo. Liver mRNA expression profiling and GR-cistrome mining identified Arginase I (ARG1) a urea cycle gene targeted by the liver GR. The liver GR controls systemic and liver urea cycle function by transcriptional regulation of ARG1 expression.

Differential regulation of the transcriptional activity of the glucocorticoid receptor through site-specific phosphorylation.

PubMed

Kumar, Raj; Calhoun, William J

2008-12-01

Post-translational modifications such as phosphorylation are known to play an important role in the gene regulation by the transcription factors including the nuclear hormone receptor superfamily of which the glucocorticoid receptor (GR) is a member. Protein phosphorylation often switches cellular activity from one state to another. Like many other transcription factors, the GR is a phosphoprotein, and phosphorylation plays an important role in the regulation of GR activity. Cell signaling pathways that regulate phosphorylation of the GR and its associated proteins are important determinants of GR function under various physiological conditions. While the role of many phosphorylation sites in the GR is still not fully understood, the role of others is clearer. Several aspects of transcription factor function, including DNA binding affinity, interaction of transactivation domains with the transcription initiation complex, and shuttling between the cytoplasmic compartments, have all been linked to site-specific phosphorylation. All major phosphorylation sites in the human GR are located in the N-terminal domain including the major transactivation domain, AF1. Available literature clearly indicates that many of these potential phosphorylation sites are substrates for multiple kinases, suggesting the potential for a very complex regulatory network. Phosphorylated GR interacts favorably with critical coregulatory proteins and subsequently enhances transcriptional activity. In addition, the activities and specificities of coregulators may be subject to similar regulation by phosphorylation. Regulation of the GR activity due to phosphorylation appears to be site-specific and dependent upon specific cell signaling cascade. Taken together, site-specific phosphorylation and related kinase pathways play an important role in the action of the GR, and more precise mechanistic information will lead to fuller understanding of the complex nature of gene regulation by the GR- and related transcription factors. This review provides currently available information regarding the role of GR phosphorylation in its action, and highlights the possible underlying mechanisms of action.

Hydrodynamic properties of the gonadotropin receptor from a murine Leydig tumor cell line are altered by desensitization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rebois, R.V.; Bradley, R.M.; Titlow, C.C.

1987-10-06

The murine Leydig tumor cell line 1 (MLTC-1) contains gonadotropin receptors (GR) that are coupled to adenylate cyclase through the stimulatory guanine nucleotide binding protein (G/sub s/). The binding of human choriogonadotropin (hGC) causes MLTC-1 cells to accumulate cAMP. With time, the ability of MLTC-1 cells to respond to hCG is attenuated by a process called desensitization. The hydrodynamic properties of GR from control and desensitized MLTC-1 cells were studied. Sucrose density gradient sedimentation in H/sub 2/O and D/sub 2/O and gel filtration chromatography were used to estimate the Stokes radius (a), partial specific volume (v/sub c/), sedimentation coefficient (s/submore » 20,w/), and molecular weight (M/sub r/) of the detergent-solubilized hormone-receptor complex (hCG-GR). (/sup 125/I)hCG was bound to MLTC-1 cells under conditions that allow (37/sup 0/C) or prevent (0/sup 0/C) desensitization, and hCG-GR was solubilized in Triton X-100. In the absence of desensitization, control hCG-GR had a M/sub r/ of 213,000, whereas desensitized hCG-GR had a M/sub r/ of 158,000. Deglycosylated hCG (DG-HCG) is an antagonist that binds to GR with high affinity but fails to stimulate adenylate cyclase or cause desensitization. (/sup 125/I)DG-hCG was bound to MLTC-1 cells and DG-hCG-GR solubilized in Triton X-100. The hydrodynamic properties of DG-hCG-GR were the same as that for control hCG-GR. There was no evidence for the association of adenylate cyclase or G/sub s/ with GR in Triton X-100 solubilized preparations. When hCG was cross-linked to GR and solubilized with sodium dodecyl sulfate (SDS), the M/sub r/ was found to be 116,000, which was similar to that determined by SDS-polyacrylamide gel electrophoresis and less than that of the Triton X-100 solubilized control hCG-GR.« less

Younger Elementary Students Waste More School Lunch Foods than Older Elementary Students

PubMed Central

Niaki, Shahrbanou F.; Moore, Carolyn E.; Chen, Tzu-An

2016-01-01

Background Children may not receive the nutritional benefits from school lunch meals if they do not eat the foods served. Objective This study investigated whether there were differences in school lunch foods consumed and wasted by grade level of elementary school students. Design In this cross-sectional study, anonymous meal observations were conducted after students selected their reimbursable school lunch meals in the cafeteria lunch line. The amount of foods selected and consumed was recorded using the quarter waste method and food waste was calculated using the information recorded. Participants/setting During the spring of 2013, eight elementary schools (50% low income) enrolling children in kindergarten through grade 5 in one school district in the Houston, Texas area were selected by the Child Nutrition Director. Main outcome measures The amount of kilocalories (kcal) and foods consumed and the percentage wasted were assessed. Statistical analyses performed Analysis of Covariance (ANCOVA) and post hoc analysis were used to examine food consumption and plate waste by grade level [kindergarten and grade 1 (K-Gr1), grade 2 and 3 (Gr2-3) and grade four and five (Gr4-5)], controlling for student sex and school level free/reduced priced meal eligibility (FRP). Results There were 568 nonrandom lunch meal observations of students included in the analyses. Approximately 48% of the observations were from boys; 50% were from low income schools, and were evenly divided by grade. In general, students in K-Gr1 consumed fewer kcal than both Gr2-3 and Gr4-5 students, and Gr2-3 students consumed significantly fewer kcal than Gr4-5 students. K-Gr1 students also consumed less and wasted more total and red-orange vegetables, total/whole/refined grains, and total protein foods than the older students. Gr2-3 students wasted more calories and total grains than Gr4-5 students. K-Gr1 wasted more fruit than Gr2-3 students. Conclusions Overall, younger students in elementary schools (K-Gr1) consumed less of the foods they selected for their lunch meals, and wasted more than older elementary school students. Future studies should investigate why younger children wasted more food and potential strategies to reduce food waste by younger students. PMID:27637576

Increasing Completion Rate of an M4 Emergency Medicine Student End-of-Shift Evaluation Using a Mobile Electronic Platform and Real-Time Completion.

PubMed

Tews, Matthew C; Treat, Robert W; Nanes, Maxwell

2016-07-01

Medical students on an emergency medicine rotation are traditionally evaluated at the end of each shift with paper-based forms, and data are often missing due to forms not being turned in or completed. Because students' grades depend on these evaluations, change was needed to increase form rate of return. We analyzed a new electronic evaluation form and modified completion process to determine if it would increase the completion rate without altering how faculty scored student performance. During fall 2013, 29 faculty completed paper N=339 evaluations consisting of seven competencies for 33 students. In fall 2014, an electronic evaluation form with the same competencies was designed using an electronic platform and completed N=319 times by 27 faculty using 25 students' electronic devices. Feedback checkboxes were added to facilitate collection of common comments. Data was analyzed with IBM® SPSS® 21.0 using multi-factor analysis of variance with the students' global rating (GR) as an outcome. Inter-item reliability was determined with Cronbach alpha. There was a significantly higher completion rate (p=0.001) of 98% electronic vs. 69% paper forms, lower (p=0.001) missed GR rate (1% electronic. vs 12% paper), and higher mean scores (p=0.001) for the GR with the electronic (7.0±1.1) vs. paper (6.8±1.2) form. Feedback checkboxes were completed on every form. The inter-item reliability for electronic and paper forms was each alpha=0.95. The use of a new electronic form and modified completion process for evaluating students at the end of shift demonstrated a higher faculty completion rate, a lower missed data rate, a higher global rating and consistent collection of common feedback. The use of the electronic form and the process for obtaining the information made our end-of-shift evaluation process for students more reliable and provided more accurate, up-to-date information for student feedback and when determining student grades.

Pilot evaluation of four experimental conditioning treatments to improve the bond strength between resin cement and Y-TZP ceramic.

PubMed

Monaco, Carlo; Cardelli, Paolo; Scotti, Roberto; Valandro, Luiz Felipe

2011-02-01

This study evaluated the bond strength between resin cement and Y-TZP ceramic (Yttrium-stabilized Tetragonal Zirconia Polycrystalline) submitted to different surface conditionings. Fifty Y-TZP ceramic discs (Ø= 10 mm) were allocated into five groups: Gr1 (control)-no conditioning; Gr2-tribochemical silica coating (30-μm SiO(2)) before sintering; Gr3-air abrasion with 50-μm Al(2)O(3) before sintering; Gr4-air abrasion with 110-μ Al(2)O(3) before sintering; Gr5 - air abrasion with 50-μm Al(2)O(3) after sintering. After specimen preparation, cylinders of composite resin were prepared and immediately cemented onto the ceramic. A shear test was performed. One-way ANOVA indicated a statistically significant difference among the groups (p= 0.0019). The mean shear bond strengths (MPa) were: Gr1 = 4.7 ± 0.8,(b) Gr2 = 4.6 ± 0.9,(b) Gr3 = 6.4 ± 1.0,(a) Gr4 = 6.5 ± 1.8,(a) Gr5 = 6 ± 1.3(ab) (same superscript letter indicates statistical similarity). Adhesive fracture between the ceramic and resin cement was the most common failure. No complete cohesive fracture at the ceramic or composite cylinders was noted. Within the limitations of this study, additional surface treatment with air abrasion before and after sintering provided a significant increase in bond strength. Tribochemical silica coating before sintering was not effective as a surface treatment. © 2011 by The American College of Prosthodontists.

Structure and Dynamic Properties of a Glucocorticoid Receptor-Induced Chromatin Transition

PubMed Central

Fletcher, Terace M.; Ryu, Byung-Woo; Baumann, Christopher T.; Warren, Barbour S.; Fragoso, Gilberto; John, Sam; Hager, Gordon L.

2000-01-01

Activation of the mouse mammary tumor virus (MMTV) promoter by the glucocorticoid receptor (GR) is associated with a chromatin structural transition in the B nucleosome region of the viral long terminal repeat (LTR). Recent evidence indicates that this transition extends upstream of the B nucleosome, encompassing a region larger than a single nucleosome (G. Fragoso, W. D. Pennie, S. John, and G. L. Hager, Mol. Cell. Biol. 18:3633–3644). We have reconstituted MMTV LTR DNA into a polynucleosome array using Drosophila embryo extracts. We show binding of purified GR to specific GR elements within a large, multinucleosome array and describe a GR-induced nucleoprotein transition that is dependent on ATP and a HeLa nuclear extract. Previously uncharacterized GR binding sites in the upstream C nucleosome region are involved in the extended region of chromatin remodeling. We also show that GR-dependent chromatin remodeling is a multistep process; in the absence of ATP, GR binds to multiple sites on the chromatin array and prevents restriction enzyme access to recognition sites. Upon addition of ATP, GR induces remodeling and a large increase in access to enzymes sites within the transition region. These findings suggest a dynamic model in which GR first binds to chromatin after ligand activation, recruits a remodeling activity, and is then lost from the template. This model is consistent with the recent description of a “hit-and-run” mechanism for GR action in living cells (J. G. McNally, W. G. Müller, D. Walker, and G. L. Hager, Science 287:1262–1264, 2000). PMID:10938123

Separation of an associated 90K heat shock protein from the glucocorticoid receptor complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller-Diener, A.; Kirsch, T.; Grove, B.

1986-05-01

A 90K heat shock protein(HSP), observed to copurify with the glucocorticoid receptor(GR), can be separated from the complex by 2 methods, allowing investigation of the role of HSP on kinase activity that was previously reported to be inherent to purified activated GR. Na/sub 2/MoO/sub 4/ stabilized unactivated rat hepatic GR complexes have been purified to >10,000-fold using a purification scheme that involves batchwise treatment of cytosol with phosphocellulose/DNAcellulose, elution from an affinity resin, gel filtration and ion exchange chromatography. Samples were subjected to 10-20% gradient SDS-PAGE. Proteins were transferred to nitrocellulose and blotted against monoclonal antibodies to GR(3A6), HSP ormore » nonspecific IgM/G. Immunoblots indicated that HSP was separated from unactivated GR complexes at the affinity step prior to elution of GR with active steroid. GR eluted from the resin with /sup 3/H Triamcinolone acetonide or /sup 3/H Dexamethasone mesylate had an apparent M/sub r/ = 94-96,000 for the steroid binding subunit and is recognized by 3A6. Purification of GR minus the affinity step resulted in copurification of HSP throughout the procedure. However, after Sephadex G75 filtration and subsequent incubation at 25/sup 0/C, 30 min., HSP was separated from activated (DNA binding) GR on DEAE cellulose-52. HSP did not enhance or inhibit /sup 32/P incorporation of the 94K steroid binding subunit nor did it affect phosphorylation of histones by GR.« less

Expression of the fructose receptor BmGr9 and its involvement in the promotion of feeding, suggested by its co-expression with neuropeptide F1 in Bombyx mori.

PubMed

Mang, Dingze; Shu, Min; Tanaka, Shiho; Nagata, Shinji; Takada, Tomoyuki; Endo, Haruka; Kikuta, Shingo; Tabunoki, Hiroko; Iwabuchi, Kikuo; Sato, Ryoichi

2016-08-01

Insect gustatory receptors (Grs) are members of a large family of proteins with seven transmembrane domains that provide insects with the ability to detect chemical signals critical for feeding, mating, and oviposition. To date, 69 Bombyx mori Grs (BmGrs) genes have been identified via genome studies. BmGr9 has been shown to respond specifically to fructose and to function as a ligand-gated ion channel selectively activated by fructose. However, the sites where this Gr are expressed remain unclear. We demonstrated using reverse transcription (RT)-PCR that BmGr9 is widely expressed in the central nervous system (CNS), as well as oral sensory organs. Additionally, immunohistochemistry was performed using anti-BmGr9 antiserum to show that BmGr9 is expressed in cells of the oral sensory organs, including the maxillary galea, maxillary palps, labrum, and labium, as well as in putative neurosecretory cells of the CNS. Furthermore, double immunohistochemical analysis showed that most BmGr9-expressing cells co-localized with putative neuropeptide F1-expressing cells in the brain, suggesting that BmGr9 is involved in the promotion of feeding behaviors. In addition, a portion of BmGr9-expressing cells in the brain co-localized with cells expressing BmGr6, a molecule of the sugar receptor clade, suggesting that sugars other than fructose are involved in the regulation of feeding behaviors in B. mori larvae. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reduced glucocorticoid receptor expression predicts bladder tumor recurrence and progression.

PubMed

Ishiguro, Hitoshi; Kawahara, Takashi; Zheng, Yichun; Netto, George J; Miyamoto, Hiroshi

2014-08-01

To assess the levels of glucocorticoid receptor (GR) expression in bladder tumors because the status and its prognostic value remain largely unknown. We immunohistochemically stained for GR in bladder tumor and matched non-neoplastic bladder tissue specimens. Overall, GR was positive in 129 (87%) of 149 urothelial tumors, which was significantly (P=.026) lower than in non-neoplastic urothelium (90 [96%] of 94). Forty-two (79%) of 53 low-grade tumors vs 45 (47%) of 96 high-grade carcinomas (P<.001) and 61 (73%) of 84 non-muscle-invasive (NMI) tumors vs 26 (40%) of 65 muscle-invasive (MI) carcinomas (P<.001) were moderately to strongly immunoreactive for GR. Kaplan-Meier and log-rank tests revealed that loss or weak positivity of GR significantly or marginally correlated with recurrence of NMI tumors (P=.025), progression of MI tumors (P=.082), and cancer-specific survival of MI tumors (P=.067). Multivariate analysis identified low GR expression as a strong predictor for recurrence of NMI tumors (P=.034). GR expression was downregulated in bladder tumors compared with nonneoplastic bladder tumors and in high-grade/MI tumors compared with low-grade/NMI tumors. Decreased expression of GR, as an independent prognosticator, predicted recurrence of NMI tumors. These results support experimental evidence suggesting an inhibitory role of GR signals in bladder cancer outgrowth. Copyright© by the American Society for Clinical Pathology.

DFT Studies of Graphene-Functionalised Derivatives of Capecitabine

NASA Astrophysics Data System (ADS)

Aramideh, Mehdi; Mirzaei, Mahmoud; Khodarahmi, Ghadamali; Gülseren, Oğuz

2017-11-01

Cancer is one of the major problems for so many people around the world; therefore, dedicating efforts to explore efficient therapeutic methodologies is very important for researchers of life sciences. In this case, nanostructures are expected to be carriers of medicinal compounds for targeted drug design and delivery purposes. Within this work, the graphene (Gr)-functionalised derivatives of capecitabine (CAP), as a representative anticancer, have been studied based on density functional theory calculations. Two different sizes of Gr molecular models have been used for the functionalisation of CAP counterparts, CAP-Gr3 and CAP-Gr5, to explore the effects of Gr-functionalisation on the original properties of CAP. All singular and functionalised molecular models have been optimised and the molecular and atomic scale properties have been evaluated for the optimised structures. Higher formation favourability has been obtained for CAP-Gr5 in comparison with CAP-Gr3 and better structural stability has been obtained in the water-solvated system than the isolated gas-phase system for all models. The CAP-Gr5 model could play a better role of electron transferring in comparison with the CAP-Gr3 model. As a concluding remark, the molecular properties of CAP changed from singular to functionalised models whereas the atomic properties remained almost unchanged, which is expected for a carrier not to use significant perturbations to the original properties of the carried counterpart.

J-R fracture characteristics of ferritic steels for RPVs and RCS piping of nuclear power plants

NASA Astrophysics Data System (ADS)

Yoon, Ji-Hyun; Lee, Bong-Sang; Hong, Jun-Hwa

2001-10-01

J-R fracture resistance tests have been performed on 3 heats of SA508-Gr.3 nuclear reactor pressure vessel (RPV) steel as well as 2 heats of SA516-Gr.70 and a heat of SA508-Gr.1a steels for nuclear reactor coolant system (RCS) piping. For the latter two steels, dynamic in addition to static J-R fracture resistances were investigated. From the test results of the SA508-Gr.3 steels, the J-R fracture resistance was superior in the following order: Si-killing steel, modified VCD steel and VCD steel. Microstructural analyses were carried out to correlate J-R fracture resistances with microstructural characteristics. According to the test results for SA508-Gr.1a and SA516-Gr.70 steels, all of the tested steels showed steep drops in fracture resistance at certain temperature and loading rate combinations. One heat of SA516-Gr.70 steel was very sensitive to dynamic strain aging and its fracture resistance was significantly low. It was concluded that microstructural and chemical factors affect the J-R fracture and DSA characteristics of SA516-Gr.70 steels.

Challenges in graphene integration for high-frequency electronics

NASA Astrophysics Data System (ADS)

Giannazzo, F.; Fisichella, G.; Greco, G.; Roccaforte, F.

2016-06-01

This paper provides an overview of the state-of-the-art research on graphene (Gr) for high-frequency (RF) devices. After discussing current limitations of lateral Gr RF transistors, novel vertical devices concepts such as the Gr Base Hot Electron Transistor (GBHET) will be introduced and the main challenges in Gr integration within these architectures will be discussed. In particular, a GBHET device based on Gr/AlGaN/GaN heterostructure will be considered. An approach to the fabrication of this heterostructure by transfer of CVD grown Gr on copper to the AlGaN surface will be presented. The morphological and electrical properties of this system have been investigated at nanoscale by atomic force microscopy (AFM) and conductive atomic force microscopy (CAFM). In particular, local current-voltage measurements by the CAFM probe revealed the formation of a Schottky contact with low barrier height (˜0.41 eV) and excellent lateral uniformity between Gr and AlGaN. Basing on the electrical parameters extracted from this characterization, the theoretical performances of a GBHET formed by a metal/Al2O3/Gr/AlGaN/GaN stack have been evaluated.

Cryptic glucocorticoid receptor-binding sites pervade genomic NF-κB response elements.

PubMed

Hudson, William H; Vera, Ian Mitchelle S de; Nwachukwu, Jerome C; Weikum, Emily R; Herbst, Austin G; Yang, Qin; Bain, David L; Nettles, Kendall W; Kojetin, Douglas J; Ortlund, Eric A

2018-04-06

Glucocorticoids (GCs) are potent repressors of NF-κB activity, making them a preferred choice for treatment of inflammation-driven conditions. Despite the widespread use of GCs in the clinic, current models are inadequate to explain the role of the glucocorticoid receptor (GR) within this critical signaling pathway. GR binding directly to NF-κB itself-tethering in a DNA binding-independent manner-represents the standing model of how GCs inhibit NF-κB-driven transcription. We demonstrate that direct binding of GR to genomic NF-κB response elements (κBREs) mediates GR-driven repression of inflammatory gene expression. We report five crystal structures and solution NMR data of GR DBD-κBRE complexes, which reveal that GR recognizes a cryptic response element between the binding footprints of NF-κB subunits within κBREs. These cryptic sequences exhibit high sequence and functional conservation, suggesting that GR binding to κBREs is an evolutionarily conserved mechanism of controlling the inflammatory response.

Glyphosate Can Decrease Germination of Glyphosate-Resistant Soybeans.

PubMed

Gomes, Marcelo Pedrosa; Bicalho, Elisa Monteze; Smedbol, Élise; Cruz, Fernanda Vieira da Silva; Lucotte, Marc; Garcia, Queila Souza

2017-03-22

We investigated the effects of different concentrations of glyphosate acid and one of its formulations (Roundup) on seed germination of two glyphosate-resistant (GR) and one non-GR variety of soybean. As expected, the herbicide affected the shikimate pathway in non-GR seeds but not in GR seeds. We observed that glyphosate can disturb the mitochondrial electron transport chain, leading to H 2 O 2 accumulation in soybean seeds, which was, in turn, related to lower seed germination. In addition, GR seeds showed increased activity of antioxidant systems when compared to non-GR seeds, making them less vulnerable to oxidative stress induced by glyphosate. The differences in the responses of GR varieties to glyphosate exposure corresponded to their differences in enzymatic activity related to H 2 O 2 scavenging and mitochondrial complex III (the proposed site of ROS induction by glyphosate). Our results showed that glyphosate ought to be used carefully as a pre-emergence herbicide in soybean field crop systems because this practice may reduce seed germination.

A report on the current status of grand rounds in radiology residency programs in the United States.

PubMed

Yablon, Corrie M; Wu, Jim S; Slanetz, Priscilla J; Eisenberg, Ronald L

2011-12-01

A national needs assessment of radiology program directors was performed to characterize grand rounds (GR) programs, assess the perceived educational value of GR programs, and determine the impact of the recent economic downturn on GR. A 28-question survey was developed querying the organizational logistics of GR programs, types of speakers, content of talks, honoraria, types of speakers invited, response to the economic downturn, types of speaker interaction with residents, and perceived educational value of GR. Questions were in multiple-choice, yes-or-no, and five-point Likert-type formats. The survey was distributed to the program directors of all radiology residencies within the United States. Fifty-seven of 163 programs responded, resulting in a response rate of 36%. Thirty-eight programs (67%) were university residencies and 10 (18%) were university affiliated. Eighty-two percent of university and 60% of university-affiliated residencies had their own GR programs, while only 14% of community and no military residencies held GR. GR were held weekly in 18% of programs, biweekly in 8%, monthly in 42%, bimonthly in 16%, and less frequently than every 2 months in 16%. All 38 programs hosting GR reported a broad spectrum of presentations, including talks on medical education (66%), clinical and evidence-based medicine (55%), professionalism (45%), ethics (45%), quality assurance (34%), global health (26%), and resident presentations (26%). All programs invited speakers from outside the institution, but there was variability with regard to the frequency of visits and whether invited speakers were from out of town. As a result of recent economic events, one radiology residency (3%) completely canceled its GR program. Others decreased the number of speakers from outside their cities (40%) or decreased the number of speakers from within their own cities (16%). Honoraria were paid to speakers by 95% of responding programs. Most program directors (79%) who had their own GR programs either strongly agreed or agreed that GR are an essential component of any academic radiology department, and this opinion was shared by a majority of all respondents (68%). Almost all respondents (97%) either strongly agreed or agreed that general radiologic education of imaging subspecialists is valuable in an academic radiology department. A majority (65%) either strongly agreed or agreed that attendance at GR should be expected of all attending radiologists. GR programs among radiology residencies tend to have similar formats involving invited speakers, although the frequency, types of talks, and honoraria may vary slightly. Most programs value GR, and all programs integrate GR within resident education to some degree. The recent economic downturn has led to a decrease in the number of invited visiting speakers but not to a decrease in the amounts of honoraria. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

A Study on Gröbner Basis with Inexact Input

NASA Astrophysics Data System (ADS)

Nagasaka, Kosaku

Gröbner basis is one of the most important tools in recent symbolic algebraic computations. However, computing a Gröbner basis for the given polynomial ideal is not easy and it is not numerically stable if polynomials have inexact coefficients. In this paper, we study what we should get for computing a Gröbner basis with inexact coefficients and introduce a naive method to compute a Gröbner basis by reduced row echelon form, for the ideal generated by the given polynomial set having a priori errors on their coefficients.

Low Phase Noise Fiber Optics Links for Space Applications

DTIC Science & Technology

2005-07-13

photo- oscillateur intégré pour 17 dB de pertes optiques Liaison active à 874,2 MHz avec photo- oscillateur intégré pour 18 dB de pertes optiques Liaison...active à 874,2 MHz avec photo- oscillateur intégré pour 20 dB de pertes optiques Liaison active à 874,2 MHz avec photo- oscillateur intégré pour 23 dB...de pertes optiques Liaison active à 874,2 MHz avec photo- oscillateur intégré pour 25 dB de pertes optiques Liaison active à 874,2 MHz avec photo

Tumor cell-released TLR4 ligands stimulate Gr-1+CD11b+F4/80+ cells to induce apoptosis of activated T cells.

PubMed

Liu, Yan-Yan; Sun, Ling-Cong; Wei, Jing-Jing; Li, Dong; Yuan, Ye; Yan, Bin; Liang, Zhi-Hui; Zhu, Hui-Fen; Xu, Yong; Li, Bo; Song, Chuan-Wang; Liao, Sheng-Jun; Lei, Zhang; Zhang, Gui-Mei; Feng, Zuo-Hua

2010-09-01

Gr-1(+)CD11b(+)F4/80(+) cells play important roles in tumor development and have a negative effect on tumor immunotherapy. So far, the mechanisms underlying the regulation of their immunosuppressive phenotype by classical and alternative macrophage activation stimuli are not well elucidated. In this study, we found that molecules from necrotic tumor cells (NTC-Ms) stimulated Gr-1(+)CD11b(+)F4/80(+) cells to induce apoptosis of activated T cells but not nonstimulated T cells. The apoptosis-inducing capacity was determined by higher expression levels of arginase I and IL-10 relative to those of NO synthase 2 and IL-12 in Gr-1(+)CD11b(+)F4/80(+) cells, which were induced by NTC-Ms through TLR4 signaling. The apoptosis-inducing capacity of NTC-Ms-stimulated Gr-1(+)CD11b(+)F4/80(+) cells could be enhanced by IL-10. IFN-gamma may reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells only if their response to IFN-gamma was not attenuated. However, the potential of Gr-1(+)CD11b(+)F4/80(+) cells to express IL-12 in response to IFN-gamma could be attenuated by tumor, partially due to the existence of active STAT3 in Gr-1(+)CD11b(+)F4/80(+) cells and NTC-Ms from tumor. In this situation, IFN-gamma could not effectively reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells. Tumor immunotherapy with 4-1BBL/soluble programmed death-1 may significantly reduce, but not abolish the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells in local microenvironment. Blockade of TLR4 signaling could further reduce the apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and enhance the suppressive effect of 4-1BBL/soluble form of programmed death-1 on tumor growth. These findings indicate the relationship of distinct signaling pathways with apoptosis-inducing capacity of Gr-1(+)CD11b(+)F4/80(+) cells and emphasize the importance of blocking TLR4 signaling to prevent the induction of T cell apoptosis by Gr-1(+)CD11b(+)F4/80(+) cells.

Current transport in graphene/AlGaN/GaN vertical heterostructures probed at nanoscale.

PubMed

Fisichella, Gabriele; Greco, Giuseppe; Roccaforte, Fabrizio; Giannazzo, Filippo

2014-08-07

Vertical heterostructures combining two or more graphene (Gr) layers separated by ultra-thin insulating or semiconductor barriers represent very promising systems for next generation electronics devices, due to the combination of high speed operation with wide-range current modulation by a gate bias. They are based on the specific mechanisms of current transport between two-dimensional-electron-gases (2DEGs) in close proximity. In this context, vertical devices formed by Gr and semiconductor heterostructures hosting an "ordinary" 2DEG can be also very interesting. In this work, we investigated the vertical current transport in Gr/Al(0.25)Ga(0.75)N/GaN heterostructures, where Gr is separated from a high density 2DEG by a ∼ 24 nm thick AlGaN barrier layer. The current transport from Gr to the buried 2DEG was characterized at nanoscale using conductive atomic force microscopy (CAFM) and scanning capacitance microscopy (SCM). From these analyses, performed both on Gr/AlGaN/GaN and on AlGaN/GaN reference samples using AFM tips with different metal coatings, the Gr/AlGaN Schottky barrier height ΦB and its lateral uniformity were evaluated, as well as the variation of the carrier densities of graphene (ngr) and AlGaN/GaN 2DEG (ns) as a function of the applied bias. A low Schottky barrier (∼ 0.40 eV) with excellent spatial uniformity was found at the Gr/AlGaN interface, i.e., lower compared to the measured values for metal/AlGaN contacts, which range from ∼ 0.6 to ∼ 1.1 eV depending on the metal workfunction. The electrical behavior of the Gr/AlGaN contact has been explained by Gr interaction with AlGaN donor-like surface states located in close proximity, which are also responsible of high n-type Gr doping (∼ 1.3 × 10(13) cm(-2)). An effective modulation of ns by the Gr Schottky contact was demonstrated by capacitance analysis under reverse bias. From this basic understanding of transport properties in Gr/AlGaN/GaN heterostructures, novel vertical field effect transistor concepts with high operating speed and I(on)/I(off) ratio can be envisaged.

[125I]-GR231118: a high affinity radioligand to investigate neuropeptide Y Y1 and Y4 receptors

PubMed Central

Dumont, Yvan; Quirion, Rémi

2000-01-01

GR231118 (also known as 1229U91 and GW1229), a purported Y1 antagonist and Y4 agonist was radiolabelled using the chloramine T method. [125I]-GR231118 binding reached equilibrium within 10 min at room temperature and remained stable for at least 4 h. Saturation binding experiments showed that [125I]-GR231118 binds with very high affinity (Kd of 0.09–0.24 nM) in transfected HEK293 cells with the rat Y1 and Y4 receptor cDNA and in rat brain membrane homogenates. No specific binding sites could be detected in HEK293 cells transfected with the rat Y2 or Y5 receptor cDNA demonstrating the absence of significant affinity of GR231118 for these two receptor classes. Competition binding experiments revealed that specific [125I]-GR231118 binding in rat brain homogenates is most similar to that observed in HEK293 cells transfected with the rat Y1, but not rat Y4, receptor cDNA. Autoradiographic studies demonstrated that [125I]-GR231118 binding sites were fully inhibited by the Y1 antagonist BIBO3304 in most areas of the rat brain. Interestingly, high percentage of [125I]-GR231118/BIBO3304-insensitive binding sites were detected in few areas. These [125I]-GR231118/BIBO3304-insensitive binding sites likely represent labelling to the Y4 receptor subtype. In summary, [125I]-GR231118 is a new radiolabelled probe to investigate the Y1 and Y4 receptors; its major advantage being its high affinity. Using highly selective Y1 antagonists such as BIBO3304 or BIBP3226 it is possible to block the binding of [125I]-GR231118 to the Y1 receptor allowing for the characterization and visualization of the purported Y4 subtype. PMID:10694200

Arabidopsis GLUTATHIONE REDUCTASE1 Plays a Crucial Role in Leaf Responses to Intracellular Hydrogen Peroxide and in Ensuring Appropriate Gene Expression through Both Salicylic Acid and Jasmonic Acid Signaling Pathways1[C][W][OA

PubMed Central

Mhamdi, Amna; Hager, Jutta; Chaouch, Sejir; Queval, Guillaume; Han, Yi; Taconnat, Ludivine; Saindrenan, Patrick; Gouia, Houda; Issakidis-Bourguet, Emmanuelle; Renou, Jean-Pierre; Noctor, Graham

2010-01-01

Glutathione is a major cellular thiol that is maintained in the reduced state by glutathione reductase (GR), which is encoded by two genes in Arabidopsis (Arabidopsis thaliana; GR1 and GR2). This study addressed the role of GR1 in hydrogen peroxide (H2O2) responses through a combined genetic, transcriptomic, and redox profiling approach. To identify the potential role of changes in glutathione status in H2O2 signaling, gr1 mutants, which show a constitutive increase in oxidized glutathione (GSSG), were compared with a catalase-deficient background (cat2), in which GSSG accumulation is conditionally driven by H2O2. Parallel transcriptomics analysis of gr1 and cat2 identified overlapping gene expression profiles that in both lines were dependent on growth daylength. Overlapping genes included phytohormone-associated genes, in particular implicating glutathione oxidation state in the regulation of jasmonic acid signaling. Direct analysis of H2O2-glutathione interactions in cat2 gr1 double mutants established that GR1-dependent glutathione status is required for multiple responses to increased H2O2 availability, including limitation of lesion formation, accumulation of salicylic acid, induction of pathogenesis-related genes, and signaling through jasmonic acid pathways. Modulation of these responses in cat2 gr1 was linked to dramatic GSSG accumulation and modified expression of specific glutaredoxins and glutathione S-transferases, but there is little or no evidence of generalized oxidative stress or changes in thioredoxin-associated gene expression. We conclude that GR1 plays a crucial role in daylength-dependent redox signaling and that this function cannot be replaced by the second Arabidopsis GR gene or by thiol systems such as the thioredoxin system. PMID:20488891

Region-specific Alterations in Glucocorticoid Receptor Expression in the Postmortem Brain of Teenage Suicide Victims

PubMed Central

Pandey, Ghanshyam N.; Rizavi, Hooriyah S.; Ren, Xinguo; Dwivedi, Yogesh; Palkovits, Miklós

2013-01-01

Introduction Abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and suicide. The purpose of this study was to test the hypothesis that the reported dysregulation of the HPA axis in suicide may be related to a disturbed feedback inhibition caused by decreased corticoid receptors in the brain. We therefore determined the protein and gene expression of glucocorticoid (GR) and mineralocorticoid receptors (MR) in the postmortem brain of teenage suicide victims and matched normal controls. Methods Protein and mRNA expression of GR (GR-α and GR-β) and MR and the mRNA expression of glucocorticoid-induced leucine zipper (GILZ), a target gene for GR were determined by immunolabeling using Western blot technique and the real-time RT-polymerase chain reaction (qPCR) technique in the prefrontal cortex (PFC), hippocampus, subiculum, and amygdala obtained from 24 teenage suicide victims and 24 teenage control subjects. Results We observed that protein and gene expression of GR-α was significantly decreased in the PFC and amygdala, but not in the hippocampus or subiculum, of teenage suicide victims compared with normal control subjects. Also, the mRNA levels of GR inducible target gene GILZ was significantly decreased in PFC and amygdaloid nuclei but not in hippocampus compared with controls. In contrast, no significant differences were observed in protein or gene expression of MR in any of the areas studied between teenage suicide victims and normal control subjects. There was no difference in the expression of GR-β in the PFC between suicide victims and normal controls. Conclusions These results suggested that the observed dysregulation of the HPA axis in suicide may be related to a decreased expression of GR-α and GR inducible genes in the PFC and amygdala of teenage suicide victims. The reason why GR receptors are not dysregulated in the hippocampus or subiculum, presumably two sites of stress action, are not clear at this time. PMID:23845513

Validation of the German revised version of the program in palliative care education and practice questionnaire (PCEP-GR).

PubMed

Fetz, Katharina; Wenzel-Meyburg, Ursula; Schulz-Quach, Christian

2017-12-28

The evaluation of the effectiveness of undergraduate palliative care education (UPCE) programs is an essential foundation to providing high-quality UPCE programs. Therefore, the implementation of valid evaluation tools is indispensable. Until today, there has been no general consensus regarding concrete outcome parameters and their accurate measurement. The Program in Palliative Care Education and Practice Questionnaire (German Revised Version; PCEP-GR) is a promising assessment tool for UPCE. The aim of the current study was to evaluate the psychometric properties of PCEP-GR and to demonstrate its feasibility for the evaluation of UPCE programs. The practical feasibility of the PCEP-GR and its acceptance in medical students were investigated in a pilot study with 24 undergraduate medical students at Heinrich Heine University Dusseldorf, Germany. Subsequently, the PCEP-GR was surveyed in a representative sample (N = 680) of medical students in order to investigate its psychometric properties. Factorial validity was investigated by means of principal component analysis (PCA). Reliability was examined by means of split-half-reliability analysis and analysis of internal consistency. After taking into consideration the PCA and distribution analysis results, an evaluation instruction for the PCEP-GR was developed. The PCEP-GR proved to be feasible and well-accepted in medical students. PCA revealed a four-factorial solution indicating four PCEP-GR subscales: preparation to provide palliative care, attitudes towards palliative care, self-estimation of competence in communication with dying patients and their relatives and self-estimation of knowledge and skills in palliative care. The PCEP-GR showed good split-half-reliability and acceptable to good internal consistency of subscales. Attitudes towards palliative care slightly missed the criterion of acceptable internal consistency. The evaluation instruction suggests a global PCEP-GR index and four subscales. The PCEP-GR has proven to be a feasible, economic, valid and reliable tool for the assessment of UPCE that comprises self-efficacy expectation and relevant attitudes towards palliative care.

Arabidopsis GLUTATHIONE REDUCTASE1 plays a crucial role in leaf responses to intracellular hydrogen peroxide and in ensuring appropriate gene expression through both salicylic acid and jasmonic acid signaling pathways.

PubMed

Mhamdi, Amna; Hager, Jutta; Chaouch, Sejir; Queval, Guillaume; Han, Yi; Taconnat, Ludivine; Saindrenan, Patrick; Gouia, Houda; Issakidis-Bourguet, Emmanuelle; Renou, Jean-Pierre; Noctor, Graham

2010-07-01

Glutathione is a major cellular thiol that is maintained in the reduced state by glutathione reductase (GR), which is encoded by two genes in Arabidopsis (Arabidopsis thaliana; GR1 and GR2). This study addressed the role of GR1 in hydrogen peroxide (H(2)O(2)) responses through a combined genetic, transcriptomic, and redox profiling approach. To identify the potential role of changes in glutathione status in H(2)O(2) signaling, gr1 mutants, which show a constitutive increase in oxidized glutathione (GSSG), were compared with a catalase-deficient background (cat2), in which GSSG accumulation is conditionally driven by H(2)O(2). Parallel transcriptomics analysis of gr1 and cat2 identified overlapping gene expression profiles that in both lines were dependent on growth daylength. Overlapping genes included phytohormone-associated genes, in particular implicating glutathione oxidation state in the regulation of jasmonic acid signaling. Direct analysis of H(2)O(2)-glutathione interactions in cat2 gr1 double mutants established that GR1-dependent glutathione status is required for multiple responses to increased H(2)O(2) availability, including limitation of lesion formation, accumulation of salicylic acid, induction of pathogenesis-related genes, and signaling through jasmonic acid pathways. Modulation of these responses in cat2 gr1 was linked to dramatic GSSG accumulation and modified expression of specific glutaredoxins and glutathione S-transferases, but there is little or no evidence of generalized oxidative stress or changes in thioredoxin-associated gene expression. We conclude that GR1 plays a crucial role in daylength-dependent redox signaling and that this function cannot be replaced by the second Arabidopsis GR gene or by thiol systems such as the thioredoxin system.

Differential Subcellular Localization of the Glucocorticoid Receptor in Distinct Neural Stem and Progenitor Populations of the Mouse Telencephalon In Vivo

PubMed Central

Tsiarli, Maria A.; Monaghan, A. Paula; DeFranco, Donald B.

2013-01-01

Glucocorticoids are given to pregnant women at risk for premature delivery to promote lung maturation. Despite reports of detrimental effects of glucocorticoids on telencephalic neural stem/progenitor cells (NSPCs), the regional and cellular expression of the glucocorticoid receptor (GR) in various NSPC populations in the intact brain has not been thoroughly assessed. Therefore in this study we performed a detailed analysis of GR protein expression in the developing mouse ventral and dorsal telencephalon in vivo. At embryonic day 11.5 (E11.5), the majority of Pax6-positive radial glial cells (RGCs) and Tbr2-positive intermediate progenitor cells (IPCs) expressed nuclear GR, while a small number of RGCs on the apical ventricular zone (aVZ), expressed cytoplasmic GR. However, on E13.5, the latter population of RGCs increased in size, whereas abventricular NSPCs and especially neurons of the cortical plate, expressed nuclear GR. In IPCs, GR was always nuclear. A similar expression profile was observed throughout the ventral telencephalon, hippocampus and olfactory bulb, with NSPCs of the aVZ primarily expressing cytoplasmic GR, while abventricular NSPCs and mature cells primarily expressed nuclear GR. Close to birth, nuclear GR accumulated within specific cortical areas such as layer V, the subplate and CA1 area of the hippocampus. In summary, our data show that GR protein is present in early NSPCs of the dorsal and ventral telencephalon at E11.5 and primarily occupies the nucleus. Moreover, our study suggests that the subcellular localization of the receptor may be subjected to region and neurodevelopmental stage-specific regulation. PMID:23751362

Differential subcellular localization of the glucocorticoid receptor in distinct neural stem and progenitor populations of the mouse telencephalon in vivo.

PubMed

Tsiarli, Maria A; Paula Monaghan, A; Defranco, Donald B

2013-07-26

Glucocorticoids are given to pregnant women at risk for premature delivery to promote lung maturation. Despite reports of detrimental effects of glucocorticoids on telencephalic neural stem/progenitor cells (NSPCs), the regional and cellular expressions of the glucocorticoid receptor (GR) in various NSPC populations in the intact brain have not been thoroughly assessed. Therefore in this study we performed a detailed analysis of GR protein expression in the developing mouse ventral and dorsal telencephalon in vivo. At embryonic day 11.5 (E11.5), the majority of Pax6-positive radial glial cells (RGCs) and Tbr2-positive intermediate progenitor cells (IPCs) expressed nuclear GR, while a small number of RGCs on the apical ventricular zone (aVZ), expressed cytoplasmic GR. However, on E13.5, the latter population of RGCs increased in size, whereas abventricular NSPCs and especially neurons of the cortical plate, expressed nuclear GR. In IPCs, GR was always nuclear. A similar expression profile was observed throughout the ventral telencephalon, hippocampus and olfactory bulb, with NSPCs of the aVZ primarily expressing cytoplasmic GR, while abventricular NSPCs and mature cells primarily expressed nuclear GR. Close to birth, nuclear GR accumulated within specific cortical areas such as layer V, the subplate and CA1 area of the hippocampus. In summary, our data show that GR protein is present in early NSPCs of the dorsal and ventral telencephalon at E11.5 and primarily occupies the nucleus. Moreover, our study suggests that the subcellular localization of the receptor may be subjected to region and neurodevelopmental stage-specific regulation. Copyright © 2013 Elsevier B.V. All rights reserved.

The sensitivity of the Greenland Ice Sheet to glacial-interglacial oceanic forcing

NASA Astrophysics Data System (ADS)

Tabone, Ilaria; Blasco, Javier; Robinson, Alexander; Alvarez-Solas, Jorge; Montoya, Marisa

2018-04-01

Observations suggest that during the last decades the Greenland Ice Sheet (GrIS) has experienced a gradually accelerating mass loss, in part due to the observed speed-up of several of Greenland's marine-terminating glaciers. Recent studies directly attribute this to warming North Atlantic temperatures, which have triggered melting of the outlet glaciers of the GrIS, grounding-line retreat and enhanced ice discharge into the ocean, contributing to an acceleration of sea-level rise. Reconstructions suggest that the influence of the ocean has been of primary importance in the past as well. This was the case not only in interglacial periods, when warmer climates led to a rapid retreat of the GrIS to land above sea level, but also in glacial periods, when the GrIS expanded as far as the continental shelf break and was thus more directly exposed to oceanic changes. However, the GrIS response to palaeo-oceanic variations has yet to be investigated in detail from a mechanistic modelling perspective. In this work, the evolution of the GrIS over the past two glacial cycles is studied using a three-dimensional hybrid ice-sheet-shelf model. We assess the effect of the variation of oceanic temperatures on the GrIS evolution on glacial-interglacial timescales through changes in submarine melting. The results show a very high sensitivity of the GrIS to changing oceanic conditions. Oceanic forcing is found to be a primary driver of GrIS expansion in glacial times and of retreat in interglacial periods. If switched off, palaeo-atmospheric variations alone are not able to yield a reliable glacial configuration of the GrIS. This work therefore suggests that considering the ocean as an active forcing should become standard practice in palaeo-ice-sheet modelling.

Characterization of an Adhesion Molecule that Mediates Leukocyte Rolling on 24 h Cytokine- or Lipopolysaccharide-stimulated Bovine Endothelial Cells under Flow Conditions

PubMed Central

Jutila, Mark A.; Wilson, Eric; Kurk, Sandy

1997-01-01

Bovine γ/δ T cells and neutrophils roll on 24 h cytokine- or lipopolysaccharide-stimulated bovine fetal umbilical cord endothelial cells in assays done under physiological flow. An antibody directed against E- and L-selectin has minimal blocking effect on this rolling interaction. mAbs were raised against the stimulated bovine endothelial cells and screened for inhibition of γ/δ T cell rolling. One mAb (GR113) was identified that recognizes an antigen (GR antigen) selectively expressed by stimulated bovine endothelial cells isolated from fetal umbilical cord, mesenteric lymph nodes, and aorta. GR113 blocked bovine γ/δ T cell as well as neutrophil rolling on the 24 h-activated endothelial cells. The GR antigen was constitutively expressed at low levels on the cell surface of platelets and its expression was not upregulated after stimulation of these cells with thrombin or phorbol myristate acetate. However, stimulated platelets released a soluble, functionally active form of the molecule that selectively bound in solution to γ/δ T cells in a mixed lymphocyte preparation. GR113 mAb blocked the binding of the soluble platelet molecule to the γ/δ T cells. Soluble GR antigen also bound a subset of human lymphocytes. Cutaneous lymphocyte-associated antigen (CLA) bright human lymphocytes exhibited the greatest capacity to bind the GR antigen, though CLA was not required for binding. Subsets of both human CD4 and CD8 T cells bound the GR antigen. Immunoprecipitation experiments showed the GR antigen to be 110-120 kD M r. The binding of soluble GR antigen was inhibited by EDTA and O-sialoglycoprotease, but not neuraminidase treatment of the target cells. PMID:9362530

Downregulation of spinal glutamate transporter EAAC1 following nerve injury is regulated by central glucocorticoid receptors in rats.

PubMed

Wang, Shuxing; Lim, Grewo; Yang, Liling; Sung, Backil; Mao, Jianren

2006-01-01

Previous studies have shown that glucocorticoid receptors (GR) were upregulated, whereas glutamate transporters were downregulated, within the spinal cord dorsal horn after peripheral nerve injury. However, the relationship between the expression of spinal GR and glutamate transporter after nerve injury remains unknown. In the present study, we examined the hypothesis that central GR would regulate the expression of spinal glutamate transporter EAAC1 following chronic constriction nerve injury (CCI) in rats. CCI induced a significant downregulation of EAAC1 expression primarily within the ipsilateral spinal cord dorsal horn when examined on postoperative day 7 using both Western blot and immunohistochemistry. The downregulation of EAAC1 was significantly diminished after either the GR antagonist RU38486 (4 > 2 = 0.5 microg = vehicle) or a GR antisense oligonucleotide was administered intrathecally twice daily for postoperative day 1-6. Moreover, CCI induced a significant downregulation of nuclear factor kappaB (NF-kappaB) within the ipsilateral spinal cord dorsal horn, which also was attenuated by either RU38486 (4 > 2 = 0.5 microg = vehicle) or a GR antisense oligonucleotide. The immunohistochemical data indicated a pattern of colocalization between GR and EAAC1 as well as GR and NF-kappaB within the spinal cord dorsal horn. Since, NF-kappaB has been shown to regulate the expression of those cellular elements linked to inflammation and tissue injury and its activity can be negatively regulated by GR activation, these results suggest that spinal GR through NF-kappaB may play a significant role in the regulation of EAAC1 expression after peripheral nerve injury, a cellular pathway that may contribute to the development of neuropathic pain behaviors in rats.

Graphene as a nanocarrier for tamoxifen induces apoptosis in transformed cancer cell lines of different origins.

PubMed

Misra, Santosh K; Kondaiah, Paturu; Bhattacharya, Santanu; Rao, C N R

2012-01-09

A cationic amphiphile, cholest-5en-3β-oxyethyl pyridinium bromide (PY(+) -Chol), is able to efficiently disperse exfoliated graphene (GR) in water by the physical adsorption of PY(+) -Chol on the surface of GR to form stable, dark aqueous suspensions at room temperature. The GR-PY(+) -Chol suspension can then be used to solubilize Tamoxifen Citrate (TmC), a breast cancer drug, in water. The resulting TmC-GR-PY(+) -Chol is stable for a long time without any precipitation. Fluorescence emission and UV absorption spectra indicate the existence of noncovalent interactions between TmC, GR, and PY(+) -Chol in these suspensions. Electron microscopy shows the existence of segregated GR sheets and TmC 'ribbons' in the composite suspensions. Atomic force microscopy indicates the presence of 'extended' structures of GR-PY(+) -Chol, which grows wider in the presence of TmC. The slow time-dependent release of TmC is noticed in a reconstituted cell culture medium, a property useful as a drug carrier. TmC-GR-PY(+) -Chol selectively enhanced the cell death (apoptosis) of the transformed cancer cells compared to normal cells. This potency is found to be true for a wide range of transformed cancer cells viz. HeLa, A549, ras oncogene-transformed NIH3T3, HepG2, MDA-MB231, MCF-7, and HEK293T compared to the normal cell HEK293 in vitro. Confocal microscopy confirmed the high efficiency of TmC-GR-PY(+) -Chol in delivering the drug to the cells, compared to the suspensions devoid of GR. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Propagation peculiarities of mean field massive gravity

DOE PAGES

Deser, S.; Waldron, A.; Zahariade, G.

2015-07-28

Massive gravity (mGR) describes a dynamical “metric” on a fiducial, background one. We investigate fluctuations of the dynamics about mGR solutions, that is about its “mean field theory”. Analyzing mean field massive gravity (m¯GR) propagation characteristics is not only equivalent to studying those of the full non-linear theory, but also in direct correspondence with earlier analyses of charged higher spin systems, the oldest example being the charged, massive spin 3/2 Rarita–Schwinger (RS) theory. The fiducial and mGR mean field background metrics in the m¯GR model correspond to the RS Minkowski metric and external EM field. The common implications in bothmore » systems are that hyperbolicity holds only in a weak background-mean-field limit, immediately ruling both theories out as fundamental theories; a situation in stark contrast with general relativity (GR) which is at least a consistent classical theory. Moreover, even though both m¯GR and RS theories can still in principle be considered as predictive effective models in the weak regime, their lower helicities then exhibit superluminal behavior: lower helicity gravitons are superluminal as compared to photons propagating on either the fiducial or background metric. Thus our approach has uncovered a novel, dispersive, “crystal-like” phenomenon of differing helicities having differing propagation speeds. As a result, this applies both to m¯GR and mGR, and is a peculiar feature that is also problematic for consistent coupling to matter.« less

Linking in situ LAI and fine resolution remote sensing data to map reference LAI over cropland and grassland using geostatistical regression method

NASA Astrophysics Data System (ADS)

He, Yaqian; Bo, Yanchen; Chai, Leilei; Liu, Xiaolong; Li, Aihua

2016-08-01

Leaf Area Index (LAI) is an important parameter of vegetation structure. A number of moderate resolution LAI products have been produced in urgent need of large scale vegetation monitoring. High resolution LAI reference maps are necessary to validate these LAI products. This study used a geostatistical regression (GR) method to estimate LAI reference maps by linking in situ LAI and Landsat TM/ETM+ and SPOT-HRV data over two cropland and two grassland sites. To explore the discrepancies of employing different vegetation indices (VIs) on estimating LAI reference maps, this study established the GR models for different VIs, including difference vegetation index (DVI), normalized difference vegetation index (NDVI), and ratio vegetation index (RVI). To further assess the performance of the GR model, the results from the GR and Reduced Major Axis (RMA) models were compared. The results show that the performance of the GR model varies between the cropland and grassland sites. At the cropland sites, the GR model based on DVI provides the best estimation, while at the grassland sites, the GR model based on DVI performs poorly. Compared to the RMA model, the GR model improves the accuracy of reference LAI maps in terms of root mean square errors (RMSE) and bias.

Melanin production by Rhizobium meliloti GR4 is linked to nonsymbiotic plasmid pRmeGR4b: cloning, sequencing, and expression of the tyrosinase gene mepA.

PubMed Central

Mercado-Blanco, J; García, F; Fernández-López, M; Olivares, J

1993-01-01

Melanin production by Rhizobium meliloti GR4 is linked to nonsymbiotic plasmid pRmeGR4b (140 MDa). Transfer of this plasmid to GR4-cured derivatives or to Agrobacterium tumefaciens enables these bacteria to produce melanin. Sequence analysis of a 3.5-kb PstI fragment of plasmid pRmeGR4b has revealed the presence of a open reading frame 1,481-bp that codes for a protein whose sequence shows strong homology to two conserved regions involved in copper binding in tyrosinases and hemocyanins. In vitro-coupled transcription-translation experiments showed that this open reading frame codes for a 55-kDa polypeptide. Melanin production in GR4 is not under the control of the RpoN-NifA regulatory system, unlike that in R. leguminosarum bv. phaseoli 8002. The GR4 tyrosinase gene could be expressed in Escherichia coli under the control of the lacZ promoter. For avoiding confusion with mel genes (for melibiose), a change of the name of the previously reported mel genes of R. leguminosarum bv. phaseoli and other organisms to mep genes (for melanin production) is proposed. Images PMID:8366027

Adipocyte Glucocorticoid Receptor Deficiency Attenuates Aging- and HFD-Induced Obesity and Impairs the Feeding-Fasting Transition.

PubMed

Mueller, Kristina M; Hartmann, Kerstin; Kaltenecker, Doris; Vettorazzi, Sabine; Bauer, Mandy; Mauser, Lea; Amann, Sabine; Jall, Sigrid; Fischer, Katrin; Esterbauer, Harald; Müller, Timo D; Tschöp, Matthias H; Magnes, Christoph; Haybaeck, Johannes; Scherer, Thomas; Bordag, Natalie; Tuckermann, Jan P; Moriggl, Richard

2017-02-01

Glucocorticoids (GCs) are important regulators of systemic energy metabolism, and aberrant GC action is linked to metabolic dysfunctions. Yet, the extent to which normal and pathophysiological energy metabolism depend on the GC receptor (GR) in adipocytes remains unclear. Here, we demonstrate that adipocyte GR deficiency in mice significantly impacts systemic metabolism in different energetic states. Plasma metabolomics and biochemical analyses revealed a marked global effect of GR deficiency on systemic metabolite abundance and, thus, substrate partitioning in fed and fasted states. This correlated with a decreased lipolytic capacity of GR-deficient adipocytes under postabsorptive and fasting conditions, resulting from impaired signal transduction from β-adrenergic receptors to adenylate cyclase. Upon prolonged fasting, the impaired lipolytic response resulted in abnormal substrate utilization and lean mass wasting. Conversely, GR deficiency attenuated aging-/diet-associated obesity, adipocyte hypertrophy, and liver steatosis. Systemic glucose tolerance was improved in obese GR-deficient mice, which was associated with increased insulin signaling in muscle and adipose tissue. We conclude that the GR in adipocytes exerts central but diverging roles in the regulation of metabolic homeostasis depending on the energetic state. The adipocyte GR is indispensable for the feeding-fasting transition but also promotes adiposity and associated metabolic disorders in fat-fed and aged mice. © 2017 by the American Diabetes Association.

Electrolyte and composition effects on the performances of asymmetric supercapacitors constructed with Mn3O4 nanoparticles-graphene nanocomposites

NASA Astrophysics Data System (ADS)

Xiao, Yuanhua; Cao, Yongbo; Gong, Yuyin; Zhang, Aiqin; Zhao, Jihong; Fang, Shaoming; Jia, Dianzeng; Li, Feng

2014-01-01

Nanocomposites of Mn3O4 nanoparticles and graphene (GR) nanosheets - Mn3O4@GR can be made by growing Mn3O4 nanoparticles directly on the surfaces of GR in solvothermal reactions. The asymmetric supercapacitors constructed with Mn3O4@GR as positive and activated carbon (AC) as negative electrodes, respectively, show highly enhanced performances in energy storage. It was found that the electrolytes employed in constructing electrodes of the devices can influence the performances of Mn3O4@GR supercapacitors dramatically. Compared to their energy density in KOH electrolyte, the devices exhibit improved charge storage performances in Na2SO4 electrolyte. Furthermore, the charge storage abilities of the devices are closely related to the amount of Mn3O4 nanoparticles loaded onto the surface of GR nanosheets. The performances of Mn3O4@GR//AC asymmetric supercapacitors can be optimized by carefully tailoring the composition of electrode materials and adjusting the electrolytes for making the devices.

The control of Asian rust by glyphosate in glyphosate-resistant soybeans.

PubMed

Feng, Paul C C; Clark, Celeste; Andrade, Gabriella C; Balbi, Maria C; Caldwell, Pat

2008-04-01

Glyphosate is a widely used broad-spectrum herbicide. Recent studies in glyphosate-resistant (GR) crops have shown that, in addition to its herbicidal activity, glyphosate exhibits activity against fungi, thereby providing disease control benefits. In GR wheat, glyphosate has shown both preventive and curative activities against Puccinia striiformis f. sp. tritici (Erikss) CO Johnston and Puccinia triticina Erikss, which cause stripe and leaf rusts respectively. Laboratory studies confirmed earlier observations that glyphosate has activity against Phakopsora pachyrhizi Syd & P Syd which causes Asian soybean rust (ASR) in GR soybeans. The results showed that glyphosate at rates between 0.84 and 1.68 kg ha(-1) delayed the onset of ASR in GR soybeans. However, field trials conducted in Argentina and Brazil under natural infestations showed variable ASR control from application of glyphosate in GR soybeans. Further field studies are ongoing to define the activity of glyphosate against ASR. These results demonstrate the disease control activities of glyphosate against rust diseases in GR wheat and GR soybeans. Copyright (c) 2007 Society of Chemical Industry.

Octopamine Neuromodulation Regulates Gr32a-Linked Aggression and Courtship Pathways in Drosophila Males

PubMed Central

Andrews, Jonathan C.; Fernández, María Paz; Yu, Qin; Leary, Greg P.; Leung, Adelaine K. W.; Kavanaugh, Michael P.; Kravitz, Edward A.; Certel, Sarah J.

2014-01-01

Chemosensory pheromonal information regulates aggression and reproduction in many species, but how pheromonal signals are transduced to reliably produce behavior is not well understood. Here we demonstrate that the pheromonal signals detected by Gr32a-expressing chemosensory neurons to enhance male aggression are filtered through octopamine (OA, invertebrate equivalent of norepinephrine) neurons. Using behavioral assays, we find males lacking both octopamine and Gr32a gustatory receptors exhibit parallel delays in the onset of aggression and reductions in aggression. Physiological and anatomical experiments identify Gr32a to octopamine neuron synaptic and functional connections in the suboesophageal ganglion. Refining the Gr32a-expressing population indicates that mouth Gr32a neurons promote male aggression and form synaptic contacts with OA neurons. By restricting the monoamine neuron target population, we show that three previously identified OA-FruM neurons involved in behavioral choice are among the Gr32a-OA connections. Our findings demonstrate that octopaminergic neuromodulatory neurons function as early as a second-order step in this chemosensory-driven male social behavior pathway. PMID:24852170

Graphene and poly(methyl methacrylate) composite laminates on flexible substrates for volatile organic compound detection

NASA Astrophysics Data System (ADS)

Rattanabut, Chanoknan; Wongwiriyapan, Winadda; Muangrat, Worawut; Bunjongpru, Win; Phonyiem, Mayuree; Song, Young Jae

2018-04-01

In this paper, we present a gas sensor for volatile organic compound (VOC) detection based on graphene and poly(methyl methacrylate) (GR/PMMA) composite laminates fabricated using CVD-grown graphene. Graphene was transferred to a poly(ethylene terephthalate) (PET) substrate by PMMA-supported wet transfer process without PMMA removal in order to achieve the deposition of GR/PMMA composite laminates on PET. The GR/PMMA and graphene sensors show completely different sensitivities to VOC vapors. The GR/PMMA and graphene sensors showed the highest sensitivities to dichloromethane (DCM). The response of the GR/PMMA sensor to DCM was 3 times higher than that of the graphene sensor but the GR/PMMA sensor hardly responded to acetone, chloroform, or benzene. The sensing mechanism of the graphene sensor can be based on the dielectric constant of VOCs, the size of VOC molecule, and electron hopping effects on defect graphene, while that of the GR/PMMA sensor can be explained in terms of the polymer swelling owing to the Hansen solubility parameter.

Improvement of the titanium implant biological properties by coating with poly (ε-caprolactone)-based hybrid nanocomposites synthesized via sol-gel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Catauro, Michelina; Bollino, Flavia; Papale, Ferdinando

When bioactive coatings are applied to medical implants by means of sol-gel dip coating technique, the biological proprieties of the implant surface can be modified to match the properties of the surrounding tissues. In this study organo-inorganic nanocomposites materials were synthesized via sol-gel. They consisted of an inorganic zirconium-based and silica-based matrix, in which a biodegradable polymer (the poly-ε-caprolactone, PCL) was incorporated in different weight percentages. The synthesized materials, in sol phase, were used to dip-coat a substrate of commercially pure titanium grade 4 (CP Ti gr. 4) in order to improve its biological properties. A microstructural analysis of themore » obtained films was carried out by scanning electron microscopy (SEM) and attenuated total reflectance (ATR) Fourier transform infrared spectroscopy (FT-IR). Biological proprieties of the coated substrates were investigated by means of in vitro tests.« less

Comparative Evaluation of the Etching Pattern of Er,Cr:YSGG & Acid Etching on Extracted Human Teeth-An ESEM Analysis

PubMed Central

Mazumdar, Dibyendu; Ranjan, Shashi; Krishna, Naveen Kumar; Kole, Ravindra; Singh, Priyankar; Lakiang, Deirimika; Jayam, Chiranjeevi

2016-01-01

Introduction Etching of enamel and dentin surfaces increases the surface area of the substrate for better bonding of the tooth colored restorative materials. Acid etching is the most commonly used method. Recently, hard tissue lasers have been used for this purpose. Aim The aim of the present study was to evaluate and compare the etching pattern of Er,Cr:YSGG and conventional etching on extracted human enamel and dentin specimens. Materials and Methods Total 40 extracted non-diseased teeth were selected, 20 anterior and 20 posterior teeth each for enamel and dentin specimens respectively. The sectioned samples were polished by 400 grit Silicon Carbide (SiC) paper to a thickness of 1.0 ± 0.5 mm. The enamel and dentin specimens were grouped as: GrE1 & GrD1 as control specimens, GrE2 & GrD2 were acid etched and GrE3 & GrD3 were lased. Acid etching was done using Conditioner 36 (37 % phosphoric acid) according to manufacturer instructions. Laser etching was done using Er,Cr:YSGG (Erbium, Chromium : Ytrium Scandium Gallium Garnet) at power settings of 3W, air 70% and water 20%. After surface treatment with assigned agents the specimens were analyzed under ESEM (Environmental Scanning Electron Microscope) at X1000 and X5000 magnification. Results Chi Square and Student “t” statistical analysis was used to compare smear layer removal and etching patterns between GrE2-GrE3. GrD2 and GrD3 were compared for smear layer removal and diameter of dentinal tubule opening using the same statistical analysis. Chi-square test for removal of smear layer in any of the treated surfaces i.e., GrE2-E3 and GrD2-D3 did not differ significantly (p>0.05). While GrE2 showed predominantly type I etching pattern (Chi-square=2.78, 0.05

0.10) and GrE3 showed type III etching (Chi-square=4.50, p<0.05). The tubule diameters were measured using GSA (Gesellschaft fur Softwareentwicklung und Analytik, Germany) image analyzer and the ‘t’ value of student ‘t’ test was 18.10 which was a highly significant result (p<.001). GrD2 had a mean dentinal tubule diameter of 2.78μm and GrD3 of 1.09μm. Conclusion The present study revealed type I etching pattern after acid etching, while type III etching pattern in enamel after laser etching. The lased dentin showed preferential removal of intertubular dentin while acid etching had more effect on the peritubular dentin. No significant differences was observed in removal of smear layer between the acid etched and lased groups. Although diameter of the exposed dentinal tubules was lesser after lased treatment in comparison to acid etching, further long term in vivo studies are needed with different parameters to establish the usage of Er,Cr:YSGG as a sole etching agent. PMID:27437337

Efficiency of different protocols for enamel clean-up after bracket debonding: an in vitro study

PubMed Central

Sigilião, Lara Carvalho Freitas; Marquezan, Mariana; Elias, Carlos Nelson; Ruellas, Antônio Carlos; Sant'Anna, Eduardo Franzotti

2015-01-01

Objective: This study aimed to assess the efficiency of six protocols for cleaning-up tooth enamel after bracket debonding. Methods: A total of 60 premolars were divided into six groups, according to the tools used for clean-up: 12-blade bur at low speed (G12L), 12-blade bur at high speed (G12H), 30-blade bur at low speed (G30L), DU10CO ORTHO polisher (GDU), Renew System (GR) and Diagloss polisher (GD). Mean roughness (Ra) and mean roughness depth (Rz) of enamel surface were analyzed with a profilometer. Paired t-test was used to assess Ra and Rz before and after enamel clean-up. ANOVA/Tukey tests were used for intergroup comparison. The duration of removal procedures was recorded. The association between time and variation in enamel roughness (∆Ra, ∆Rz) were evaluated by Pearson's correlation test. Enamel topography was assessed by scanning electron microscopy (SEM). Results: In Groups G12L and G12H, original enamel roughness did not change significantly. In Groups G30L, GDU, GR and GD, a smoother surface (p < 0.05) was found after clean-up. In Groups G30L and GD, the protocols used were more time-consuming than those used in the other groups. Negative and moderate correlation was observed between time and (∆Ra, ∆Rz); Ra and (∆Ra, ∆Rz); Rz (r = - 0.445, r = - 0.475, p < 0.01). Conclusion: All enamel clean-up protocols were efficient because they did not result in increased surface roughness. The longer the time spent performing the protocol, the lower the surface roughness. PMID:26560825

Magnetic graphene oxide-polystyrene and magnetic activated carbon-polystyrene nanocomposites as sorbents for bisphenol A.

NASA Astrophysics Data System (ADS)

Rekos, Kyriazis; Kampouraki, Zoi Christina; Samanidou, Victoria; Deliyanni, Eleni

2016-04-01

Magnetic graphene oxide-polystyrene and magnetic activated carbon-polystyrene nanocomposites as sorbents for bisphenol A. Kyriazis Rekos1, Zoi Christina Kampouraki1, Victoria Samanidou2, Eleni Deliyanni1 1 Laboratory of General and Inorganic Chemical Technology, Department of Chemistry, Aristotle University of Thessaloniki, GR-541 24 Thessaloniki, Greece 2 Laboratory of Analytical Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, GR-541 24 Thessaloniki, Greece The aim of this work was to prepare and characterize novel composites of magnetic activated carbon or magnetic graphene oxide with polystyrene (GO/PSm), through one step simple and effective route. Μagnetite nanoparticles, prepared in the laboratory, were dispersed in the presence of activated carbon (C) or graphene oxide (GO) in a polystyrene (PS) solution in dimethylformamide, at elevated temperature, for the fabrication of the magnetite-Carbon-PS (C-PSm) and magnetite- Graphene Oxide-PS (GO-PSm) hybrid-nanoparticles. For comparison, C-PS and GO-PS composites were also prepared in the same route. The nanocomposites were tested for their sorption ability for an endocrine disruptor, bisphenol A. The effect of solution pH, initial concentration, contact time and temperature were examined. The magnetic graphite oxide-polystyrene presented higher adsorption capacity (100 mg/g) than the non magnetic composites (70 mg/g), as well as than initial graphite oxide (20 mg/g). FTIR, XRD, BET, TGA, VSM and SEM were performed in order to investigate the role of the PS on the better adsorption performance of the mGO-PS nanocomposites. The characterization with these techniques revealed the possible interactions of the surface functional groups of activated carbon and/or graphite oxide with polystyrene that resulted in the better performance of the magnetic nanocomposites for bisphenol A adsorption.

Morphology and conductivity study of solid electrolyte Li{sub 3}PO{sub 4}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prayogi, Lugas Dwi, E-mail: ldprayodi@gmail.com; Faisal, Muhamad; Kartini, Evvy, E-mail: kartini@batan.go.id

2016-02-08

The comparison between two different methods of synthesize of solid electrolyte Li{sub 3}PO{sub 4} as precursor material for developing lithium ion battery, has been performed. The first method is to synthesize Li{sub 3}PO{sub 4} prepared by wet chemical reaction from LiOH and H{sub 3}PO{sub 4} which provide facile, abundant available resource, low cost, and low toxicity. The second method is solid state reaction prepared by Li{sub 2}CO{sub 3} and NH{sub 4}H{sub 2}PO{sub 4.} In addition, the possible morphology identification of comparison between two different methods will also be discussed. The composition, morphology, and additional identification phase and another compound ofmore » Li{sub 3}PO{sub 4} powder products from two different reaction are characterized by SEM, EDS, and EIS. The Li{sub 3}PO{sub 4} powder produced from wet reaction and solid state reaction have an average diameter of 0.834 – 7.81 µm and 2.15 – 17.3 µm, respectively. The density of Li{sub 3}PO{sub 4} prepared by wet chemical reaction is 2.238 gr/cm{sup 3}, little bit lower than the sample prepared by solid state reaction which density is 2.3560 gr/cm{sup 3}. The EIS measurement result shows that the conductivity of Li{sub 3}PO{sub 4} is 1.7 x 10{sup −9} S.cm{sup −1} for wet chemical reaction and 1.8 x 10{sup −10} S.cm{sup −1} for solid state reaction. The conductivity of Li{sub 3}PO{sub 4} is not quite different between those two samples even though they were prepared by different method of synthesize.« less

On the Computation of Comprehensive Boolean Gröbner Bases

NASA Astrophysics Data System (ADS)

Inoue, Shutaro

We show that a comprehensive Boolean Gröbner basis of an ideal I in a Boolean polynomial ring B (bar A,bar X) with main variables bar X and parameters bar A can be obtained by simply computing a usual Boolean Gröbner basis of I regarding both bar X and bar A as variables with a certain block term order such that bar X ≫ bar A. The result together with a fact that a finite Boolean ring is isomorphic to a direct product of the Galois field mathbb{GF}_2 enables us to compute a comprehensive Boolean Gröbner basis by only computing corresponding Gröbner bases in a polynomial ring over mathbb{GF}_2. Our implementation in a computer algebra system Risa/Asir shows that our method is extremely efficient comparing with existing computation algorithms of comprehensive Boolean Gröbner bases.

General Relativity and Cosmology: Unsolved Questions and Future Directions

NASA Astrophysics Data System (ADS)

Debono, Ivan; Smoot, George F.

2016-09-01

For the last 100 years, General Relativity (GR) has taken over the gravitational theory mantle held by Newtonian Gravity for the previous 200 years. This article reviews the status of GR in terms of its self-consistency, completeness, and the evidence provided by observations, which have allowed GR to remain the champion of gravitational theories against several other classes of competing theories. We pay particular attention to the role of GR and gravity in cosmology, one of the areas in which one gravity dominates and new phenomena and effects challenge the orthodoxy. We also review other areas where there are likely conflicts pointing to the need to replace or revise GR to represent correctly observations and consistent theoretical framework. Observations have long been key both to the theoretical liveliness and viability of GR.We conclude with a discussion of the likely developments over the next 100 years.

A Ground Validation Network for the Global Precipitation Measurement Mission

NASA Technical Reports Server (NTRS)

Schwaller, Mathew R.; Morris, K. Robert

2011-01-01

A prototype Validation Network (VN) is currently operating as part of the Ground Validation System for NASA's Global Precipitation Measurement (GPM) mission. The VN supports precipitation retrieval algorithm development in the GPM prelaunch era. Postlaunch, the VN will be used to validate GPM spacecraft instrument measurements and retrieved precipitation data products. The period of record for the VN prototype starts on 8 August 2006 and runs to the present day. The VN database includes spacecraft data from the Tropical Rainfall Measuring Mission (TRMM) precipitation radar (PR) and coincident ground radar (GR) data from operational meteorological networks in the United States, Australia, Korea, and the Kwajalein Atoll in the Marshall Islands. Satellite and ground radar data products are collected whenever the PR satellite track crosses within 200 km of a VN ground radar, and these data are stored permanently in the VN database. VN products are generated from coincident PR and GR observations when a significant rain event occurs. The VN algorithm matches PR and GR radar data (including retrieved precipitation data in the case of the PR) by calculating averages of PR reflectivity (both raw and attenuation corrected) and rain rate, and GR reflectivity at the geometric intersection of the PR rays with the individual GR elevation sweeps. The algorithm thus averages the minimum PR and GR sample volumes needed to "matchup" the spatially coincident PR and GR data types. The result of this technique is a set of vertical profiles for a given rainfall event, with coincident PR and GR samples matched at specified heights throughout the profile. VN data can be used to validate satellite measurements and to track ground radar calibration over time. A comparison of matched TRMM PR and GR radar reflectivity factor data found a remarkably small difference between the PR and GR radar reflectivity factor averaged over this period of record in stratiform and convective rain cases when samples were taken from high in the atmosphere. A significant difference in PR and GR reflectivity was found in convective cases, particularly in convective samples from the lower part of the atmosphere. In this case, the mean difference between PR and corrected GR reflectivity was -1.88 dBZ. The PR-GR bias was found to increase with the amount of PR attenuation correction applied, with the PR-GR bias reaching -3.07 dBZ in cases where the attenuation correction applied is greater than 6 dBZ. Additional analysis indicated that the version 6 TRMM PR retrieval algorithm underestimates rainfall in case of convective rain in the lower part of the atmosphere by 30%-40%.

Glucocorticoid receptor represses brain-derived neurotrophic factor expression in neuron-like cells.

PubMed

Chen, Hui; Lombès, Marc; Le Menuet, Damien

2017-04-12

Brain-derived neurotrophic factor (BDNF) is involved in many functions such as neuronal growth, survival, synaptic plasticity and memorization. Altered expression levels are associated with many pathological situations such as depression, epilepsy, Alzheimer's, Huntington's and Parkinson's diseases. Glucocorticoid receptor (GR) is also crucial for neuron functions, via binding of glucocorticoid hormones (GCs). GR actions largely overlap those of BDNF. It has been proposed that GR could be a regulator of BDNF expression, however the molecular mechanisms involved have not been clearly defined yet. Herein, we analyzed the effect of a GC agonist dexamethasone (DEX) on BDNF expression in mouse neuronal primary cultures and in the newly characterized, mouse hippocampal BZ cell line established by targeted oncogenesis. Mouse Bdnf gene exhibits a complex genomic structure with 8 untranslated exons (I to VIII) splicing onto one common and unique coding exon IX. We found that DEX significantly downregulated total BDNF mRNA expression by around 30%. Expression of the highly expressed exon IV and VI containing transcripts was also reduced by DEX. The GR antagonist RU486 abolished this effect, which is consistent with specific GR-mediated action. Transient transfection assays allowed us to define a short 275 bp region within exon IV promoter responsible for GR-mediated Bdnf repression. Chromatin immunoprecipitation experiments demonstrated GR recruitment onto this fragment, through unidentified transcription factor tethering. Altogether, GR downregulates Bdnf expression through direct binding to Bdnf regulatory sequences. These findings bring new insights into the crosstalk between GR and BDNF signaling pathways both playing a major role in physiology and pathology of the central nervous system.

Charge-transfer channel in quantum dot-graphene hybrid materials

NASA Astrophysics Data System (ADS)

Cao, Shuo; Wang, Jingang; Ma, Fengcai; Sun, Mengtao

2018-04-01

The energy band theory of a classical semiconductor can qualitatively explain the charge-transfer process in low-dimensional hybrid colloidal quantum dot (QD)-graphene (GR) materials; however, the definite charge-transfer channels are not clear. Using density functional theory (DFT) and time-dependent DFT, we simulate the hybrid QD-GR nanostructure, and by constructing its orbital interaction diagram, we show the quantitative coupling characteristics of the molecular orbitals (MOs) of the hybrid structure. The main MOs are derived from the fragment MOs (FOs) of GR, and the Cd13Se13 QD FOs merge with the GR FOs in a certain proportion to afford the hybrid system. Upon photoexcitation, electrons in the GR FOs jump to the QD FOs, leaving holes in the GR FOs, and the definite charge-transfer channels can be found by analyzing the complex MOs coupling. The excited electrons and remaining holes can also be localized in the GR or the QD or transfer between the QD and GR with different absorption energies. The charge-transfer process for the selected excited states of the hybrid QD-GR structure are testified by the charge difference density isosurface. The natural transition orbitals, charge-transfer length analysis and 2D site representation of the transition density matrix also verify the electron-hole delocalization, localization, or coherence chacracteristics of the selected excited states. Therefore, our research enhances understanding of the coupling mechanism of low-dimensional hybrid materials and will aid in the design and manipulation of hybrid photoelectric devices for practical application in many fields.

Epigenetic changes in the hypothalamic proopiomelanocortin and glucocorticoid receptor genes in the ovine fetus after periconceptional undernutrition.

PubMed

Stevens, Adam; Begum, Ghazala; Cook, Alice; Connor, Kristin; Rumball, Christopher; Oliver, Mark; Challis, John; Bloomfield, Frank; White, Anne

2010-08-01

Maternal food restriction is associated with the development of obesity in offspring. This study examined how maternal undernutrition in sheep affects the fetal hypothalamic glucocorticoid receptor (GR) and the appetite-regulating neuropeptides, proopiomelanocortin (POMC) and neuropeptide Y, which it regulates. In fetuses from ewes undernourished from -60 to +30 d around conception, there was increased histone H3K9 acetylation (1.63-fold) and marked hypomethylation (62% decrease) of the POMC gene promoter but no change in POMC expression. In the same group, acetylation of histone H3K9 associated with the hypothalamic GR gene was increased 1.60-fold and the GR promoter region was hypomethylated (53% decrease). In addition, there was a 4.7-fold increase in hypothalamic GR expression but no change in methylation of GR gene expression in the anterior pituitary or hippocampus. Interestingly, hypomethylation of both POMC and GR promoter markers in fetal hypothalami was also identified after maternal undernutrition from -60 to 0 d and -2 to +30 d. In comparison, the Oct4 gene, was hypermethylated in both control and underfed groups. Periconceptional undernutrition is therefore associated with marked epigenetic changes in hypothalamic genes. Increase in GR expression in the undernourished group may contribute to fetal programming of a predisposition to obesity, via altered GR regulation of POMC and neuropeptide Y. These epigenetic changes in GR and POMC in the hypothalamus may also predispose the offspring to altered regulation of food intake, energy expenditure, and glucose homeostasis later in life.

Free-standing graphene/vanadium oxide composite as binder-free electrode for asymmetrical supercapacitor.

PubMed

Deng, Lingjuan; Gao, Yihong; Ma, Zhanying; Fan, Guang

2017-11-01

Preparation of free-standing electrode materials with three-dimensional network architecture has emerged as an effective strategy for acquiring advanced portable and wearable power sources. Herein, graphene/vanadium oxide (GR/V 2 O 5 ) free-standing monolith composite has been prepared via a simple hydrothermal process. Flexible GR sheets acted as binder to connect the belt-like V 2 O 5 for assembling three-dimensional network architecture. The obtained GR/V 2 O 5 composite can be reshaped into GR/V 2 O 5 flexible film which exhibits more compact structure by ultrasonication and vacuum filtration. A high specific capacitance of 358Fg -1 for GR/V 2 O 5 monolith compared with that of GR/V 2 O 5 flexible film (272Fg -1 ) has been achieved in 0.5molL -1 K 2 SO 4 solution when used as binder free electrodes in three-electrode system. An asymmetrical supercapacitor has been assembled using GR/V 2 O 5 monolith as positive electrode and GR monolith as negative electrode, and it can be reversibly charged-discharged at a cell voltage of 1.7V in 0.5molL -1 K 2 SO 4 electrolyte. The asymmetrical capacitor can deliver an energy density of 26.22Whkg -1 at a power density of 425Wkg -1 , much higher than that of the symmetrical supercapacitor based on GR/V 2 O 5 monolith electrode. Moreover, the asymmetrical supercapacitor preserves 90% of its initial capacitance over 1000 cycles at a current density of 5Ag -1 . Copyright © 2017 Elsevier Inc. All rights reserved.

Antibacterial Effects of Glycyrrhetinic Acid and Its Derivatives on Staphylococcus aureus

PubMed Central

Oyama, Kentaro; Kawada-Matsuo, Miki; Oogai, Yuichi; Hayashi, Tetsuya; Nakamura, Norifumi; Komatsuzawa, Hitoshi

2016-01-01

Staphylococcus aureus is a major pathogen in humans and causes serious problems due to antibiotic resistance. We investigated the antimicrobial effect of glycyrrhetinic acid (GRA) and its derivatives against 50 clinical S. aureus strains, including 18 methicillin-resistant strains. The minimum inhibitory concentrations (MICs) of GRA, dipotassium glycyrrhizate, disodium succinoyl glycyrrhetinate (GR-SU), stearyl glycyrrhetinate and glycyrrhetinyl stearate were evaluated against various S. aureus strains. Additionally, we investigated the bactericidal effects of GRA and GR-SU against two specific S. aureus strains. DNA microarray analysis was also performed to clarify the mechanism underlying the antibacterial activity of GR-SU. We detected the antimicrobial activities of five agents against S. aureus strains. GRA and GR-SU showed strong antibacterial activities compared to the other three agents tested. At a higher concentration (above 2x MIC), GRA and GR-SU showed bactericidal activity, whereas at a concentration of 1x MIC, they showed a bacteriostatic effect. Additionally, GRA and GR-SU exhibited a synergistic effect with gentamicin. The expression of a large number of genes (including transporters) and metabolic factors (carbohydrates and amino acids) was altered by the addition of GR-SU, suggesting that the inhibition of these metabolic processes may influence the degree of the requirement for carbohydrates or amino acids. In fact, the requirement for carbohydrates or amino acids was increased in the presence of either GRA or GR-SU. GRA and GR-SU exhibited strong antibacterial activity against several S. aureus strains, including MRSA. This activity may be partly due to the inhibition of several pathways involved in carbohydrate and amino acid metabolism. PMID:27820854

Gold Rods Irradiated with Ultrasound for Combination of Hyperthermia and Cancer Chemotherapy.

PubMed

Barros, Andre; Austerlitz, Carlos; Gkigkitzis, Ioannis; Campos, Diana; Andrade, Jeyce; Peixoto, Christina; Aguiar, Jaciana; Nascimento, Silene; Silva, Teresinha G; Haranas, Ioannis

2017-01-01

The aim of this study was to analyze feasibility (in vitro and in vivo) the use of hyperthermia produced by gold rods irradiated with ultrasound and their combination with chemotherapy with doxorubicin. initially was determined the cell viability and Hsp70 levels after treatment by gold rods irradiated with ultrasound (GR+U) in cell culture. The pretreatment with GR+U combined with doxorubicin (DOX) was evaluated from IC 50 , caspase-3 expression and mechanisms of cell death by electron microscopy. For evaluate the in vivo effects was used solid Ehrlich carcinoma (SEC) Tumor. The animals received three treatments with the combination of GR+U+DOX over 16 days. The cell viability was completely inhibited after 40 min of treatment with GR+U and significant increases the expression of HSP70 was only observed after 10 min of treatment. GR+U+DOX presented significant reduction of IC 50 representing 50.7%, 76.5% 45.2% and 46.6% for cell lines K562, NCI-H292, Hep-2 and MCF-7 respectively. GR+U+DOX presented significant reduction of IC 50 representing 50.7%, 76.5% 45.2% and 46.6% for cell lines K562, NCI-H292, Hep-2 and MCF-7 respectively. The caspase-3 level and ultraestructural analysis showed that treatment with GR+U+DOX enhances induction of apoptosis. Pretreatment with GR+U combined with doxorubicin (1 mg) showed 87% inhibition against SEC. and no showed cardiotoxic effect. The combined treatment of GR+U and DOX exhibit synergistic characteristics observed by increasing the efficiency of doxorubicin.

Charge-transfer channel in quantum dot-graphene hybrid materials.

PubMed

Cao, Shuo; Wang, Jingang; Ma, Fengcai; Sun, Mengtao

2018-04-06

The energy band theory of a classical semiconductor can qualitatively explain the charge-transfer process in low-dimensional hybrid colloidal quantum dot (QD)-graphene (GR) materials; however, the definite charge-transfer channels are not clear. Using density functional theory (DFT) and time-dependent DFT, we simulate the hybrid QD-GR nanostructure, and by constructing its orbital interaction diagram, we show the quantitative coupling characteristics of the molecular orbitals (MOs) of the hybrid structure. The main MOs are derived from the fragment MOs (FOs) of GR, and the Cd 13 Se 13 QD FOs merge with the GR FOs in a certain proportion to afford the hybrid system. Upon photoexcitation, electrons in the GR FOs jump to the QD FOs, leaving holes in the GR FOs, and the definite charge-transfer channels can be found by analyzing the complex MOs coupling. The excited electrons and remaining holes can also be localized in the GR or the QD or transfer between the QD and GR with different absorption energies. The charge-transfer process for the selected excited states of the hybrid QD-GR structure are testified by the charge difference density isosurface. The natural transition orbitals, charge-transfer length analysis and 2D site representation of the transition density matrix also verify the electron-hole delocalization, localization, or coherence chacracteristics of the selected excited states. Therefore, our research enhances understanding of the coupling mechanism of low-dimensional hybrid materials and will aid in the design and manipulation of hybrid photoelectric devices for practical application in many fields.

Transcriptome analysis of reproductive-stage Arabidopsis plants exposed gamma-ray irradiation at various doses.

PubMed

Hwang, Sun-Goo; Kim, Dong Sub; Kim, Jin-Baek; Hwang, Jung Eun; Park, Hyun Mi; Kim, Jin Hyuk; Jang, Cheol Seong

2016-08-01

Gamma rays (GR) induce significant changes in the structure and expression of genes involved in the regulation of diverse biochemical and physiological processes. Arabidopsis plants exhibit different growth and development patterns in response to exposure to GR. The effects on gene expression of different radiation doses of GR (100 and 800 Gy) administered to Arabidopsis plants were examined at the reproductive stage. We irradiated 26-day-old plants with three replications [developmental stages 5.1-6.0, according to Boyes et al. ( 2001 )] using a GR irradiator (60 Co, ca. 150 TBq capacity, Atomic Energy of Canada Limited, Ontario, Canada) at the Korea Atomic Energy Research Institute. Plants were treated with 100, 200, 300, 400, 800, 1200, 1600, or 2000 Gy, and the doses were made from varying the distance to the source. We conducted a high-throughput screening analysis and detected 883 GR-responsive genes that showed significant changes; these were involved in several putative metabolic pathways related to biotic stress. Additionally, five overrepresented cis-regulatory elements were identified in the 1-kb upstream regions of GR-responsive genes by using motif enrichment analysis. We also detected three GR-responsive genes associated with stamen development and confirmed their co-regulation with functionally interacting genes. This finding suggests that a network-based analysis is a viable approach to identify significant GR-responsive genes associated with the reproductive stage of Arabidopsis. Our results provide further insights into the complex biological systems involved in the response to different doses of GR in plants.

Effect of orthophosphate on the oxidation products of Fe(II)-Fe(III) hydroxycarbonate: the transformation of green rust to ferrihydrite

NASA Astrophysics Data System (ADS)

Benali, Omar; Abdelmoula, Mustapha; Refait, Philippe; Génin, Jean-Marie Robert

2001-06-01

Hydroxycarbonate green rust GR(CO 32-) has been synthesized by oxidation of aqueous suspensions of Fe(OH) 2 by aeration at the air-liquid interface, in the presence of HCO 3- ions at pH 7.5 to 9. During the oxidation of GR(CO 32-), ferrihydrite formed first and then turned into goethite by dissolution and precipitation. The oxidation of GR(CO 32-) in the presence of orthophosphate ions, which were added as Na 2HPO 4 · 7H 2O salt, also involved the formation of ferrihydrite but not that of goethite, because the dissolution of ferrihydrite is inhibited by the adsorption of phosphate ions on its surface. The oxidation was slowed down because of the suppression of the catalytic effect of iron(III) hydroxide on the oxidation of Fe(II). In anoxic conditions without phosphate, a mixture of GR(CO 32-), goethite, and ferrihydrite was observed to transform spontaneously into a mixture of siderite and magnetite. It is thermodynamically consistent, which shows that GR(CO 32-) is metastable with respect to the two-phase system FeCO 3-Fe 3O 4. In the presence of phosphate, this transformation was inhibited and GR(CO 32-) did not transform in anoxic conditions. Anionic phosphate species dissolved in solution did not give rise to a corresponding GR, i.e., phosphate species did not substitute for carbonate inside the interlayers of the GR. Moreover, iron phosphates did not appear, neither during the oxidation of GR(CO 32-) in the presence of oxygen nor in anoxic conditions.

Extending Clause Learning of SAT Solvers with Boolean Gröbner Bases

NASA Astrophysics Data System (ADS)

Zengler, Christoph; Küchlin, Wolfgang

We extend clause learning as performed by most modern SAT Solvers by integrating the computation of Boolean Gröbner bases into the conflict learning process. Instead of learning only one clause per conflict, we compute and learn additional binary clauses from a Gröbner basis of the current conflict. We used the Gröbner basis engine of the logic package Redlog contained in the computer algebra system Reduce to extend the SAT solver MiniSAT with Gröbner basis learning. Our approach shows a significant reduction of conflicts and a reduction of restarts and computation time on many hard problems from the SAT 2009 competition.

The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sato, Shoko, E-mail: satosho@rs.tus.ac.jp; Shirakawa, Hitoshi, E-mail: shirakah@m.tohoku.ac.jp; Tomita, Shuhei, E-mail: tomita@med.tottori-u.ac.jp

2013-11-15

Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHRmore » or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction.« less

Hsp90 Inhibition Results in Glucocorticoid Receptor Degradation in Association with Increased Sensitivity to Paclitaxel in Triple-Negative Breast Cancer.

PubMed

Agyeman, Abena S; Jun, Wesley J; Proia, David A; Kim, Caroline R; Skor, Maxwell N; Kocherginsky, Masha; Conzen, Suzanne D

2016-04-01

Targetable molecular drivers for triple-negative breast cancer (TNBC) have been difficult to identify; therefore, standard treatment remains limited to conventional chemotherapy. Recently, new-generation small-molecule Hsp90 inhibitors (e.g., ganetespib and NVP-AUY922) have demonstrated improved safety and activity profiles over the first-generation ansamycin class. In breast cancer, clinical responses have been observed in a subset of TNBC patients following ganetespib monotherapy; however, the underlying biology of Hsp90 inhibitor treatment and tumor response is not well understood. Glucocorticoid receptor (GR) activity in TNBC is associated with chemotherapy resistance. Here, we find that treatment of TNBC cell lines with ganetespib resulted in GR degradation and decreased GR-mediated gene expression. Ganetespib-associated GR degradation also sensitized TNBC cells to paclitaxel-induced cell death both in vitro and in vivo. The beneficial effect of the Hsp90 inhibitor on paclitaxel-induced cytotoxicity was reduced when GR was depleted in TNBC cells but could be recovered with GR overexpression. These findings suggest that GR-regulated anti-apoptotic and pro-proliferative signaling networks in TNBC are disrupted by Hsp90 inhibitors, thereby sensitizing TNBC to paclitaxel-induced cell death. Thus, GR+ TNBC patients may be a subgroup of breast cancer patients who are most likely to benefit from adding an Hsp90 inhibitor to taxane therapy.

Gromwell (Lithospermum erythrorhizon) root extract protects against glycation and related inflammatory and oxidative stress while offering UV absorption capability.

PubMed

Glynn, Kelly M; Anderson, Penny; Fast, David J; Koedam, James; Rebhun, John F; Velliquette, Rodney A

2018-06-15

Glycation and advanced glycation endproducts (AGE) damage skin which is compounded by AGE-induced oxidative stress and inflammation. Lip and facial skin could be susceptible to glycation damage as they are chronically stressed. As Gromwell (Lithospermum erythrorhizon) root (GR) has an extensive traditional medicine history that includes providing multiple skin benefits, our objective was to determine if GR extract and its base naphthoquinone, shikonin, might protect skin by inhibiting glycation, increasing oxidative defenses, suppressing inflammatory responses, and offering ultraviolet (UV) absorptive potential in lip and facial cosmetic matrices. We show GR extract and shikonin dose-dependently inhibited glycation and enhanced oxidative defenses through nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) activation. Inflammatory targets, nuclear factor kappa light chain enhancer of activated B cells (NFκB) and tumor necrosis factor alpha (TNFα), were suppressed by GR extract and shikonin. Glyoxalase 1 (GLO1) and glutathione synthesis genes were significantly upregulated by GR extract and shikonin. GR extract boosted higher wavelength UV absorption in select cosmetic matrices. Rationale for the use of GR extract and shikonin are supported by our research. By inhibiting glycation, modulating oxidative stress, suppressing inflammation, and UV-absorptive properties, GR extract and shikonin potentially offer multiple skin benefits. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Maltose-Binding Protein Enhances Secretion of Recombinant Human Granzyme B Accompanied by In Vivo Processing of a Precursor MBP Fusion Protein

PubMed Central

Dälken, Benjamin; Jabulowsky, Robert A.; Oberoi, Pranav; Benhar, Itai; Wels, Winfried S.

2010-01-01

Background The apoptosis-inducing serine protease granzyme B (GrB) is an important factor contributing to lysis of target cells by cytotoxic lymphocytes. Expression of enzymatically active GrB in recombinant form is a prerequisite for functional analysis and application of GrB for therapeutic purposes. Methods and Findings We investigated the influence of bacterial maltose-binding protein (MBP) fused to GrB via a synthetic furin recognition motif on the expression of the MBP fusion protein also containing an N-terminal α-factor signal peptide in the yeast Pichia pastoris. MBP markedly enhanced the amount of GrB secreted into culture supernatant, which was not the case when GrB was fused to GST. MBP-GrB fusion protein was cleaved during secretion by an endogenous furin-like proteolytic activity in vivo, liberating enzymatically active GrB without the need of subsequent in vitro processing. Similar results were obtained upon expression of a recombinant fragment of the ErbB2/HER2 receptor protein or GST as MBP fusions. Conclusions Our results demonstrate that combination of MBP as a solubility enhancer with specific in vivo cleavage augments secretion of processed and functionally active proteins from yeast. This strategy may be generally applicable to improve folding and increase yields of recombinant proteins. PMID:21203542

Feasibility analysis of using inverse modeling for estimating natural groundwater recharge from a large-scale soil moisture monitoring network

NASA Astrophysics Data System (ADS)

Wang, Tiejun; Franz, Trenton E.; Yue, Weifeng; Szilagyi, Jozsef; Zlotnik, Vitaly A.; You, Jinsheng; Chen, Xunhong; Shulski, Martha D.; Young, Aaron

2016-02-01

Despite the importance of groundwater recharge (GR), its accurate estimation still remains one of the most challenging tasks in the field of hydrology. In this study, with the help of inverse modeling, long-term (6 years) soil moisture data at 34 sites from the Automated Weather Data Network (AWDN) were used to estimate the spatial distribution of GR across Nebraska, USA, where significant spatial variability exists in soil properties and precipitation (P). To ensure the generality of this study and its potential broad applications, data from public domains and literature were used to parameterize the standard Hydrus-1D model. Although observed soil moisture differed significantly across the AWDN sites mainly due to the variations in P and soil properties, the simulations were able to capture the dynamics of observed soil moisture under different climatic and soil conditions. The inferred mean annual GR from the calibrated models varied over three orders of magnitude across the study area. To assess the uncertainties of the approach, estimates of GR and actual evapotranspiration (ETa) from the calibrated models were compared to the GR and ETa obtained from other techniques in the study area (e.g., remote sensing, tracers, and regional water balance). Comparison clearly demonstrated the feasibility of inverse modeling and large-scale (>104 km2) soil moisture monitoring networks for estimating GR. In addition, the model results were used to further examine the impacts of climate and soil on GR. The data showed that both P and soil properties had significant impacts on GR in the study area with coarser soils generating higher GR; however, different relationships between GR and P emerged at the AWDN sites, defined by local climatic and soil conditions. In general, positive correlations existed between annual GR and P for the sites with coarser-textured soils or under wetter climatic conditions. With the rapidly expanding soil moisture monitoring networks around the globe, this study may have important applications in aiding water resources management in different regions.

Expression of glucocorticoid receptor and early growth response gene 1 during postnatal development of two inbred strains of mice exposed to early life stress.

PubMed

Navailles, Sylvia; Zimnisky, Ross; Schmauss, Claudia

2010-07-01

Early life stress can elicit profound changes in adult gene expression and behavior. One consequence of early life stress is a decreased expression of glucocorticoid receptors (GRs) in the frontal cortex and hippocampus. However, neither the time of onset nor the mechanism(s) leading to decreased GR expression during postnatal development are known. The present study used two inbred strains of mice that differ in their behavioral responsiveness to stress (Balb/c and C57Bl/6), exposed them to an established paradigm of early life stress (infant maternal separation), and measured their expression of frontal cortical and hippocampal GRs and the putative transcriptional activator of the GR gene, early growth response gene (egr)-1, at defined stages of postnatal development. In both strains, real-time RT-PCR experiments revealed that decreased expression of GR in adolescence and adulthood is, in fact, preceded by increased GR expression during early life stress exposure. Thus, the early life stress-induced disruption of the normal stress-hyporesponsive period during infancy is accompanied by increased GR expression. Moreover, chronic treatment with the antidepressant drug fluoxetine during adolescence or adulthood reversed the effect of early life stress on adult GR mRNA expression. In contrast to the strain-independent effect of early life stress on GR expression, however, changes in egr-1 expression occurred only in Balb/c mice, and unlike the biphasic developmental changes in GR mRNA expression, egr-1 mRNA was decreased throughout postnatal development. Moreover, there was no consistent overlap of anatomic regions affected by decreased GR and egr-1 protein expression. Thus, in Balb/c mice, changes in GR and egr-1 expression can independently contribute to the phenotypes resulting from early life stress exposure. These findings illustrate that the impact of early life stress on gene expression changes is modulated by the genetic background and that the persistent changes in GR and egr-1 expression that arise early during postnatal developmental are reversible by chronic fluoxetine treatment during adolescence and adulthood. Copyright 2010 S. Karger AG, Basel.

The Sensitivity of the Greenland Ice Sheet to Glacial-Interglacial Oceanic Forcing

NASA Astrophysics Data System (ADS)

Tabone, I.; Blasco Navarro, J.; Robinson, A.; Alvarez-Solas, J.; Montoya, M.

2017-12-01

Up to now, the scientific community has mainly focused on the sensitivity of the Greenland Ice Sheet (GrIS) to atmospheric variations. However, several studies suggest that the enhanced ice mass loss experienced by the GrIS in the past decades is directly connected to the increasing North Atlantic temperatures. Melting of GrIS outlet glaciers triggers grounding-line retreat increasing ice discharge into the ocean. This new evidence leads to consider the ocean as a relevant driver to be taken into account when modeling the evolution of the GrIS. The ice-ocean interaction is a primary factor controling not only the likely future retreat of GrIS outlet glaciers, or the huge ice loss in past warming climates, but also, and more strongly, the past GrIS glacial expansion. The latter assumption is supported by reconstructions which propose the GrIS to be fully marine-based during glacials, and thus more exposed to the influence of the ocean. Here, for the first time, we investigate the response of the GrIS to past oceanic changes using a three-dimensional hybrid ice-sheet/ice-shelf model, which combines the Shallow Ice Approximation (SIA) for slow grounded ice sheets and the Shallow Shelf Approximation (SSA) in ice shelves and ice streams. The model accounts for a time-dependent parametrisation of the marine basal melting rate, which is used to reproduce past oceanic variations. In this work simulations of the last two glacial cycles are performed. Our results show that the GrIS is very sensitive to the ocean-triggered submarine melting (freezing). Mild oceanic temperature variations lead to a rapid retreat (expansion) of the GrIS margins, which, inducing a dynamic adjustment of the grounded ice sheet, drive the evolution of the whole ice sheet. Our results strongly suggest the need to consider the ocean as an active forcing in paleo ice sheet models.

A ubiquitin carboxyl extension protein secreted from a plant-parasitic nematode Globodera rostochiensis is cleaved in planta to promote plant parasitism.

PubMed

Chronis, Demosthenis; Chen, Shiyan; Lu, Shunwen; Hewezi, Tarek; Carpenter, Sara C D; Loria, Rosemary; Baum, Thomas J; Wang, Xiaohong

2013-04-01

Nematode effector proteins originating from esophageal gland cells play central roles in suppressing plant defenses and in formation of the plant feeding cells that are required for growth and development of cyst nematodes. A gene (GrUBCEP12) encoding a unique ubiquitin carboxyl extension protein (UBCEP) that consists of a signal peptide for secretion, a mono-ubiquitin domain, and a 12 amino acid carboxyl extension protein (CEP12) domain was cloned from the potato cyst nematode Globodera rostochiensis. This GrUBCEP12 gene was expressed exclusively within the nematode's dorsal esophageal gland cell, and was up-regulated in the parasitic second-stage juvenile, correlating with the time when feeding cell formation is initiated. We showed that specific GrUBCEP12 knockdown via RNA interference reduced nematode parasitic success, and that over-expression of the secreted Gr(Δ) (SP) UBCEP12 protein in potato resulted in increased nematode susceptibility, providing direct evidence that this secreted effector is involved in plant parasitism. Using transient expression assays in Nicotiana benthamiana, we found that Gr(Δ) (SP) UBCEP12 is processed into free ubiquitin and a CEP12 peptide (GrCEP12) in planta, and that GrCEP12 suppresses resistance gene-mediated cell death. A target search showed that expression of RPN2a, a gene encoding a subunit of the 26S proteasome, was dramatically suppressed in Gr(Δ) (SP) UBCEP12 but not GrCEP12 over-expression plants when compared with control plants. Together, these results suggest that, when delivered into host plant cells, Gr(Δ) (SP) UBCEP12 becomes two functional units, one acting to suppress plant immunity and the other potentially affecting the host 26S proteasome, to promote feeding cell formation. © 2013 The Authors The Plant Journal © 2013 Blackwell Publishing Ltd.

Investigation of Tribological Behavior of a Novel Hybrid Composite Prepared with Al-Coconut Shell Ash Mixed with Graphite

NASA Astrophysics Data System (ADS)

Siva Sankara Raju, R.; Panigrahi, M. K.; Ganguly, R. I.; Srinivasa Rao, G.

2017-08-01

The present investigation develops a next-generation hybrid Al metal matrix composite using coconut shell ash (CSA) and graphite (Gr) reinforcement. Stir-casting is adapted to prepare an Al-1100-based composite. Three other composites of Al-Al2O3, Al-Al2O3-Gr, and Al-CSA are prepared that contain equivalent volume fractions of Al2O3, CSA, and Gr. These assist in comparisons among the three composites and the developed hybrid Al-CSA-Gr composite. The study reveals that the addition of 3 pct Gr improves the specific strength, toughness, and tribological properties. The Al-CSA composite shows better mechanical properties, such as tensile strength and hardness, than the other three composites. Gr addition helps the hybrid Al-CSA-Gr composite to attain better tribological properties with a slightly lower specific strength. Scanning electron microscopy studies of the worn material surfaces corroborate the findings of the abrasion testing. Elemental analyses by energy-dispersive X-ray spectroscopy of the debris from the counter-face of the tribo surface confirm the presence of Al, O, Si, Fe, Mn, and C.

[Effects of jingui shenqi pill combined prednisone on expression of glucocorticoid receptor and its clinical effect in treating bullous pemphigoid patients].

PubMed

Liu, Bao-guo; Li, Zhi-ying; Du, Ming

2006-10-01

To investigate the effect of Jingui Shenqi Pill (JSP) on the expression of glucocorticoid receptor (GR) in the skin lesion and its clinical effect in treating bullous pemphigoid (BP) patients. Thirty BP patients were randomly divided into the treatment group (n=15) treated with JSP plus prednisone and the prednisone group (n=15) with prednisone alone both for 4 weeks. And a normal control group was set up also. Expressions of GR-alpha and GR-beta in the skin lesion of BP patients and the normal skin of the normal control were detected by immunohistochemical assay. Results The total effective rate was 93.33% in the treatment group, significantly higher than that in the prednisone group which was 73.33% (P < 0.05); GR-alpha expression was higher in the treatment group than that in other two groups (P < 0.01), while GR-beta expression in the treatment group was lower than that in the prednisone group (P < 0.01). JSP could increase GR-alpha expression and decrease GR-beta expression in the skin lesion of BP patients, so as to improve sensitivity of skin to glucocorticoid.

Kinetic Study on Mutagenic Chemical Degradation through Three Pot Synthesiszed Graphene@ZnO Nanocomposite

PubMed Central

Shoeb, Mohd; Singh, Braj Raj; Mobin, Mohammad; Afreen, Gul; Khan, Wasi; Naqvi, Alim H.

2015-01-01

The study was taken up with the objective to synthesize graphene-zinc oxide nano particles (NPs) nanocomposite (Gr@ZnO-Nc) via In-situ synthesis method. The structural, optical, thermal, electrical and photocatalytic properties of the synthesized Gr@ZnO-Nc were studied. The characterization data confirmed that the ZnO NPs were successfully incorporated into the graphene sheets. Further, TGA/DTA results exhibited an enhanced thermal stability of the Gr@ZnO-Nc compared with the graphene. The Gr@ZnO-Nc, graphene sheets were uniformly wrapped by ZnO NPs, which can protect graphene and delay their oxidation in air. The synthesized Gr@ZnO-Nc was used for the efficient photodegradation of a carcinogenic methyl orange (MO) dye. The results exhibited promising photodegradation of the MO dye under UV light irradiation through the production of reactive oxygen species (ROS). The promising effect of Gr@ZnO-Nc on the photodegradation properties was conferred by the large surface area which increased adsorption capacity, and the strong electron transfer ability. Thus, it is encouraging to conclude that the synthesized Gr@ZnO-Nc has environmental significance with its utility in remediation in the hazardous MO dye. PMID:26287672

Epigenetic regulation of the glucocorticoid receptor promoter 1(7) in adult rats.

PubMed

Witzmann, Simone R; Turner, Jonathan D; Mériaux, Sophie B; Meijer, Onno C; Muller, Claude P

2012-11-01

Regulation of glucocorticoid receptor (GR) levels is an important stress adaptation mechanism. Transcription factor Nfgi-a and environmentally induced Gr promoter 1 7 methylation have been implicated in fine-tuning the expression of Gr 1 7 transcripts. Here, we investigated Gr promoter 1 7 methylation and Gr 1 7 expression in adult rats exposed to either acute or chronic stress paradigms. A strong negative correlation was observed between the sum of promoter-wide methylation levels and Gr 1 7 transcript levels, independent of the stressor. Methylation of individual sites did not, however, correlate with transcript levels. This suggested that promoter 1 7 was directly regulated by promoter-wide DNA methylation. Although acute stress increased Ngfi-a expression in the hypothalamic paraventricular nucleus (PVN), Gr 1 7 transcript levels remained unaffected despite low methylation levels. Acute stress had little effect on these low methylation levels, except at four hippocampal CpGs. Chronic stress altered the corticosterone response to an acute stressor. In the adrenal and pituitary glands, but not in the brain, this was accompanied by an increase in methylation levels in orchestrated clusters rather than individual CpGs. PVN methylation levels, unaffected by acute or chronic stress, were significantly more variable within- than between-groups, suggesting that they were instated probably during the perinatal period and represent a pre-established trait. Thus, in addition to the known perinatal programming, the Gr 1 7 promoter is epigenetically regulated by chronic stress in adulthood, and retains promoter-wide tissue-specific plasticity. Differences in methylation susceptibility between the PVN in the perinatal period and the peripheral HPA axis tissues in adulthood may represent an important "trait" vs. "state" regulation of the Gr gene.

Characterization of a Novel Dithiocarbamate Glutathione Reductase Inhibitor and Its Use as a Tool to Modulate Intracellular Glutathione*

PubMed Central

Seefeldt, Teresa; Zhao, Yong; Chen, Wei; Raza, Ashraf S.; Carlson, Laura; Herman, Jocqueline; Stoebner, Adam; Hanson, Sarah; Foll, Ryan; Guan, Xiangming

2009-01-01

Thiol redox state (TRS) is an important parameter to reflect intracellular oxidative stress and is associated with various normal and abnormal biochemical processes. Agents that can be used to increase intracellular TRS will be valuable tools in TRS-related research. Glutathione reductase (GR) is a critical enzyme in the homeostasis of TRS. The enzyme catalyzes the reduction of GSSG to GSH to maintain a high GSH:GSSG ratio. Inhibition of the enzyme can be used to increase TRS. Despite the reports of various GR inhibitors, N,N-bis(2-chloroethyl)-N-nitrosourea, an anticancer drug with IC50 = 647 μm against yeast GR, remains the most commonly used GR inhibitor in the literature. However, the toxicity caused by nonspecific interactions, as well as inhibition of DNA synthesis, complicates the use of N,N-bis(2-chloroethyl)-N-nitrosourea as a GR inhibitor. We report 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanylthiocarbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA) as a novel irreversible GR inhibitor. 2-AAPA was prepared by one-step synthesis from commercially available reagents. The Ki and kinact of 2-AAPA against yeast GR were determined to be 56 μm and 0.1 min–1, respectively. At the concentration that produced >80% yeast GR inhibition, 2-AAPA showed no inhibition against glutamylcysteine synthetase, glutathione synthetase, catalase, and superoxide dismutase, but minimal inhibition against glutathione S-transferase and glutathione peroxidase. In CV-1 cells, 2-AAPA (0.1 mm) produced 97% GR inhibition, 25% GSH reduction, and a 5-fold increase in GSSG in 20 min. The compound can be a useful tool in TRS-related research. PMID:19049979

Pathophysiology of Glucocorticoid Signaling.

PubMed

Vitellius, Géraldine; Trabado, Séverine; Bouligand, Jérôme; Delemer, Brigitte; Lombès, Marc

2018-06-01

Glucocorticoids (GC), such as cortisol or dexamethasone, control various physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert most of their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene). GC signaling follows several consecutive steps leading to target gene transactivation, including ligand binding, nuclear translocation of ligand-activated GR complexes, DNA binding, coactivator interaction and recruitment of functional transcriptional machinery. Any step may be impaired and may account for altered GC signaling. Partial or generalized glucocorticoid resistance syndrome may result in a reduced level of functional GR, a decreased hormone affinity and binding, a defect in nuclear GR translocation, a decrease or lack of DNA binding and/or post-transcriptional GR modifications. To date, 26 loss-of-function NR3C1 mutations have been reported in the context of hypertension, hirsutism, adrenal hyperplasia or metabolic disorders. These clinical signs are generally associated with biological features including hypercortisolism without negative regulatory feedback loop on the hypothalamic-pituitary-adrenal axis. Patients had often low plasma aldosterone and renin levels despite hypertension. Only one GR gain-of-function mutation has been described associating Cushing's syndrome phenotype with normal urinary-free cortisol. Some GR polymorphisms (ER22/23EK, GR-9β) have been linked to glucocorticoid resistance and a healthier metabolic profile whereas some others seemed to be associated with GC hypersensitivity (N363S, BclI), increasing cardiovascular risk (diabetes type 2, visceral obesity). This review focuses on the earlier findings on the pathophysiology of GR signaling and presents criteria facilitating identification of novel NR3C1 mutations in selected patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Glucocorticoid receptors participate in the opiate withdrawal-induced stimulation of rats NTS noradrenergic activity and in the somatic signs of morphine withdrawal.

PubMed

Navarro-Zaragoza, Javier; Hidalgo, Juana M; Laorden, M Luisa; Milanés, M Victoria

2012-08-01

Recent evidence suggests that glucocorticoid receptor (GR) is a major molecular substrate of addictive properties of drugs of abuse. Hence, we performed a series of experiments to further characterize the role of GR signalling in opiate withdrawal-induced physical signs of dependence, enhanced noradrenaline (NA) turnover in the hypothalamic paraventricular nucleus (PVN) and tyrosine hydroxylase (TH) phosphorylation (activation) as well as GR expression in the nucleus of the solitary tract noradrenergic cell group (NTS-A₂). The role of GR signalling was assessed by i.p. pretreatment of the selective GR antagonist, mifepristone. Rats were implanted with two morphine (or placebo) pellets. Six days later, rats were pretreated with mifepristone or vehicle 30 min before naloxone and physical signs of abstinence, NA turnover, TH activation, GR expression and the hypothalamus-pituitary-adrenocortical axis activity were measured using HPLC, immunoblotting and RIA. Mifepristone alleviated the somatic signs of naloxone-induced opiate withdrawal. Mifepristone attenuated the increase in the NA metabolite, 3-methoxy-4-hydroxyphenylethylen glycol (MHPG), in the PVN, and the enhanced NA turnover observed in morphine-withdrawn rats. Mifepristone antagonized the TH phosphorylation at Ser³¹ and the expression of c-Fos expression induced by morphine withdrawal. Finally, naloxone-precipitated morphine withdrawal induced up-regulation of GR in the NTS. These results suggest that the physical signs of opiate withdrawal, TH activation and stimulation of noradrenergic pathways innervating the PVN are modulated by GR signalling. Overall, the present data suggest that drugs targeting the GR may ameliorate stress and aversive effects associated with opiate withdrawal. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

A general strategy toward graphitized carbon coating on iron oxides as advanced anodes for lithium-ion batteries.

PubMed

Ding, Chunyan; Zhou, Weiwei; Wang, Bin; Li, Xin; Wang, Dong; Zhang, Yong; Wen, Guangwu

2017-08-25

Integration of carbon materials with benign iron oxides is blazing a trail in constructing high-performance anodes for lithium-ion batteries (LIBs). In this paper, a unique general, simple, and controllable strategy is developed toward in situ uniform coating of iron oxide nanostructures with graphitized carbon (GrC) layers. The basic synthetic procedure only involves a simple dip-coating process for the loading of Ni-containing seeds and a subsequent Ni-catalyzed chemical vapor deposition (CVD) process for the growth of GrC layers. More importantly, the CVD treatment is conducted at a quite low temperature (450 °C) and with extremely facile liquid carbon sources consisting of ethylene glycol (EG) and ethanol (EA). The GrC content of the resulting hybrids can be controllably regulated by altering the amount of carbon sources. The electrochemical results reveal remarkable performance enhancements of iron oxide@GrC hybrids compared with pristine iron oxides in terms of high specific capacity, excellent rate and cycling performance. This can be attributed to the network-like GrC coating, which can improve not only the electronic conductivity but also the structural integrity of iron oxides. Moreover, the lithium storage performance of samples with different GrC contents is measured, manifesting that optimized electrochemical property can be achieved with appropriate carbon content. Additionally, the superiority of GrC coating is demonstrated by the advanced performance of iron oxide@GrC compared with its corresponding counterpart, i.e., iron oxides with amorphous carbon (AmC) coating. All these results indicate the as-proposed protocol of GrC coating may pave the way for iron oxides to be promising anodes for LIBs.

Two-dimensional Core-collapse Supernova Explosions Aided by General Relativity with Multidimensional Neutrino Transport

NASA Astrophysics Data System (ADS)

O’Connor, Evan P.; Couch, Sean M.

2018-02-01

We present results from simulations of core-collapse supernovae in FLASH using a newly implemented multidimensional neutrino transport scheme and a newly implemented general relativistic (GR) treatment of gravity. We use a two-moment method with an analytic closure (so-called M1 transport) for the neutrino transport. This transport is multienergy, multispecies, velocity dependent, and truly multidimensional, i.e., we do not assume the commonly used “ray-by-ray” approximation. Our GR gravity is implemented in our Newtonian hydrodynamics simulations via an effective relativistic potential that closely reproduces the GR structure of neutron stars and has been shown to match GR simulations of core collapse quite well. In axisymmetry, we simulate core-collapse supernovae with four different progenitor models in both Newtonian and GR gravity. We find that the more compact proto–neutron star structure realized in simulations with GR gravity gives higher neutrino luminosities and higher neutrino energies. These differences in turn give higher neutrino heating rates (upward of ∼20%–30% over the corresponding Newtonian gravity simulations) that increase the efficacy of the neutrino mechanism. Three of the four models successfully explode in the simulations assuming GREP gravity. In our Newtonian gravity simulations, two of the four models explode, but at times much later than observed in our GR gravity simulations. Our results, in both Newtonian and GR gravity, compare well with several other studies in the literature. These results conclusively show that the approximation of Newtonian gravity for simulating the core-collapse supernova central engine is not acceptable. We also simulate four additional models in GR gravity to highlight the growing disparity between parameterized 1D models of core-collapse supernovae and the current generation of 2D models.

INTRARENAL GHRELIN RECEPTOR INHIBITION AMELIORATES ANGIOTENSIN II-DEPENDENT HYPERTENSION IN RATS.

PubMed

Kemp, Brandon A; Howell, Nancy L; Padia, Shetal H

2018-06-20

The intrarenal ghrelin receptor (GR) is localized to collecting duct (CD) cells where it increases αENaC-dependent sodium reabsorption in rodents. We hypothesized that chronic GR inhibition with intrarenal GR siRNA lowers blood pressure (BP) in Angiotensin II-dependent hypertension via reductions in αENaC-dependent sodium reabsorption. Uninephrectomized Sprague-Dawley rats (N=121) received subcutaneous osmotic pumps for chronic systemic delivery of Angiotensin II or vehicle (5% dextrose in water). Rats also received intrarenal infusion of vehicle, GR siRNA, or scrambled (SCR) siRNA. In rats receiving intrarenal vehicle or intrarenal SCR siRNA, systemic Angiotensin II infusion increased sodium retention and BP on day 1, and BP remained elevated throughout the 5-day study. These rats also demonstrated increased CD GR expression after 5 days of infusion. However, intrarenal GR siRNA infusion prevented Angiotensin II-mediated sodium retention on day 1, induced a continuously negative cumulative sodium balance compared with Angiotensin II alone, and reduced BP chronically. Glomerular filtration rate and renal blood flow remained unchanged in GR siRNA-infused rats. Systemic Angiotensin II infusion also increased serum aldosterone levels, CD αENaC and pSGK1 expression in rats with intrarenal SCR siRNA; however these effects were not observed in the presence of intrarenal GR siRNA, despite exposure to the same systemic Angiotensin II. These data demonstrate that chronic inhibition of intrarenal GR activity significantly reduces αENaC -dependent sodium retention, resulting in a negative cumulative sodium balance, thereby ameliorating Angiotensin II-induced hypertension in rats. Renal GRs represent a novel therapeutic target for the treatment of hypertension and other sodium-retaining states.

GLUCOCORTICOID RECEPTOR EXPRESSION DURING THE DEVELOPMENT OF THE EMBRYONIC MOUSE SECONDARY PALATE

EPA Science Inventory

Glucocorticoids are important regulators of embryonic growth and development. hese effects are mediated through glucocorticoid receptors (GR) which bind to glucocorticoid response elements upstream of regulated genes. his study examines the expression of GR and GR mRNA in embryon...

Pollination and reproduction of an invasive plant inside and outside its ancestral range

NASA Astrophysics Data System (ADS)

Petanidou, Theodora; Price, Mary V.; Bronstein, Judith L.; Kantsa, Aphrodite; Tscheulin, Thomas; Kariyat, Rupesh; Krigas, Nikos; Mescher, Mark C.; De Moraes, Consuelo M.; Waser, Nickolas M.

2018-05-01

Comparing traits of invasive species within and beyond their ancestral range may improve our understanding of processes that promote aggressive spread. Solanum elaeagnifolium (silverleaf nightshade) is a noxious weed in its ancestral range in North America and is invasive on other continents. We compared investment in flowers and ovules, pollination success, and fruit and seed set in populations from Arizona, USA ("AZ") and Greece ("GR"). In both countries, the populations we sampled varied in size and types of present-day disturbance. Stature of plants increased with population size in AZ samples whereas GR plants were uniformly tall. Taller plants produced more flowers, and GR plants produced more flowers for a given stature and allocated more ovules per flower. Similar functional groups of native bees pollinated in AZ and GR populations, but visits to flowers decreased with population size and we observed no visits in the largest GR populations. As a result, plants in large GR populations were pollen-limited, and estimates of fecundity were lower on average in GR populations despite the larger allocation to flowers and ovules. These differences between plants in our AZ and GR populations suggest promising directions for further study. It would be useful to sample S. elaeagnifolium in Mediterranean climates within the ancestral range (e.g., in California, USA), to study asexual spread via rhizomes, and to use common gardens and genetic studies to explore the basis of variation in allocation patterns and of relationships between visitation and fruit set.

Lateral assembly of oxidized graphene flakes into large-scale transparent conductive thin films with a three-dimensional surfactant 4-sulfocalix[4]arene

PubMed Central

Sundramoorthy, Ashok K.; Wang, Yilei; Wang, Jing; Che, Jianfei; Thong, Ya Xuan; Lu, Albert Chee W.; Chan-Park, Mary B.

2015-01-01

Graphene is a promising candidate material for transparent conductive films because of its excellent conductivity and one-carbon-atom thickness. Graphene oxide flakes prepared by Hummers method are typically several microns in size and must be pieced together in order to create macroscopic films. We report a macro-scale thin film fabrication method which employs a three-dimensional (3-D) surfactant, 4-sulfocalix[4]arene (SCX), as a lateral aggregating agent. After electrochemical exfoliation, the partially oxidized graphene (oGr) flakes are dispersed with SCX. The SCX forms micelles, which adsorb on the oGr flakes to enhance their dispersion, also promote aggregation into large-scale thin films under vacuum filtration. A thin oGr/SCX film can be shaved off from the aggregated oGr/SCX cake by immersing the cake in water. The oGr/SCX thin-film floating on the water can be subsequently lifted from the water surface with a substrate. The reduced oGr (red-oGr) films can be as thin as 10−20 nm with a transparency of >90% and sheet resistance of 890 ± 47 kΩ/sq. This method of electrochemical exfoliation followed by SCX-assisted suspension and hydrazine reduction, avoids using large amounts of strong acid (unlike Hummers method), is relatively simple and can easily form a large scale conductive and transparent film from oGr/SCX suspension. PMID:26040436

Insight into the Role of Size Modulation on Tuning the Band Gap and Photocatalytic Performance of Semiconducting Nitrogen-Doped Graphene.

PubMed

Yang, Mei-Ling; Zhang, Nan; Lu, Kang-Qiang; Xu, Yi-Jun

2017-04-04

Considerable attention has been focused on transforming graphene (GR) into semiconducting GR by diverse strategies, which can perform as one type of promising photocatalyst toward various photoredox reactions. Herein, we report a facile alkali-assisted hydrothermal method for simultaneous tailoring of the lateral size of GR and nitrogen (N) doping into the GR matrix, by which small-sized N-doped GR (S-NGR) can be obtained. For comparison, large-sized N-doped GR (L-NGR) has also been achieved through the same hydrothermal treatment except for the addition of alkali. The photocatalytic activity test shows that S-NGR exhibits much higher activity than L-NGR toward the degradation of organic pollutants under visible-light irradiation. Structure-photoactivity correlation analysis and characterization suggest that the underlying origin for the significantly enhanced visible-light photoactivity of S-NGR in comparison with L-NGR can be assigned to the lateral size decrease in the NGR sheet, which is able to tune the band gap of semiconducting NGR, to facilitate the separation and transfer of photogenerated charge carriers, and to improve the adsorption capacity of NGR toward the reactant. It is expected that this work will cast new light on the judicious utilization of semiconducting GR with controlled size modulation and heteroatom doping to tune its physicochemical properties, thereby advancing further developments in the rational design of more efficient semiconducting GR materials for diverse applications in photocatalysis.

Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: effects on energy metabolism.

PubMed

Adzic, Miroslav; Lukic, Iva; Mitic, Milos; Djordjevic, Jelena; Elaković, Ivana; Djordjevic, Ana; Krstic-Demonacos, Marija; Matić, Gordana; Radojcic, Marija

2013-12-01

Antidepressants affect glucocorticoid receptor (GR) functioning partly through modulation of its phosphorylation but their effects on mitochondrial GR have remained undefined. We investigated the ability of chronic fluoxetine treatment to affect chronic stress-induced changes of mitochondrial GR and its phosphoisoforms (pGRs) in the prefrontal cortex and hippocampus of female and male rats. Since mitochondrial GR regulates oxidative phosphorylation, expression of mitochondrial-encoded subunits of cytochrome (cyt) c oxidase and its activity were also investigated. Chronic stress caused accumulation of the GR in mitochondria of female prefrontal cortex, while the changes in the hippocampus were sex-specific at the levels of pGRs. Expression of mitochondrial COXs genes corresponded to chronic stress-modulated mitochondrial GR in both tissues of both genders and to cyt c oxidase activity in females. Moreover, the metabolic parameters in stressed animals were affected by fluoxetine therapy only in the hippocampus. Namely, fluoxetine effects on mitochondrial COXs and cyt c oxidase activity in the hippocampus seem to be conveyed through pGR232 in females, while in males this likely occurs through other mechanisms. In summary, sex-specific regulation of cyt c oxidase by the stress and antidepressant treatment and its differential convergence with mitochondrial GR signaling in the prefrontal cortex and hippocampus could contribute to clarification of sex-dependent vulnerability to stress-related disorders and sex-specific clinical impact of antidepressants. Copyright © 2013 Elsevier Ltd. All rights reserved.

The pharmacology of GR203040, a novel, potent and selective non-peptide tachykinin NK1 receptor antagonist.

PubMed Central

Beattie, D. T.; Beresford, I. J.; Connor, H. E.; Marshall, F. H.; Hawcock, A. B.; Hagan, R. M.; Bowers, J.; Birch, P. J.; Ward, P.

1995-01-01

1. The in vitro and in vivo pharmacology of GR203040 ((2S, 3S)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), a novel, highly potent and selective non-peptide tachykinin NK1 receptor antagonist, was investigated in the present study. 2. GR203040 potently inhibited [3H]-substance P binding to human NK1 receptors expressed in Chinese hamster ovary (CHO) and U373 MG astrocytoma cells, and NK1 receptors in ferret and gerbil cortex (pKi values of 10.3, 10.5, 10.1 and 10.1 respectively). GR203040 had lower affinity at rat NK1 receptors (pKi = 8.6) and little affinity for human NK2 receptors (pKi < 5.0) in CHO cells and NK3 receptors in guinea-pig cortex (pKi < 6.0). With the exception of the histamine H1 receptor (pIC50 = 7.5). GR203040 had little affinity (pIC50 < 6.0) at all non-NK1 receptors and ion channels examined. Furthermore, GR203040 produced only weak inhibition of Na+ currents in SH-SY5Y neuroblastoma and superior cervical ganglion cells (pIC50 values < 4.0). GR203040 produced only weak antagonism of Ca(2+)-evoked contractions of rat isolated portal vein (pKn = 4.1). The enantiomer of GR203040, GR205608 (2R, 3R)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), had 10,000 fold lower affinity at the human NK1 receptor expressed in CHO cells (pKi = 6.3). 3. In gerbil ex vivo binding experiments, GR203040 produced a dose-dependent inhibition of the binding of [3H]-substance P to cerebral cortical membranes (ED50 = 15 micrograms kg-1 s.c. and 0.42 mg kg-1 p.o.). At 10 micrograms kg-1 s.c., the inhibition of [3H]-substance P binding was maintained for > 6 h. In the rat, GR203040 was less potent (ED50 = 15.4 mg kg-1 s.c.) probably reflecting, at least in part, its lower affinity at the rat NK1 receptor. 4. In guinea-pig isolated ileum and dog isolated middle cerebral and basilar arteries, GR203040 produced a rightward displacement of the concentration-effect curves to substance P methyl ester (SPOMe) with suppression of the maximum agonist response (apparent pKB values of 11.9, 11.2 and 11.1 respectively). 5. In anaesthetized rabbits, GR203040 antagonized reductions in carotid arterial vascular resistance evoked by SPOMe, injected via the lingual artery (DR10 (i.e. the dose producing a dose-ratio of 10) = 1.1 micrograms kg-1, i.v.). At a dose 20 fold greater than its DR10 value (i.e. 22 micrograms kg-1, i.v.), significant antagonism was evident more than 2 h after GR203040 administration. 6. In anaesthetized rats, GR203040 (3 and 10 mg kg-1, i.v.) produced a dose-dependent inhibition of plasma protein extravasation in dura mater, conjunctiva, eyelid and lip in response to electrical stimulation of the trigeminal ganglion. 7. It is concluded that GR203040 is one of the most potent and selective NK1 receptor antagonists yet described, and as such, has considerable potential as a pharmacological tool to characterize the physiological and pathological roles of substance P and NK1 receptors. GR203040 may also have potential as a novel therapeutic agent for the treatment of conditions such as migraine, emesis and pain. PMID:8719789

Sensitivity of Spaceborne and Ground Radar Comparison Results to Data Analysis Methods and Constraints

NASA Technical Reports Server (NTRS)

Morris, Kenneth R.; Schwaller, Mathew

2011-01-01

With the availability of active weather radar observations from space from the Precipitation Radar (PR) on board the Tropical Rainfall Measuring Mission (TR.MM) satellite, numerous studies have been performed comparing PR reflectivity and derived rain rates to similar observations from ground-based weather radars (GR). These studies have used a variety of algorithms to compute matching PR and GR volumes for comparison. Most studies have used a fixed 3-dimensional Cartesian grid centered on the ground radar, onto which the PR and GR data are interpolated using a proprietary approach and/or commonly available GR analysis software (e.g., SPRINT, REORDER). Other studies have focused on the intersection of the PR and GR viewing geometries either explicitly or using a hybrid of the fixed grid and PR/GR common fields of view. For the Dual-Frequency Precipitation Radar (DPR) of the upcoming Global Precipitation Measurement (GPM) mission, a prototype DPR/GR comparison algorithm based on similar TRMM PR data has been developed that defines the common volumes in terms of the geometric intersection of PR and GR rays, where smoothing of the PR and GR data are minimized and no interpolation is performed. The PR and GR volume-averaged reflectivity values of each sample volume are accompanied by descriptive metadata, for attributes including the variability and maximum of the reflectivity within the sample volume, and the fraction of range gates in the sample average having reflectivity values above an adjustable detection threshold (typically taken to be 18 dBZ for the PR). Sample volumes are further characterized by rain type (Stratiform or Convective), proximity to the melting layer, underlying surface (land/water/mixed), and the time difference between the PR and GR observations. The mean reflectivity differences between the PR and GR can differ between data sets produced by the different analysis methods; and for the GPM prototype, by the type of constraints and categorization applied to the data. In this paper, we will show results comparing the 3-D gridded analysis "black box" approach to the GPM prototype volume-matching approach, using matching TRMM PR and WSR-88D ground radar data. The affects of applying data constraints and data categorizations on the volume-matched data to the results will be shown, and explanations of the differences in terms of data and analysis algorithm characteristics will be presented. Implications of the differences to the determination of PR/DPR calibration differences and use of ground radar data to evaluate the PR and DPR attenuation correction algorithms will be discussed.

Evolution of Serum 25OHD in Response to Vitamin D3–Fortified Yogurts Consumed by Healthy Menopausal Women: A 6-Month Randomized Controlled Trial Assessing the Interactions between Doses, Baseline Vitamin D Status, and Seasonality

PubMed Central

Bonjour, Jean-Philippe; Dontot-Payen, Flore; Rouy, Emilien; Walrand, Stephane; Rousseau, Brigitte

2018-01-01

ABSTRACT Background: Adequate vitamin D status contributes to bone fragility risk reduction and possibly other pathological conditions that occur with aging. In response to pharmaceutical vitamin D3 supplements, several studies have documented the influence of doses, baseline status, and seasonality on serum 25-hydroyvitamin D (s25OHD). Objective: Using fortified yogurt, we investigated in one randomized controlled trial how both baseline status, as assessed by measuring s25OHD prior the onset of the trial, and the season of enrollment quantitatively influenced the response to the supplemented (Suppl.) of vitamin D3 (VitD3) in healthy community-dwelling women. Methods: A 24-week controlled trial was conducted in menopausal women (mean age: 61.5). Participants were randomized into 3 groups (Gr): Gr.Suppl.0, time controls maintaining dietary habits; Gr.Suppl.5 and Gr.Suppl.10 consuming one and two 125-g servings of VitD3-fortified yogurts with 5- and 10-µg daily doses, respectively. The 16 intervention weeks lasted from early January to mid-August, the 8 follow-up weeks, without product, from late August to mid-October. Before enrollment, subjects were randomized into 2 s25OHD strata: low stratum (LoStr): 25–50 nmol/L; high stratum (HiStr): >50–75 nmol/L. Results: All enrolled participants adhered to the protocol throughout the 24-week study: Gr.Suppl.0 (n = 45), Gr.Suppl.5 (n = 44), and Gr.Suppl.10 (n = 44). Over the 16 intervention and 8 follow-up weeks, s25OHD increased in both supplemented groups, more in Gr.Suppl.10 than in Gr.Suppl.5. At the end of the intervention, the subject proportion with s25OHD ≥ 50 nmol/L was 37.8, 54.5, and 63.6% in Gr.Suppl.0, Gr.Suppl.5, and Gr.Suppl.10, respectively. The constant rate of s25OHD per supplemental VitD3 microgram was greater in LoStr than HiStr. The s25OHD increase was greater with late (mid-March) than early (mid-January) inclusion. Conclusion: This randomized trial demonstrates (1) a dose-dependent s25OHD improvement related to fortified yogurt consumption; (2) an inversely baseline-dependent increase in s25OHD; and (3) a seasonal effect that highlights the importance of VitD3-fortified foods during winter, even at 5 µg/d, in healthy menopausal women. PMID:28976265

Evolution of Serum 25OHD in Response to Vitamin D3-Fortified Yogurts Consumed by Healthy Menopausal Women: A 6-Month Randomized Controlled Trial Assessing the Interactions between Doses, Baseline Vitamin D Status, and Seasonality.

PubMed

Bonjour, Jean-Philippe; Dontot-Payen, Flore; Rouy, Emilien; Walrand, Stephane; Rousseau, Brigitte

2018-01-01

Adequate vitamin D status contributes to bone fragility risk reduction and possibly other pathological conditions that occur with aging. In response to pharmaceutical vitamin D 3 supplements, several studies have documented the influence of doses, baseline status, and seasonality on serum 25-hydroyvitamin D (s25OHD). Using fortified yogurt, we investigated in one randomized controlled trial how both baseline status, as assessed by measuring s25OHD prior the onset of the trial, and the season of enrollment quantitatively influenced the response to the supplemented (Suppl.) of vitamin D 3 (VitD 3 ) in healthy community-dwelling women. A 24-week controlled trial was conducted in menopausal women (mean age: 61.5). Participants were randomized into 3 groups (Gr): Gr.Suppl.0, time controls maintaining dietary habits; Gr.Suppl.5 and Gr.Suppl.10 consuming one and two 125-g servings of VitD 3 -fortified yogurts with 5- and 10-µg daily doses, respectively. The 16 intervention weeks lasted from early January to mid-August, the 8 follow-up weeks, without product, from late August to mid-October. Before enrollment, subjects were randomized into 2 s25OHD strata: low stratum (LoStr): 25-50 nmol/L; high stratum (HiStr): >50-75 nmol/L. All enrolled participants adhered to the protocol throughout the 24-week study: Gr.Suppl.0 (n = 45), Gr.Suppl.5 (n = 44), and Gr.Suppl.10 (n = 44). Over the 16 intervention and 8 follow-up weeks, s25OHD increased in both supplemented groups, more in Gr.Suppl.10 than in Gr.Suppl.5. At the end of the intervention, the subject proportion with s25OHD ≥ 50 nmol/L was 37.8, 54.5, and 63.6% in Gr.Suppl.0, Gr.Suppl.5, and Gr.Suppl.10, respectively. The constant rate of s25OHD per supplemental VitD 3 microgram was greater in LoStr than HiStr. The s25OHD increase was greater with late (mid-March) than early (mid-January) inclusion. This randomized trial demonstrates (1) a dose-dependent s25OHD improvement related to fortified yogurt consumption; (2) an inversely baseline-dependent increase in s25OHD; and (3) a seasonal effect that highlights the importance of VitD 3 -fortified foods during winter, even at 5 µg/d, in healthy menopausal women.

Science Adventures Calendar

Science.gov Websites

:00 AM - 2:30 PM for Students, Gr.4-6 July, 2018 9-13 Best Games Ever! Your Own!, 9:00 AM - 12:00 PM for Students, Gr.5-8 9-13 The Forces are with You!, 9:00 AM - 12:00 PM for Students, Gr.1-4 14 Games

Comparative Corrosion Behavior of Two Palladium Containing Titanium Alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lian, T; Yashiki, T; Nakayama, T

2006-02-05

The ASTM standard B 265 provides the requirements for the chemical composition of titanium (Ti) alloys. It is planned to use corrosion resistant and high strength titanium alloys to fabricate the drip shield at the proposed Yucca Mountain Repository. Titanium grade (Gr) 7 (R52400) and other Ti alloys are currently being characterized for this application. Ti Gr 7 contains 0.15% Palladium (Pd) to increase its corrosion performance. In this article we report results on the comparative short term corrosion behavior of Ti Gr 7 and a Ruthenium (Ru) containing alloy (Ti Gr 33). Ti Gr 33 also contains a smallmore » amount of Pd. Limited electrochemical testing such as polarization resistance and cyclic potentiodynamic curves showed that both alloys have a similar corrosion behavior in the tested environments.« less

COMPARATIVE CORROSION BEHAVIOR OF TWO PALLADIUM CONTAINING TITANIUM ALLOYS

DOE Office of Scientific and Technical Information (OSTI.GOV)

T. Lian, T. Yashiki, T. Nakayama, T. Nakanishi, R. B. Rebak

2006-07-23

The ASTM standard B 265 provides the requirements for the chemical composition of titanium (Ti) alloys. It is planned to use corrosion resistant and high strength titanium alloys to fabricate the drip shield at the proposed Yucca Mountain Repository. Titanium grade (Gr) 7 (R52400) and other Ti alloys are currently being characterized for this application. Ti Gr 7 contains 0.15% Palladium (Pd) to increase its corrosion performance. In this article we report results on the comparative short term corrosion behavior of Ti Gr 7 and a Ruthenium (Ru) containing alloy (Ti Gr 33). Ti Gr 33 also contains a smallmore » amount of Pd. Limited electrochemical testing such as polarization resistance and cyclic potentiodynamic curves showed that both alloys have a similar corrosion behavior in the tested environments.« less

Cationic Biomimetic Particles of Polystyrene/Cationic Bilayer/Gramicidin for Optimal Bactericidal Activity.

PubMed

Xavier, Gabriel R S; Carmona-Ribeiro, Ana M

2017-12-02

Nanostructured particles of polystyrene sulfate (PSS) covered by a cationic lipid bilayer of dioctadecyldimethylammonium bromide (DODAB) incorporated gramicidin D (Gr) yielding optimal and broadened bactericidal activity against both Escherichia coli and Staphylococcus aureus . The adsorption of DODAB/Gr bilayer onto PSS nanoparticles (NPs) increased the zeta-average diameter by 8-10 nm, changed the zeta-potential of the NPs from negative to positive, and yielded a narrow size distributions for the PSS/DODAB/Gr NPs, which displayed broad and maximal microbicidal activity at very small concentrations of the antimicrobials, namely, 0.057 and 0.0057 mM DODAB and Gr, respectively. The results emphasized the advantages of highly-organized, nanostructured, and cationic particles to achieve hybrid combinations of antimicrobials with broad spectrum activity at considerably reduced DODAB and Gr concentrations.

Plastid-Localized Glutathione Reductase2–Regulated Glutathione Redox Status Is Essential for Arabidopsis Root Apical Meristem Maintenance[C][W

PubMed Central

Yu, Xin; Pasternak, Taras; Eiblmeier, Monika; Ditengou, Franck; Kochersperger, Philip; Sun, Jiaqiang; Wang, Hui; Rennenberg, Heinz; Teale, William; Paponov, Ivan; Zhou, Wenkun; Li, Chuanyou; Li, Xugang; Palme, Klaus

2013-01-01

Glutathione is involved in thiol redox signaling and acts as a major redox buffer against reactive oxygen species, helping to maintain a reducing environment in vivo. Glutathione reductase (GR) catalyzes the reduction of glutathione disulfide (GSSG) into reduced glutathione (GSH). The Arabidopsis thaliana genome encodes two GRs: GR1 and GR2. Whereas the cytosolic/peroxisomal GR1 is not crucial for plant development, we show here that the plastid-localized GR2 is essential for root growth and root apical meristem (RAM) maintenance. We identify a GR2 mutant, miao, that displays strong inhibition of root growth and severe defects in the RAM, with GR activity being reduced to ∼50%. miao accumulates high levels of GSSG and exhibits increased glutathione oxidation. The exogenous application of GSH or the thiol-reducing agent DTT can rescue the root phenotype of miao, demonstrating that the RAM defects in miao are triggered by glutathione oxidation. Our in silico analysis of public microarray data shows that auxin and glutathione redox signaling generally act independently at the transcriptional level. We propose that glutathione redox status is essential for RAM maintenance through both auxin/PLETHORA (PLT)-dependent and auxin/PLT-independent redox signaling pathways. PMID:24249834

Uterine glucocorticoid receptors are critical for fertility in mice through control of embryo implantation and decidualization

PubMed Central

Whirledge, Shannon D.; Oakley, Robert H.; Myers, Page H.; Lydon, John P.; DeMayo, Francesco; Cidlowski, John A.

2015-01-01

In addition to the well-characterized role of the sex steroid receptors in fertility and reproduction, organs of the female reproductive tract are also regulated by the hypothalamic–pituitary–adrenal axis. These endocrine organs are sensitive to stress-mediated actions of glucocorticoids, and the mouse uterus contains high levels of the glucocorticoid receptor (GR). Although the presence of GR in the uterus is well established, uterine glucocorticoid signaling has been largely ignored in terms of its reproductive and/or immunomodulatory functions on fertility. To define the direct in vivo function of glucocorticoid signaling in adult uterine physiology, we generated a uterine-specific GR knockout (uterine GR KO) mouse using the PRcre mouse model. The uterine GR KO mice display a profound subfertile phenotype, including a significant delay to first litter and decreased pups per litter. Early defects in pregnancy are evident as reduced blastocyst implantation and subsequent defects in stromal cell decidualization, including decreased proliferation, aberrant apoptosis, and altered gene expression. The deficiency in uterine GR signaling resulted in an exaggerated inflammatory response to induced decidualization, including altered immune cell recruitment. These results demonstrate that GR is required to establish the necessary cellular context for maintaining normal uterine biology and fertility through the regulation of uterine-specific actions. PMID:26598666

Glucocorticoid receptor expression on circulating leukocytes in healthy and asthmatic adolescents in response to exercise

PubMed Central

Lu, Kim D.; Cooper, Dan; Haddad, Fadia; Zaldivar, Frank; Kraft, Monica; Radom-Aizik, Shlomit

2017-01-01

Background Poor aerobic fitness is associated with worsening of asthma symptoms and fitness training may improve asthma control. The mechanism linking fitness with asthma is not known. We hypothesized that repeated bouts of exercise would lead to a downregulation of glucocorticoid receptor (GR) expression on circulating leukocytes reflecting a reduced responsiveness to stress. Methods In a prospective exercise training intervention of healthy and asthmatic adolescents, GR expression in leukocytes was measured using flow cytometry in response to a brief exercise challenge before and after the training intervention. PBMC gene expression of GR, GRβ, HSP70, and TGFβ1, 2 were determined using RT-PCR. Results Peak V̇O2 increased by 14.6 ± 2.3% indicating an effective training (p<0.01). There was a significant difference in GR expression among leukocyte subtypes, with highest expression in eosinophils. Following the training intervention, there was a significant decrease in baseline GR expression (p<0.05) in leukocyte and monocyte subtypes in both healthy and asthmatic adolescents. Conclusions This is the first study in adolescents to show that exercise training reduces GR expression on circulating leukocytes. We speculate that exercise training downregulates the stress response in general, manifested by decreased GR expression, and may explain why improving fitness improves asthma health. PMID:28796240

Switchable Ionic Liquids: An Environmentally Friendly Medium to Synthesise Nanoparticulate Green Rust

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lao, David; Kukkadapu, Ravi; Kovarik, Libor

Under anoxic conditions, a novel nanoparticulate green rust with carbonate (nano GR) was synthesized by addition of methanol to degassed switchable ionic liquid (SWIL) solution comprised of 1-hexanol, diazabicycloundec-7-ene (DBU), CO2 and Fe(C2H3O2)2 (Fe(OAc)2). Variable temperature Mössbauer spectroscopy studies indicated the product to be predominantly GR while TEM-SAED method confirmed it be nanoparticulate in nature. Experiments with and without methanol in the SWIL medium suggest that methanol may be responsible for Fe(II) oxidation to Fe(III) necessary for GR formation. Studies with Ar instead of CO2 trigger gas indicated that CO2 is essential for GR formation. Conditions to generate CO32- anionmore » was most likely provided by basic environment of the medium. The nano GR suspension was very reactive and instantaneously oxidized completely to a reddish-brown precipitate upon exposure to ambient atmosphere. The nature of the oxidized sample is not certain. The oxidized product, however, appears to be a mix of ferric green rust- [GR(CO32-]*; major] and ferrihydrite-like minerals. To our knowledge, this is first report of use of environmentally-friendly SWIL reagents to synthesize very reactive nano GR materials.« less

Poly(GR) in C9ORF72-Related ALS/FTD Compromises Mitochondrial Function and Increases Oxidative Stress and DNA Damage in iPSC-Derived Motor Neurons.

PubMed

Lopez-Gonzalez, Rodrigo; Lu, Yubing; Gendron, Tania F; Karydas, Anna; Tran, Helene; Yang, Dejun; Petrucelli, Leonard; Miller, Bruce L; Almeida, Sandra; Gao, Fen-Biao

2016-10-19

GGGGCC repeat expansions in C9ORF72 are the most common genetic cause of both ALS and FTD. To uncover underlying pathogenic mechanisms, we found that DNA damage was greater, in an age-dependent manner, in motor neurons differentiated from iPSCs of multiple C9ORF72 patients than control neurons. Ectopic expression of the dipeptide repeat (DPR) protein (GR) 80 in iPSC-derived control neurons increased DNA damage, suggesting poly(GR) contributes to DNA damage in aged C9ORF72 neurons. Oxidative stress was also increased in C9ORF72 neurons in an age-dependent manner. Pharmacological or genetic reduction of oxidative stress partially rescued DNA damage in C9ORF72 neurons and control neurons expressing (GR) 80 or (GR) 80 -induced cellular toxicity in flies. Moreover, interactome analysis revealed that (GR) 80 preferentially bound to mitochondrial ribosomal proteins and caused mitochondrial dysfunction. Thus, poly(GR) in C9ORF72 neurons compromises mitochondrial function and causes DNA damage in part by increasing oxidative stress, revealing another pathogenic mechanism in C9ORF72-related ALS and FTD. Copyright © 2016 Elsevier Inc. All rights reserved.

CD11b+Gr-1dim Tolerogenic Dendritic Cell-Like Cells Are Expanded in Interstitial Lung Disease in SKG Mice.

PubMed

Sendo, Sho; Saegusa, Jun; Okano, Takaichi; Takahashi, Soshi; Akashi, Kengo; Morinobu, Akio

2017-12-01

SKG mice develop interstitial lung disease (ILD) resembling rheumatoid arthritis-associated ILD in humans. The aim of this study was to clarify the mechanism underlying the lung pathology by analyzing lung-infiltrating cells in SKG mice with ILD. We assessed the severity of zymosan A (ZyA)-induced ILD in SKG mice histologically, and we examined lung-infiltrating cells by flow cytometry. Total lung cells and isolated monocytic myeloid-derived suppressor cells (MDSCs) were cultured in vitro with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4. The proliferation of 5,6-carboxyfluorescein diacetate N-succinimidyl ester-labeled naive T cells cocultured with isolated CD11b+Gr-1 dim cells and MDSCs was evaluated by flow cytometry. CD11b+Gr-1 dim cells were adoptively transferred to ZyA-treated SKG mice. MDSCs, Th17 cells, and group 1 and 3 innate lymphoid cells (ILC1s and ILC3s) were increased in the lungs; the proportion of these cells varied with ILD severity. In this process, we found that a unique cell population, CD11b+Gr-1 dim cells, was expanded in the severely inflamed lungs. Approximately half of the CD11b+Gr-1 dim cells expressed CD11c. CD11b+Gr-1 dim cells were induced from monocytic MDSCs with GM-CSF in vitro and were considered tolerogenic because they suppressed T cell proliferation. These CD11b+Gr-1 dim cells have never been described previously, and we termed them CD11b+Gr-1 dim tolerogenic dendritic cell (DC)-like cells. Th17 cells, ILC1s, and ILC3s in the inflamed lung produced GM-CSF, which may have expanded CD11b+Gr-1 dim tolerogenic DC-like cells in vivo. Furthermore, adoptive transfer of CD11b+Gr-1 dim tolerogenic DC-like cells significantly suppressed progression of ILD in SKG mice. We identified unique suppressive myeloid cells that were differentiated from monocytic MDSCs in SKG mice with ILD, and we termed them CD11b+Gr-1 dim tolerogenic DC-like cells. © 2017, American College of Rheumatology.

[Control of postoperative hemorrhage in isolated coronary bypass surgery: comparison of tranexamic acid effects in off-pump surgery with aprotinin effects in conventional surgery].

PubMed

Bordalo, Alvaro D B; Nobre, Angelo L; Silva, Fernanda; Serpa, Carlos; Cravino, João

2011-01-01

In spite of the strong criticism elicited thereafter, the results of a multicentric study on the consequences of several perioperative anti-hemorrhagic strategies in cardiac surgery, published five years ago, led to the aprotinin (Aprot) withdrawal from the market and its progressive replacement by tranexamic acid (TrAc) in many surgical departments. To evaluate the hemostatic effects and clinical consequences of TrAc use or non-use in off-pump coronary bypass surgery (CABG) and compare them with those of Aprot use or non-use in conventional (conv) CABG. Retrospective analysis of 2 groups (Gr) of patients (pts): GrA - 252 pts undergoing isolated conv CABG (GrA1 - 185 pts submitted to an intra-operative full-dose Aprot protocol; GrA2 - 67 pts operated without Aprot); GrB - 383 pts undergoing isolated off-pump CABG (GrB1 - 136 pts submitted to an intra-operative low-dose TrAc protocol; GrB2 - 247 pts operated in absence of TrAc). Pre-operative clinical characteristics (GrA1 vs GrA2, GrB1 vs GrB2): mean age (years) - 65 vs 64 (NS), 64 vs 64; female gender - 20% vs 21% (NS), 23% vs 20% (NS); logistic Euroscore - 5.1% vs 6.2% (NS), 6.3% vs 5.5% (NS); chronic renal failure - 21% vs 27% (NS), 27% vs 25% (NS); diffuse coronary artery disease - 34% vs 42% (NS), 36% vs 30% (NS); pre-operative betablocker treatment - 64% vs 55% (NS), 74% vs 71% (NS); statin therapy for > 3 months - 78% vs 82% (NS), 81% vs 85% (NS). Pts have been operated by 4 surgeons largely experienced in both CABG modalities. Antiplatelet therapy was stopped => 4 days prior to surgery (but aspirin was maintained in high-risk pts). Results (GrA1 vs GrA2, GrB1 vs GrB2): 1) Bleeding (mL/pt - mean): 783 vs 1375 (p < 0.001), 1061 vs 1368 (p < 0.001); blood loss > 1500 mL (%pts) - 5.4% vs 34% (p < 0.0001), 12% vs 28% (p < 0.001); surgical re-exploration for bleeding - 1.1% vs 3.0% (NS), 2.2% vs 2.0% (NS). 2) Transfusion of blood products (U/pt - mean): plasma - 0.56 vs 2.19 (p < 0.001), 1.45 vs 1.03 (p < 0.05); platelets - 0.09 vs 0.22 (p < 0.02), 0.24 vs 0.15 (NS). 3) Renal function (%pts): increased serum cre- atinine - 56% vs 56%, 55% vs 38% (p < 0.001); hemofiltration use - 1.1% vs 1.5% (NS), 1.5% vs 0.4% (NS). 4) Perioperative myocardial infarction - 21.6% vs 17.9% (NS), 17.6% vs 14.6% (NS); other ischemic events - 3.2% vs 3.0% (NS), 1.5% vs 1.2% (NS). 5) Hospital mortality: 4.8% vs 4.5% (NS), 4.4% vs 1.6% (NS). 1) TrAc does not reduce the risk of surgical re-exploration for bleeding. 2) Taking into account the differences between conv CABG and off-pump CABG, TrAc hemostatic effect seems to be inferior to that of Aprot, without offering a better safety profile in terms of lesser renal or ischemic risk as a counterpart.

Late glacial and Holocene history of the Greenland Ice Sheet margin, Nunatarssuaq, Northwestern Greenland

NASA Astrophysics Data System (ADS)

Farnsworth, L. B.; Kelly, M. A.; Axford, Y.; Bromley, G. R.; Osterberg, E. C.; Howley, J. A.; Zimmerman, S. R. H.; Jackson, M. S.; Lasher, G. E.; McFarlin, J. M.

2015-12-01

Defining the late glacial and Holocene fluctuations of the Greenland Ice Sheet (GrIS) margin, particularly during periods that were as warm or warmer than present, provides a longer-term perspective on present ice margin fluctuations and informs how the GrIS may respond to future climate conditions. We focus on mapping and dating past GrIS extents in the Nunatarssuaq region of northwestern Greenland. During the summer of 2014, we conducted geomorphic mapping and collected rock samples for 10Be surface exposure dating as well as subfossil plant samples for 14C dating. We also obtained sediment cores from an ice-proximal lake. Preliminary 10Be ages of boulders deposited during deglaciation of the GrIS subsequent to the Last Glacial Maximum range from ~30-15 ka. The apparently older ages of some samples indicate the presence of 10Be inherited from prior periods of exposure. These ages suggest deglaciation occurred by ~15 ka however further data are needed to test this hypothesis. Subfossil plants exposed at the GrIS margin on shear planes date to ~ 4.6-4.8 cal. ka BP and indicate less extensive ice during middle Holocene time. Additional radiocarbon ages from in situ subfossil plants on a nunatak date to ~3.1 cal. ka BP. Geomorphic mapping of glacial landforms near Nordsø, a large proglacial lake, including grounding lines, moraines, paleo-shorelines, and deltas, indicate the existence of a higher lake level that resulted from a more extensive GrIS margin likely during Holocene time. A fresh drift limit, characterized by unweathered, lichen-free clasts approximately 30-50 m distal to the modern GrIS margin, is estimated to be late Holocene in age. 10Be dating of samples from these geomorphic features is in progress. Radiocarbon ages of subfossil plants exposed by recent retreat of the GrIS margin suggest that the GrIS was at or behind its present location at AD ~1650-1800 and ~1816-1889. Results thus far indicate that the GrIS margin in northwestern Greenland responded sensitively to Holocene climate changes. Ongoing research will improve the chronological constraints on these fluctuations.

Expression of glucocorticoid receptor isoforms and associations with serine/arginine-rich protein 30c and 40 in patients with systemic lupus erythematosus.

PubMed

Guan, Yan-Chun; Jiang, Lei; Ma, Liang-Liang; Sun, Xiang-Nan; Yu, Dan-Dan; Liu, Jing; Qu, Dong-Xia; Fang, Mei-Yun

2015-01-01

To investigate the expression of glucocorticoid receptor (GR) isoforms in patients with systemic lupus erythematosus (SLE), confirm the main GR isoforms involving in glucocorticoids (GC) resistance, and explore the associations of GR isoforms with serine/arginine-rich protein (SRp) 30c and SRp40. Seventy patients with SLE and thirty-eight age- and sex-matched controls were recruited. All patients received prednisone (0.5-1 mg/kg/d) as their routine therapy. According to the therapeutic effect, patients were divided into glucocorticoid-resistant (GCR) and glucocorticoid-sensitive (GCS) groups. Transcript levels of GRα, GRβ, GRγ, GR-P, SRp30c and SRp40 in peripheral blood mononuclear cells (PBMCs) were determined by real-time PCR. GRα and GRβ proteins were detected by western blotting. Trial registration number is ChiCTR-RCH-12002808. Four GR transcripts in SLE patients showed the following trend: GRα (51.85%) > GR-P (23.78%) > GRγ (13.08%) >GRβ (0.03%). GR-P transcript and ratio of GRα/GR-P in SLE patients were significantly higher than that in controls (p<0.05). GRα transcript and protein as well as SRp40 transcript in GCS group were significantly higher than that in the GCR group before GC treatment (p<0.05). In the GCS group, GRα transcript and SRp40 transcript were significantly higher after GC treatment than that before GC treatment (p<0.05). In the GCR group, GR-P transcript was significantly higher after GC treatment than that before GC treatment (p<0.05). Positive correlation between SRp40 and GRα transcript was found (p<0.05). Additionally, SLE Disease Activity Index scores were significantly negatively correlated with GRα transcript and protein expression (p<0.05). Our data demonstrated that the decreased expression of GRα might be the evidence of high disease activity and help to predict GC resistance. GR-P isoform might be implicated in the development of resistance. Additionally, the preliminary finding suggested that SRp40 might be associated with GRα transcripts in SLE patients.

The Progestin-Only Contraceptive Medroxyprogesterone Acetate, but Not Norethisterone Acetate, Enhances HIV-1 Vpr-Mediated Apoptosis in Human CD4+ T Cells through the Glucocorticoid Receptor

PubMed Central

Tomasicchio, Michele; Avenant, Chanel; Du Toit, Andrea; Ray, Roslyn M.; Hapgood, Janet P.

2013-01-01

The glucocorticoid receptor (GR) regulates several physiological functions, including immune function and apoptosis. The HIV-1 virus accessory protein, viral protein R (Vpr), can modulate the transcriptional response of the GR. Glucocorticoids (GCs) and Vpr have been reported to induce apoptosis in various cells, including T-cells. We have previously shown that the injectable contraceptive, medroxyprogesterone acetate (MPA) is a partial to full agonist for the GR, unlike norethisterone acetate (NET-A). We investigated the functional cross talk between the GR and Vpr in inducing apoptosis in CD4+ T-cells, in the absence and presence of GCs and these progestins, as well as progesterone. By using flow cytometry, we show that, in contrast to NET-A and progesterone, the synthetic GR ligand dexamethasone (Dex), cortisol and MPA induce apoptosis in primary CD4+ T-cells. Furthermore, the C-terminal part of the Vpr peptide, or HIV-1 pseudovirus, together with Dex or MPA further increased the apoptotic phenotype, unlike NET-A and progesterone. By a combination of Western blotting, PCR and the use of receptor- selective agonists, we provide evidence that the GR and the estrogen receptor are the only steroid receptors expressed in peripheral blood mononuclear cells. These results, together with the findings that RU486, a GR antagonist, prevents Dex-, MPA- and Vpr-mediated apoptosis, provide evidence for the first time that GR agonists or partial agonists increase apoptosis in primary CD4+ T-cells via the GR. We show that apoptotic induction involves differential expression of key apoptotic genes by both Vpr and GCs/MPA. This work suggests that contraceptive doses of MPA but not NET-A or physiological doses of progesterone could potentially accelerate depletion of CD4+ T-cells in a GR-dependent fashion in HIV-1 positive women, thereby contributing to immunodeficiency. The results imply that choice of progestin used in contraception may be critical to susceptibility and progression of diseases such as HIV-1. PMID:23658782

Geometric Verification of Dynamic Wave Arc Delivery With the Vero System Using Orthogonal X-ray Fluoroscopic Imaging.

PubMed

Burghelea, Manuela; Verellen, Dirk; Poels, Kenneth; Gevaert, Thierry; Depuydt, Tom; Tournel, Koen; Hung, Cecilia; Simon, Viorica; Hiraoka, Masahiro; de Ridder, Mark

2015-07-15

The purpose of this study was to define an independent verification method based on on-board orthogonal fluoroscopy to determine the geometric accuracy of synchronized gantry-ring (G/R) rotations during dynamic wave arc (DWA) delivery available on the Vero system. A verification method for DWA was developed to calculate O-ring-gantry (G/R) positional information from ball-bearing positions retrieved from fluoroscopic images of a cubic phantom acquired during DWA delivery. Different noncoplanar trajectories were generated in order to investigate the influence of path complexity on delivery accuracy. The G/R positions detected from the fluoroscopy images (DetPositions) were benchmarked against the G/R angulations retrieved from the control points (CP) of the DWA RT plan and the DWA log files recorded by the treatment console during DWA delivery (LogActed). The G/R rotational accuracy was quantified as the mean absolute deviation ± standard deviation. The maximum G/R absolute deviation was calculated as the maximum 3-dimensional distance between the CP and the closest DetPositions. In the CP versus DetPositions comparison, an overall mean G/R deviation of 0.13°/0.16° ± 0.16°/0.16° was obtained, with a maximum G/R deviation of 0.6°/0.2°. For the LogActed versus DetPositions evaluation, the overall mean deviation was 0.08°/0.15° ± 0.10°/0.10° with a maximum G/R of 0.3°/0.4°. The largest decoupled deviations registered for gantry and ring were 0.6° and 0.4° respectively. No directional dependence was observed between clockwise and counterclockwise rotations. Doubling the dose resulted in a double number of detected points around each CP, and an angular deviation reduction in all cases. An independent geometric quality assurance approach was developed for DWA delivery verification and was successfully applied on diverse trajectories. Results showed that the Vero system is capable of following complex G/R trajectories with maximum deviations during DWA below 0.6°. Copyright © 2015 Elsevier Inc. All rights reserved.

Differential expression of a fructose receptor gene in honey bee workers according to age and behavioral role.

PubMed

Takada, Tomoyuki; Sasaki, Taiyo; Sato, Ryoichi; Kikuta, Shingo; Inoue, Maki N

2018-02-01

Honey bee (Apis mellifera) workers contribute to the maintenance of colonies in various ways. The primary functions of workers are divided into two types depending on age: young workers (nurses) primarily engage in such behaviors as cleaning and food handling within the hive, whereas older workers (foragers) acquire floral nutrients beyond the colony. Concomitant with this age-dependent change in activity, physiological changes occur in the tissues and organs of workers. Nurses supply younger larvae with honey containing high levels of glucose and supply older larvae with honey containing high levels of fructose. Given that nurses must determine both the concentration and type of sugar used in honey, gustatory receptors (Gr) expressed in the chemosensory organs likely play a role in distinguishing between sugars. Glucose is recognized by Gr1 in honey bees (AmGr1); however, it remains unclear which Gr are responsible for fructose recognition. This study aimed to identify fructose receptors in honey bees and reported that AmGr3, when transiently expressed in Xenopus oocytes, responded only to fructose, and to no other sugars. We analyzed expression levels of AmGr3 to identify which tissues and organs of workers are involved in fructose recognition and determined that expression of AmGr3 was particularly high in the antennae and legs of nurses. Our results suggest that nurses use their antennae and legs to recognize fructose, and that AmGr3 functions as an accurate nutrient sensor used to maintain food quality in honey bee hives. © 2017 Wiley Periodicals, Inc.

Glyphosate resistance in Ambrosia trifida: Part 2. Rapid response physiology and non-target-site resistance.

PubMed

Moretti, Marcelo L; Van Horn, Christopher R; Robertson, Renae; Segobye, Kabelo; Weller, Stephen C; Young, Bryan G; Johnson, William G; Douglas Sammons, R; Wang, Dafu; Ge, Xia; d' Avignon, André; Gaines, Todd A; Westra, Philip; Green, Amanda C; Jeffery, Taylor; Lespérance, Mackenzie A; Tardif, François J; Sikkema, Peter H; Christopher Hall, J; McLean, Michael D; Lawton, Mark B; Schulz, Burkhard

2018-05-01

The glyphosate-resistant rapid response (GR RR) resistance mechanism in Ambrosia trifida is not due to target-site resistance (TSR) mechanisms. This study explores the physiology of the rapid response and the possibility of reduced translocation and vacuolar sequestration as non-target-site resistance (NTSR) mechanisms. GR RR leaf discs accumulated hydrogen peroxide within minutes of glyphosate exposure, but only in mature leaf tissue. The rapid response required energy either as light or exogenous sucrose. The combination of phenylalanine and tyrosine inhibited the rapid response in a dose-dependent manner. Reduced glyphosate translocation was observed in GR RR, but only when associated with tissue death caused by the rapid response. Nuclear magnetic resonance studies indicated that glyphosate enters the cytoplasm and reaches chloroplasts, and it is not moved into the vacuole of GR RR, GR non-rapid response or glyphosate-susceptible A. trifida. The GR RR mechanism of resistance is not associated with vacuole sequestration of glyphosate, and the observed reduced translocation is likely a consequence of rapid tissue death. Rapid cell death was inhibited by exogenous application of aromatic amino acids phenylalanine and tyrosine. The mechanism by which these amino acids inhibit rapid cell death in the GR RR phenotype remains unknown, and it could involve glyphosate phytotoxicity or other agents generating reactive oxygen species. Implications of these findings are discussed. The GR RR mechanism is distinct from the currently described glyphosate TSR or NTSR mechanisms in other species. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Factors affecting operational tolerance after pediatric living-donor liver transplantation: impact of early post-transplant events and HLA match.

PubMed

Ohe, Hidenori; Waki, Kayo; Yoshitomi, Mami; Morimoto, Takeshi; Nafady-Hego, Hanaa; Satoda, Naoki; Li, Ying; Zhao, Xiangdong; Sakaguchi, Shimon; Uemoto, Shinji; Bishop, G Alex; Koshiba, Takaaki

2012-01-01

Pediatric recipients of living-donor liver transplants (LDLT) can often discontinue immunosuppression (IS). We examined factors affecting development of operational tolerance (OT), defined as off IS for >1 year, in this population. A historic cohort analysis was conducted in 134 pediatric primary semi-allogeneic LDLT. Multivariate logistic regression analysis was used. The frequency of peripheral regulatory T cells (Tregs) was determined at >10 years post-Tx by FACS analysis. IS was successfully discontinued in 84 tolerant patients (Gr-tol), but not in 50 intolerant patients (Gr-intol). The Gr-intol consisted of 24 patients with rejection (Gr-rej) and 26 with fibrosis of grafts (Gr-fib). The absence of early rejection [odds ratio (OR) 2.79, 95% CI 1.11-7.02, P = 0.03], was a positive independent predictor, whereas HLA-A mismatch (0.18, 0.03-0.91, P = 0.04) was a negative predictor. HLA-DR mismatches did not affect OT. The Treg frequency was significantly decreased in Gr-intol (4.9%) compared with Gr-tol (7.6%) (P = 0.003). There were increased levels of tacrolimus in the first week in Gr-Tol (P = 0.02). Although HLA-B mismatch (8.73, 1.09-70.0, P = 0.04) was a positive independent predictor of OT, its clinical significance remains doubtful. In this large cohort of pediatric LDLT recipients, absence of early rejection, HLA-A match and the later predominance of Tregs are factors associated with OT. © 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.

Dibutyltin disrupts glucocorticoid receptor function and impairs glucocorticoid-induced suppression of cytokine production.

PubMed

Gumy, Christel; Chandsawangbhuwana, Charlie; Dzyakanchuk, Anna A; Kratschmar, Denise V; Baker, Michael E; Odermatt, Alex

2008-01-01

Organotins are highly toxic and widely distributed environmental chemicals. Dibutyltin (DBT) is used as stabilizer in the production of polyvinyl chloride plastics, and it is also the major metabolite formed from tributyltin (TBT) in vivo. DBT is immunotoxic, however, the responsible targets remain to be defined. Due to the importance of glucocorticoids in immune-modulation, we investigated whether DBT could interfere with glucocorticoid receptor (GR) function. We used HEK-293 cells transiently transfected with human GR as well as rat H4IIE hepatoma cells and native human macrophages and human THP-1 macrophages expressing endogenous receptor to study organotin effects on GR function. Docking of organotins was used to investigate the binding mechanism. We found that nanomolar concentrations of DBT, but not other organotins tested, inhibit ligand binding to GR and its transcriptional activity. Docking analysis indicated that DBT inhibits GR activation allosterically by inserting into a site close to the steroid-binding pocket, which disrupts a key interaction between the A-ring of the glucocorticoid and the GR. DBT inhibited glucocorticoid-induced expression of phosphoenolpyruvate carboxykinase (PEPCK) and tyrosine-aminotransferase (TAT) and abolished the glucocorticoid-mediated transrepression of TNF-alpha-induced NF-kappaB activity. Moreover, DBT abrogated the glucocorticoid-mediated suppression of interleukin-6 (IL-6) and TNF-alpha production in lipopolysaccharide (LPS)-stimulated native human macrophages and human THP-1 macrophages. DBT inhibits ligand binding to GR and subsequent activation of the receptor. By blocking GR activation, DBT may disturb metabolic functions and modulation of the immune system, providing an explanation for some of the toxic effects of this organotin.

The Great Recession worsened blood pressure and blood glucose levels in American adults.

PubMed

Seeman, Teresa; Thomas, Duncan; Merkin, Sharon Stein; Moore, Kari; Watson, Karol; Karlamangla, Arun

2018-03-27

Longitudinal, individual-specific data from the Multi-Ethnic Study of Atherosclerosis (MESA) provide support for the hypothesis that the 2008 to 2010 Great Recession (GR) negatively impacted the health of US adults. Results further advance understanding of the relationship by ( i ) illuminating hypothesized greater negative impacts in population subgroups exposed to more severe impacts of the GR and ( ii ) explicitly controlling for confounding by individual differences in age-related changes in health over time. Analyses overcome limitations of prior work by ( i ) employing individual-level data that avoid concerns about ecological fallacy associated with prior reliance on group-level data, ( ii ) using four waves of data before the GR to estimate and control for underlying individual-level age-related trends, ( iii ) focusing on objective, temporally appropriate health outcomes rather than mortality, and ( iv ) leveraging a diverse cohort to investigate subgroup differences in the GR's impact. Innovative individual fixed-effects modeling controlling for individual-level age-related trajectories yielded substantively important insights: ( i ) significant elevations post-GR for blood pressure and fasting glucose, especially among those on medication pre-GR, and ( ii ) reductions in prevalence and intensity of medication use post-GR. Important differences in the effects of the GR are seen across subgroups, with larger effects among younger adults (who are likely still in the labor force) and older homeowners (whose declining home wealth likely reduced financial security, with less scope for recouping losses during their lifetime); least affected were older adults without a college degree (whose greater reliance on Medicare and Social Security likely provided more protection from the recession).

Activation of Antigen-Specific CD8(+) T Cells by Poly-DL-Lactide/Glycolide (PLGA) Nanoparticle-Primed Gr-1(high) Cells.

PubMed

Luo, Wen-Hui; Yang, Ya-Wun

2016-04-01

The aim of this study was to investigate the induction of antigen-specific T cell activation and cell cycle modulation by a poly-DL-lactide/glycolide (PLGA) nanoparticle (NP)-primed CD11b(+)Gr-1(high) subset isolated from mouse bone marrow. PLGA NPs containing the ovalbumin (OVA) antigen were prepared using the double emulsion and solvent evaporation method, and protein release rate and cell viability were determined. The Lin2(¯)CD11b(+)Gr-1(high)Ly6c(low) (Gr-1(high)) subset was sorted from the bone marrow of C57BL/6 J mice by fluorescence-activated cell sorting (FACS) and co-cultured with OT-I CD8(+) splenic T cells. Proliferation of OT-I CD8(+) T cells was monitored, and cell cycles were determined by 5-bromo-2'-deoxyuridine (BrdU) labeling. Treatment of Gr-1(high) cells with PLGA/OVA NPs upregulated expression of the SIINFEKL-H2K(b) complex in the context of MHC I. Co-cultures of OT-I CD8(+) T cells with the PLGA/OVA NP-primed Gr-1(high) cells induced the proliferation of T cells in vitro and modulated cell division and morphology. Treatment of Gr-1(high) cells with PLGA/OVA NPs also induced cell apoptosis and necrosis. This study demonstrated the function of PLGA/OVA NPs in the activation of OT-I CD8(+) T cells and the capability of cross-presentation via the Gr-1(high) polymorphonuclear subset from mouse bone marrow.

Optimization of the production of thermostable endo-beta-1,4 mannanases from a newly isolated Aspergillus niger gr and Aspergillus flavus gr.

PubMed

Kote, Naganagouda V; Patil, Aravind Goud G; Mulimani, V H

2009-02-01

The aim of this work was to establish optimal conditions for the maximum production of endo-beta-1,4 mannanases using cheaper sources. Eight thermotolerant fungal strains were isolated from garden soil and compost samples collected in and around the Gulbarga University campus, India. Two strains were selected based on their ability to produce considerable endo-beta-1,4 mannanases activity while growing in liquid medium at 37 degrees C with locust bean gum (LBG) as the only carbon source. They were identified as Aspergillus niger gr and Aspergillus flavus gr. The experiment to evaluate the effect of different carbon sources, nitrogen sources, temperatures and initial pH of the medium on maximal enzyme production was studied. Enzyme productivity was influenced by the type of polysaccharide used as the carbon source. Copra meal defatted with n-hexane showed to be a better substrate than LBG and guar gum for endo-beta-1,4 mannanases production by A. niger gr (40.011 U/ml), but for A. flavus gr (33.532 U/ml), the difference was not significant. Endo-beta-1,4 mannanases produced from A. niger gr and A. flavus gr have high optimum temperature (65 and 60 degrees C) and good thermostability in the absence of any stabilizers (maintaining 50% of residual activity for 8 and 6 h, respectively, at 60 degrees C) and are stable over in a wide pH range. These new strains offer an attractive alternative source of enzymes for the food and feed processing industries.

Assessment of the Etiologic Factors of Gingival Recession in a Group of Patients in Northwest Iran

PubMed Central

Lafzi, Ardeshir; Abolfazli, Nader; Eskandari, Amir

2009-01-01

Background and aims Gingival recession (GR), a common problem in periodontium, is associated with various etiologic factors. There is controversy over the role and importance of these factors. The aim of this study was to evaluate the etiologic factors of GR in a group of subjects in Northwest Iran. Materials and methods In this case-control study, patients referring to a university clinic (123 patients with GR and 123 patients without GR) were evaluated. Patients were examined by an experienced periodontist. A checklist assessing the history of systemic disease, smoking, radiotherapy, orthodontic treatment, chemical and mechanical trauma, tooth-brushing method, type of occlusion, axial inclination of tooth, width and thickness of keratinized gingiva, presence of calculus, prosthesis, faulty restorations and food impaction, and frenum pull was completed for each patient. Chi-square test was used for data analysis. Results Presence of calculus was significantly associated with GR in the evaluated patients (P = 0.000). Low width and thickness of keratinized gingiva, smoking and traumatic tooth brushing were other significant factors (P < 0.05). The type of occlusion, axial inclination of teeth, existence of prosthesis, high frenal attachment, radiotherapy, systemic diseases and chemical trauma were not significantly associated with GR in the evaluated patients (P > 0.05). Conclusion Supra- and sub-gingival calculus, inadequate width and thickness of keratinized tissue, and incorrect tooth brushing techniques are most important etiologic factors of GR. Oral hygiene instructions including correct tooth brushing techniques as well as scaling and root planing with periodic recalls can play a significant role in prevention of GR. PMID:23230492

Assessment of the etiologic factors of gingival recession in a group of patients in northwest iran.

PubMed

Lafzi, Ardeshir; Abolfazli, Nader; Eskandari, Amir

2009-01-01

Gingival recession (GR), a common problem in periodontium, is associated with various etiologic factors. There is controversy over the role and importance of these factors. The aim of this study was to evaluate the etiologic factors of GR in a group of subjects in Northwest Iran. In this case-control study, patients referring to a university clinic (123 patients with GR and 123 patients without GR) were evaluated. Patients were examined by an experienced periodontist. A checklist assessing the history of systemic disease, smoking, radiotherapy, orthodontic treatment, chemical and mechanical trauma, tooth-brushing method, type of occlusion, axial inclination of tooth, width and thickness of keratinized gingiva, presence of calculus, prosthesis, faulty restorations and food impaction, and frenum pull was completed for each patient. Chi-square test was used for data analysis. Presence of calculus was significantly associated with GR in the evaluated patients (P = 0.000). Low width and thickness of keratinized gingiva, smoking and traumatic tooth brushing were other significant factors (P < 0.05). The type of occlusion, axial inclination of teeth, existence of prosthesis, high frenal attachment, radiotherapy, systemic diseases and chemical trauma were not significantly associated with GR in the evaluated patients (P > 0.05). Supra- and sub-gingival calculus, inadequate width and thickness of keratinized tissue, and incorrect tooth brushing techniques are most important etiologic factors of GR. Oral hygiene instructions including correct tooth brushing techniques as well as scaling and root planing with periodic recalls can play a significant role in prevention of GR.

77 FR 40511 - Safety Zone; GR Symphony Fireworks Display, Kalamazoo Lake, Saugatuck, MI

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-10

...-AA00 Safety Zone; GR Symphony Fireworks Display, Kalamazoo Lake, Saugatuck, MI AGENCY: Coast Guard, DHS... Kalamazoo Lake during the GR Symphony Fireworks display. This temporary safety zone is necessary to protect spectators and vessels from the hazards associated with a fireworks display. DATES: This rule will be...

Protective coatings for composite tubes in space applications

NASA Technical Reports Server (NTRS)

Dursch, Harry W.; Hendricks, Carl L.

1987-01-01

Protective coatings for graphite/epoxy (Gr/Ep) tubular structures for a manned Space Station truss structure were evaluated. The success of the composite tube truss structure depends on its stability to long-term exposure to the low earth orbit (LEO) environment, with particular emphasis placed on atomic oxygen. Concepts for protectively coating Gr/Ep tubes include use of inorganic coated metal foils and electroplating. These coatings were applied to Gr/Ep tubes and then subjected to simulated LEO environment to evaluate survivability of coatings and coated tubes. Evaluation included: atomic oxygen resistance, changes in optical properties and adhesion, abrasion resistance, surface preparation required, coating uniformity, and formation of microcracks in the Gr/Ep tubes caused by thermal cycling. Program results demonstrated that both phosphoric and chromic acid anodized Al foil provided excellent adhesion to Gr/Ep tubes and exhibited stable optical properties when subjected to simulated LEO environment. The SiO2/Al coatings sputtered onto Al foils also resulted in an excellent protective coating. Electroplated Ni exhibited unacceptable adhesion loss to Gr/Ep tubes during atomic oxygen exposure.

Protective coatings for composite tubes in space applications

NASA Technical Reports Server (NTRS)

Dursch, Harry W.; Hendricks, Carl L.

1987-01-01

Protective coatings for graphite/epoxy (Gr/Ep) tubular structures for a Manned Space Station truss structure were evaluated. The success of the composite tube truss structure depends on its stability to long-term exposure to the Low Earth Orbit (LEO) environment with particular emphasis placed on atomic oxygen. Concepts for protectively coating Gr/Ep tubes include use of inorganic coated metal foils and electroplating. These coatings were applied to Gr/Ep tubes and then subjected to simulated LEO environmnet to evaluate survivability of coatings and coated tubes. Evaluation included: atomic oxygen resistance, changes in optical properties and adhesion, abrasion resistancem surface preparation required, coating uniformity, and formation of microcracks in the Gr/Ep tubes caused by thermal cycling. Program results demonstrated that both phosphoric and chromic acid anodized Al foil provided excellent adhesion to Gr/Ep tubes and exhibited stable optical properties when subjected to simulated LEO environment. The SiO2/Al coatings speuttered onto Al foils also resulted in an excellent protective coating. Electroplated Ni exhibited unaccepatble adhesion loss to Gr/Ep tubes during atomic oxygen exposure.

Preparation of β-cyclodextrin entrapped graphite composite for sensitive detection of dopamine.

PubMed

Palanisamy, Selvakumar; Sakthinathan, S; Chen, Shen-Ming; Thirumalraj, Balamurugan; Wu, Tsung-Han; Lou, Bih-Show; Liu, Xiaoheng

2016-01-01

A simple dopamine (DA) electrochemical sensor was developed based on a screen-printed carbon electrode (SPCE) modified with β-cyclodextrin entrapped graphite (GR/β-CD) composite for the first time. The polar hydroxyl groups on the β-CD rims interact with polar groups of edges of GR sheets resulting into the high dispersion ability of GR in β-CD solution. The GR/β-CD modified electrode exhibited a higher electrochemical response to DA with a lower oxidation potential (0.224V) than that of bare/β-CD (0.38V) and GR (0.525V) modified SPCEs, revealing an excellent electro-oxidation behavior of GR/β-CD composite toward DA. Under optimum conditions, the fabricated sensor detects the DA in the linear concentration range from 0.1 to 58.5μM with a limit of detection of 0.011μM and the sensitivity of 1.27±0.02μAμM(-1)cm(-2). The fabricated sensor also exhibits the excellent repeatability, practicality, reproducibility, storage stability along with acceptable selectivity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Glucocorticoid receptor activation inhibits p53-induced apoptosis of MCF10Amyc cells via induction of protein kinase Cε.

PubMed

Aziz, Moammir H; Shen, Hong; Maki, Carl G

2012-08-24

Glucocorticoid receptor (GR) is a ligand-dependent transcription factor that can promote apoptosis or survival in a cell-specific manner. Activated GR has been reported to inhibit apoptosis in mammary epithelial cells and breast cancer cells by increasing pro-survival gene expression. In this study, activated GR inhibited p53-dependent apoptosis in MCF10A cells and human mammary epithelial cells that overexpress the MYC oncogene. Specifically, GR agonists hydrocortisone or dexamethasone inhibited p53-dependent apoptosis induced by cisplatin, ionizing radiation, or the MDM2 antagonist Nutlin-3. In contrast, the GR antagonist RU486 sensitized the cells to apoptosis by these agents. Apoptosis inhibition was associated with maintenance of mitochondrial membrane potential, diminished caspase-3 and -7 activation, and increased expression at both the mRNA and protein level of the anti-apoptotic PKC family member PKCε. Knockdown of PKCε via siRNA targeting reversed the protective effect of dexamethasone and restored apoptosis sensitivity. These data provide evidence that activated GR can inhibit p53-dependent apoptosis through induction of the anti-apoptotic factor PKCε.

Studies on graphene zinc-oxide nanocomposites photoanodes for high-efficient dye-sensitized solar cells

NASA Astrophysics Data System (ADS)

Effendi, N. A. S.; Samsi, N. S.; Zawawi, S. A.; Hassan, O. H.; Zakaria, R.; Yahya, M. Z. A.; Ali, A. M. M.

2017-09-01

A dye-sensitized solar cells (DSSCs) using a nanocomposite (NC) semiconductor film, consisting of graphene layer and ZnO nanosheets (Gr-ZnO) is fabricated by electrodeposition process. The DSSCs based on Gr-ZnO NC were determined via electrochemical impedance spectra (EIS), UV-Visible diffused reflectance spectroscopy (UV-Vis), and photovoltaic performances J-V curves to substantiate the explanations. Impedance spectra shows that a smaller charge transport time constant occurs in DSSCs based on Gr-ZnO NC comparing to ZnO. This improved the electron collecting efficiency significantly, resulting in high open circuit voltage. Moreover, Gr-ZnO NC shows an efficient photoinduced charge separation and transportation can be achieved at the interface thus exhibit excellent potential for photocurrent generation compared with sole ZnO. Gr-ZnO NC obtained a maximum photocurrent response for an open-circuit voltage and a power conversion efficiency of 0.96 V and 7.01% respectively, which is doubled from sole ZnO. The fabricated Gr-ZnO NC cells show better performances compared to conventional ZnO structure reference cell.

Drought susceptibility of modern rice varieties: an effect of linkage of drought tolerance with undesirable traits

PubMed Central

Vikram, Prashant; Swamy, B. P. Mallikarjuna; Dixit, Shalabh; Singh, Renu; Singh, Bikram P.; Miro, Berta; Kohli, Ajay; Henry, Amelia; Singh, N. K.; Kumar, Arvind

2015-01-01

Green Revolution (GR) rice varieties are high yielding but typically drought sensitive. This is partly due to the tight linkage between the loci governing plant height and drought tolerance. This linkage is illustrated here through characterization of qDTY1.1, a QTL for grain yield under drought that co-segregates with the GR gene sd1 for semi-dwarf plant height. We report that the loss of the qDTY1.1 allele during the GR was due to its tight linkage in repulsion with the sd1 allele. Other drought-yield QTLs (qDTY) also showed tight linkage with traits rejected in GR varieties. Genetic diversity analysis for 11 different qDTY regions grouped GR varieties separately from traditional drought-tolerant varieties, and showed lower frequency of drought tolerance alleles. The increased understanding and breaking of the linkage between drought tolerance and undesirable traits has led to the development of high-yielding drought-tolerant dwarf lines with positive qDTY alleles and provides new hope for extending the benefits of the GR to drought-prone rice-growing regions. PMID:26458744

MyD88-dependent expansion of an immature GR-1+CD11b+ population induces T cell suppression and Th2 polarization in sepsis

PubMed Central

Delano, Matthew J.; Scumpia, Philip O.; Weinstein, Jason S.; Coco, Dominique; Nagaraj, Srinivas; Kelly-Scumpia, Kindra M.; O'Malley, Kerri A.; Wynn, James L.; Antonenko, Svetlana; Al-Quran, Samer Z.; Swan, Ryan; Chung, Chun-Shiang; Atkinson, Mark A.; Ramphal, Reuben; Gabrilovich, Dmitry I.; Reeves, Wesley H.; Ayala, Alfred; Phillips, Joseph; LaFace, Drake; Heyworth, Paul G.; Clare-Salzler, Michael; Moldawer, Lyle L.

2007-01-01

Polymicrobial sepsis alters the adaptive immune response and induces T cell suppression and Th2 immune polarization. We identify a GR-1+CD11b+ population whose numbers dramatically increase and remain elevated in the spleen, lymph nodes, and bone marrow during polymicrobial sepsis. Phenotypically, these cells are heterogeneous, immature, predominantly myeloid progenitors that express interleukin 10 and several other cytokines and chemokines. Splenic GR-1+ cells effectively suppress antigen-specific CD8+ T cell interferon (IFN) γ production but only modestly suppress antigen-specific and nonspecific CD4+ T cell proliferation. GR-1+ cell depletion in vivo prevents both the sepsis-induced augmentation of Th2 cell–dependent and depression of Th1 cell–dependent antibody production. Signaling through MyD88, but not Toll-like receptor 4, TIR domain–containing adaptor-inducing IFN-β, or the IFN-α/β receptor, is required for complete GR-1+CD11b+ expansion. GR-1+CD11b+ cells contribute to sepsis-induced T cell suppression and preferential Th2 polarization. PMID:17548519

Expression of AmGR10 of the Gustatory Receptor Family in Honey Bee Is Correlated with Nursing Behavior.

PubMed

Paerhati, Yisilahaiti; Ishiguro, Shinichi; Ueda-Matsuo, Risa; Yang, Ping; Yamashita, Tetsuro; Ito, Kikukatsu; Maekawa, Hideaki; Tani, Hiroko; Suzuki, Koichi

2015-01-01

We investigated the association between the expression of a gene encoding gustatory receptor (G10) and division of labor in the honey bee, Apis mellifera. Among 10 GR genes encoding proteins 15% ~ 99% amino acid identity in the honey bee, we found that AmGR10 with 99% identity is involved in nursing or brood care. Expression of AmGR10 was restricted to organs of the hypopharyngeal gland, brain, and ovary in the nurse bee phase. Members of an extended nursing caste under natural conditions continued to express this gene. RNAi knockdown of AmGR10 accelerated the transition to foraging. Our findings demonstrate that this one gene has profound effects on the division of labor associated with the development and physiology of honeybee society.

Origin, distribution and 3D-modeling of Gr-EXPB1, an expansin from the potato cyst nematode Globodera rostochiensis.

PubMed

Kudla, Urszula; Qin, Ling; Milac, Adina; Kielak, Anna; Maissen, Cyril; Overmars, Hein; Popeijus, Herman; Roze, Erwin; Petrescu, Andrei; Smant, Geert; Bakker, Jaap; Helder, Johannes

2005-04-25

Southern analysis showed that Gr-EXPB1, a functional expansin from the potato cyst nematode Globodera rostochiensis, is member of a multigene family, and EST data suggest expansins to be present in other plant parasitic nematodes as well. Homology modeling predicted that Gr-EXPB1 domain 1 (D1) has a flat beta-barrel structure with surface-exposed aromatic rings, whereas the 3D structure of Gr-EXPB1-D2 was remarkably similar to plant expansins. Gr-EXPB1 shows highest sequence similarity to two extracellular proteins from saprophytic soil-inhabiting Actinobacteria, and includes a bacterial type II carbohydrate-binding module. These results support the hypothesis that a number of pathogenicity factors of cyst nematodes is of procaryotic origin and were acquired by horizontal gene transfer.

α Actinin 4 (ACTN4) Regulates Glucocorticoid Receptor-mediated Transactivation and Transrepression in Podocytes*

PubMed Central

Zhao, Xuan; Khurana, Simran; Charkraborty, Sharmistha; Tian, Yuqian; Sedor, John R.; Bruggman, Leslie A.; Kao, Hung-Ying

2017-01-01

Glucocorticoids are a general class of steroids that possess renoprotective activity in glomeruli through their interaction with the glucocorticoid receptor. However, the mechanisms by which glucocorticoids ameliorate proteinuria and glomerular disease are not well understood. In this study, we demonstrated that α actinin 4 (ACTN4), an actin-cross-linking protein known to coordinate cytoskeletal organization, interacts with the glucocorticoid receptor (GR) in the nucleus of human podocytes (HPCs), a key cell type in the glomerulus critical for kidney filtration function. The GR-ACTN4 complex enhances glucocorticoid response element (GRE)-driven reporter activity. Stable knockdown of ACTN4 by shRNA in HPCs significantly reduces dexamethasone-mediated induction of GR target genes and GRE-driven reporter activity without disrupting dexamethasone-induced nuclear translocation of GR. Synonymous mutations or protein expression losses in ACTN4 are associated with kidney diseases, including focal segmental glomerulosclerosis, characterized by proteinuria and podocyte injury. We found that focal segmental glomerulosclerosis-linked ACTN4 mutants lose their ability to bind liganded GR and support GRE-mediated transcriptional activity. Mechanistically, GR and ACTN4 interact in the nucleus of HPCs. Furthermore, disruption of the LXXLL nuclear receptor-interacting motif present in ACTN4 results in reduced GR interaction and dexamethasone-mediated transactivation of a GRE reporter while still maintaining its actin-binding activity. In contrast, an ACTN4 isoform, ACTN4 (Iso), that loses its actin-binding domain is still capable of potentiating a GRE reporter. Dexamethasone induces the recruitment of ACTN4 and GR to putative GREs in dexamethasone-transactivated promoters, SERPINE1, ANGPLT4, CCL20, and SAA1 as well as the NF-κB (p65) binding sites on GR-transrepressed promoters such as IL-1β, IL-6, and IL-8. Taken together, our data establish ACTN4 as a transcriptional co-regulator that modulates both dexamethasone-transactivated and -transrepressed genes in podocytes. PMID:27998979

The role of synoptic weather variability in Greenland ice sheet dynamics

NASA Astrophysics Data System (ADS)

Walker, J. M.; Radic, V.

2017-12-01

Much of the large uncertainty in predictions of future global sea level rise is due to our limited understanding of Greenland ice sheet (GrIS) motion and its interactions with climate. Over the next century, climate models predict that the GrIS will experience not only gradual warming, but also changes in atmospheric circulation, hydrology, and weather, including a northward shift of the North Atlantic storm track, with greater frequency and intensity of rain storms over the GrIS. Recent studies of GrIS dynamics have focused on the effects of increased seasonal mean meltwater on ice velocities, finding only a modest impact due to compensation by subglacial drainage systems, but subglacial hydraulic theory indicates that variability on shorter timescales is also relevant: short-term surges in meltwater or rainfall can overload drainage systems at rates faster than they can adjust, leading to water pressure spikes and ice acceleration. If the magnitude or frequency of these transient ice accelerations increase substantially as synoptic weather patterns change over the next century, there could be a significant cumulative impact on seasonal mean ice velocities. However, this issue has not been addressed in the literature and represents a major source of uncertainty. In this study, we investigate the role of synoptic weather variability in GrIS dynamics, with the ultimate goal of evaluating the relationships between extreme weather events and ice sheet flow in different seasons and regions of the GrIS. As a first step, we apply the machine learning technique of self-organizing maps to atmospheric reanalysis data to categorize the predominant synoptic weather systems over the GrIS domain, evaluating atmospheric moisture transport and rainfall to assess the impacts of each weather system on GrIS surface hydrology. The preliminary results presented here will be used in conjunction with ice velocity satellite measurements in future work, to identify any correlations between seasonal mean GrIS velocities and the frequency or intensity of storms during the season.

Relationship of ambient air pollutants and hazardous household factors with birth weight among Bedouin-Arabs.

PubMed

Yitshak-Sade, Maayan; Novack, Lena; Landau, Daniella; Kloog, Itai; Sarov, Batia; Hershkovitz, Reli; Karakis, Isabella

2016-10-01

Air pollution and meteorology exposures during pregnancy have been suggested to be associated with Birth Weight (BW). Yet, the individual medical background and close household environment is rarely addressed. We aimed to evaluate the independent association of BW with meteorological and air pollution exposures during pregnancy, in addition to individual, parental and household risk factors, among the Bedouin-Arab population in Southern Israel; a semi nomadic population, featured by low socio-economic levels and poor housing and household environment. In a retrospective cohort study we enrolled pregnant women upon their arrival in the local hospital for delivery during December 2011-April 2013. We interviewed the women and collected data on socio-demographic characteristics, medical history and household environmental hazards. Air pollution (NO2, SO2, CO, Ozone and Particulate Matter <2.5 μ and 10 μ in diameter) and meteorological data (temperature, relative humidity), retrieved from 13 monitoring sites, were linked to each woman based on the proximity of her residential address. A total of 959 women were eligible for the study, half of them resided in temporary tribal localities. Ozone IQR elevation in the 3rd trimester was associated with 0.119 gr decrease in BW (95%CI -0.127 gr; -0.112 gr); temperature IQR elevation in the 3rd trimester was associated with 0.002 gr (95%CI -0.004 gr; -0.001 gr) decrease in BW. Waste in the house surroundings was associated with a decrease of 117.27 gr in BW (95%CI -209.19 gr; -25.34 gr). Although exposure to high levels of temperature and O3 were associated with lower BW, the contribution of poor household environment indicators to BW reduction was substantially higher. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mutations of glucocorticoid receptor differentially affect AF2 domain activity in a steroid-selective manner to alter the potency and efficacy of gene induction and repression†

PubMed Central

Tao, Yong-guang; Xu, Yong; Xu, H. Eric; Simons, S. Stoney

2009-01-01

The transcriptional activity of steroid hormones is intimately associated with their structure. Deacylcortivazol (DAC) contains several features that were predicted to make it an inactive glucocorticoid. Nevertheless, gene induction and repression by complexes of glucocorticoid receptor (GR) with DAC occurs with greater potency (lower EC50) than, and equal efficacy (maximal activity, or Amax) to, the very active and smaller synthetic glucocorticoid dexamethasone (Dex). Guided by a recent x-ray structure of DAC bound to the GR ligand binding domain (LBD), we now report that several point mutants in the LBD have little effect on the binding of either agonist steroid. However, these same mutations dramatically alter the Amax and/or EC50 of exogenous and endogenous genes in a manner that depends on steroid structure. In some cases, Dex is no longer a full agonist. These properties appear to result from a preferential inactivation of the AF2 activation domain in the GR LBD of Dex-, but not DAC-, bound receptors. The Dex-bound receptors display normal binding to, but greatly reduced response to, the coactivator TIF2, thus indicating a defect in the transmission efficiency of GR-steroid complex information to the coactivator TIF2. In addition, all GR mutants that are active in gene induction with either Dex or DAC have greatly reduced activity in gene repression. This contrasts with the reports of GR mutations preferentially suppressing GR-mediated induction. The properties of these GR mutants in gene induction support the hypothesis that the Amax and EC50 of GR-controlled gene expression can be independently modified, indicate that the receptor can be modified to favor activity with a specific agonist steroid, and suggest that new ligands with suitable substituents may be able to affect the same LBD conformational changes and thereby broaden the therapeutic applications of glucocorticoid steroids PMID:18578507

Peripheral Arterial and Venous Response to Tilt Test after a 60-Day Bedrest with and without Countermeasures (ES-IBREP)

PubMed Central

Coupé, Mickael; Bai, Yanqiang; Gauquelin-Koch, Guillemette; Jiang, Shizhong; Aubry, Patrick; Wan, Yumin; Custaud, Marc-Antoine; Li, Yinghui

2012-01-01

We quantified the impact of 60-day head-down bed rest (HDBR) with countermeasures on arterial and venous response to tilt. Methods: Twenty-one males: 7 control (Con), 7 resistive vibration exercise (RVE) and 7 Chinese herb (Herb) were assessed. Subjects were identified as finisher (F) or non-finishers (NF) at the post-HDBR 20-min tilt test. The cerebral (MCA), femoral (FEM) arterial flow velocity and leg vascular resistance (FRI), the portal vein section (PV), the flow redistribution ratios (MCA/FEM; MCA/PV), the tibial (Tib), gastrocnemius (Gast), and saphenous (Saph) vein sections were measured by echography and Doppler ultrasonography. Arterial and venous parameters were measured at 3-min pre-tilt in the supine position, and at 1 min before the end of the tilt. Results: At post-HDBR tilt, MCA decreased more compared with pre-HDBR tilt in the Con, RVE, and Herb groups, the MCA/FEM tended to decrease in the Con and Herb groups (not significant) but remained stable in the RVE gr. FRI dropped in the Con gr, but remained stable in the Herb gr and increased in the RVE gr. PV decreased less in the Con and Herb groups but remained unchanged in the RVE gr. MCA/PV decreased in the Con and Herb groups, but increased to a similar extent in the RVE gr. Gast section significantly increased more in the Con gr only, whereas Tib section increased more in the Con and Herb groups but not in the RVE gr. The percent change in Saph section was similar at pre- and post-HDBR tilt. Conclusion: In the Con gr, vasoconstriction was reduced in leg and splanchnic areas. RVE and Herb contributed to prevent the loss of vasoconstriction in both areas, but the effect of RVE was higher. RVE and Herb contributed to limit Gast distension whereas only RVE had a protective effect on the Tib. PMID:22412933

Glucocorticoid-induced tethered transrepression requires SUMOylation of GR and formation of a SUMO-SMRT/NCoR1-HDAC3 repressing complex

PubMed Central

Hua, Guoqiang; Ganti, Krishna Priya; Chambon, Pierre

2016-01-01

Upon binding of a glucocorticoid (GC), the GC receptor (GR) can exert one of three transcriptional regulatory functions. We recently reported that SUMOylation of the GR at position K293 in humans (K310 in mice) within the N-terminal domain is indispensable for GC-induced evolutionary conserved inverted repeated negative GC response element (IR nGRE)-mediated direct transrepression. We now demonstrate that the integrity of this GR SUMOylation site is mandatory for the formation of a GR-small ubiquitin-related modifiers (SUMOs)-SMRT/NCoR1-HDAC3 repressing complex, which is indispensable for NF-κB/AP1-mediated GC-induced tethered indirect transrepression in vitro. Using GR K310R mutant mice or mice containing the N-terminal truncated GR isoform GRα-D3 lacking the K310 SUMOylation site, revealed a more severe skin inflammation than in WT mice. Importantly, cotreatment with dexamethasone (Dex) could not efficiently suppress a 12-O-tetradecanoylphorbol-13-acetate (TPA)–induced skin inflammation in these mutant mice, whereas it was clearly decreased in WT mice. In addition, in mice selectively ablated in skin keratinocytes for either nuclear receptor corepressor 1 (NCoR1)/silencing mediator for retinoid or thyroid-hormone receptors (SMRT) corepressors or histone deacetylase 3 (HDAC3), Dex-induced tethered transrepression and the formation of a repressing complex on DNA-bound NF-κB/AP1 were impaired. We previously suggested that GR ligands that would lack both (+)GRE-mediated transactivation and IR nGRE-mediated direct transrepression activities of GCs may preferentially exert the therapeutically beneficial GC antiinflammatory properties. Interestingly, we now identified a nonsteroidal antiinflammatory selective GR agonist (SEGRA) that selectively lacks both Dex-induced (+)GRE-mediated transactivation and IR nGRE-mediated direct transrepression functions, while still exerting a tethered indirect transrepression activity and could therefore be clinically lesser debilitating on long-term GC therapy. PMID:26712006

Early Formation of Serum Advanced Glycation End-Products in Children with Type 1 Diabetes Mellitus: Relationship with Glycemic Control.

PubMed

Jaisson, Stéphane; Souchon, Pierre-François; Desmons, Aurore; Salmon, Anne-Sophie; Delemer, Brigitte; Gillery, Philippe

2016-05-01

To quantify serum advanced glycation end-products (AGEs) at the onset of type 1 diabetes mellitus and to determine their potential usefulness as retrospective indicators of glycemic balance. Carboxymethyllysine (CML) and pentosidine concentrations were determined by liquid chromatography-tandem mass spectrometry in 3 groups of children with type 1 diabetes mellitus: group (Gr) 1, subjects included at disease onset (n = 36); Gr2, subjects with diabetes of 5 years duration (n = 48); Gr3, subjects with diabetes of 10 years duration and in control subjects (n = 33). Hemoglobin A1c (HbA1c) values were recorded over the entire course of treatment for assessing long-term glycemic balance. Serum AGE concentrations were increased in all groups of subjects with diabetes compared with control subjects, but were highest in Gr1 (for CML: 0.155, 0.306, 0.219, and 0.224 mmol/mol Lys in control, Gr1, Gr2, and Gr3 subjects, respectively; for pentosidine: 312, 492, 365, and 403 nmol/mol Lys, respectively). AGE concentrations were closely correlated with HbA1c values (r = 0.78 for CML; r = 0.49 for pentosidine). In Gr2 and Gr3, the overall glycemic balance estimated by average HbA1c values was positively correlated with CML and pentosidine concentrations, especially in the first year of follow-up. Our results indicate that AGE concentrations are elevated in serum at the time of diabetes mellitus diagnosis, suggesting that the deleterious role of AGEs in the development of long-term complications should be taken into account even at the initial stages of the disease. Moreover, in some circumstances, AGEs could serve as surrogate markers of HbA1c for monitoring glycemic control. Copyright © 2016 Elsevier Inc. All rights reserved.

A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas.

PubMed

Attia, Steven; Kolesar, Jill; Mahoney, Michelle R; Pitot, Henry C; Laheru, Daniel; Heun, James; Huang, Wei; Eickhoff, Jens; Erlichman, Charles; Holen, Kyle D

2008-08-01

3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine) is a novel small molecule inhibitor of ribonucleotide reductase (RR) with clinical signs of activity in pancreatic cancer. Therefore, the Phase 2 Consortium (P2C) initiated a trial (two single stage studies with planned interim analysis) of 3-AP at 96 mg/m(2) intravenously days 1-4 and 15-18 of a 28-day cycle in both chemotherapy-naive and gemcitabine-refractory (GR) patients with advanced pancreatic cancer. The primary endpoint was survival at six months (chemotherapy-naive) and four months (GR). Secondary endpoints were toxicity, response, overall survival, time to progression and mechanistic studies. Fifteen patients were enrolled including one chemotherapy-naïve and 14 GR. The chemotherapy-naïve patient progressed during cycle 1 with grade 3 and 4 toxicities. Of 14 GR patients, seven received two cycles, six received one cycle and one received eight cycles. Progression precluded further treatment in 11 GR patients. Additionally, one died of an ileus in cycle 1 considered related to treatment and two stopped treatment due to toxicity. Five GR patients had grade 4 toxicities possibly related to 3-AP and six GR patients had grade 3 fatigue. Toxicities and lack of meaningful clinical benefit prompted early study closure. Four-month survival in GR patients was 21% (95% CI: 8-58%). Correlative studies confirmed that 3-AP increased the percentage of S-phase buccal mucosal cells, the presence of multidrug resistance gene polymorphisms appeared to predict leukopenia, and baseline pancreatic tumor RR M2 expression was low relative to other tumors treated with 3-AP. In conclusion, this regimen appears inactive against predominantly GR pancreatic cancer. RR M2 protein may not have a critical role in the malignant potential of pancreatic cancer.

A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas

PubMed Central

Attia, Steven; Kolesar, Jill; Mahoney, Michelle R.; Pitot, Henry C.; Laheru, Daniel; Heun, James; Huang, Wei; Eickhoff, Jens; Erlichman, Charles

2015-01-01

Summary 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine®) is a novel small molecule inhibitor of ribonucleotide reductase (RR) with clinical signs of activity in pancreatic cancer. Therefore, the Phase 2 Consortium (P2C) initiated a trial (two single stage studies with planned interim analysis) of 3-AP at 96 mg/m2 intravenously days 1–4 and 15–18 of a 28-day cycle in both chemotherapy-naive and gemcitabine-refractory (GR) patients with advanced pancreatic cancer. The primary endpoint was survival at six months (chemotherapy-naive) and four months (GR). Secondary endpoints were toxicity, response, overall survival, time to progression and mechanistic studies. Fifteen patients were enrolled including one chemotherapy-naïve and 14 GR. The chemotherapy-naïve patient progressed during cycle 1 with grade 3 and 4 toxicities. Of 14 GR patients, seven received two cycles, six received one cycle and one received eight cycles. Progression precluded further treatment in 11 GR patients. Additionally, one died of an ileus in cycle 1 considered related to treatment and two stopped treatment due to toxicity. Five GR patients had grade 4 toxicities possibly related to 3-AP and six GR patients had grade 3 fatigue. Toxicities and lack of meaningful clinical benefit prompted early study closure. Four-month survival in GR patients was 21% (95% CI: 8–58%). Correlative studies confirmed that 3-AP increased the percentage of S-phase buccal mucosal cells, the presence of multidrug resistance gene polymorphisms appeared to predict leukopenia, and baseline pancreatic tumor RR M2 expression was low relative to other tumors treated with 3-AP. In conclusion, this regimen appears inactive against predominantly GR pancreatic cancer. RR M2 protein may not have a critical role in the malignant potential of pancreatic cancer. PMID:18278438

REVIEWS OF TOPICAL PROBLEMS Gravitational radiation of systems and the role of their force field

NASA Astrophysics Data System (ADS)

Nikishov, Anatolii I.; Ritus, Vladimir I.

2011-02-01

Gravitational radiation (GR) from compact relativistic systems with a known energy-momentum tensor (EMT) and GR from two masses elliptically orbiting their common center of inertia are considered. In the ultrarelativistic limit, the GR spectrum of a charge rotating in a uniform magnetic field, a Coulomb field, a magnetic moment field, and a combination of the last two fields differs by a factor 4πGm2Γ2/e2 (Γ being of the order of the charge Lorentz factor) from its electromagnetic radiation (EMR) spectrum. This factor is independent of the radiation frequency but does depend on the wave vector direction and the way the field behaves outside of the orbit. For a plane wave external field, the proportionality between the gravitational and electromagnetic radiation spectra is exact, whatever the velocity of the charge. Qualitative estimates of Γ are given for a charge moving ultrarelativistically in an arbitrary field, showing that it is of the order of the ratio of the nonlocal and local source contributions to the GR. The localization of external forces near the orbit violates the proportionality of the spectra and reduces GR by about the Lorentz factor squared. The GR spectrum of a rotating relativistic string with masses at the ends is given, and it is shown that the contributions by the masses and string are of the same order of magnitude. In the nonrelativistic limit, the harmonics of GR spectra behave universally for all the rotating systems considered. A trajectory method is developed for calculating the GR spectrum. In this method, the spatial (and hence polarization) components of the conserved EMT are calculated in the long wavelength approximation from the time component of the EMTs of the constituent masses of the system. Using this method, the GR spectrum of two masses moving in elliptic orbits about their common center of inertia is calculated, as are the relativistic corrections to it.

Design of Copper and Titanium Dioxide Nanoparticles Doped with Reduced Graphene Oxide for Hydrogen Evolution by Water Splitting

NASA Astrophysics Data System (ADS)

Yang, Yuhao; Huang, Wenhuan

2018-05-01

TiO2-graphene (P25-GR, PG) nanocomposite was fabricated from P25 titania and graphite oxide by hydrothermal method, and then Cu nanoparticles (Cu NPs) were assembled in P25-GR composite (Cu- P25-GR, CPG) under microwave-assisted chemical reduction. The prepared samples were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), UV-Vis absorption (UV-Vis) and Raman spectroscopies. Cu NPs were well dispersed on the surface of PG and are in metallic state. The ternary Cu-P25-GR (CPG) nanocomposites show an extended light absorption range and more efficient charge separation properties compared to binary P25-GR (PG) composite. Methylene blue photodegradation experiment proved that surface plasmon resonance (SPR) phenomenon had an effect on photoreaction efficiency. The corresponding hydrogen evolution rate for CPG prepared using 0.002 M Cu(NO3)2 solution was 10 times higher than with pure P25, and 2.3 times higher than with PG in the same test conditions. The improved photocatalytic performance can be attributed to the presence of GR in the prepared composite and to the SPR effect, leading to the longer lifetime of photogenerated electronhole pairs and faster interfacial charge transfer rate. We expect that our work would be useful for the further exploration of GR-based nanocomposites.

Determination of Optimal Harvest Time of Chuchung Variety Green Rice® (Oryza sativa L.) with High Contents of GABA, γ-Oryzanol, and α-Tocopherol

PubMed Central

Kim, Hoon; Kim, Oui-Woung; Ha, Ae Wha; Park, Soojin

2016-01-01

In our previous study, an early-maturing variety of rice (Oryza sativa L.), Jinbu can have feature with unique green color, various phytochemicals as well as nutritive components by the optimal early harvesting, called Green Rice® (GR). The aims of the present field experiments were to evaluate the changes in the weight of 1,000 kernels, yield, and contents of proximate and bioactive compounds in Chuchung, a mid-late maturing variety, during the pre-harvest maturation of rough rice and to research the appropriate harvest time and potent bioactivity of Chuchung GR. The weights of 1,000 kernels of Chuchung GR dramatically increased until 27 days after heading (DAH). The yields of Chuchung GR declined after 27 DAH and significantly declined to 0.0% after 45 DAH. The caloric value and total mineral contents were higher in the GR than in the full ripe stage, the brown rice (BR). In the GR, the contents of bioactive compounds, such as γ-aminobutyric acid, γ-oryzanol, and α-tocopherol, were much higher (P<0.05) than those in the BR, specifically during 24~27 DAH. Therefore, bioactive Chuchung GR can be produced with a reasonable yield at 24~27 DAH and it could be useful for applications in various nutritive and functional food products. PMID:27390725

Determination of Optimal Harvest Time of Chuchung Variety Green Rice(®) (Oryza sativa L.) with High Contents of GABA, γ-Oryzanol, and α-Tocopherol.

PubMed

Kim, Hoon; Kim, Oui-Woung; Ha, Ae Wha; Park, Soojin

2016-06-01

In our previous study, an early-maturing variety of rice (Oryza sativa L.), Jinbu can have feature with unique green color, various phytochemicals as well as nutritive components by the optimal early harvesting, called Green Rice(®) (GR). The aims of the present field experiments were to evaluate the changes in the weight of 1,000 kernels, yield, and contents of proximate and bioactive compounds in Chuchung, a mid-late maturing variety, during the pre-harvest maturation of rough rice and to research the appropriate harvest time and potent bioactivity of Chuchung GR. The weights of 1,000 kernels of Chuchung GR dramatically increased until 27 days after heading (DAH). The yields of Chuchung GR declined after 27 DAH and significantly declined to 0.0% after 45 DAH. The caloric value and total mineral contents were higher in the GR than in the full ripe stage, the brown rice (BR). In the GR, the contents of bioactive compounds, such as γ-aminobutyric acid, γ-oryzanol, and α-tocopherol, were much higher (P<0.05) than those in the BR, specifically during 24~27 DAH. Therefore, bioactive Chuchung GR can be produced with a reasonable yield at 24~27 DAH and it could be useful for applications in various nutritive and functional food products.

Grosnaja ABCs: Magnesium isotope compositions

NASA Technical Reports Server (NTRS)

Goswami, J. N.; Srinivasan, G.; Ulyanov, A. A.

1993-01-01

Three CAI's from the Grosnaja CV3 chondrite were analyzed for their magnesium isotopic compositions by the ion microprobe. The selected CAI's represent three distinct types: GR4(compact Type A), GR7(Type B) and GR2(Type C). Petrographic studies indicate that all three Grosnaja inclusions were subjected to secondary alterations. The Type A CAI GR4 is primarily composed of melilite with spinel and pyroxene occurring as minor phases. The rim of the inclusion does not exhibit distinct layered structure and secondary alteration products (garnet, Fe-rich olivine and Na-rich plagioclase) are present in some localized areas near the rim region. The average major element compositions of different mineral phases in GR4 are given. Preliminary REE data suggest a depletion of HREE relative to LREE by about a factor of 3 without any clear indication of interelement fractionation. The CAI GR7 has textural and minerological characteristics similar to Type B inclusions. The REE data show a pattern that is similar to Group 6 with enrichment in Eu and Yb. In addition, a depletion of HREE compared to LREE is also evident in this object. Melilite composition shows a broad range of akermanite content (Ak(sub 15-55)). Detailed petrographic study is in progress. GR2 is a anorthite-rich Type C inclusion with large plagioclase laths intergrown with Ti-rich pyroxene. The average plagioclase composition is close to pure anorthite (An99).

HPA axis dysregulation and behavioral analysis of mouse mutants with altered GR or MR function

PubMed Central

Kolber, Benedict J.; Wieczorek, Lindsay; Muglia, Louis J.

2009-01-01

Corticosteroid receptors are critical for the maintenance of homeostasis after both psychological and physiological stress. To properly understand the different roles and interactions of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) during stress, it is necessary to dissect the role of corticosteroid signaling at both the system and sub-system level. A variety of GR transgenic mouse lines have recently been used to characterize the role of GR in the CNS as a whole and particularly in the forebrain. We will describe both the behavioral and cellular/molecular implications of disrupting GR function in these animal models and describe the implications of this data for our understanding of normal endocrine function and stress adaptation. MRs in tight epithelia have a long established role in sodium homeostasis. Recently however, evidence has suggested that limbic MRs also play an important role in psychological stress. Just as with GR, targeted mutations in MR induce a variety of behavioral changes associated with stress adaptation. In this review, we will discuss the implications of this work on MR. Finally, we will discuss the possible interaction between MR and GR and how future work using double mutants (through conventional means or virus based gene alteration) will be needed to fully understand how signaling through these two steroid receptors provides the adaptive mechanisms to deal with a variety of stressors. PMID:18609295

A comparative study of nitrite reduction by synthetic and biogenic Fe(II-III) hydroxysalts green rusts: Evidence for hydroxyl-nitrite green rust formation as an intermediate reaction product.

NASA Astrophysics Data System (ADS)

Ona-Nguema, G.; Guerbois, D.; Morin, G.; Zhang, Y.; Noel, V.; Brest, J.

2013-12-01

The occurrence of high nitrite concentrations as a result of anthropogenic activities is an important water quality concern as it is highly toxic to human and fauna, and it is used as a nitrogen source for the assimilation process. The toxicity of nitrite is related to its transformation into carcinogenic N-nitroso compounds, which are suspected to be responsible for some gastric cancers, and to its ability to convert the hemoglobin to methaemoglobin what is then unable to fix oxygen and to transport it to the tissues, involving hypoxia and the blue-baby syndrome [1]. To reduce the adverse effect of nitrite on human health and on macroalgal blooms, any process enhancing the transformation of nitrite ions to nitrogen gas is of interest for the remediation of natural environments. To achieve this purpose the use of processes involving Fe(II)-containing minerals could be considered as one of the best options. Green-rusts are mixed Fe(II-III) layered double hydroxides commonly found in anoxic zones of natural environments such as sediments and hydromorphic soils. In such anoxic environments, green rust minerals play an important role in the biogeochemical redox cycling of iron and nitrogen, and can affect the speciation and mobility of many organic and inorganic contaminants. The present study investigates the reduction of nitrite by two synthetic and two biogenic green rusts. On the one hand, Fe(II-III) hydroxychloride and Fe(II-III) hydroxycarbonate green rusts were used as synthetic interlayer forms of GR, which are referred to as ';syn-GR(CO3)' and ';syn-GR(Cl)', respectively. On the other hand, the study was performed with biogenic Fe(II-III) hydroxycarbonate green rusts obtained from the bioreduction of two ferric precursors, either Fe(III)-oxyhydroxycarbonate or lepidocrocite; these biogenic green rusts are referred to as ';bio-GR(CO3)F' and ';bio-GR(CO3)L', respectively. For synthetic green rusts, results showed that the oxidation of both syn-GR(CO3) and syn-GR(Cl) led to the reduction of nitrite ions to ammonium, and that the production of ammonium depended on their Fe(II) content. XRD patterns indicated that both synthetic green rusts were fully oxidized into magnetite during the reaction with nitrite. For biogenic green rusts, the study revealed that both bio-GR(CO3)F and bio-GR(CO3)L were capable of reducing nitrite ions without ammonium production, suggesting the conversion of nitrite ions to nitrogen gas. Moreover, we provided evidence for the first time that the interactions of bio-GR(CO3)F with nitrite led to the formation of an hydroxy-nitrite green rust as a result of the incorporation of nitrite in the interlayer region of bio-GR(CO3)F; such an intercalation of nitrite ions was not observed in experiments with bio-GR(CO3)L. XRD analysis indicated that GR(NO2) was formed as an intermediate reaction product prior to the fully oxidation of GR to ferric oxyhydroxides. [1] Philips S., Laanbroek H. J. and Verstraete W. (2002). Rev. Environ. Sci. Biotechnol. 1, 115-141.

Evaluation of the efficacy of perorally administered glutamic acid-chelated iron and iron-dextran injected subcutaneously in Duroc and Norwegian Landrace piglets.

PubMed

Egeli, A K; Framstad, T

1998-02-01

The goals of this study were to evaluate the effect of orally administered amino acid-chelated iron (Fe) compared to injected Fe-dextran on haematology and weight gain in two different breeds raised under commercial conditions. Altogether 92 Duroc (D) pigs and 84 Norwegian Landrace (L) pigs from two different herds were included in the study. The day after birth the litters were divided in two groups (split litters). Group (Gr.) 1 was given 4 ml of a 50% solution of Super Fe-MAX (52 mg glutamic acid-chelated Fe in a water solution) orally, while Gr. 2 was subcutaneously (s.c.) injected with Idofer (180 mg Fe as ferridextran). Until weaning at 5 weeks, all the piglets had free access to a 3% solution of Super Fe-MAX (0.78 mg Fe/ml), access to pelleted food being given from 1 week of age. The piglets were weighed and bled before treatment the day after birth (day 1) and on days 4, 7, 14, 21 and 35. All piglets were weighed on days 28 and 49, while 72 of the L pigs were also weighed on days 77, 98 and 119. At weaning D pigs in Gr. 1 and Gr. 2 had a mean body weight of 8.64 kg and 8.30 kg, respectively, the corresponding figures for the L pigs being 10.82 kg and 10.34 kg. As regards the 72 L pigs followed to day 119, the mean weight in Gr. 1 and Gr. 2 was 80.6 kg and 80.2 kg, respectively. A significantly lower weight gain in the piglets with a birth weight below 1.2 kg in Gr. 2 compared with Gr. 1 indicated that excess administration of Fe to small piglets may have a detrimental effect on weight gain. From day 7 (D pigs) and on days 14 and 21 (L pigs), Gr. 2 had a significantly higher haemoglobin concentration (Hb) than Gr. 1. Nevertheless, Hb levels were also adequate in Gr. 1 in both breeds. There was a negative correlation between changes in Hb during the first weeks and the initial value. Though haematological values seemed to show inter-breed differences, with higher average erythrocyte counts (RBC) and Hb and lower mean cell volume (MCV) in the D pigs, the ability to avoid Fe deficiency nevertheless appeared to be the same in both breeds.

Tool to address green roof widespread implementation effect in flood characteristics for water management planning

NASA Astrophysics Data System (ADS)

Tassi, R.; Lorenzini, F.; Allasia, D. G.

2015-06-01

In the last decades, new approaches were adopted to manage stormwater as close to its source as possible through technologies and devices that preserve and recreate natural landscape features. Green Roofs (GR) are examples of these devices that are also incentivized by city's stormwater management plans. Several studies show that GR decreases on-site runoff from impervious surfaces, however, the analysis of the effect of widespread implementation of GR in the flood characteristics at the urban basin scale in subtropical areas are little discussed, mainly because of the absence of data. Thereby, this paper shows results related to the monitoring of an extensive modular GR under subtropical weather conditions, the development of a rainfall-runoff model based on the modified Curve Number (CN) and SCS Triangular Unit Hydrograph (TUH) methods and the analysis of large-scale impact of GR by modelling different basins. The model was calibrated against observed data and showed that GR absorbed almost all the smaller storms and reduced runoff even during the most intense rainfall. The overall CN was estimated in 83 (consistent with available literature) with the shape of hydrographs well reproduced. Large-scale modelling (in basins ranging from 0.03 ha to several square kilometers) showed that the widespread use of GRs reduced peak flows (volumes) around 57% (48%) at source and 38% (32%) at the basin scale. Thus, this research validated a tool for the assessment of structural management measures (specifically GR) to address changes in flood characteristics in the city's water management planning. From the application of this model it was concluded that even if the efficiency of GR decreases as the basin scale increase they still provide a good option to cope with urbanization impact.

Cytokines Alter Glucocorticoid Receptor Phosphorylation in Airway Cells

PubMed Central

Bouazza, Belaid; Krytska, Kateryna; Debba-Pavard, Manel; Amrani, Yassine; Honkanen, Richard E.; Tran, Jennifer

2012-01-01

Corticosteroid insensitivity (CSI) represents a profound challenge in managing patients with asthma. We recently demonstrated that short exposure of airway smooth muscle cells (ASMCs) to proasthmatic cytokines drastically reduced their responsiveness to glucocorticoids (GCs), an effect that was partially mediated via interferon regulatory factor-1, suggesting the involvement of additional mechanisms (Am J Respir Cell Mol Biol 2008;38:463–472). Although GC receptor (GR) can be phosphorylated at multiple serines in the N-terminal region, the major phosphorylation sites critical for GR transcriptional activity are serines 211 (Ser211) and 226 (Ser226). We tested the novel hypothesis that cytokine-induced CSI in ASMCs is due to an impaired GR phosphorylation. Cells were treated with TNF-α (10 ng/ml) and IFN-γ (500 UI/ml) for 6 hours and/or fluticasone (100 nm) added 2 hours before. GR was constitutively phosphorylated at Ser226 but not at Ser211 residues. Cytokines dramatically suppressed fluticasone-induced phosphorylation of GR on Ser211 but not on Ser226 residues while increasing the expression of Ser/Thr protein phosphatase (PP)5 but not that of PP1 or PP2A. Transfection studies using a reporter construct containing GC responsive elements showed that the specific small interfering RNA–induced mRNA knockdown of PP5, but not that of PP1 or PP2A, partially prevented the cytokine suppressive effects on GR-meditated transactivation activity. Similarly, cytokines failed to inhibit GC-induced GR-Ser211 phosphorylation when expression of PP5 was suppressed. We propose that the novel mechanism that proasthmatic cytokine-induced CSI in ASMCs is due, in part, to PP5-mediated impairment of GR-Ser211 phosphorylation. PMID:22592921

PA1 Protein, a New Competitive Decelerator Acting at More than One Step to Impede Glucocorticoid Receptor-mediated Transactivation*

PubMed Central

Zhang, Zhenhuan; Sun, Yunguang; Cho, Young-Wook; Chow, Carson C.; Simons, S. Stoney

2013-01-01

Numerous cofactors modulate the gene regulatory activity of glucocorticoid receptors (GRs) by affecting one or more of the following three major transcriptional properties: the maximal activity of agonists (Amax), the potency of agonists (EC50), and the partial agonist activity of antisteroids (PAA). Here, we report that the recently described nuclear protein, Pax2 transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is a new inhibitor of GR transactivation. PA1 suppresses Amax, increases the EC50, and reduces the PAA of an exogenous reporter gene in a manner that is independent of associated PTIP. PA1 is fully active with, and strongly binds to, the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR-mediated gene induction but is unable to augment the actions of the corepressor SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous reporter indicates that the kinetic definition of PA1 action is a competitive decelerator at two sites upstream from where TIF2 acts. With the endogenous genes IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC50, and decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes this inhibition of the two genes via different mechanisms as follows: PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that PA1 is a new competitive decelerator of GR transactivation and can act at more than one molecularly defined step in a manner that depends upon the specific gene. PMID:23161582

PA1 protein, a new competitive decelerator acting at more than one step to impede glucocorticoid receptor-mediated transactivation.

PubMed

Zhang, Zhenhuan; Sun, Yunguang; Cho, Young-Wook; Chow, Carson C; Simons, S Stoney

2013-01-04

Numerous cofactors modulate the gene regulatory activity of glucocorticoid receptors (GRs) by affecting one or more of the following three major transcriptional properties: the maximal activity of agonists (A(max)), the potency of agonists (EC(50)), and the partial agonist activity of antisteroids (PAA). Here, we report that the recently described nuclear protein, Pax2 transactivation domain interaction protein (PTIP)-associated protein 1 (PA1), is a new inhibitor of GR transactivation. PA1 suppresses A(max), increases the EC(50), and reduces the PAA of an exogenous reporter gene in a manner that is independent of associated PTIP. PA1 is fully active with, and strongly binds to, the C-terminal half of GR. PA1 reverses the effects of the coactivator TIF2 on GR-mediated gene induction but is unable to augment the actions of the corepressor SMRT. Analysis of competition assays between PA1 and TIF2 with an exogenous reporter indicates that the kinetic definition of PA1 action is a competitive decelerator at two sites upstream from where TIF2 acts. With the endogenous genes IGFBP1 and IP6K3, PA1 also represses GR induction, increases the EC(50), and decreases the PAA. ChIP and re-ChIP experiments indicate that PA1 accomplishes this inhibition of the two genes via different mechanisms as follows: PA1 appears to increase GR dissociation from and reduce GR transactivation at the IGFBP1 promoter regions but blocks GR binding to the IP6K3 promoter. We conclude that PA1 is a new competitive decelerator of GR transactivation and can act at more than one molecularly defined step in a manner that depends upon the specific gene.

Transient ice mass variations over Greenland detected by the combination of GPS and GRACE data

NASA Astrophysics Data System (ADS)

Zhang, B.; Liu, L.; Khan, S. A.; van Dam, T. M.; Zhang, E.

2017-12-01

Over the past decade, the Greenland Ice Sheet (GrIS) has been undergoing significant warming and ice mass loss. Such mass loss was not always a steady process but had substantial temporal and spatial variabilities. Here we apply multi-channel singular spectral analysis to crustal deformation time series measured at about 50 Global Positioning System (GPS) stations mounted on bedrock around the Greenland coast and mass changes inferred from Gravity Recovery and Climate Experiment (GRACE) to detect transient changes in ice mass balance over the GrIS. We detect two transient anomalies: one is a negative melting anomaly (Anomaly 1) that peaked around 2010; the other is a positive melting anomaly (Anomaly 2) that peaked between 2012 and 2013. The GRACE data show that both anomalies caused significant mass changes south of 74°N but negligible changes north of 74°N. Both anomalies caused the maximum mass change in southeast GrIS, followed by in west GrIS near Jakobshavn. Our results also show that the mass change caused by Anomaly 1 first reached the maximum in late 2009 in the southeast GrIS and then migrated to west GrIS. However, in Anomaly 2, the southeast GrIS was the last place that reached the maximum mass change in early 2013 and the west GrIS near Jakobshavn was the second latest place that reached the maximum mass change. Most of the GPS data show similar spatiotemporal patterns as those obtained from the GRACE data. However, some GPS time series show discrepancies in either space or time, because of data gaps and different sensitivities of mass loading change. Namely, loading deformation measured by GPS can be significantly affected by local dynamical mass changes, which, yet, has little impact on GRACE observations.

Is rigid endoscopy necessary with childhood corrosive ingestion? a retrospective comparative analysis of 458 cases.

PubMed

Bosnali, O; Moralioglu, S; Celayir, A; Pektas, O Z

2017-02-01

The aim of this study was to determine the necessity of endoscopy in cases in which a corrosive substance was ingested and to find a practical way to avoid unnecessary endoscopies for similar cases in the future. The clinical records of 458 hospitalized cases with clinical histories of corrosive substance ingestion between January 2007 and December 2013 were retrospectively reviewed. The demographics of the cases, the ingested substances, and the rigid endoscopy findings were evaluated. The three most commonly ingested corrosive agents were household bleach (22.9%), household degreaser (15.9%), and drain cleaner (13.1%). Rigid esophagoscopy was performed in 367 of the 458 cases. Corrosive agents were grouped according to their purpose of household use; eight groups were created. The degree of corrosive injury observed in the different groups was compared with the degree of injury caused by household bleach. Among the corrosive agent groups, dishwashing machine products (Gr.1), laundry products (Gr.2), liquid cleaners (Gr.3), and household bleach (Gr.4) did not cause high-grade injuries. The resulting injuries and esophagoscopy results among the above groups, whether symptomatic or not, did not differ from one another. Corrosive agents such as drain cleaner (Gr.6), household degreaser (Gr.7), and several other acidic products (Gr.8) caused high-grade injuries in the esophagus; however, lime remover/HCl (Gr.5) did not. Thus, hospitalization and rigid endoscopy seem unnecessary to assess esophageal injury in most cases, if the ingested corrosive agent fits into group 1, 2, 3, or 4 and if the patient can be easily fed. Esophagoscopy is useful to shorten the hospitalization times in cases where strong corrosive agents were ingested, such as those in groups 5, 6, 7, and 8. © 2016 International Society for Diseases of the Esophagus.

Dibutyltin Disrupts Glucocorticoid Receptor Function and Impairs Glucocorticoid-Induced Suppression of Cytokine Production

PubMed Central

Gumy, Christel; Chandsawangbhuwana, Charlie; Dzyakanchuk, Anna A.; Kratschmar, Denise V.; Baker, Michael E.; Odermatt, Alex

2008-01-01

Background Organotins are highly toxic and widely distributed environmental chemicals. Dibutyltin (DBT) is used as stabilizer in the production of polyvinyl chloride plastics, and it is also the major metabolite formed from tributyltin (TBT) in vivo. DBT is immunotoxic, however, the responsible targets remain to be defined. Due to the importance of glucocorticoids in immune-modulation, we investigated whether DBT could interfere with glucocorticoid receptor (GR) function. Methodology We used HEK-293 cells transiently transfected with human GR as well as rat H4IIE hepatoma cells and native human macrophages and human THP-1 macrophages expressing endogenous receptor to study organotin effects on GR function. Docking of organotins was used to investigate the binding mechanism. Principal Findings We found that nanomolar concentrations of DBT, but not other organotins tested, inhibit ligand binding to GR and its transcriptional activity. Docking analysis indicated that DBT inhibits GR activation allosterically by inserting into a site close to the steroid-binding pocket, which disrupts a key interaction between the A-ring of the glucocorticoid and the GR. DBT inhibited glucocorticoid-induced expression of phosphoenolpyruvate carboxykinase (PEPCK) and tyrosine-aminotransferase (TAT) and abolished the glucocorticoid-mediated transrepression of TNF-α-induced NF-κB activity. Moreover, DBT abrogated the glucocorticoid-mediated suppression of interleukin-6 (IL-6) and TNF-α production in lipopolysaccharide (LPS)-stimulated native human macrophages and human THP-1 macrophages. Conclusions DBT inhibits ligand binding to GR and subsequent activation of the receptor. By blocking GR activation, DBT may disturb metabolic functions and modulation of the immune system, providing an explanation for some of the toxic effects of this organotin. PMID:18958157

A hotspot in the glucocorticoid receptor DNA-binding domain susceptible to loss of function mutation

PubMed Central

Banuelos, Jesus; Shin, Soon Cheon; Lu, Nick Z.

2015-01-01

Glucocorticoids (GCs) are used to treat a variety of inflammatory disorders and certain cancers. However, GC resistance occurs in subsets of patients. We found that EL4 cells, a GC-resistant mouse thymoma cell line, harbored a point mutation in their GC receptor (GR) gene, resulting in the substitution of arginine 493 by a cysteine in the second zinc finger of the DNA-binding domain. Allelic discrimination analyses revealed that the R493C mutation occurred on both alleles. In the absence of GCs, the GR in EL4 cells localized predominantly in the cytoplasm and upon dexamethasone treatment underwent nuclear translocation, suggesting the ligand binding ability of the GR in EL4 cells was intact. In transient transfection assays, the R493C mutant could not transactivate the MMTV-luciferase reporter. Site-directed mutagenesis to revert the R493C mutation restored the transactivation activity. Cotransfection experiments showed that the R493C mutant did not inhibit the transcriptional activities of the wild-type GR. In addition, the R493C mutant did not repress either the AP-1 or NF-κB reporters as effectively as WT GR. Furthermore, stable expression of the WT GR in the EL4 cells enabled GC-mediated gene regulation, specifically upregulation of IκBα and downregulation of interferon γ and interleukin 17A. Arginine 493 is conserved among multiple species and all human nuclear receptors and its mutation has also been found in the human GR, androgen receptor, and mineralocorticoid receptor. Thus, R493 is necessary for the transcriptional activity of the GR and a hotspot for mutations that result in GC resistance. PMID:25676786

Bupropion induces social anxiety in adolescent mice: Influence of housing conditions.

PubMed

Gómez, Carmen; Redolat, Rosa; Carrasco, Carmen

2017-08-01

The antidepressant bupropion has received increasing attention as a pharmacological tool to treat addiction although little is known about its effects on social behaviour in adolescents. The present study aimed to evaluate if environmental housing conditions influence bupropion's actions on social behaviour of adolescent mice. Mice were either group- or individually housed for 2-weeks and then randomly divided into 2 cohorts: half of the mice remained in the initial housing condition and the other half were changed to isolated conditions for further 2-weeks. The following groups were compared: isolated/isolated (ISO/ISO), isolated/group-housed (ISO/GR), group-housed/isolated (GR/ISO), and group-housed/group-housed (GR/GR). The effects of bupropion (40, 20, 10mg/kg) or saline on social interaction were assessed for each housing condition. Social encounters were evaluated using ethological analysis. Data showed significant effects of bupropion on grooming and digging. This drug diminished time mice allocated to these behavioural categories in all housing conditions. In ISO/GR and GR/ISO conditions, bupropion increased environmental exploration (non-social exploration and exploration from a distance), reduced social investigation and increased avoidance/flee and defence/submission behaviours. An augment of avoidance/flee during social interactions was observed in bupropion-treated mice in GR/GR housing condition. These results suggest that this drug exhibits anxiogenic-like properties in social encounters between adolescent mice, especially when a transition in housing conditions has been experienced during this period. Changes in housing conditions may be a useful model for evaluating the effects of bupropion on social behaviour and the role of environmental housing conditions. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Fiber post cementation strategies: effect of mechanical cycling on push-out bond strength and cement polymerization stress.

PubMed

Bergoli, Cesar Dalmolin; Amaral, Marina; Boaro, Leticia Cristina; Braga, Roberto Ruggiero; Valandro, Luiz Felipe

2012-08-01

To evaluate the effect of mechanical cycling and cementation strategies on the push-out bond strength between fiber posts and root dentin and the polymerization stresses produced using three resin cements. Eighty bovine mandibular teeth were sectioned to a length of 16 mm, prepared to 12 mm, and embedded in self-curing acrylic resin. The specimens were then distributed into 8 groups (n = 10): Gr1 - Scotchbond Multi Purpose + RelyX ARC; Gr2 - Scotchbond Multi Purpose + RelyX ARC + mechanical cycling; Gr3 - AdheSE + Multilink Automix; Gr4 - AdheSE + Multilink Automix + mechanical cycling; Gr5 - phosphoric acid + RelyX U100 (self-adhesive cement); Gr6 - phosphoric acid+ RelyX U100 + mechanical cycling; Gr7 - RelyX U100; Gr8 - RelyX U100 + mechanical cycling. The values obtained from the push-out bond strength test were submitted to two-way ANOVA and Tukey's test (p = 0.05), while the values obtained from the polymerization stress test were subjected to one-way ANOVA and Tukey's test (α = 0.05). Mechanical cycling did not affect the bond strength values (p = 0.236), while cementation strategies affected the push-out bond strength (p < 0.001). Luting with RelyX U100 and Scotch Bond Multi Purpose + RelyX ARC yielded higher push-out bond strength values. The polymerization stress results were affected by the factor "cement" (p = 0.0104): the self-adhesive cement RelyX U100 exhibited the lowest values, RelyX ARC resulted in the highest values, while Multilink Automix presented values statistically similar to the other two cements. The self-adhesive cement appears to be a good alternative for luting fiber posts due to the high push-out bond strengths and lower polymerization stress values.

The role of digestive factors in determining glycemic response in a multiethnic Asian population.

PubMed

Tan, Verena Ming Hui; Ooi, Delicia Shu Qin; Kapur, Jeevesh; Wu, Ting; Chan, Yiong Huak; Henry, Christiani Jeyakumar; Lee, Yung Seng

2016-06-01

There are wide inter-individual differences in glycemic response (GR). We aimed to examine key digestive parameters that influence inter-individual and ethnic differences in GR in healthy Asian individuals. Seventy-five healthy male subjects (25 Chinese, 25 Malays, and 25 Asian-Indians) were served equivalent available carbohydrate amounts (50 g) of jasmine rice (JR) and basmati rice (BR) on separate occasions. Postprandial blood glucose concentrations were measured at fasting (-5 and 0 min) and at 15- to 30-min interval over 180 min. Mastication parameters (number of chews per mouth and chewing time per mouthful), saliva α-amylase activity, AMY1 gene copy numbers and gastric emptying rate were measured to investigate their relationships with GR. The GR for jasmine rice was significantly higher than for basmati rice (P < 0.001). The median number of AMY1 gene copies was 6, with a range of 2-15. There was a significant positive relationship between AMY1 copy number and α-amylase activity (P = 0.002). There were no significant ethnic differences in GR. For both rice varieties, the number of chews per mouthful was positively associated with the GR (JR, P = 0.011; BR, P = 0.005), while chewing time per mouthful showed a negative association (JR, P = 0.039; BR, P = 0.016). Ethnicity, salivary α-amylase activity, particle size distribution, gastric emptying rate and AMY1 gene copy numbers were not significant contributors to GR (P > 0.05). Mastication parameters contribute significantly to GR. Eating slowly and having larger food boluses before swallowing (less chewing), both potentially modifiable, may be beneficial in glycemic control.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Getachew, Yonas, E-mail: yonas.getachew@utsouthwestern.edu; Cusimano, Frank A.; James, Laura P.

The role of the immune system, specifically NK, NKT and CD3 cells, in acetaminophen (APAP) induced liver injury remains inconsistently defined. In the present study, wild type (C57BL/6J) mice and granzyme B deficient (GrB −/−) mice were treated with acetaminophen to assess the role of the immune system in acute liver injury. Doses of acetaminophen that induced sub lethal liver injury in wild type mice unexpectedly produced fatal hepatotoxicity in granzyme B deficient (GrB −/−) mice. Analysis revealed that GrB −/− mice had an increased population of intrahepatic CD3 (+), CD4 (−), and CD8 (−) lymphocytes expressing the CD69 activationmore » marker and Fas ligand. Depletion of these cells in the GrB −/− and wild type mice made them less susceptible to APAP injury, while depletion of NK1.1 (+) cells or both CD4 (+) and CD8 (+) T cells failed to provide the same hepatoprotection. Transfer of the GrB −/− IHLs further exacerbated liver injury and increased mortality in wild type mice but not in LRP/LPR mice, lacking fas expression. Conclusions: Acetaminophen toxicity is enhanced by the presence of activated, FasL expressing intrahepatic CD3 (+), CD4 (−), CD8 (−), NK1.1 (−) T cells. Depletion of these cells from GrB −/− mice and wild type mice greatly reduces mortality and improves the course of liver injury recovery. - Highlights: • Intrahepatic lymphocytes (IHLs) from GrB −/− mice harbor activated DNT cells. • IHLs from GrB −/− mice exhibit enhanced Fas ligand expression. • Acetaminophen toxicity is enhanced by activated, FasL expressing DNT cells.« less

Green Rust: Structure, Redox Reaction Mechanisms, Transformation and Colloidal Behaviour

NASA Astrophysics Data System (ADS)

Stipp, S.; Skovbjerg, L.; Christiansen, B.; Hansson, E.; Utsunomiya, S.; Schild, D.; Geckeis, H.; Ewing, R.

2006-05-01

Green rust (GR) forms where pH is neutral to basic, iron concentration is high and oxidation potential provides a small amount of Fe(III). GR is best known from metallic iron corrosion but it has also been reported in soil. It typically forms nano-particles, so surface area is high. It has a layered structure and is reactive, adsorbing species on its surface, providing exchange of interlayer ions, and allowing reaction of redox active species. Corroding stainless-steel canisters in a concrete and steel radioactive waste repository would offer geochemical conditions for GR formation. We used surface-sensitive and high resolution techniques (atomic force microscopy, AFM, transmission electron microscopy, TEM, X-ray photoelectron spectroscopy, XPS) to supplement data from traditional methods (X-ray diffraction, XRD, and wet chemistry). The purpose was to refine structural and compositional parameters for green rust sulfate; to define trace component uptake mechanisms; and to assess potential mobility of GR colloids and thus, sorbed radionuclides. Green rust reduced dissolved Np(V), Cr(VI) and Se(VI), rapidly decreasing solution concentration. High resolution TEM and AFM images showed that chromate penetrates GR interlayers to a distance of about 100 nm from crystal edges. It reduces to Cr(III), blocking further movement and GR transforms topotactically to Cr- goethite, thus immobilising the contaminant in a phase significantly less soluble than pure goethite. Further oxidation results in dissolution of GR and growth of more Cr-goethite. In-situ AFM imaging showed that GR can nucleate and grow both in solution and on minerals typical of fractures in granite, i.e. graphite, muscovite, biotite, quartz and amorphous silica. Particles are more likely to stick to each other or to a substrate than to remain monodispersed.

The transformed glucocorticoid receptor has a lower steroid-binding affinity than the nontransformed receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nemoto, Takayuki; Ohara-Nemoto, Yuko; Denis, M.

1990-02-20

High-salt treatment of cytosolic glucocorticoid receptor (GR) preparations reduces the steroid-binding ability of the receptor and induces the conversion of the receptor from a nontransformed (non-DNA-binding) 9S form to a transformed (DNA-binding) 4S entity. Therefore, the authors decided to investigate the possible relationship between these two phenomena. The binding of ({sup 3}H)triamcinolone acetonide (({sup 3}H)TA) to the 9S form was almost saturated at a concentration of 20 nM, whereas ({sup 3}H)TA was hardly bound to the 4S form at this concentration. The 4S form was efficiently labeled at 200 nM. Scatchard analysis of the GR showed the presence of twomore » types of binding sites. In the absence of molybdate, the ratio of the lower affinity site was increased, but the total number of binding sites was not modified. The GR with the low ({sup 3}H)TA-binding affinity bound to DNA-cellulose even in its unliganded state, whereas the form with the high affinity did not. These results indicate that the transformed GR has a reduced ({sup 3}H)TA-binding affinity as compared to the nontransformed GR. The steroid-binding domain (amino acids 477-777) and the DNA- and steroid-binding domains (amino acids 415-777) of the human GR were expressed in Escherichia coli as protein A fused proteins. Taken together, these results suggest that the component(s) associating with the nontransformed GR, possibly the heat shock protein hsp 90, play(s) an important role in stabilizing the GR in a high-affinity state for steroids.« less

CRTC2 Is a Coactivator of GR and Couples GR and CREB in the Regulation of Hepatic Gluconeogenesis.

PubMed

Hill, Micah J; Suzuki, Shigeru; Segars, James H; Kino, Tomoshige

2016-01-01

Glucocorticoid hormones play essential roles in the regulation of gluconeogenesis in the liver, an adaptive response that is required for the maintenance of circulating glucose levels during fasting. Glucocorticoids do this by cooperating with glucagon, which is secreted from pancreatic islets to activate the cAMP-signaling pathway in hepatocytes. The cAMP-response element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) is a coactivator known to be specific to CREB and plays a central role in the glucagon-mediated activation of gluconeogenesis in the early phase of fasting. We show here that CRTC2 also functions as a coactivator for the glucocorticoid receptor (GR). CRTC2 strongly enhances GR-induced transcriptional activity of glucocorticoid-responsive genes. CRTC2 physically interacts with the ligand-binding domain of the GR through a region spanning amino acids 561-693. Further, CRTC2 is required for the glucocorticoid-associated cooperative mRNA expression of the glucose-6-phosphatase, a rate-limiting enzyme for hepatic gluconeogenesis, by facilitating the attraction of GR and itself to its promoter region already occupied by CREB. CRTC2 is required for the maintenance of blood glucose levels during fasting in mice by enhancing the GR transcriptional activity on both the G6p and phosphoenolpyruvate carboxykinase (Pepck) genes. Finally, CRTC2 modulates the transcriptional activity of the progesterone receptor, indicating that it may influence the transcriptional activity of other steroid/nuclear receptors. Taken together, these results reveal that CRTC2 plays an essential role in the regulation of hepatic gluconeogenesis through coordinated regulation of the glucocorticoid/GR- and glucagon/CREB-signaling pathways on the key genes G6P and PEPCK.

Mismodeling in gravitational-wave astronomy: The trouble with templates

NASA Astrophysics Data System (ADS)

Sampson, Laura; Cornish, Neil; Yunes, Nicolás

2014-03-01

Waveform templates are a powerful tool for extracting and characterizing gravitational wave signals, acting as highly restrictive priors on the signal morphologies that allow us to extract weak events buried deep in the instrumental noise. The templates map the waveform shapes to physical parameters, thus allowing us to produce posterior probability distributions for these parameters. However, there are attendant dangers in using highly restrictive signal priors. If strong field gravity is not accurately described by general relativity (GR), then using GR templates may result in fundamental bias in the recovered parameters, or even worse, a complete failure to detect signals. Here we study such dangers, concentrating on three distinct possibilities. First, we show that there exist modified theories compatible with all existing observations that would fail to be detected by the LIGO/Virgo network using searches based on GR templates, but which would be detected using a one parameter post-Einsteinian extension. Second, we study modified theories that produce departures from GR that turn on suddenly at a critical frequency, producing waveforms that do not directly fit into the simplest parametrized post-Einsteinian (ppE) scheme. We show that even the simplest ppE templates are still capable of picking up these strange signals and diagnosing a departure from GR. Third, we study whether using inspiral-only ppE waveforms for signals that include merger and ringdown can lead to problems in misidentifying a GR departure. We present a simple technique that allows us to self-consistently identify the inspiral portion of the signal, and thus remove these potential biases, allowing GR tests to be performed on higher mass signals that merge within the detector band. We close by studying a parametrized waveform model that may allow us to test GR using the full inspiral-merger-ringdown signal.

Simulating changes in cropping practices in conventional and glyphosate-resistant maize. II. Weed impacts on crop production and biodiversity.

PubMed

Colbach, Nathalie; Darmency, Henri; Fernier, Alice; Granger, Sylvie; Le Corre, Valérie; Messéan, Antoine

2017-05-01

Overreliance on the same herbicide mode of action leads to the spread of resistant weeds, which cancels the advantages of herbicide-tolerant (HT) crops. Here, the objective was to quantify, with simulations, the impact of glyphosate-resistant (GR) weeds on crop production and weed-related wild biodiversity in HT maize-based cropping systems differing in terms of management practices. We (1) simulated current conventional and probable HT cropping systems in two European regions, Aquitaine and Catalonia, with the weed dynamics model FLORSYS; (2) quantified how much the presence of GR weeds contributed to weed impacts on crop production and biodiversity; (3) determined the effect of cultural practices on the impact of GR weeds and (4) identified which species traits most influence weed-impact indicators. The simulation study showed that during the analysed 28 years, the advent of glyphosate resistance had little effect on plant biodiversity. Glyphosate-susceptible populations and species were replaced by GR ones. Including GR weeds only affected functional biodiversity (food offer for birds, bees and carabids) and weed harmfulness when weed effect was initially low; when weed effect was initially high, including GR weeds had little effect. The GR effect also depended on cultural practices, e.g. GR weeds were most detrimental for species equitability when maize was sown late. Species traits most harmful for crop production and most beneficial for biodiversity were identified, using RLQ analyses. None of the species presenting these traits belonged to a family for which glyphosate resistance was reported. An advice table was built; the effects of cultural practices on crop production and biodiversity were synthesized, explained, quantified and ranked, and the optimal choices for each management technique were identified.

Compound A, a Selective Glucocorticoid Receptor Modulator, Enhances Heat Shock Protein Hsp70 Gene Promoter Activation

PubMed Central

Beck, Ilse M.; Drebert, Zuzanna J.; Hoya-Arias, Ruben; Bahar, Ali A.; Devos, Michael; Clarisse, Dorien; Desmet, Sofie; Bougarne, Nadia; Ruttens, Bart; Gossye, Valerie; Denecker, Geertrui; Lievens, Sam; Bracke, Marc; Tavernier, Jan; Declercq, Wim; Gevaert, Kris; Berghe, Wim Vanden; Haegeman, Guy; De Bosscher, Karolien

2013-01-01

Compound A possesses glucocorticoid receptor (GR)-dependent anti-inflammatory properties. Just like classical GR ligands, Compound A can repress NF-κB-mediated gene expression. However, the monomeric Compound A-activated GR is unable to trigger glucocorticoid response element-regulated gene expression. The heat shock response potently activates heat shock factor 1 (HSF1), upregulates Hsp70, a known GR chaperone, and also modulates various aspects of inflammation. We found that the selective GR modulator Compound A and heat shock trigger similar cellular effects in A549 lung epithelial cells. With regard to their anti-inflammatory mechanism, heat shock and Compound A are both able to reduce TNF-stimulated IκBα degradation and NF-κB p65 nuclear translocation. We established an interaction between Compound A-activated GR and Hsp70, but remarkably, although the presence of the Hsp70 chaperone as such appears pivotal for the Compound A-mediated inflammatory gene repression, subsequent novel Hsp70 protein synthesis is uncoupled from an observed CpdA-induced Hsp70 mRNA upregulation and hence obsolete in mediating CpdA’s anti-inflammatory effect. The lack of a Compound A-induced increase in Hsp70 protein levels in A549 cells is not mediated by a rapid proteasomal degradation of Hsp70 or by a Compound A-induced general block on translation. Similar to heat shock, Compound A can upregulate transcription of Hsp70 genes in various cell lines and BALB/c mice. Interestingly, whereas Compound A-dependent Hsp70 promoter activation is GR-dependent but HSF1-independent, heat shock-induced Hsp70 expression alternatively occurs in a GR-independent and HSF1-dependent manner in A549 lung epithelial cells. PMID:23935933

Rectal Toxicity After Proton Therapy For Prostate Cancer: An Analysis of Outcomes of Prospective Studies Conducted at the University of Florida Proton Therapy Institute

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colaco, Rovel J.; Hoppe, Bradford S.; Flampouri, Stella

2015-01-01

Purpose: Study goals were to characterize gastrointestinal effects of proton therapy (PT) in a large cohort of patients treated for prostate cancer, identify factors associated with rectal bleeding (RB), and compare RB between patients receiving investigational protocols versus those in outcome-tracking protocols. Methods and Materials: A total of 1285 consecutive patients were treated with PT between August 2006 and May 2010. Potential pre-existing clinical and treatment-related risk factors for rectal toxicity were recorded. Common Terminology Criteria for Adverse Events version 3.0 was used to score toxicity. Results: Transient RB was the predominant grade 2 or higher (GR2+) toxicity after PT,more » accounting for 95% of gastrointestinal events. GR1 RB occurred in 217 patients (16.9%), GR2 RB in 187 patients (14.5%), and GR3 in 11 (0.9%) patients. There were no GR4 or GR5 events. Univariate analyses showed correlations between GR2+ RB and anticoagulation therapy (P=.008) and rectal and rectal wall dose-volume histogram (DVH) parameters (P<.001). On multivariate analysis, anticoagulation therapy (P=.0034), relative volume of rectum receiving 75 Gy (V75; P=.0102), and relative rectal wall V75 (P=.0017) were significant predictors for G2+ RB. Patients treated with investigational protocols had toxicity rates similar to those receiving outcome-tracking protocols. Conclusions: PT was associated with a low rate of GR2+ gastrointestinal toxicity, predominantly transient RB, which was highly correlated with anticoagulation and rectal DVH parameters. Techniques that limit rectal exposure should be used when possible.« less

Liver-selective glucocorticoid antagonists: a novel treatment for type 2 diabetes.

PubMed

von Geldern, Thomas W; Tu, Noah; Kym, Philip R; Link, James T; Jae, Hwan-Soo; Lai, Chunqiu; Apelqvist, Theresa; Rhonnstad, Patrik; Hagberg, Lars; Koehler, Konrad; Grynfarb, Marlena; Goos-Nilsson, Annika; Sandberg, Johnny; Osterlund, Marie; Barkhem, Tomas; Höglund, Marie; Wang, Jiahong; Fung, Steven; Wilcox, Denise; Nguyen, Phong; Jakob, Clarissa; Hutchins, Charles; Färnegårdh, Mathias; Kauppi, Björn; Ohman, Lars; Jacobson, Peer B

2004-08-12

Hepatic blockade of glucocorticoid receptors (GR) suppresses glucose production and thus decreases circulating glucose levels, but systemic glucocorticoid antagonism can produce adrenal insufficiency and other undesirable side effects. These hepatic and systemic responses might be dissected, leading to liver-selective pharmacology, when a GR antagonist is linked to a bile acid in an appropriate manner. Bile acid conjugation can be accomplished with a minimal loss of binding affinity for GR. The resultant conjugates remain potent in cell-based functional assays. A novel in vivo assay has been developed to simultaneously evaluate both hepatic and systemic GR blockade; this assay has been used to optimize the nature and site of the linker functionality, as well as the choice of the GR antagonist and the bile acid. This optimization led to the identification of A-348441, which reduces glucose levels and improves lipid profiles in an animal model of diabetes. Copyright 2004 American Chemical Society

Studies of Second Layer Hydrogens on Graphite: Hydrogen/hd/gr and Hd/hd/gr.

NASA Astrophysics Data System (ADS)

Liu, Yuanming

Quasi-adiabatic heat capacity and volumetric vapor pressure isotherm techniques were used to study the thermodynamic properties of monolayer H_2 adsorbed on HD plated graphite (H_2/HD/Gr) and bilayer HD on bare graphite (HD/HD/Gr). Quasielastic neutron scattering (QENS) measurements were performed at the Laboratoire Leon Brillouin (LLB) in Saclay, France, to study the mobility of the bilayer HD films. The three techniques complemented each other. Three types of graphite were used: graphite foam for the heat capacity measurements, more loose and homogeneous graphite 'worms' for the isotherm measurements, and Papyex (similar to Grafoil) with a high surface-to-volume ratio for the QENS measurements. The heat capacity study on the mixture system H_2/HD/Gr is a continuation of the previous study on H_2/D _2/Gr by F. C. Liu et al. The results show three peculiar features which have not been seen in the pure bilayer hydrogen films: a tilted triple line, a distorted liquid(L)-vapor(V) coexistence region, and weak heat capacity anomalies at 10.1K. The triple line tilts backwards, from 6.58K to 6.25K as the H2 coverage increases. The lowest triple point temperature (6.25K) is still higher than both 5.96K of H_2/H _2/Gr (Wiechert et al.) and 5.74K of H_2/D_2/Gr (F. C. Liu et al.). The behavior of the triple line can be semi-quantitatively explained by a model of interlayer mixing which is based on the consideration that interlayer mixing lowers the system's free energy. The distortion of the L-V region and appearance of weak heat capacity anomalies are also believed to be due to interlayer mixing. The heat capacity measurements on HD/HD/Gr show a phase diagram similar to those of H_2 /H_2/MgO, H_2 /H_2/Gr, and 3D van der Waals systems, with the 2D triple and critical points at T _{t} = 8.44K and T_ {c} = 11.45K. The entropy change and heat of fusion at the triple point melting in HD/HD/Gr are comparable with those of H_2/H _2/Gr and D_2/D _2/Gr, but are considerably less (only about 1/3) than the ones of H_2/H _2/MgO. The vapor pressure isotherm measurements discover a relatively narrow solid(S)-liquid(L) coexistence region, confirming the small solid-liquid density difference expected from the relatively small entropy change upon the triple point melting. The triple point and critical point temperatures determined by the isotherms are consistent with the heat capacity measurements. The preliminary results of the QENS measurements show that the phase existing above T_{t } in the 2nd layer HD is a 2D liquid with a diffusion coefficient about 1/2-1/3 of that of the bulk liquid at its triple point (T_{t} (3D) = 16.60K), while surprisingly showing that there is a substantial liquid fraction and mobility at least 1^circK below the solidification temperature.

Some Applications of Gröbner Bases in Robotics and Engineering

NASA Astrophysics Data System (ADS)

Abłamowicz, Rafał

Gröbner bases in polynomial rings have numerous applications in geometry, applied mathematics, and engineering. We show a few applications of Gröbner bases in robotics, formulated in the language of Clifford algebras, and in engineering to the theory of curves, including Fermat and Bézier cubics, and interpolation functions used in finite element theory.

Lagrangian transport in a class of three-dimensional buoyancy-driven flows

NASA Astrophysics Data System (ADS)

Contreras, Sebastian; Speetjens, Michel; Clercx, Herman

2017-11-01

The study concerns the Lagrangian dynamics of three-dimensional (3D) buoyancy-driven cavity flows under steady and laminar conditions due to a global temperature gradient imposed via an opposite hot and cold sidewall. This serves as archetypal configuration for natural-convection flows in which gravity is perpendicular to the global temperature gradient. Limited insight into the Lagrangian properties of this class of flows motivates this study. The 3D Lagrangian dynamics are investigated in terms of the generic structure of the Lagrangian flow topology that is described in terms of the Grashof number (Gr) and the Prandtl number (Pr). Gr is the principal control parameter for the flow topology: vanishing Gr yields a state of closed streamlines (integrable state); increasing Gr causes the formation of toroidal coherent structures embedded in chaotic streamlines governed by Hamiltonian mechanisms. Fluid inertia prevails for ``smaller'' Gr. A buoyancy-induced bifurcation of the flow topology occurs for ``larger'' Gr and underlies the emergence of ``secondary rolls'' and secondary tori for ``larger'' Pr. Stagnation points and corresponding manifold interactions are key to the dynamics. S.C. acknowledges financial support from Consejo Nacional de Ciencia y Tecnología (CONACYT).

Rapid, single-step most-probable-number method for enumerating fecal coliforms in effluents from sewage treatment plants

NASA Technical Reports Server (NTRS)

Munoz, E. F.; Silverman, M. P.

1979-01-01

A single-step most-probable-number method for determining the number of fecal coliform bacteria present in sewage treatment plant effluents is discussed. A single growth medium based on that of Reasoner et al. (1976) and consisting of 5.0 gr. proteose peptone, 3.0 gr. yeast extract, 10.0 gr. lactose, 7.5 gr. NaCl, 0.2 gr. sodium lauryl sulfate, and 0.1 gr. sodium desoxycholate per liter is used. The pH is adjusted to 6.5, and samples are incubated at 44.5 deg C. Bacterial growth is detected either by measuring the increase with time in the electrical impedance ratio between the innoculated sample vial and an uninnoculated reference vial or by visual examination for turbidity. Results obtained by the single-step method for chlorinated and unchlorinated effluent samples are in excellent agreement with those obtained by the standard method. It is suggested that in automated treatment plants impedance ratio data could be automatically matched by computer programs with the appropriate dilution factors and most probable number tables already in the computer memory, with the corresponding result displayed as fecal coliforms per 100 ml of effluent.

A gauge-theoretic approach to gravity.

PubMed

Krasnov, Kirill

2012-08-08

Einstein's general relativity (GR) is a dynamical theory of the space-time metric. We describe an approach in which GR becomes an SU(2) gauge theory. We start at the linearized level and show how a gauge-theoretic Lagrangian for non-interacting massless spin two particles (gravitons) takes a much more simple and compact form than in the standard metric description. Moreover, in contrast to the GR situation, the gauge theory Lagrangian is convex. We then proceed with a formulation of the full nonlinear theory. The equivalence to the metric-based GR holds only at the level of solutions of the field equations, that is, on-shell. The gauge-theoretic approach also makes it clear that GR is not the only interacting theory of massless spin two particles, in spite of the GR uniqueness theorems available in the metric description. Thus, there is an infinite-parameter class of gravity theories all describing just two propagating polarizations of the graviton. We describe how matter can be coupled to gravity in this formulation and, in particular, how both the gravity and Yang-Mills arise as sectors of a general diffeomorphism-invariant gauge theory. We finish by outlining a possible scenario of the ultraviolet completion of quantum gravity within this approach.

Seasonal changes in cortisol sensitivity and glucocorticoid receptor affinity and number in leukocytes of coho salmon

USGS Publications Warehouse

Maule, Alec G.; Schreck, Carl B.; Sharpe, Cameron

1993-01-01

To determine if there were organ-specific changes in immune responses or immune-endocrine interaction, we monitored in vitro immune response, cortisol sensitivity and number and affinity of glucocorticoid receptors (GR) in leukocytes from freshwater-adapted juvenile coho salmon (Oncorhynchus kisutch) during the physiological changes that prepare them to enter the marine environment. During this period, absolute immune response declined, but splenic leukocytes generated more antibody-producing cells than did cells from anterior kidney. Splenic leukocytes were initially more sensitive to the suppressive effects of cortisol and had fewer GR than leukocytes from the anterior kidney. Leukocytes from the anterior kidney were initially insensitive to cortisol but developed sensitivity at about the same time as the dissociation constant and number of GR increased. In vitro incubation of anterior kidney leukocytes in cortisol altered GR variables when experiments were conducted during March through September but not during November through February. In some years, changes in GR or immune responses were correlated with plasma cortisol titers, but in other years there was no correlation. Thus, the exact relation between cortisol, GR and immune response in anadromous salmonids is unclear and other factors are involved.

Why do human B cells secrete granzyme B? Insights into a novel B-cell differentiation pathway.

PubMed

Hagn, Magdalena; Jahrsdörfer, Bernd

2012-11-01

B cells are generally believed to operate as producers of high affinity antibodies to defend the body against microorganisms, whereas cellular cytotoxicity is considered as an exclusive prerogative of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). In conflict with this dogma, recent studies have demonstrated that the combination of interleukin-21 (IL-21) and B-cell receptor (BCR) stimulation enables B cells to produce and secrete the active form of the cytotoxic serine protease granzyme B (GrB). Although the production of GrB by B cells is not accompanied by that of perforin as in the case of many other GrB-secreting cells, recent findings suggest GrB secretion by B cells may play a significant role in early antiviral immune responses, in the regulation of autoimmune responses, and in cancer immunosurveillance. Here, we discuss in detail how GrB-secreting B cells may influence a variety of immune processes. A better understanding of the role that GrB-secreting B cells are playing in the immune system may allow for the development and improvement of novel immunotherapeutic approaches against infectious, autoimmune and malignant diseases.

Master curve characterization of the fracture toughness behavior in SA508 Gr.4N low alloy steels

NASA Astrophysics Data System (ADS)

Lee, Ki-Hyoung; Kim, Min-Chul; Lee, Bong-Sang; Wee, Dang-Moon

2010-08-01

The fracture toughness properties of the tempered martensitic SA508 Gr.4N Ni-Mo-Cr low alloy steel for reactor pressure vessels were investigated by using the master curve concept. These results were compared to those of the bainitic SA508 Gr.3 Mn-Mo-Ni low alloy steel, which is a commercial RPV material. The fracture toughness tests were conducted by 3-point bending with pre-cracked charpy (PCVN) specimens according to the ASTM E1921-09c standard method. The temperature dependency of the fracture toughness was steeper than those predicted by the standard master curve, while the bainitic SA508 Gr.3 steel fitted well with the standard prediction. In order to properly evaluate the fracture toughness of the Gr.4N steels, the exponential coefficient of the master curve equation was changed and the modified curve was applied to the fracture toughness test results of model alloys that have various chemical compositions. It was found that the modified curve provided a better description for the overall fracture toughness behavior and adequate T0 determination for the tempered martensitic SA508 Gr.4N steels.

Geophysical data analysis and visualization using the Grid Analysis and Display System

NASA Technical Reports Server (NTRS)

Doty, Brian E.; Kinter, James L., III

1995-01-01

Several problems posed by the rapidly growing volume of geophysical data are described, and a selected set of existing solutions to these problems is outlined. A recently developed desktop software tool called the Grid Analysis and Display System (GrADS) is presented. The GrADS' user interface is a natural extension of the standard procedures scientists apply to their geophysical data analysis problems. The basic GrADS operations have defaults that naturally map to data analysis actions, and there is a programmable interface for customizing data access and manipulation. The fundamental concept of the GrADS' dimension environment, which defines both the space in which the geophysical data reside and the 'slice' of data which is being analyzed at a given time, is expressed The GrADS' data storage and access model is described. An argument is made in favor of describable data formats rather than standard data formats. The manner in which GrADS users may perform operations on their data and display the results is also described. It is argued that two-dimensional graphics provides a powerful quantitative data analysis tool whose value is underestimated in the current development environment which emphasizes three dimensional structure modeling.

In vitro effect of adenosine agonist GR79236 on the insulin sensitivity of glucose utilisation in rat soleus and human rectus abdominus muscle.

PubMed

Webster, J M; Heseltine, L; Taylor, R

1996-06-07

The dose-response effects of a new adenosine agonist, GR79236, were examined in isolated rat soleus muscle strips and human rectus abdominus muscle strips. Effects on the insulin sensitivity of carbohydrate metabolism were examined, in particular upon insulin stimulated glycogen synthesis and glycolytic flux. In the presence of adenosine deaminase (ADA), GR79236 increased insulin sensitivity of pyruvate release from rat soleus muscle strips by 24% from 82.5 +/- 10.0 to 102.5 +/- 10.0 (P < 0.01), by 27% to 105.0 +/- 12.5 (P < 0.01) and by 24% to 102.5 +/- 10.0 (P < 0.01) nmol/25 mg per h at 0.1 and 10 microM GR79236, respectively. Rates of lactate release followed a similar but non-significant trend. Addition of GR79236 in the presence of ADA had no effect on rates of glycogen synthesis. Insulin stimulated rates of pyruvate or lactate release or of glycogen synthesis were unaffected by the addition of adenosine deaminase or GR79236 in human rectus abdominus muscle strips. Adenosine agonists may act indirectly to modulate insulin sensitivity of carbohydrate metabolism.

Tuning near-gap electronic structure, interface charge transfer and visible light response of hybrid doped graphene and Ag3PO4 composite: Dopant effects

PubMed Central

He, Chao-Ni; Huang, Wei-Qing; Xu, Liang; Yang, Yin-Cai; Zhou, Bing-Xin; Huang, Gui-Fang; Peng, P.; Liu, Wu-Ming

2016-01-01

The enhanced photocatalytic performance of doped graphene (GR)/semiconductor nanocomposites have recently been widely observed, but an understanding of the underlying mechanisms behind it is still out of reach. As a model system to study the dopant effects, we investigate the electronic structures and optical properties of doped GR/Ag3PO4 nanocomposites using the first-principles calculations, demonstrating that the band gap, near-gap electronic structure and interface charge transfer of the doped GR/Ag3PO4(100) composite can be tuned by the dopants. Interestingly, the doping atom and C atoms bonded to dopant become active sites for photocatalysis because they are positively or negatively charged due to the charge redistribution caused by interaction. The dopants can enhance the visible light absorption and photoinduced electron transfer. We propose that the N atom may be one of the most appropriate dopants for the GR/Ag3PO4 photocatalyst. This work can rationalize the available experimental results about N-doped GR-semiconductor composites, and enriches our understanding on the dopant effects in the doped GR-based composites for developing high-performance photocatalysts. PMID:26923338

Mis-modelling in Gravitational Wave Astronomy: The Trouble with Templates

NASA Astrophysics Data System (ADS)

Sampson, Laura; Cornish, Neil; Yunes, Nicolas

2014-03-01

Waveform templates are a powerful tool for extracting and characterizing gravitational wave signals. There are, however, attendant dangers in using these highly restrictive signal priors. If strong field gravity is not accurately described by General Relativity (GR), then using GR templates may result in fundamental bias in the recovered parameters, or worse - a complete failure to detect signals. Here we study such dangers, concentrating on three distinct possibilities. First, we show that there exist modified theories compatible with all existing tests that would fail to be detected by the LIGO/Virgo network using searches based on GR templates, but which would be detected using a one parameter post-Einsteinian extension. Second, we study modified theories that produce departures from GR that do not naively fit into the simplest parameterized post-Einsteinian (ppE) scheme. We show that even the simplest ppE templates are still capable of picking up these strange signals and diagnosing a departure from GR. Third, we study how using inspiral-only ppE waveforms for signals that include merger and ringdown can lead to problems in misidentifying a GR departure. We present an easy technique that allows us to self-consistently identify the inspiral portion of the signal.

Numerical binary black hole mergers in dynamical Chern-Simons gravity: Scalar field

NASA Astrophysics Data System (ADS)

Okounkova, Maria; Stein, Leo C.; Scheel, Mark A.; Hemberger, Daniel A.

2017-08-01

Testing general relativity in the nonlinear, dynamical, strong-field regime of gravity is one of the major goals of gravitational wave astrophysics. Performing precision tests of general relativity (GR) requires numerical inspiral, merger, and ringdown waveforms for binary black hole (BBH) systems in theories beyond GR. Currently, GR and scalar-tensor gravity are the only theories amenable to numerical simulations. In this article, we present a well-posed perturbation scheme for numerically integrating beyond-GR theories that have a continuous limit to GR. We demonstrate this scheme by simulating BBH mergers in dynamical Chern-Simons gravity (dCS), to linear order in the perturbation parameter. We present mode waveforms and energy fluxes of the dCS pseudoscalar field from our numerical simulations. We find good agreement with analytic predictions at early times, including the absence of pseudoscalar dipole radiation. We discover new phenomenology only accessible through numerics: a burst of dipole radiation during merger. We also quantify the self-consistency of the perturbation scheme. Finally, we estimate bounds that GR-consistent LIGO detections could place on the new dCS length scale, approximately ℓ≲O (10 ) km .

Graphene and CdS nanocomposite: a facile interface for construction of DNA-based electrochemical biosensor and its application to the determination of phenformin.

PubMed

Zeng, Lijiao; Wang, Rui; Zhu, Lihua; Zhang, Jingdong

2013-10-01

Graphene/cadmium sulphide (GR-CdS) nanocomposite was synthesized via a low temperature process in aqueous solution. The as-prepared nanocomposite was characterized by scanning electron microscopy, UV-visible spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. The impedance analysis indicated that GR-CdS nanocomposite possessed outstanding electrochemical performance for facile electron transfer. When DNA was immobilized on GR-CdS (DNA/GR-CdS) modified electrode, the electrochemical oxidation of guanine and adenine in DNA residue bases was significantly promoted. Due to the interaction of DNA with phenformin, the voltammetric current of guanine or adenine on the DNA/GR-CdS electrode was decreased when phenformin was present in the electrolytic solution. Under optimized conditions, the signal of guanine on DNA/GR-CdS electrode decreased linearly with increasing the concentration of phenformin in the range of 1.0×10(-6)molL(-1) to 1.0×10(-3)molL(-1). The proposed DNA-based electrochemical biosensor was successfully applied to the determination of phenformin in real samples. Copyright © 2013 Elsevier B.V. All rights reserved.

Germline replacement by blastula cell transplantation in the fish medaka.

PubMed

Li, Mingyou; Hong, Ni; Xu, Hongyan; Song, Jianxing; Hong, Yunhan

2016-07-13

Primordial germ cell (PGC) specification early in development establishes the germline for reproduction and reproductive technologies. Germline replacement (GR) is a powerful tool for conservation of valuable or endangered animals. GR is achievable by germ cell transplantation into the PGC migration pathway or gonads. Blastula cell transplantation (BCT) can also lead to the chimeric germline containing PGCs of both donor and host origins. It has remained largely unknown whether BCT is able to achieve GR at a high efficiency. Here we report efficient GR by BCT into blastula embryos in the fish medaka (Oryzias latipes). Specifically, dnd depletion completely ablated host PGCs and fertility, and dnd overexpression remarkably boosted PGCs in donor blastulae. BCT between normal donor and host produced a germline transmission rate of ~4%. This rate was enhanced up to ~30% upon PGC boosting in donors. Most importantly, BCT between PGC-boosted donors and PGC-ablated hosts led to more than 90% fertility restoration and 100% GR. Therefore, BCT features an extremely high efficiency of fertility recovery and GR in medaka. This finding makes medaka an ideal model to analyze genetic and physiological donor-host compatibilities for BCT-mediated surrogate production and propagation of endangered lower vertebrates and biodiversity.

Germline replacement by blastula cell transplantation in the fish medaka

PubMed Central

Li, Mingyou; Hong, Ni; Xu, Hongyan; Song, Jianxing; Hong, Yunhan

2016-01-01

Primordial germ cell (PGC) specification early in development establishes the germline for reproduction and reproductive technologies. Germline replacement (GR) is a powerful tool for conservation of valuable or endangered animals. GR is achievable by germ cell transplantation into the PGC migration pathway or gonads. Blastula cell transplantation (BCT) can also lead to the chimeric germline containing PGCs of both donor and host origins. It has remained largely unknown whether BCT is able to achieve GR at a high efficiency. Here we report efficient GR by BCT into blastula embryos in the fish medaka (Oryzias latipes). Specifically, dnd depletion completely ablated host PGCs and fertility, and dnd overexpression remarkably boosted PGCs in donor blastulae. BCT between normal donor and host produced a germline transmission rate of ~4%. This rate was enhanced up to ~30% upon PGC boosting in donors. Most importantly, BCT between PGC-boosted donors and PGC-ablated hosts led to more than 90% fertility restoration and 100% GR. Therefore, BCT features an extremely high efficiency of fertility recovery and GR in medaka. This finding makes medaka an ideal model to analyze genetic and physiological donor-host compatibilities for BCT-mediated surrogate production and propagation of endangered lower vertebrates and biodiversity. PMID:27406328

Electronic states of aryl radical functionalized graphenes: Density functional theory study

NASA Astrophysics Data System (ADS)

Tachikawa, Hiroto; Kawabata, Hiroshi

2016-06-01

Functionalized graphenes are known as a high-performance molecular device. In the present study, the structures and electronic states of the aryl radical functionalized graphene have been investigated by the density functional theory (DFT) method to elucidate the effects of functionalization on the electronic states of graphene (GR). Also, the mechanism of aryl radical reaction with GR was investigated. The benzene, biphenyl, p-terphenyl, and p-quaterphenyl radicals [denoted by (Bz) n (n = 1-4), where n means numbers of benzene rings in aryl radical] were examined as aryl radicals. The DFT calculation of GR-(Bz) n (n = 1-4) showed that the aryl radical binds to the carbon atom of GR, and a C-C single bond was formed. The binding energies of aryl radicals to GR were calculated to be ca. 6.0 kcal mol-1 at the CAM-B3LYP/6-311G(d,p) level. It was found that the activation barrier exists in the aryl radical addition: the barrier heights were calculated to be 10.0 kcal mol-1. The electronic states of GR-(Bz) n were examined on the basis of theoretical results.

The role of the substrate in Graphene/Silicon photodiodes

NASA Astrophysics Data System (ADS)

Luongo, G.; Giubileo, F.; Iemmo, L.; Di Bartolomeo, A.

2018-01-01

The Graphene/Silicon (Gr/Si) junction can function as a Schottky diode with performances strictly related to the quality of the interface. Here, we focus on the substrate geometry and on its effects on Gr/Si junction physics. We fabricate and study the electrical and optical behaviour of two types of devices: one made of a Gr/Si planar junction, the second realized with graphene on an array of Si nanotips. We show that the Gr/Si flat device exhibits a reverse photocurrent higher than the forward current and achieves a photoresponsivity of 2.5 A/W. The high photoresponse is due to the charges photogenerated in Si below a parasitic graphene/SiO2/Si structure, which are injected into the Gr/Si junction region. The other device with graphene on Si-tips displays a reverse current that grows exponentially with the bias. We explain this behaviour by taking into account the tip geometry of the substrate, which magnifies the electric field and shifts the Fermi level of graphene, thus enabling fine-tuning of the Schottky barrier height. The Gr/Si-tip device achieves a higher photoresponsivity, up to 3 A/W, likely due to photocharge internal multiplication.

Temporal variability of glucocorticoid receptor activity is functionally important for the therapeutic action of fluoxetine in the hippocampus.

PubMed

Lee, M-S; Kim, Y-H; Park, W-S; Park, O-K; Kwon, S-H; Hong, K S; Rhim, H; Shim, I; Morita, K; Wong, D L; Patel, P D; Lyons, D M; Schatzberg, A F; Her, S

2016-02-01

Previous studies have shown inconsistent results regarding the actions of antidepressants on glucocorticoid receptor (GR) signalling. To resolve these inconsistencies, we used a lentiviral-based reporter system to directly monitor rat hippocampal GR activity during stress adaptation. Temporal GR activation was induced significantly by acute stress, as demonstrated by an increase in the intra-individual variability of the acute stress group compared with the variability of the non-stress group. However, the increased intra-individual variability was dampened by exposure to chronic stress, which was partly restored by fluoxetine treatment without affecting glucocorticoid secretion. Immobility in the forced-swim test was negatively correlated with the intra-individual variability, but was not correlated with the quantitative GR activity during fluoxetine therapy; this highlights the temporal variability in the neurobiological links between GR signalling and the therapeutic action of fluoxetine. Furthermore, we demonstrated sequential phosphorylation between GR (S224) and (S232) following fluoxetine treatment, showing a molecular basis for hormone-independent nuclear translocation and transcriptional enhancement. Collectively, these results suggest a neurobiological mechanism by which fluoxetine treatment confers resilience to the chronic stress-mediated attenuation of hypothalamic-pituitary-adrenal axis activity.

Atmospheric river impacts on Greenland Ice Sheet surface melt and mass balance

NASA Astrophysics Data System (ADS)

Mattingly, K.; Mote, T. L.

2017-12-01

Mass loss from the Greenland Ice Sheet (GrIS) has accelerated during the early part of the 21st Century. Several episodes of widespread GrIS melt in recent years have coincided with intense poleward moisture transport by atmospheric rivers (ARs), suggesting that variability in the frequency and intensity of these events may be an important driver of the surface mass balance (SMB) of the GrIS. ARs may contribute to GrIS surface melt through the greenhouse effect of water vapor, the radiative effects of clouds, condensational latent heating within poleward-advected air masses, and the energy provided by liquid precipitation. However, ARs may also provide significant positive contributions to GrIS SMB through enhanced snow accumulation. Prior research on the role of ARs in Arctic climate has consisted of case studies of ARs associated with major GrIS melt events or examined the effects of poleward moisture flux on Arctic sea ice. In this study, a long-term (1979-2016) record of intense moisture transport events affecting Greenland is compiled using a conventional AR identification algorithm as well as a self-organizing map (SOM) classification applied to integrated water vapor transport (IVT) data from several atmospheric reanalysis datasets. An analysis of AR effects on GrIS melt and SMB is then performed with GrIS surface melt data from passive microwave satellite observations and the Modèle Atmosphérique Régional (MAR) regional climate model. Results show that meltwater production is above normal during and after AR impact days throughout the GrIS during all seasons, with surface melt enhanced most by strong (> 85th percentile IVT) and extreme (> 95th percentile IVT) ARs. This relationship holds at the seasonal scale, as the total amount of water vapor transported to the GrIS by ARs is significantly greater during above-normal melt seasons. ARs exert a more complex influence on SMB. Normal (< 85th percentile IVT) ARs generally do not have a substantial impact on SMB, while strong and extreme ARs result in reduced SMB in the ablation zone for several days following the event during summer. Conversely, strong and extreme ARs increased SMB in the ablation zone during spring, autumn, and winter, and AR impacts on SMB are positive in the accumulation zone during all seasons.

Expression map of a complete set of gustatory receptor genes in chemosensory organs of Bombyx mori.

PubMed

Guo, Huizhen; Cheng, Tingcai; Chen, Zhiwei; Jiang, Liang; Guo, Youbing; Liu, Jianqiu; Li, Shenglong; Taniai, Kiyoko; Asaoka, Kiyoshi; Kadono-Okuda, Keiko; Arunkumar, Kallare P; Wu, Jiaqi; Kishino, Hirohisa; Zhang, Huijie; Seth, Rakesh K; Gopinathan, Karumathil P; Montagné, Nicolas; Jacquin-Joly, Emmanuelle; Goldsmith, Marian R; Xia, Qingyou; Mita, Kazuei

2017-03-01

Most lepidopteran species are herbivores, and interaction with host plants affects their gene expression and behavior as well as their genome evolution. Gustatory receptors (Grs) are expected to mediate host plant selection, feeding, oviposition and courtship behavior. However, due to their high diversity, sequence divergence and extremely low level of expression it has been difficult to identify precisely a complete set of Grs in Lepidoptera. By manual annotation and BAC sequencing, we improved annotation of 43 gene sequences compared with previously reported Grs in the most studied lepidopteran model, the silkworm, Bombyx mori, and identified 7 new tandem copies of BmGr30 on chromosome 7, bringing the total number of BmGrs to 76. Among these, we mapped 68 genes to chromosomes in a newly constructed chromosome distribution map and 8 genes to scaffolds; we also found new evidence for large clusters of BmGrs, especially from the bitter receptor family. RNA-seq analysis of diverse BmGr expression patterns in chemosensory organs of larvae and adults enabled us to draw a precise organ specific map of BmGr expression. Interestingly, most of the clustered genes were expressed in the same tissues and more than half of the genes were expressed in larval maxillae, larval thoracic legs and adult legs. For example, BmGr63 showed high expression levels in all organs in both larval and adult stages. By contrast, some genes showed expression limited to specific developmental stages or organs and tissues. BmGr19 was highly expressed in larval chemosensory organs (especially antennae and thoracic legs), the single exon genes BmGr53 and BmGr67 were expressed exclusively in larval tissues, the BmGr27-BmGr31 gene cluster on chr7 displayed a high expression level limited to adult legs and the candidate CO 2 receptor BmGr2 was highly expressed in adult antennae, where few other Grs were expressed. Transcriptional analysis of the Grs in B. mori provides a valuable new reference for finding genes involved in plant-insect interactions in Lepidoptera and establishing correlations between these genes and vital insect behaviors like host plant selection and courtship for mating. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Glycaemic responses to liquid food supplements among three Asian ethnic groups.

PubMed

Tey, Siew Ling; Van Helvoort, Ardy; Henry, Christiani Jeyakumar

2016-12-01

A limited number of studies have compared the glycaemic index (GI) and glycaemic responses (GR) to solid foods between Caucasians and Asians. These studies have demonstrated that Asians have greater GI and GR values for solid foods than Caucasians. However, no study has compared the GI and GR to liquids among various Asian ethnic groups. A total of forty-eight males and females (16 Chinese, 16 Indians, and 16 Malay) took part in this randomised, crossover study. Glycaemic response to the reference food (glucose beverage) was measured on three occasions, and GR to three liquids were measured on one occasion each. Liquids with different macronutrient ratio's and carbohydrate types were chosen to be able to evaluate the response to products with different GIs. Blood glucose concentrations were measured in duplicate at baseline (-5 and 0 min) and once at 15, 30, 45, 60, 90, and 120 min after the commencement of beverage consumption. There were statistically significant differences in GI and GR between the three liquids (P < 0.01 in all cases). However, there were no statistically significant differences in GI and GR for the liquids between the ethnic groups (Chinese vs. Indian vs. Malay). The GR for three different types of liquid nutritional supplements did not differ between the three main ethnic groups in Asia. It appears that the GI of liquid food derived from one Asian ethnicity can be applicable to other Asian populations.

An energy dependent earthquake frequency-magnitude distribution

NASA Astrophysics Data System (ADS)

Spassiani, I.; Marzocchi, W.

2017-12-01

The most popular description of the frequency-magnitude distribution of seismic events is the exponential Gutenberg-Richter (G-R) law, which is widely used in earthquake forecasting and seismic hazard models. Although it has been experimentally well validated in many catalogs worldwide, it is not yet clear at which space-time scales the G-R law still holds. For instance, in a small area where a large earthquake has just happened, the probability that another very large earthquake nucleates in a short time window should diminish because it takes time to recover the same level of elastic energy just released. In short, the frequency-magnitude distribution before and after a large earthquake in a small area should be different because of the different amount of available energy.Our study is then aimed to explore a possible modification of the classical G-R distribution by including the dependence on an energy parameter. In a nutshell, this more general version of the G-R law should be such that a higher release of energy corresponds to a lower probability of strong aftershocks. In addition, this new frequency-magnitude distribution has to satisfy an invariance condition: when integrating over large areas, that is when integrating over infinite energy available, the G-R law must be recovered.Finally we apply a proposed generalization of the G-R law to different seismic catalogs to show how it works and the differences with the classical G-R law.

Simple preparation and highly selective detection of silver ions using an electrochemical sensor based on sulfur-doped graphene and a 3,3',5,5'-tetramethylbenzidine composite modified electrode.

PubMed

Fu, Yang; Yang, Yajie; Tuersun, Tayierjiang; Yu, Yuan; Zhi, Jinfang

2018-04-30

A novel electrochemical sensor based on sulfur (S)-doped graphene (S-Gr) and a 3,3',5,5'-tetramethylbenzidine (TMB) composite (S-Gr-TMB) modified glassy carbon (GCE) electrode for highly selective quantitative detection of silver ions (Ag+) were fabricated. The S-Gr-TMB composite was first prepared via electrostatic interaction between TMB and S-Gr and then, the composite was coated on the surface of GCE. The resultant S-Gr-TMB/GCE electrode showed a significant voltammetric response to Ag+ at 0.3 V vs. Ag/AgCl due to the synergistic effect of S-Gr and TMB. The sensor showed good linearity from 50 μM to 400 μM with a detection limit of 2.15 μM towards the determination of Ag+. In addition, after the addition of Fe3+ and other metal ions, including Al3+, Ca2+, Cd2+, Co2+, Cu2+, K+, Mg2+, Na+, Ni2+, Pb2+ and Zn2+, in the same concentration, the current signal remained almost unchanged, revealing that the proposed electrochemical sensor exhibited a high selectivity for Ag+, which solves the nonselective problem of TMB as a spectral probe. This enhanced detection performance is attributed to two factors: (1) S-Gr has excellent electrical conductivity; (2) the coupling interactions between Ag-S are speculated to result in strengthened enrichment for Ag and good selective performance.

A minichaperone-based fusion system for producing insoluble proteins in soluble stable forms.

PubMed

Sharapova, Olga A; Yurkova, Maria S; Fedorov, Alexey N

2016-02-01

We have developed a fusion system for reliable production of insoluble hydrophobic proteins in soluble stable forms. A carrier is thermophilic minichaperone, GroEL apical domain (GrAD), a 15 kDa monomer able to bind diverse protein substrates. The Met-less variant of GrAD has been made for further convenient use of Met-specific CNBr chemical cleavage, if desired. The Met-less GrAD retained stability and solubility of the original protein. Target polypeptides can be fused to either C-terminus or N-terminus of GrAD. The system has been tested with two unrelated insoluble proteins fused to the C-terminus of GrAD. One of the proteins was also fused to GrAD N-terminus. The fusions formed inclusion bodies at 25°C and above and were partly soluble only at lower expression temperatures. Most importantly, however, after denaturation in urea, all fusions without exception were completely renatured in soluble stable forms that safely survived freezing-thawing as well as lyophilization. All fusions for both tested target proteins retained solubility at high concentrations for days. Functional analysis revealed that a target protein may retain functionality in the fusion. Convenience features include potential thermostability of GrAD fusions, capacity for chemical and enzymatic cleavage of a target and His6 tag for purification. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

CCR2-dependent Gr1high monocytes promote kidney injury in shiga toxin-induced hemolytic uremic syndrome in mice.

PubMed

Pohl, Judith-Mira; Volke, Julia K; Thiebes, Stephanie; Brenzel, Alexandra; Fuchs, Kerstin; Beziere, Nicolas; Ehrlichmann, Walter; Pichler, Bernd J; Squire, Anthony; Gueler, Faikah; Engel, Daniel R

2018-06-01

The hemolytic uremic syndrome (HUS) is a life-threatening disease of the kidney that is induced by shiga toxin-producing E.coli. Major changes in the monocytic compartment and in CCR2-binding chemokines have been observed. However, the specific contribution of CCR2-dependent Gr1 high monocytes is unknown. To investigate the impact of these monocytes during HUS, we injected a combination of LPS and shiga toxin into mice. We observed an impaired kidney function and elevated levels of the CCR2-binding chemokine CCL2 after shiga toxin/LPS- injection, thus suggesting Gr1 high monocyte infiltration into the kidney. Indeed, the number of Gr1 high monocytes was strongly increased one day after HUS induction. Moreover, these cells expressed high levels of CD11b suggesting activation after tissue entry. Non-invasive PET-MR imaging revealed kidney injury mainly in the kidney cortex and this damage coincided with the detection of Gr1 high monocytes. Lack of Gr1 high monocytes in Ccr2-deficient animals reduced neutrophil gelatinase-associated lipocalin and blood urea nitrogen levels. Moreover, the survival of Ccr2-deficient animals was significantly improved. Conclusively, this study demonstrates that CCR2-dependent Gr1 high monocytes contribute to the kidney injury during HUS and targeting these cells is beneficial during this disease. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel functions of prototype foamy virus Gag glycine- arginine-rich boxes in reverse transcription and particle morphogenesis.

PubMed

Müllers, Erik; Uhlig, Tobias; Stirnnagel, Kristin; Fiebig, Uwe; Zentgraf, Hanswalter; Lindemann, Dirk

2011-02-01

Prototype foamy virus (PFV) Gag lacks the characteristic orthoretroviral Cys-His motifs that are essential for various steps of the orthoretroviral replication cycle, such as RNA packaging, reverse transcription, infectivity, integration, and viral assembly. Instead, it contains three glycine-arginine-rich boxes (GR boxes) in its C terminus that putatively represent a functional equivalent. We used a four-plasmid replication-deficient PFV vector system, with uncoupled RNA genome packaging and structural protein translation, to analyze the effects of deletion and various substitution mutations within each GR box on particle release, particle-associated protein composition, RNA packaging, DNA content, infectivity, particle morphology, and intracellular localization. The degree of viral particle release by all mutants was similar to that of the wild type. Only minimal effects on Pol encapsidation, exogenous reverse transcriptase (RT) activity, and genomic viral RNA packaging were observed. In contrast, particle-associated DNA content and infectivity were drastically reduced for all deletion mutants and were undetectable for all alanine substitution mutants. Furthermore, GR box I mutants had significant changes in particle morphology, and GR box II mutants lacked the typical nuclear localization pattern of PFV Gag. Finally, it could be shown that GR boxes I and III, but not GR box II, can functionally complement each other. It therefore appears that, similar to the orthoretroviral Cys-His motifs, the PFV Gag GR boxes are important for RNA encapsidation, genome reverse transcription, and virion infectivity as well as for particle morphogenesis.

General Relativity solutions in modified gravity

NASA Astrophysics Data System (ADS)

Motohashi, Hayato; Minamitsuji, Masato

2018-06-01

Recent gravitational wave observations of binary black hole mergers and a binary neutron star merger by LIGO and Virgo Collaborations associated with its optical counterpart constrain deviation from General Relativity (GR) both on strong-field regime and cosmological scales with high accuracy, and further strong constraints are expected by near-future observations. Thus, it is important to identify theories of modified gravity that intrinsically possess the same solutions as in GR among a huge number of theories. We clarify the three conditions for theories of modified gravity to allow GR solutions, i.e., solutions with the metric satisfying the Einstein equations in GR and the constant profile of the scalar fields. Our analysis is quite general, as it applies a wide class of single-/multi-field scalar-tensor theories of modified gravity in the presence of matter component, and any spacetime geometry including cosmological background as well as spacetime around black hole and neutron star, for the latter of which these conditions provide a necessary condition for no-hair theorem. The three conditions will be useful for further constraints on modified gravity theories as they classify general theories of modified gravity into three classes, each of which possesses i) unique GR solutions (i.e., no-hair cases), ii) only hairy solutions (except the cases that GR solutions are realized by cancellation between singular coupling functions in the Euler-Lagrange equations), and iii) both GR and hairy solutions, for the last of which one of the two solutions may be selected dynamically.

U(VI) Reduction by Biogenic and Abiotic Hydroxycarbonate Green Rusts: Impacts on U(IV) Speciation and Stability Over Time

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yan, Sen; Boyanov, Maxim I.; Mishra, Bhoopesh

Green rusts (GRs) are redox active Fe II-Fe III minerals that form in the environment via various biotic and abiotic processes. Although both biogenic (BioGR) and abiotic (ChemGR) GRs have been shown to reduce U VI, the dynamics of the transformations and the speciation and stability of the resulting U IV phases are poorly understood. We used carbonate extraction and XAFS spectroscopy to investigate the products of U VI reduction by BioGR and ChemGR. The results show that both GRs can rapidly remove U VI from synthetic groundwater via reduction to U IV. The initial products in the ChemGR systemmore » are solids-associated U IV-carbonate complexes that gradually transform to nanocrystalline uraninite over time, leading to a decrease in the proportion of carbonate-extractable U from ~95% to ~10%. In contrast, solid-phase U IV atoms in the BioGR system remain relatively extractable, non-uraninite U IV species over the same reaction period. The presence of calcium and carbonate in groundwater significantly increase the extractability of U IV in the BioGR system. Furthermore, these data provide new insights into the transformations of U under anoxic conditions in groundwater that contains calcium and carbonate, and have major implications for predicting uranium stability within redox dynamic environments and designing approaches for the remediation of uranium-contaminated groundwater.« less

U(VI) Reduction by Biogenic and Abiotic Hydroxycarbonate Green Rusts: Impacts on U(IV) Speciation and Stability Over Time

DOE PAGES

Yan, Sen; Boyanov, Maxim I.; Mishra, Bhoopesh; ...

2018-04-09

Green rusts (GRs) are redox active Fe II-Fe III minerals that form in the environment via various biotic and abiotic processes. Although both biogenic (BioGR) and abiotic (ChemGR) GRs have been shown to reduce U VI, the dynamics of the transformations and the speciation and stability of the resulting U IV phases are poorly understood. We used carbonate extraction and XAFS spectroscopy to investigate the products of U VI reduction by BioGR and ChemGR. The results show that both GRs can rapidly remove U VI from synthetic groundwater via reduction to U IV. The initial products in the ChemGR systemmore » are solids-associated U IV-carbonate complexes that gradually transform to nanocrystalline uraninite over time, leading to a decrease in the proportion of carbonate-extractable U from ~95% to ~10%. In contrast, solid-phase U IV atoms in the BioGR system remain relatively extractable, non-uraninite U IV species over the same reaction period. The presence of calcium and carbonate in groundwater significantly increase the extractability of U IV in the BioGR system. Furthermore, these data provide new insights into the transformations of U under anoxic conditions in groundwater that contains calcium and carbonate, and have major implications for predicting uranium stability within redox dynamic environments and designing approaches for the remediation of uranium-contaminated groundwater.« less

Effect of Nano-CuO on Engineering and Microstructure Properties of Fibre-Reinforced Mortars Incorporating Metakaolin: Experimental and Numerical Studies

PubMed Central

Ghanei, Amir; Jafari, Faezeh; Mehrinejad Khotbehsara, Mojdeh; Mohseni, Ehsan; Cui, Hongzhi

2017-01-01

In this study, the effects of nano-CuO (NC) on engineering properties of fibre-reinforced mortars incorporating metakaolin (MK) were investigated. The effects of polypropylene fibre (PP) were also examined. A total of twenty-six mixtures were prepared. The experimental results were compared with numerical results obtained by adaptive neuro-fuzzy inference system (ANFIS) and Primal Estimated sub-GrAdient Solver for SVM (Pegasos) algorithm. Scanning Electron Microscope (SEM) was also employed to investigate the microstructure of the cement matrix. The mechanical test results showed that both compressive and flexural strengths of cement mortars decreased with the increase of MK content, however the strength values increased significantly with increasing NC content in the mixture. The water absorption of samples decreased remarkably with increasing NC particles in the mixture. When PP fibres were added, the strengths of cement mortars were further enhanced accompanied with lower water absorption values. The addition of 2 wt % and 3 wt % nanoparticles in cement mortar led to a positive contribution to strength and resistance to water absorption. Mixture of PP-MK10NC3 indicated the best results for both compressive and flexural strengths at 28 and 90 days. SEM images illustrated that the morphology of cement matrix became more porous with increasing MK content, but the porosity reduced with the inclusion of NC. In addition, it is evident from the SEM images that more cement hydration products adhered onto the surface of fibres, which would improve the fibre–matrix interface. The numerical results obtained by ANFIS and Pegasos were close to the experimental results. The value of R2 obtained for each data set (validate, test and train) was higher than 0.90 and the values of mean absolute percentage error (MAPE) and the relative root mean squared error (PRMSE) were near zero. The ANFIS and Pegasos models can be used to predict the mechanical properties and water absorptions of fibre-reinforced mortars with MK and NC. PMID:29065559

Greenland ice sheet beyond 2100: Simulating its evolution and influence using the coupled climate-ice sheet model EC-Earth - PISM

NASA Astrophysics Data System (ADS)

Yang, S.; Christensen, J. H.; Madsen, M. S.; Ringgaard, I. M.; Petersen, R. A.; Langen, P. P.

2017-12-01

Greenland ice sheet (GrIS) is observed undergoing a rapid change in the recent decades, with an increasing area of surface melting and ablation and a speeding mass loss. Predicting the GrIS changes and their climate consequences relies on the understanding of the interaction of the GrIS with the climate system on both global and local scales, and requires climate model systems incorporating with an explicit and physically consistent ice sheet module. In this work we study the GrIS evolution and its interaction with the climate system using a fully coupled global climate model with a dynamical ice sheet model for the GrIS. The coupled model system, EC-EARTH - PISM, consisting of the atmosphere-ocean-sea ice model system EC-EARTH, and the Parallel Ice Sheet Model (PISM), has been employed for a 1400-year simulation forced by CMIP5 historical forcing from 1850 to 2005 and continued along an extended RCP8.5 scenario with the forcing peaking at 2200 and stabilized hereafter. The simulation reveals that, following the anthropogenic forcing increase, the global mean surface temperature rapidly rises about 10 °C in the 21st and 22nd century. After the forcing stops increasing after 2200, the temperature change slows down and eventually stabilizes at about 12.5 °C above the preindustrial level. In response to the climate warming, the GrIS starts losing mass slowly in the 21st century, but the ice retreat accelerates substantially after 2100 and ice mass loss continues hereafter at a constant rate of approximately 0.5 m sea level rise equivalence per 100 years, even as the warming rate gradually levels off. Ultimately the volume and extent of GrIS reduce to less than half of its preindustrial value. To understand the interaction of GrIS with the climate system, the characteristics of atmospheric and oceanic circulation in the warm climate are analyzed. The circulation patterns associated with the negative surface mass balance that leads to GrIS retreat are investigated. The impact of the simulated surface warming on the ice flow and ice dynamics is explored.

Evaluation of a colorimetric reagent strip assay for urine specific gravity.

PubMed

Kirschbaum, B B

1983-06-01

N-Multistix SG provides a convenient colorimetric assay for the determination of the specific gravity (sp. gr.) of freshly voided urine. When compared with results obtained by standard hydrometry, the colorimetric assay sp. gr. was observed to decrease by as much as 0.010 units as urine pH increased from 5 to 7. Moderate levels of proteinuria that did not alter hydrometer readings effectively raised the colorimetric sp. gr. by 0.005-0.010 units. The colorimetric assay was almost completely insensitive to clinically encountered concentrations of glucose and urea but responded appropriately to monovalent salts. The magnitude of these observed discrepancies places serious limitations on the value of the colorimetric sp. gr. measurement.

Effects of thermal cycling on composite materials for space structures

NASA Technical Reports Server (NTRS)

Tompkins, Stephen S.

1989-01-01

The effects of thermal cycling on the thermal and mechanical properties of composite materials that are candidates for space structures are briefly described. The results from a thermal analysis of the orbiting Space Station Freedom is used to define a typical thermal environment and the parameters that cause changes in the thermal history. The interactions of this environment with composite materials are shown and described. The effects of this interaction on the integrity as well as the properties of GR/thermoset, Gr/thermoplastic, Gr/metal and Gr/glass composite materials are discussed. Emphasis is placed on the effects of the interaction that are critical to precision spacecraft. Finally, ground test methodology are briefly discussed.

A fructose receptor functions as a nutrient sensor in the Drosophila brain

PubMed Central

Miyamoto, Tetsuya; Slone, Jesse; Song, Xiangyu; Amrein, Hubert

2012-01-01

SUMMARY Internal nutrient sensors play important roles in feeding behavior, yet their molecular structure and mechanism of action are poorly understood. Using Ca2+ imaging and behavioral assays, we show that the Gustatory Receptor 43a functions as a narrowly tuned fructose receptor in taste neurons. Remarkably, GR43a also functions as a fructose receptor in the brain. Interestingly, hemolymph fructose levels are tightly linked to feeding status: after nutritious carbohydrate consumption, fructose levels rise several fold and reach a concentration sufficient to activate GR43a in the brain. By using different feeding paradigms and artificial activation of Gr43a-expressing brain neurons, we show that GR43a is both necessary and sufficient to sense hemolymph fructose and promote feeding in hungry flies, but suppress feeding in satiated flies. Thus, our studies indicate that the Gr43a-expressing brain neurons function as a nutrient sensor for hemolymph fructose and assign opposing valence to feeding experiences in a satiation-dependent manner. PMID:23178127

NRIP enhances HPV gene expression via interaction with either GR or E2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Szu-Wei; Lu, Pei-Yu; Guo, Jih-Huong

We previously identified a gene, nuclear receptor-interaction protein (NRIP), which functions as a transcription cofactor in glucocorticoid receptor (GR) and human papillomavirus E2 (HPV E2)-driven gene expression. Here, we comprehensively evaluated the role of NRIP in HPV-16 gene expression. NRIP acts as a transcription cofactor to enhance GR-regulated HPV-16 gene expression in the presence of hormone. NRIP also can form complex with E2 that caused NRIP-induced HPV gene expression via E2-binding sites in a hormone-independent manner. Furthermore, NRIP can associate with GR and E2 to form tri-protein complex to activate HPV gene expression via GRE, not the E2-binding site, inmore » a hormone-dependent manner. These results indicate that NRIP and GR are viral E2-binding proteins and that NRIP regulates HPV gene expression via GRE and/or E2 binding site in the HPV promoter in a hormone-dependent or independent manner, respectively.« less

Adjuvant treatment or primary topical monotherapy for ocular surface squamous neoplasia: a systematic review.

PubMed

Viani, Gustavo Arruda; Fendi, Ligia Issa de

2017-01-01

In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN). The findings were: (i) adjuvant 5-fluorouracil (5-FU) reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR) A]. (ii) Primary topical mitomycin (MMC) produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A). (iii) Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B). (iv) Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C). (v) Primary topical 5-FU versus MMC versus interferon (IFN) showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C).

Peroxisome proliferator-activated receptor {alpha} agonist-induced down-regulation of hepatic glucocorticoid receptor expression in SD rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Xiang; Li Ming; Sun Weiping

2008-04-18

It was reported that glucocorticoid production was inhibited by fenofibrate through suppression of type-1 11{beta}-hydroxysteroid dehydrogenase gene expression in liver. The inhibition might be a negative-feedback regulation of glucocorticoid receptor (GR) activity by peroxisome proliferator-activated receptor alpha (PPAR{alpha}), which is quickly induced by glucocorticoid in the liver. However, it is not clear if GR expression is changed by fenofibrate-induced PPAR{alpha} activation. In this study, we tested this possibility in the liver of Sprague-Dawley rats. GR expression was reduced by fenofibrate in a time- and does-dependent manner. The inhibition was observed in liver, but not in fat and muscle. The corticosteronemore » level in the blood was increased significantly by fenofibrate. These effects of fenofibrate were abolished by PPAR{alpha} inhibitor MK886, suggesting that fenofibrate activated through PPAR{alpha}. In conclusion, inhibition of GR expression may represent a new molecular mechanism for the negative feedback regulation of GR activity by PPAR{alpha}.« less

Functional characterization of PhGR and PhGRL1 during flower senescence in the petunia.

PubMed

Yang, Weiyuan; Liu, Juanxu; Tan, Yinyan; Zhong, Shan; Tang, Na; Chen, Guoju; Yu, Yixun

2015-09-01

Petunia PhGRL1 suppression accelerated flower senescence and increased the expression of the genes downstream of ethylene signaling, whereas PhGR suppression did not. Ethylene plays an important role in flowers senescence. Homologous proteins Green-Ripe and Reversion to Ethylene sensitivity1 are positive regulators of ethylene responses in tomato and Arabidopsis, respectively. The petunia flower has served as a model for the study of ethylene response during senescence. In this study, petunia PhGR and PhGRL1 expression was analyzed in different organs, throughout floral senescence, and after exogenous ethylene treatment; and the roles of PhGR and PhGRL1 during petunia flower senescence were investigated. PhGRL1 suppression mediated by virus-induced gene silencing accelerated flower senescence and increased ethylene production; however, the suppression of PhGR did not. Taken together, these data suggest that PhGRL1 is involved in negative regulation of flower senescence, possibly via ethylene production inhibition and consequently reduced ethylene signaling activation.

How glucocorticoid receptors modulate the activity of other transcription factors: a scope beyond tethering.

PubMed

Ratman, Dariusz; Vanden Berghe, Wim; Dejager, Lien; Libert, Claude; Tavernier, Jan; Beck, Ilse M; De Bosscher, Karolien

2013-11-05

The activity of the glucocorticoid receptor (GR), a nuclear receptor transcription factor belonging to subclass 3C of the steroid/thyroid hormone receptor superfamily, is typically triggered by glucocorticoid hormones. Apart from driving gene transcription via binding onto glucocorticoid response elements in regulatory regions of particular target genes, GR can also inhibit gene expression via transrepression, a mechanism largely based on protein:protein interactions. Hereby GR can influence the activity of other transcription factors, without contacting DNA itself. GR is known to inhibit the activity of a growing list of immune-regulating transcription factors. Hence, GCs still rule the clinic for treatments of inflammatory disorders, notwithstanding concomitant deleterious side effects. Although patience is a virtue when it comes to deciphering the many mechanisms GR uses to influence various signaling pathways, the current review is testimony of the fact that groundbreaking mechanistic work has been accumulating over the past years and steadily continues to grow. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Genesis analysis of high-gamma ray sandstone reservoir and its log evaluation techniques: a case study from the Junggar basin, northwest China.

PubMed

Wang, Liang; Mao, Zhiqiang; Sun, Zhongchun; Luo, Xingping; Song, Yong; Liu, Zhen

2013-01-01

In the Junggar basin, northwest China, many high gamma-ray (GR) sandstone reservoirs are found and routinely interpreted as mudstone non-reservoirs, with negative implications for the exploration and exploitation of oil and gas. Then, the high GR sandstone reservoirs' recognition principles, genesis, and log evaluation techniques are systematically studied. Studies show that the sandstone reservoirs with apparent shale content greater than 50% and GR value higher than 110API can be regarded as high GR sandstone reservoir. The high GR sandstone reservoir is mainly and directly caused by abnormally high uranium enrichment, but not the tuff, feldspar or clay mineral. Affected by formation's high water sensitivity and poor borehole quality, the conventional logs can not recognize reservoir and evaluate the physical property of reservoirs. Then, the nuclear magnetic resonance (NMR) logs is proposed and proved to be useful in reservoir recognition and physical property evaluation.

Genesis Analysis of High-Gamma Ray Sandstone Reservoir and Its Log Evaluation Techniques: A Case Study from the Junggar Basin, Northwest China

PubMed Central

Wang, Liang; Mao, Zhiqiang; Sun, Zhongchun; Luo, Xingping; Song, Yong; Liu, Zhen

2013-01-01

In the Junggar basin, northwest China, many high gamma-ray (GR) sandstone reservoirs are found and routinely interpreted as mudstone non-reservoirs, with negative implications for the exploration and exploitation of oil and gas. Then, the high GR sandstone reservoirs' recognition principles, genesis, and log evaluation techniques are systematically studied. Studies show that the sandstone reservoirs with apparent shale content greater than 50% and GR value higher than 110API can be regarded as high GR sandstone reservoir. The high GR sandstone reservoir is mainly and directly caused by abnormally high uranium enrichment, but not the tuff, feldspar or clay mineral. Affected by formation's high water sensitivity and poor borehole quality, the conventional logs can not recognize reservoir and evaluate the physical property of reservoirs. Then, the nuclear magnetic resonance (NMR) logs is proposed and proved to be useful in reservoir recognition and physical property evaluation. PMID:24078797

Gene-specific mechanisms direct glucocorticoid-receptor-driven repression of inflammatory response genes in macrophages

PubMed Central

Sacta, Maria A; Tharmalingam, Bowranigan; Coppo, Maddalena; Rollins, David A; Deochand, Dinesh K; Benjamin, Bradley; Yu, Li; Zhang, Bin; Hu, Xiaoyu; Li, Rong; Chinenov, Yurii

2018-01-01

The glucocorticoid receptor (GR) potently represses macrophage-elicited inflammation, however, the underlying mechanisms remain obscure. Our genome-wide analysis in mouse macrophages reveals that pro-inflammatory paused genes, activated via global negative elongation factor (NELF) dissociation and RNA Polymerase (Pol)2 release from early elongation arrest, and non-paused genes, induced by de novo Pol2 recruitment, are equally susceptible to acute glucocorticoid repression. Moreover, in both cases the dominant mechanism involves rapid GR tethering to p65 at NF-kB-binding sites. Yet, specifically at paused genes, GR activation triggers widespread promoter accumulation of NELF, with myeloid cell-specific NELF deletion conferring glucocorticoid resistance. Conversely, at non-paused genes, GR attenuates the recruitment of p300 and histone acetylation, leading to a failure to assemble BRD4 and Mediator at promoters and enhancers, ultimately blocking Pol2 initiation. Thus, GR displays no preference for a specific pro-inflammatory gene class; however, it effects repression by targeting distinct temporal events and components of transcriptional machinery. PMID:29424686

Glyphosate degradation in glyphosate-resistant and -susceptible crops and weeds.

PubMed

Duke, Stephen O

2011-06-08

High levels of aminomethylphosphonic acid (AMPA), the main glyphosate metabolite, have been found in glyphosate-treated, glyphosate-resistant (GR) soybean, apparently due to plant glyphosate oxidoreductase (GOX)-like activity. AMPA is mildly phytotoxic, and under some conditions the AMPA accumulating in GR soybean correlates with glyphosate-caused phytotoxicity. A bacterial GOX is used in GR canola, and an altered bacterial glyphosate N-acetyltransferase is planned for a new generation of GR crops. In some weed species, glyphosate degradation could contribute to natural resistance. Neither an isolated plant GOX enzyme nor a gene for it has yet been reported in plants. Gene mutation or amplification of plant genes for GOX-like enzyme activity or horizontal transfer of microbial genes from glyphosate-degrading enzymes could produce GR weeds. Yet, there is no evidence that metabolic degradation plays a significant role in evolved resistance to glyphosate. This is unexpected, considering the extreme selection pressure for evolution of glyphosate resistance in weeds and the difficulty in plants of evolving glyphosate resistance via other mechanisms.

GNU Radio Sandia Utilities v. 1.0

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gilbert, Jacob; Knee, Peter

This software adds a data handling module to the GNU Radio (GR) software defined radio (SDR) framework as well as some general-purpose function blocks (filters, metadata control, etc). This software is useful for processing bursty RF transmissions with GR, and serves as a base for applying SDR signal processing techniques to a whole burst of data at a time, as opposed to streaming data which GR has been primarily focused around.

Preparation of layered graphene and tungsten oxide hybrids for enhanced performance supercapacitors.

PubMed

Xing, Ling-Li; Huang, Ke-Jing; Fang, Lin-Xia

2016-11-01

Tungsten oxide (WO 3 ), which was originally poor in capacitive performance, is made into an excellent electrode material for supercapacitors by dispersing it on graphene (Gr). The obtained Gr-WO 3 hybrids are characterized by X-ray diffraction, Raman spectroscopy, high-resolution transmission electron microscopy and scanning electron microscopy techniques, and evaluated as electrode materials for high-performance supercapacitors by cyclic voltammetry, galvanostatic charge-discharge curves and electrochemical impedance spectroscopy. A great improvement in specific capacitance is achieved with the present hybrids, from 255 F g -1 for WO 3 nanoparticles to 580 F g -1 for Gr-WO 3 hybrids (scanned at 1 A g -1 in 2 M KOH over a potential window of 0 to 0.45 V). The Gr-WO 3 hybrid exhibits an excellent high rate capability and good cycling stability with more than 92% capacitance retention over 1000 cycles at a current density of 5 A g -1 . The enhancement in supercapacitor performance of Gr-WO 3 is not only attributed to its unique nanostructure with large specific surface area, but also its excellent electro-conductivity, which facilitates efficient charge transport and promotes electrolyte diffusion. As a whole, this work indicates that Gr-WO 3 hybrids are a promising electrode material for high-performance supercapacitors.

Mass spectrometry-based metabolic profiling of gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cells.

PubMed

Fujimura, Yoshinori; Ikenaga, Naoki; Ohuchida, Kenoki; Setoyama, Daiki; Irie, Miho; Miura, Daisuke; Wariishi, Hiroyuki; Murata, Masaharu; Mizumoto, Kazuhiro; Hashizume, Makoto; Tanaka, Masao

2014-03-01

Gemcitabine resistance (GR) is one of the critical issues for therapy for pancreatic cancer, but the mechanism still remains unclear. Our aim was to increase the understanding of GR by metabolic profiling approach. To establish GR cells, 2 human pancreatic cancer cell lines, SUIT-2 and CAPAN-1, were exposed to increasing concentration of gemcitabine. Both parental and chemoresistant cells obtained by this treatment were subjected to metabolic profiling based on liquid chromatography-mass spectrometry. Multivariate statistical analyses, both principal component analysis and orthogonal partial least squares discriminant analysis, distinguished metabolic signature of responsiveness and resistance to gemcitabine in both SUIT-2 and CAPAN-1 cells. Among significantly different (P < 0.005) metabolite peaks between parental and GR cells, we identified metabolites related to several metabolic pathways such as amino acid, nucleotide, energy, cofactor, and vitamin pathways. Decreases in glutamine and proline levels as well as increases in aspartate, hydroxyproline, creatine, and creatinine levels were observed in chemoresistant cells from both cell lines. These results suggest that metabolic profiling can isolate distinct features of pancreatic cancer in the metabolome of gemcitabine-sensitive and GR cells. These findings may contribute to the biomarker discovery and an enhanced understanding of GR in pancreatic cancer.

Glucocorticoid receptors in bronchial epithelial cells in asthma.

PubMed

Vachier, I; Chiappara, G; Vignola, A M; Gagliardo, R; Altieri, E; Térouanne, B; Vic, P; Bousquet, J; Godard, P; Chanez, P

1998-09-01

The expression of the glucocorticoid receptor (GR) in untreated or in steroid-dependent asthmatic patients is poorly understood. We therefore studied GR mRNA and protein levels in bronchial biopsies obtained from seven untreated asthmatic patients, seven control volunteers, and seven patients with chronic bronchitis. We also studied in bronchial epithelial cells obtained by brushing from 13 untreated asthmatics, 18 steroid-dependent asthmatics, 11 control volunteers, and 12 patients with chronic bronchitis, GR and heat shock protein 90 kD (hsp90) mRNA as well as the immunoreactivity of GR, intercellular adhesion molecule (ICAM-1), and granulocyte macrophage-colony-stimulating factor (GM-CSF). GR mRNA and protein level was similar in all subject groups in both biopsies and bronchial epithelial cells. Hsp90 mRNA level was also similar in all subject groups. ICAM-1 expression was significantly increased in bronchial epithelial cells from untreated asthmatics, but ICAM-1 was not expressed in those from steroid-dependent asthmatic patients. GM-CSF expression was significantly increased in bronchial epithelial cells from untreated and steroid-dependent asthmatic patients. GR expression within the airways is unaltered by oral long-term steroid treatment in asthma, but the expression of some but not all specific markers for asthma is modified by oral steroid.

Lead exposure and hair lead level of workers in a lead refinery industry in Iran

PubMed Central

Pirsaraei, Seyed Reza Azimi

2007-01-01

This study was carried out on the workers of a lead refinery industry and two control groups in Zanjan city in Iran. The scalp hair samples were collected from 25 workers who were occupationally exposed to lead contamination as a case group and from 25 subjects among the staff of the same industry and 25 subjects among Zanjan citizens as the first and second control groups respectively. A flame atomic absorption spectrophotometer used to determine lead level in all of the samples. The age of all subjects in the three groups was matched. The mean concentrations of hair lead in the workers (case group), the staff (control groupA) and the citizens (control group B) were 131.7±93.4 µgr/gr, 21.1±13.2 µgr/gr and 27.9±14.1 µgr/gr respectively. The mean concentration of hair lead in the case group was more than hair lead of normal range found in humans (0-30 µgr/gr). The mean of hair lead level in the citizens who had used gas vehicles was statistically higher than who had not used it (36.9±12.2 µgr/gr vs. 16.6±4.9 µgr/gr, P<0.001). PMID:21957365

Post impact compressive strength in composites

NASA Technical Reports Server (NTRS)

Demuts, Edvins; Sandhu, Raghbir S.; Daniels, John A.

1992-01-01

Presented in this paper are the plan, equipment, procedures, and findings of an experimental investigation of the tolerance to low velocity impact of a graphite epoxy (AS4/3501-6) and graphite bismaleimide (M6/CYCOM3100) advanced composites. The applied impacts were governed by the Air Force Guide Specification 87221. Specimens of each material system having a common nominal layup (10% 0 deg; 80% +/-45 deg; 10% 90 deg), a common 7 inch (17.78 cm) by 10 inch (25.40 cm) size, five different thicknesses (9, 26, 48, 74, and 96 plies), and ambient moisture content were impacted and strength tested at room temperature. Damaged areas and post impact compression strengths (PICS) were among the most significant findings obtained. While the undamaged per ply compression strength of both materials is a strong function of laminate thickness, the per ply PICS is not. The average difference in per ply PICS between the two material systems is about seven percent. Although a smaller percentage of the applied kinetic energy was absorbed by the Gr/BMI than by the Gr/Epoxy composites, larger damaged areas were produced in the Gr/BMI than in Gr/Epoxy. Within the limitations of this investigation, the Gr/BMI system seems to offer no advantage in damage tolerance over the Gr/Epoxy system examined.

Single prolonged stress enhances hippocampal glucocorticoid receptor and phosphorylated protein kinase B levels

PubMed Central

Eagle, Andrew L.; Knox, Dayan; Roberts, Megan M.; Mulo, Kostika; Liberzon, Israel; Galloway, Matthew P.; Perrine, Shane A.

2012-01-01

Animal models of posttraumatic stress disorder (PTSD) can explore neurobiological mechanisms by which trauma enhances fear and anxiety reactivity. Single prolonged stress (SPS) shows good validity in producing PTSD-like behavior. While SPS-induced behaviors have been linked to enhanced glucocorticoid receptor (GR) expression, the molecular ramifications of enhanced GR expression have yet to be identified. Phosphorylated protein kinase B (pAkt) is critical for stress-mediated enhancement in general anxiety and memory, and may be regulated by GRs. However, it is currently unknown if pAkt levels are modulated by SPS, as well as if the specificity of GR and pAkt related changes contribute to anxiety-like behavior after SPS. The current study set out to examine the effects of SPS on GR and pAkt protein levels in the amygdala and hippocampus and to examine the specificity of these changes to unconditioned anxiety-like behavior. Levels of GR and pAkt were increased in the hippocampus, but not amygdala. Furthermore, SPS had no effect on unconditioned anxiety-like behavior suggesting that generalized anxiety is not consistently observed following SPS. The results suggest that SPS-enhanced GR expression is associated with phosphorylation of Akt, and also suggest that these changes are not related to an anxiogenic phenotype. PMID:23201176

Influence of carbon nanotubes and graphene nanosheets on photothermal effect of hydroxyapatite.

PubMed

Neelgund, Gururaj M; Oki, Aderemi R

2016-12-15

Herein we present a successful strategy for enhancement of photothermal efficiency of hydroxyapatite (HAP) by its conjugation with carbon nanotubes (CNTs) and graphene nanosheets (GR). Owing to excellent biocompatibility with human body and its non-toxicity, implementation of HAP based nanomaterials in photothermal therapy (PTT) provides non-replaceable benefits over PTE agents. Therefore, in this report, it has been experimentally exploited that the photothermal effect (PTE) of HAP has significantly improved by its assembly with CNTs and GR. It is found that the type of carbon nanomaterial used to conjugate with HAP has influence on its PTE in such a way that the photothermal efficiency of GR-HAP was higher than CNTs-COOH-HAP under exposure to 980nm near-infrared (NIR) laser. The temperature attained by aqueous dispersions of both CNTs-COOH-HAP and GR-HAP after illuminating to NIR radiations for 7min was found to be above 50°C, which is beyond the temperature tolerance of cancer cells. So that the rise in temperature shown by both CNTs-COOH-HAP and GR-HAP is enough to induce the death of tumoral or cancerous cells. Overall, this approach in modality of HAP with CNTs and GR provide a great potential for development of future nontoxic PTE agents. Copyright © 2016 Elsevier Inc. All rights reserved.

Observation of Image Potential State in Oxygen Intercalated Graphene on Iridium by Two-Photon-Photoemission Spectroscopy

NASA Astrophysics Data System (ADS)

Lin, Yi; Li, Yunzhe; Sadowski, Jerzy; Dadap, Jerry; Jin, Wencan; Osgood, Richard

In this talk, we report our experimental results on the first direct observation of image potential state (IPS) in oxygen-intercalated graphene on iridium by two-photo-photoemission spectroscopy. We demonstrate how oxygen intercalation influences the IPS in Gr/Ir and decouples the interlayer interaction. We present measurements of the electronic dispersion and work function in pristine Gr/Ir, oxygen-intercalated Gr/O/Ir, and deintercalated Gr/Ir. LEED patterns are measured during the pristine, oxygen-intercalated, and deintercalated phases of the Gr/Ir sample. Based on these measurements, relative to the pristine case, the work function and the energy location of n =1 IPS relative to the Fermi level increases by 0.39 eV and 0.3 eV, respectively, due to oxygen intercalation, whereas the effective mass of n =1 IPS is hardly influenced by the intercalation process. Moreover, we achieve the quenching and restoration of the resonance from Ir Rashba states to n =1 IPS in Gr/Ir by oxygen intercalation and deintercalation. This work was supported by the DOE, Office of Basic Energy Sciences, Division of MSE under Contract No. DE-FG 02-04-ER-46157. This research used resources of the CFN, which is the U.S. DOE Office of Science User Facility, under Contract No. DE-SC0012704.

The Response of the Root Proteome to the Synthetic Strigolactone GR24 in Arabidopsis*

PubMed Central

Walton, Alan; Stes, Elisabeth; Goeminne, Geert; Braem, Lukas; Vuylsteke, Marnik; Matthys, Cedrick; De Cuyper, Carolien; Staes, An; Vandenbussche, Jonathan; Boyer, François-Didier; Vanholme, Ruben; Fromentin, Justine; Boerjan, Wout; Gevaert, Kris; Goormachtig, Sofie

2016-01-01

Strigolactones are plant metabolites that act as phytohormones and rhizosphere signals. Whereas most research on unraveling the action mechanisms of strigolactones is focused on plant shoots, we investigated proteome adaptation during strigolactone signaling in the roots of Arabidopsis thaliana. Through large-scale, time-resolved, and quantitative proteomics, the impact of the strigolactone analog rac-GR24 was elucidated on the root proteome of the wild type and the signaling mutant more axillary growth 2 (max2). Our study revealed a clear MAX2-dependent rac-GR24 response: an increase in abundance of enzymes involved in flavonol biosynthesis, which was reduced in the max2–1 mutant. Mass spectrometry-driven metabolite profiling and thin-layer chromatography experiments demonstrated that these changes in protein expression lead to the accumulation of specific flavonols. Moreover, quantitative RT-PCR revealed that the flavonol-related protein expression profile was caused by rac-GR24-induced changes in transcript levels of the corresponding genes. This induction of flavonol production was shown to be activated by the two pure enantiomers that together make up rac-GR24. Finally, our data provide much needed clues concerning the multiple roles played by MAX2 in the roots and a comprehensive view of the rac-GR24-induced response in the root proteome. PMID:27317401

Chronic stress decreases availability of heat shock proteins to glucocorticoid receptor in response to novel acute stress in Wistar rat hypothalamus.

PubMed

Simic, Iva; Mitic, Milos; Djordjevic, Jelena; Radojcic, Marija; Adzic, Miroslav

2012-05-01

Chronic psychosocial isolation (CPSI) is known to cause several maladaptive changes in the limbic brain structures, which regulate the hypothalamic-pituitary-adrenal (HPA) axis activity. In this study, we focused our investigation on CPSI effects in the hypothalamus (HT) since it is a major driver of HPA axis activity. We also investigated whether the exposure to CPSI could alter the response to subsequent acute stress (30-min immobilization). In the HT, we followed cytosolic and nuclear levels of the glucocorticoid receptor (GR), as a mediator of HPA axis feedback inhibition, and its chaperones, the heat shock proteins (HSPs), hsp70 and hsp90. The CPSI did not cause any changes in either GR or HSPs levels. However, we observed increase of the GR and hsp70 in both HT cellular compartments as a response of naïve rats to acute stress, whereas the response of CPSI rats to acute stress was associated with elevation of the GR in the cytosol and decrease of HSPs in the nucleus. Thus, our data indicated reduced availability of HSPs to GR in both cytosol and nucleus of the HT under acute stress of CPSI animals, and therefore, pointed out to potentially negative effects of CPSI on GR function in the HT.

Molecular and cytogenetic investigation of Y chromosome deletions over three generations facilitated by intracytoplasmic sperm injection.

PubMed

Minor, Agata; Wong, Edgar Chan; Harmer, Karynn; Ma, Sai

2007-08-01

The azoospermic factor (AZF) region is critical for normal spermatogenesis since microdeletions and partial deletions have been associated with infertility. We investigate the diagnostic ability of karyotyping in detecting clinically relevant Y chromosome deletions. The clinical significance of heterochromatin deletions, microdeletions and partial AZFc deletions is also evaluated. A patient with a Yq deletion, affected by severe oligoasthenoteratozoospermia, underwent intracytoplasmic sperm injection (ICSI) which resulted in the birth of a healthy baby boy. The patient, his father and his son underwent Y chromosome microdeletion and partial AZFc deletion screening. We also studied the aneuploidy rate in the sperm of the patient by fluorescent in situ hybridization. AZF microdeletions were absent in the family. However, microdeletion analysis confirmed that the Yq deletion was limited to the heterochromatin. We found a partial AZFc gr/gr deletion in all three family members. We observed an increased rate of sex chromosome aneuploidy in the infertile patient. Cytogenetic analysis was misleading in identifying the Yq breakpoint. Infertility observed in the patient was associated with the gr/gr partial deletion. However, because of the incomplete penetrance of gr/gr deletions, the consequence of the vertical transmission of the deletion through ICSI remains unknown. Copyright (c) 2007 John Wiley & Sons, Ltd.

Kinetically-Defined Component Actions in Gene Repression

PubMed Central

Chow, Carson C.; Finn, Kelsey K.; Storchan, Geoffery B.; Lu, Xinping; Sheng, Xiaoyan; Simons, S. Stoney

2015-01-01

Gene repression by transcription factors, and glucocorticoid receptors (GR) in particular, is a critical, but poorly understood, physiological response. Among the many unresolved questions is the difference between GR regulated induction and repression, and whether transcription cofactor action is the same in both. Because activity classifications based on changes in gene product level are mechanistically uninformative, we present a theory for gene repression in which the mechanisms of factor action are defined kinetically and are consistent for both gene repression and induction. The theory is generally applicable and amenable to predictions if the dose-response curve for gene repression is non-cooperative with a unit Hill coefficient, which is observed for GR-regulated repression of AP1LUC reporter induction by phorbol myristate acetate. The theory predicts the mechanism of GR and cofactors, and where they act with respect to each other, based on how each cofactor alters the plots of various kinetic parameters vs. cofactor. We show that the kinetically-defined mechanism of action of each of four factors (reporter gene, p160 coactivator TIF2, and two pharmaceuticals [NU6027 and phenanthroline]) is the same in GR-regulated repression and induction. What differs is the position of GR action. This insight should simplify clinical efforts to differentially modulate factor actions in gene induction vs. gene repression. PMID:25816223

A gauge-theoretic approach to gravity

PubMed Central

Krasnov, Kirill

2012-01-01

Einstein's general relativity (GR) is a dynamical theory of the space–time metric. We describe an approach in which GR becomes an SU(2) gauge theory. We start at the linearized level and show how a gauge-theoretic Lagrangian for non-interacting massless spin two particles (gravitons) takes a much more simple and compact form than in the standard metric description. Moreover, in contrast to the GR situation, the gauge theory Lagrangian is convex. We then proceed with a formulation of the full nonlinear theory. The equivalence to the metric-based GR holds only at the level of solutions of the field equations, that is, on-shell. The gauge-theoretic approach also makes it clear that GR is not the only interacting theory of massless spin two particles, in spite of the GR uniqueness theorems available in the metric description. Thus, there is an infinite-parameter class of gravity theories all describing just two propagating polarizations of the graviton. We describe how matter can be coupled to gravity in this formulation and, in particular, how both the gravity and Yang–Mills arise as sectors of a general diffeomorphism-invariant gauge theory. We finish by outlining a possible scenario of the ultraviolet completion of quantum gravity within this approach. PMID:22792040

Activated glucocorticoid receptor interacts with the INHAT component Set/TAF-Ibeta and releases it from a glucocorticoid-responsive gene promoter, relieving repression: implications for the pathogenesis of glucocorticoid resistance in acute undifferentiated leukemia with Set-Can translocation.

PubMed

Ichijo, Takamasa; Chrousos, George P; Kino, Tomoshige

2008-02-13

Set/template-activating factor (TAF)-Ibeta, part of the Set-Can oncogene product found in acute undifferentiated leukemia, is a component of the inhibitor of acetyltransferases (INHAT) complex. Set/TAF-Ibeta interacted with the DNA-binding domain of the glucocorticoid receptor (GR) in yeast two-hybrid screening, and repressed GR-induced transcriptional activity of a chromatin-integrated glucocorticoid-responsive and a natural promoter. Set/TAF-Ibeta was co-precipitated with glucocorticoid response elements (GREs) of these promoters in the absence of dexamethasone, while addition of the hormone caused dissociation of Set/TAF-Ibeta from and attraction of the p160-type coactivator GRIP1 to the promoter GREs. Set-Can fusion protein, on the other hand, did not interact with GR, was constitutively co-precipitated with GREs and suppressed GRIP1-induced enhancement of GR transcriptional activity and histone acetylation. Thus, Set/TAF-Ibeta acts as a ligand-activated GR-responsive transcriptional repressor, while Set-Can does not retain physiologic responsiveness to ligand-bound GR, possibly contributing to the poor responsiveness of Set-Can-harboring leukemic cells to glucocorticoids.

Activated Glucocorticoid Receptor Interacts with the INHAT Component Set/TAF-Iβ and Releases it from a Glucocorticoid-responsive Gene Promoter, Relieving Repression: Implications for the Pathogenesis of Glucocorticoid Resistance in Acute Undifferentiated Leukemia with Set-Can Translocation

PubMed Central

Ichijo, Takamasa; Chrousos, George P.; Kino, Tomoshige

2008-01-01

SUMMARY Set/template-activating factor (TAF)-Iβ, part of the Set-Can oncogene product found in acute undifferentiated leukemia, is a component of the inhibitor of acetyltransferases (INHAT) complex. Set/TAF-Iβ interacted with the DNA-binding domain of the glucocorticoid receptor (GR) in yeast two-hybrid screening, and repressed GR-induced transcriptional activity of a chromatin-integrated glucocorticoid-responsive and a natural promoter. Set/TAF-Iβ was co-precipitated with glucocorticoid response elements (GREs) of these promoters in the absence of dexamethasone, while addition of the hormone caused dissociation of Set/TAF-Iβ from and attraction of the p160-type coactivator GRIP1 to the promoter GREs. Set-Can fusion protein, on the other hand, did not interact with GR, was constitutively co-precipitated with GREs and suppressed GRIP1-induced enhancement of GR transcriptional activity and histone acetylation. Thus, Set/TAF-Iβ acts as a ligand-activated GR-responsive transcriptional repressor, while Set-Can does not retain physiologic responsiveness to ligand-bound GR, possibly contributing to the poor responsiveness of Set-Can-harboring leukemic cells to glucocorticoids. PMID:18096310

Gene delivery by a steroid-peptide nucleic acid conjugate.

PubMed

Rebuffat, Alexandre G; Nawrocki, Andrea R; Nielsen, Peter E; Bernasconi, Alessio G; Bernal-Mendez, Eloy; Frey, Brigitte M; Frey, Felix J

2002-09-01

We previously introduced a method called steroid-mediated gene delivery (SMGD), which uses steroid receptors as shuttles to facilitate the nuclear uptake of transfected DNA. Here, we describe a SMGD strategy with peptide nucleic acids (PNAs) that allowed linkage of a steroid molecule to a defined position in a plasmid without disturbing its gene expression. We synthesized and tested several bifunctional steroid derivatives [patent in process of nationalization] and finally selected the compound named DEX-bisPNA, a molecule consisting of a dexamethasone moiety linked to a PNA clamp (bisPNA) through a 30-atom chemical spacer. Dex-bisPNA binds to the glucocorticoid receptor (GR) as well as to reporter plasmids containing the corresponding PNA binding sites, translocates the GR from the cytoplasm into the nucleus, and increases the delivery of plasmid to the nucleus, resulting in enhanced GR-dependent expression of the reporter gene. The SMGD effect was more pronounced in growth-arrested cells than in proliferating cells. The specificity for the GR was shown by the reversion of the SMGD effect in the presence of dexamethasone as well as an enhanced expression in GR-positive cells but not in GR-negative cells. Thus, SMGD with PNA is a promising strategy for nonviral gene delivery into target tissues expressing specific steroid receptors.

Development of composite tube protective coatings

NASA Technical Reports Server (NTRS)

Dursch, H.; Hendricks, C.

1986-01-01

Protective coatings for graphite/epoxy (Gr/Ep) tubular structures proposed for the Space Station are evaluated. The program was divided into four parts; System Definition, Coating Concept Selection and Evaluation, Scale-up and Assembly, and Reporting. System Definition involved defining the structural and environmental properties required of the Gr/Ep tubes. The prepreg and ply sequence selected was a P75S/934 (O2, + or - 20, O2)sub s layup which meets the various structural requirements of the Space Station. Coating Concept and Selection comprised the main emphasis of the effort. Concepts for protectively coating the Gr/Ep tubes included the use of metal foil and electroplating. The program results demonstrated that both phosphoric and chromic acid anodized Al foil provided adequate adhesion to the Gr/Ep tubes and stability of optical properties when subjected to atomic oxygen and thermal cycling representative of the LEO environment. SiO2/Al coatings sputtered onto Al foils also resulted in an excellent protective coating. The electroplated Ni possessed unacceptable adhesion loss to the Gr/Ep tubes during atomic oxygen testing. Scale-Up and Assembly involved fabricating and wrapping 8-ft-long by 2-in-diameter Gr/EP tubes with chromic acid anodized foil and delivering these tubes, along with representative Space Station erectable end fittings, to NASA LaRC.

On a family of KP multi-line solitons associated to rational degenerations of real hyperelliptic curves and to the finite non-periodic Toda hierarchy

NASA Astrophysics Data System (ADS)

Abenda, Simonetta

2017-09-01

We continue the program started in Abenda and Grinevich (2015) of associating rational degenerations of M-curves to points in GrTNN(k , n) using KP theory for real finite gap solutions. More precisely, we focus on the inverse problem of characterizing the soliton data which produce Krichever divisors compatible with the KP reality condition when Γ is a certain rational degeneration of a hyperelliptic M-curve. Such choice is motivated by the fact that Γ is related to the curves associated to points in GrTP(1 , n) and in GrTP(n - 1 , n) in Abenda and Grinevich (2015). We prove that the reality condition on the Krichever divisor on Γ singles out a special family of KP multi-line solitons (T-hyperelliptic solitons) in GrTP(k , n) , k ∈ [ n - 1 ] , naturally connected to the finite non-periodic Toda hierarchy. We discuss the relations between the algebraic-geometric description of KP T-hyperelliptic solitons and of the open Toda system. Finally, we also explain the effect of the space-time transformation which conjugates soliton data in GrTP(k , n) to soliton data in GrTP(n - k , n) on the Krichever divisor for such KP solitons.

Hybrid graphene/silicon Schottky photodiode with intrinsic gating effect

NASA Astrophysics Data System (ADS)

Di Bartolomeo, Antonio; Luongo, Giuseppe; Giubileo, Filippo; Funicello, Nicola; Niu, Gang; Schroeder, Thomas; Lisker, Marco; Lupina, Grzegorz

2017-06-01

We propose a hybrid device consisting of a graphene/silicon (Gr/Si) Schottky diode in parallel with a Gr/SiO2/Si capacitor for high-performance photodetection. The device, fabricated by transfer of commercial graphene on low-doped n-type Si substrate, achieves a photoresponse as high as 3 \\text{A} {{\\text{W}}-1} and a normalized detectivity higher than 3.5× {{10}12} \\text{cm} \\text{H}{{\\text{z}}1/2} {{\\text{W}}-1} in the visible range. It exhibits a photocurrent exceeding the forward current because photo-generated minority carriers, accumulated at Si/SiO2 interface of the Gr/SiO2/Si capacitor, diffuse to the Gr/Si junction. We show that the same mechanism, when due to thermally generated carriers, although usually neglected or disregarded, causes the increased leakage often measured in Gr/Si heterojunctions. We perform extensive I-V and C-V characterization at different temperatures and we measure a zero-bias Schottky barrier height of 0.52 eV at room temperature, as well as an effective Richardson constant A **  =  4× {{10}-5} \\text{A} \\text{c}{{\\text{m}}-2} {{\\text{K}}-2} and an ideality factor n≈ 3.6 , explained by a thin (<1 nm) oxide layer at the Gr/Si interface.

Cross-talk between an activator of nuclear receptors-mediated transcription and the D1 dopamine receptor signaling pathway.

PubMed

Schmidt, Azriel; Vogel, Robert; Rutledge, Su Jane; Opas, Evan E; Rodan, Gideon A; Friedman, Eitan

2005-03-01

Nuclear receptors are transcription factors that usually interact, in a ligand-dependent manner, with specific DNA sequences located within promoters of target genes. The nuclear receptors can also be controlled in a ligand-independent manner via the action of membrane receptors and cellular signaling pathways. 5-Tetradecyloxy-2-furancarboxylic acid (TOFA) was shown to stimulate transcription from the MMTV promoter via chimeric receptors that consist of the DNA binding domain of GR and the ligand binding regions of the PPARbeta or LXRbeta nuclear receptors (GR/PPARbeta and GR/LXRbeta). TOFA and hydroxycholesterols also modulate transcription from NF-kappaB- and AP-1-controlled reporter genes and induce neurite differentiation in PC12 cells. In CV-1 cells that express D(1) dopamine receptors, D(1) dopamine receptor stimulation was found to inhibit TOFA-stimulated transcription from the MMTV promoter that is under the control of chimeric GR/PPARbeta and GR/LXRbeta receptors. Treatment with the D(1) dopamine receptor antagonist, SCH23390, prevented dopamine-mediated suppression of transcription, and by itself increased transcription controlled by GR/LXRbeta. Furthermore, combined treatment of CV-1 cells with TOFA and SCH23390 increased transcription controlled by the GR/LXRbeta chimeric receptor synergistically. The significance of this in vitro synergy was demonstrated in vivo, by the observation that SCH23390 (but not haloperidol)-mediated catalepsy in rats was potentiated by TOFA, thus showing that an agent that mimics the in vitro activities of compounds that activate members of the LXR and PPAR receptor families can influence D1 dopamine receptor elicited responses.

A Cross-Section Study of the Ontogeny of Gender Roles in Women with DSD.

PubMed

Wisniewski, Amy; Aston, Christopher E

2015-01-01

A review of gender role (GR) differentiation from early childhood through adulthood was conducted on males and females in general, as well as on females affected by congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency or complete androgen insensitivity syndrome (CAIS). Additionally, retrospective and current, self-rated GR assessments were evaluated from women with CAH (n = 9) or CAIS (n = 12), and unaffected women and men ranging in age from 16 to 59 years. Overall, GR differentiation occurs in early childhood and persists through adulthood. With advanced age, this differentiation may evolve into androgyny or even become undifferentiated for the general population. While more studies of GR exist for girls and women with CAH compared to those affected by CAIS, some developmental patterns can be observed from the limited data that exist. First, girls and women with CAIS report a female GR that persists through adulthood. Second, girls and women with CAH are more likely to report less feminine/ more masculine play in childhood followed by interests in male-typical leisure activities and career choices in adulthood. However, our data indicate that women with CAH report more feminine/ less masculine patterns of GR with age. Self-reported GR for women with CAH was indistinguishable from that of women with CAIS at the time of study participation in adulthood. With the availability of effective medications for treating hormone deficiencies associated with CAH, affected women are expected to live a full lifespan. Thus, our understanding of psychosexual development into older age is warranted.

Change in general relativistic precession rates due to Lidov-Kozai oscillations in Solar system

NASA Astrophysics Data System (ADS)

Sekhar, A.; Asher, D. J.; Werner, S. C.; Vaubaillon, J.; Li, G.

2017-06-01

Both general relativistic (GR) precession and the Lidov-Kozai mechanism, separately, are known to play an important role in the orbital evolution of Solar system bodies. Previous works have studied these two mechanisms independently in great detail. However, both these phenomena occurring at the same time in real Solar system bodies have rarely been explored. In this work, we find a continuum connecting the GR precession dominant and Lidov-Kozai-like mechanism dominant regimes, I.e. an intermediate regime where the competing effects of GR precession and Lidov-Kozai-like oscillations coexist simultaneously. We find some real examples in the Solar system in this intermediate regime. Moreover, we identify a rare example among them, comet 96P/Machholz 1, which shows significant changes in the rates of GR precession (an order of magnitude higher than Mercury's GR precession rate) due to sungrazing and sun-colliding phases induced by Lidov-Kozai-like oscillations. This comet's combination of orbital elements and initial conditions (at the present epoch) favour this measurable rapid change in GR precession (at some points peaking up to 60 times Mercury's GR precession rate) along with prograde-retrograde inclination flip (due to Lidov-Kozai-like oscillations). Similar tests are performed for hundreds of bodies lying in the moderately low perihelion distance and moderately low semimajor axis phase space in the Solar system, the present lowest perihelion distance asteroid 322P/SOHO 1, and further examples connected with 96P/Machholz 1 namely, the Marsden and Kracht families of sungrazing comets plus low perihelion meteoroid streams like Daytime Arietids and Southern Delta Aquariids.

Endocrine-Disrupting Effects of Pesticides through Interference with Human Glucocorticoid Receptor.

PubMed

Zhang, Jianyun; Zhang, Jing; Liu, Rui; Gan, Jay; Liu, Jing; Liu, Weiping

2016-01-05

Many pesticides have been identified as endocrine-disrupting chemicals (EDCs) due to their ability to bind sex-steroid hormone receptors. However, little attention has been paid to the ability of pesticides to interfere with other steroid hormone receptors such as glucocorticoid receptor (GR) that plays a critical role in metabolic, endocrine, immune, and nervous systems. In this study, the glucocorticoidic and antiglucocorticoidic effects of 34 pesticides on human GR were investigated using luciferase reporter gene assay. Surprisingly, none of the test chemicals showed GR agonistic activity, but 12 chemicals exhibited apparent antagonistic effects. Bifenthrin, λ-cyhalothrin, cypermethrin, resmethrin, o,p'-DDT, p,p'-DDT, methoxychlor, ethiofencarb, and tolylfluanid showed remarkable GR antagonistic properties with RIC20 values lower than 10(-6) M. The disruption of glucocorticoid-responsive genes in H4IIE and J774A.1 cells was further evaluated on these 12 GR antagonists. In H4IIEcells, four organochlorine insecticides, bifenthrin, and 3-PBA decreased cortisol-induced PEPCK gene expression, while o,p'-DDT and methoxychlor inhibited cortisol-stimulated Arg and TAT gene expression. Cypermethrin and tolyfluanid attenuated cortisol-induced TAT expression. In J774A.1 cells, λ-cyhalothrin, resmethrin, 3-PBA, o,p'-DDT, p,p'-DDT, p,p'-DDE, methoxychlor- and tolylfluanid-reduced cortisol-stimulated GILZ expression. Furthermore, molecular docking simulation indicated that different interactions may stabilize the binding between molecules and GR. Our findings suggest that comprehensive screening and evaluation of GR antagonists and agonists should be considered to better understand the health and ecological risks of man-made chemicals such as pesticides.

Longitudinal changes in glucocorticoid receptor exon 1F methylation and psychopathology after military deployment

PubMed Central

Schür, R R; Boks, M P; Rutten, B P F; Daskalakis, N P; de Nijs, L; van Zuiden, M; Kavelaars, A; Heijnen, C J; Joëls, M; Kahn, R S; Geuze, E; Vermetten, E; Vinkers, C H

2017-01-01

Several cross-sectional studies have demonstrated the relevance of DNA methylation of the glucocorticoid receptor exon 1F region (GR-1F) for trauma-related psychopathology. We conducted a longitudinal study to examine GR-1F methylation changes over time in relation to trauma exposure and the development of post-deployment psychopathology. GR-1F methylation (52 loci) was quantified using pyrosequencing in whole blood of 92 military men 1 month before and 6 months after a 4-month deployment period to Afghanistan. GR-1F methylation overall (mean methylation and the number of methylated loci) and functional methylation (methylation at loci associated with GR exon 1F expression) measures were examined. We first investigated the effect of exposure to potentially traumatic events during deployment on these measures. Subsequently, changes in GR-1F methylation were related to changes in mental health problems (total Symptom Checklist-90 score) and posttraumatic stress disorder (PTSD) symptoms (Self-Report Inventory for PTSD). Trauma exposure during deployment was associated with an increase in all methylation measures, but development of mental health problems 6 months after deployment was only significantly associated with an increased functional methylation. Emergence of post-deployment PTSD symptoms was not related to increased functional methylation over time. Pre-deployment methylation levels did not predict post-deployment psychopathology. To our knowledge, this is the first study to prospectively demonstrate trauma-related increases in GR-1F methylation, and it shows that only increases at specific functionally relevant sites predispose for post-deployment psychopathology. PMID:28742078

Prenatal stress changes courtship vocalizations and bone mineral density in mice.

PubMed

Schmidt, Michaela; Lapert, Florian; Brandwein, Christiane; Deuschle, Michael; Kasperk, Christian; Grimsley, Jasmine M; Gass, Peter

2017-01-01

Stress during the prenatal period has various effects on social and sexual behavior in both human and animal offspring. The present study examines the effects of chronic restraint stress in the second vs third trimester in pregnancy and glucocorticoid receptor (GR) heterozygous mutation on C57BL/6N male offspring's vocal courtship behavior in adulthood by applying a novel analyzing method. Finally, corticosterone and testosterone levels as well as bone mineral density were measured. Prenatal stress in the third, but not in the second trimester caused a significant qualitative change in males' courtship vocalizations, independent of their GR genotype. Bone mineral density was decreased also by prenatal stress exclusively in the third trimester in GR mutant and wildtype mice and - in contrast to corticosterone and testosterone - highly correlated with courtship vocalizations. In Gr +/- males corticosterone serum levels were significantly increased in animals that had experienced prenatal stress in the third trimester. Testosterone serum levels were overall increased in Gr +/- males in comparison to wildtypes as a tendency - whereas prenatal stress had no influence. Prenatal stress alters adult males' courtship vocalizations exclusively when applied in the third trimester, with closely related changes in bone mineral density. Bone mineral density seems to reflect best the complex neuroendocrine mechanisms underlying the production of courtship vocalizations. Besides, we demonstrated for the first time elevated basal corticosterone levels in Gr +/- males after prenatal stress which suggests that the Gr +/- mouse model of depression might also serve as a model of prenatal stress in male offspring. Copyright © 2016 Elsevier Ltd. All rights reserved.

Growth and Reproduction of Glyphosate-Resistant and Susceptible Populations of Kochia scoparia

PubMed Central

Kumar, Vipan; Jha, Prashant

2015-01-01

Evolution of glyphosate-resistant kochia is a threat to no-till wheat-fallow and glyphosate-resistant (GR) cropping systems of the US Great Plains. The EPSPS (5-enol-pyruvylshikimate-3-phosphate synthase) gene amplification confers glyphosate resistance in the tested Kochia scoparia (L.) Schrad populations from Montana. Experiments were conducted in spring to fall 2014 (run 1) and summer 2014 to spring 2015 (run 2) to investigate the growth and reproductive traits of the GR vs. glyphosate-susceptible (SUS) populations of K. scoparia and to determine the relationship of EPSPS gene amplification with the level of glyphosate resistance. GR K. scoparia inbred lines (CHES01 and JOP01) exhibited 2 to 14 relative copies of the EPSPS gene compared with the SUS inbred line with only one copy. In the absence of glyphosate, no differences in growth and reproductive parameters were evident between the tested GR and SUS inbred lines, across an intraspecific competition gradient (1 to 170 plants m-2). GR K. scoparia plants with 2 to 4 copies of the EPSPS gene survived the field-use rate (870 g ha-1) of glyphosate, but failed to survive the 4,350 g ha-1 rate of glyphosate (five-times the field-use rate). In contrast, GR plants with 5 to 14 EPSPS gene copies survived the 4,350 g ha-1 of glyphosate. The results from this research indicate that GR K. scoparia with 5 or more EPSPS gene copies will most likely persist in field populations, irrespective of glyphosate selection pressure. PMID:26580558

Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones.

PubMed

Hay, Colin W; Shanley, Lynne; Davidson, Scott; Cowie, Philip; Lear, Marissa; McGuffin, Peter; Riedel, Gernot; McEwan, Iain J; MacKenzie, Alasdair

2014-09-01

Expression or introduction of the neuropeptide substance-P (SP; encoded by the TAC1 gene in humans and Tac1 in rodents) in the amygdala induces anxiety related behaviour in rodents. In addition, pharmacological antagonism of the main receptor of SP in humans; NK1, is anxiolytic. In the current study, we show that the Tac1 locus is up-regulated in primary rat amygdala neurones in response to activation of the glucocorticoid receptor (GR); a classic component of the stress response. Using a combination of bioinformatics, electrophoretic mobility shift assays (EMSA) and reporter plasmid magnetofection into rat primary amygdala neurones we identified a highly conserved GR response sequence (2GR) in the human TAC1 promoter that binds GR in response to dexamethasone (Dex) or forskolin. We also identified a second GR binding site in the human promoter that was polymorphic and whose T-allele is only found in Japanese and Chinese populations. We present evidence that the T-allele of SNPGR increases the activity of the TAC1 promoter through de-sequestration or de-repression of 2GR. The identification of Dex/forskolin response elements in the TAC1 promoter in amygdala neurones suggests a possible link in the chain of molecular events connecting GR activation and anxiety. In addition, the discovery of a SNP which can alter this response may have implications for our understanding of the role of regulatory variation in susceptibility to stress in specific populations. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hydroxylation of the herbicide isoproturon by fungi isolated from agricultural soil.

PubMed

Rønhede, Stig; Jensen, Bo; Rosendahl, Søren; Kragelund, Birthe B; Juhler, René K; Aamand, Jens

2005-12-01

Several asco-, basidio-, and zygomycetes isolated from an agricultural field were shown to be able to hydroxylate the phenylurea herbicide isoproturon [N-(4-isopropylphenyl)-N',N'-dimethylurea] to N-(4-(2-hydroxy-1-methylethyl)phenyl)-N',N'-dimethylurea and N-(4-(1-hydroxy-1-methylethyl)phenyl)-N',N'-dimethylurea. Bacterial metabolism of isoproturon has previously been shown to proceed by an initial demethylation to N-(4-isopropylphenyl)-N'-methylurea. In soils, however, hydroxylated metabolites have also been detected. In this study we identified fungi as organisms that potentially play a major role in the formation of these hydroxylated metabolites in soils treated with isoproturon. Isolates of Mortierella sp. strain Gr4, Phoma cf. eupyrena Gr61, and Alternaria sp. strain Gr174 hydroxylated isoproturon at the first position of the isopropyl side chain, yielding N-(4-(2-hydroxy-1-methylethyl)phenyl)-N',N'-dimethylurea, while Mucor sp. strain Gr22 hydroxylated the molecule at the second position, yielding N-(4-(1-hydroxy-1-methylethyl)phenyl)-N',N'-dimethylurea. Hydroxylation was the dominant mode of isoproturon transformation in these fungi, although some cultures also produced traces of the N-demethylated metabolite N-(4-isopropylphenyl)-N'-methylurea. A basidiomycete isolate produced a mixture of the two hydroxylated and N-demethylated metabolites at low concentrations. Clonostachys sp. strain Gr141 and putative Tetracladium sp. strain Gr57 did not hydroxylate isoproturon but N demethylated the compound to a minor extent. Mortierella sp. strain Gr4 also produced N-(4-(2-hydroxy-1-methylethyl)phenyl)-N'-methylurea, which is the product resulting from combined N demethylation and hydroxylation.

Hydroxylation of the Herbicide Isoproturon by Fungi Isolated from Agricultural Soil

PubMed Central

Rønhede, Stig; Jensen, Bo; Rosendahl, Søren; Kragelund, Birthe B.; Juhler, René K.; Aamand, Jens

2005-01-01

Several asco-, basidio-, and zygomycetes isolated from an agricultural field were shown to be able to hydroxylate the phenylurea herbicide isoproturon [N-(4-isopropylphenyl)-N′,N′-dimethylurea] to N-(4-(2-hydroxy-1-methylethyl)phenyl)-N′,N′-dimethylurea and N-(4-(1-hydroxy-1-methylethyl)phenyl)-N′,N′-dimethylurea. Bacterial metabolism of isoproturon has previously been shown to proceed by an initial demethylation to N-(4-isopropylphenyl)-N′-methylurea. In soils, however, hydroxylated metabolites have also been detected. In this study we identified fungi as organisms that potentially play a major role in the formation of these hydroxylated metabolites in soils treated with isoproturon. Isolates of Mortierella sp. strain Gr4, Phoma cf. eupyrena Gr61, and Alternaria sp. strain Gr174 hydroxylated isoproturon at the first position of the isopropyl side chain, yielding N-(4-(2-hydroxy-1-methylethyl)phenyl)-N′,N′-dimethylurea, while Mucor sp. strain Gr22 hydroxylated the molecule at the second position, yielding N-(4-(1-hydroxy-1-methylethyl)phenyl)-N′,N′-dimethylurea. Hydroxylation was the dominant mode of isoproturon transformation in these fungi, although some cultures also produced traces of the N-demethylated metabolite N-(4-isopropylphenyl)-N′-methylurea. A basidiomycete isolate produced a mixture of the two hydroxylated and N-demethylated metabolites at low concentrations. Clonostachys sp. strain Gr141 and putative Tetracladium sp. strain Gr57 did not hydroxylate isoproturon but N demethylated the compound to a minor extent. Mortierella sp. strain Gr4 also produced N-(4-(2-hydroxy-1-methylethyl)phenyl)-N′-methylurea, which is the product resulting from combined N demethylation and hydroxylation. PMID:16332769

Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones

PubMed Central

Hay, Colin W.; Shanley, Lynne; Davidson, Scott; Cowie, Philip; Lear, Marissa; McGuffin, Peter; Riedel, Gernot; McEwan, Iain J.; MacKenzie, Alasdair

2014-01-01

Summary Expression or introduction of the neuropeptide substance-P (SP; encoded by the TAC1 gene in humans and Tac1 in rodents) in the amygdala induces anxiety related behaviour in rodents. In addition, pharmacological antagonism of the main receptor of SP in humans; NK1, is anxiolytic. In the current study, we show that the Tac1 locus is up-regulated in primary rat amygdala neurones in response to activation of the glucocorticoid receptor (GR); a classic component of the stress response. Using a combination of bioinformatics, electrophoretic mobility shift assays (EMSA) and reporter plasmid magnetofection into rat primary amygdala neurones we identified a highly conserved GR response sequence (2GR) in the human TAC1 promoter that binds GR in response to dexamethasone (Dex) or forskolin. We also identified a second GR binding site in the human promoter that was polymorphic and whose T-allele is only found in Japanese and Chinese populations. We present evidence that the T-allele of SNPGR increases the activity of the TAC1 promoter through de-sequestration or de-repression of 2GR. The identification of Dex/forskolin response elements in the TAC1 promoter in amygdala neurones suggests a possible link in the chain of molecular events connecting GR activation and anxiety. In addition, the discovery of a SNP which can alter this response may have implications for our understanding of the role of regulatory variation in susceptibility to stress in specific populations. PMID:25001955

Expression Profiling Identifies Klf15 as a Glucocorticoid Target That Regulates Airway Hyperresponsiveness

PubMed Central

Masuno, Kiriko; Haldar, Saptarsi M.; Jeyaraj, Darwin; Mailloux, Christina M.; Huang, Xiaozhu; Panettieri, Rey A.; Jain, Mukesh K.

2011-01-01

Glucocorticoids (GCs), which activate GC receptor (GR) signaling and thus modulate gene expression, are widely used to treat asthma. GCs exert their therapeutic effects in part through modulating airway smooth muscle (ASM) structure and function. However, the effects of genes that are regulated by GCs on airway function are not fully understood. We therefore used transcription profiling to study the effects of a potent GC, dexamethasone, on human ASM (HASM) gene expression at 4 and 24 hours. After 24 hours of dexamethasone treatment, nearly 7,500 genes had statistically distinguishable changes in expression; quantitative PCR validation of a 40-gene subset of putative GR-regulated genes in 6 HASM cell lines suggested that the early transcriptional targets of GR signaling are similar in independent HASM lines. Gene ontology analysis implicated GR targets in controlling multiple aspects of ASM function. One GR-regulated gene, the transcription factor, Kruppel-like factor 15 (Klf15), was already known to modulate vascular smooth and cardiac muscle function, but had no known role in the lung. We therefore analyzed the pulmonary phenotype of Klf15−/− mice after ovalbumin sensitization and challenge. We found diminished airway responses to acetylcholine in ovalbumin-challenged Klf15−/− mice without a significant change in the induction of asthmatic inflammation. In cultured cells, overexpression of Klf15 reduced proliferation of HASM cells, whereas apoptosis in Klf15−/− murine ASM cells was increased. Together, these results further characterize the GR-regulated gene network in ASM and establish a novel role for the GR target, Klf15, in modulating airway function. PMID:21257922

Simple, rapid and green one-step strategy to synthesis of graphene/carbon nanotubes/chitosan hybrid as solid-phase extraction for square-wave voltammetric detection of methyl parathion.

PubMed

Liu, Yan; Yang, Shanli; Niu, Weifen

2013-08-01

Simple, rapid, green and one-step electrodeposition strategy was first proposed to synthesis of graphene/carbon nanotubes/chitosan (GR/CNTs/CS) hybrid. The one-step electrodeposition approach for the construction of GR-based hybrid is green environmentally, which would not involve the chemical reduction of graphene oxide (GO) and therefore result in no further contamination. The whole procedure is simple and needs only several minutes. Combining the advantages of GR (large surface area, high conductivity and good adsorption ability), CNTs (high surface area, high enrichment capability and good adsorption ability) and CS (good adsorption and excellent film-forming ability), the obtained GR/CNTs/CS composite could be highly efficient to capture organophosphate pesticides (OPs) and used as solid phase extraction (SPE). The GR/CNTs/CS sensor is used for enzymeless detection of OPs, using methyl parathion (MP) as a model analyte. Significant redox response of MP on GR/CNTs/CS sensor is proved. The linear range is wide from 2.0ngmL(-1) to 500ngmL(-1), with a detection limit of 0.5ngmL(-1). Detection limit of the proposed sensor is much lower than those enzyme-based sensors and many other enzymeless sensors. Moreover, the proposed sensor exhibits high reproducibility, long-time storage stability and satisfactory anti-interference ability. This work provides a green and one-step route for the preparation of GR-based hybrid, and also offers a new promising protocol for OPs analysis. Copyright © 2013 Elsevier B.V. All rights reserved.

Converging shock flows for a Mie-Grüneisen equation of state

NASA Astrophysics Data System (ADS)

Ramsey, Scott D.; Schmidt, Emma M.; Boyd, Zachary M.; Lilieholm, Jennifer F.; Baty, Roy S.

2018-04-01

Previous work has shown that the one-dimensional (1D) inviscid compressible flow (Euler) equations admit a wide variety of scale-invariant solutions (including the famous Noh, Sedov, and Guderley shock solutions) when the included equation of state (EOS) closure model assumes a certain scale-invariant form. However, this scale-invariant EOS class does not include even simple models used for shock compression of crystalline solids, including many broadly applicable representations of Mie-Grüneisen EOS. Intuitively, this incompatibility naturally arises from the presence of multiple dimensional scales in the Mie-Grüneisen EOS, which are otherwise absent from scale-invariant models that feature only dimensionless parameters (such as the adiabatic index in the ideal gas EOS). The current work extends previous efforts intended to rectify this inconsistency, by using a scale-invariant EOS model to approximate a Mie-Grüneisen EOS form. To this end, the adiabatic bulk modulus for the Mie-Grüneisen EOS is constructed, and its key features are used to motivate the selection of a scale-invariant approximation form. The remaining surrogate model parameters are selected through enforcement of the Rankine-Hugoniot jump conditions for an infinitely strong shock in a Mie-Grüneisen material. Finally, the approximate EOS is used in conjunction with the 1D inviscid Euler equations to calculate a semi-analytical Guderley-like imploding shock solution in a metal sphere and to determine if and when the solution may be valid for the underlying Mie-Grüneisen EOS.

Ultrastructure of kidney of ducks exposed to methylmercury, lead and cadmium in combination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rao, P.V.; Jordan, S.A.; Bhatnagar, M.K.

1989-01-01

Ultrastructural alterations in the kidneys of Pekin ducks exposed to various combinations of methylmercury chloride (MeHgCl), lead acetate (PbAC) and cadmium chloride (CdCl2) for 12 weeks were studied. Eight groups (Gr), each consisting of 6 female ducks, were fed diets containing no heavy metals (control), 8 mg of methylmercury chloride (MeHgCl)/kg of feed (GrII), 80 mg of lead acetate (PbAC)/kg of feed (GrIII), 80 mg of cadmium chloride (CdCl2)/kg of feed (GrIV), 8 mg of MeHgCl + 80 mg of PbAC/kg of feed (GrV), 8 mg of MeHgCl + 80 mg of CdCl2/kg of feed (GrVI), 80 mg of PbACmore » + 80 mg of CdCl2/kg of feed (GrVII), and 8 mg of MeHgCl + 80 mg of PbAC + 80 mg of CdCl2/kg of feed (GrVIII). Renal corpuscles of the ducks treated with methylmercury (MdHg), lead (Pb), the cadmium (Cd), either alone or in two way combinations exhibited minor ultrastructural changes. The thickness of the glomerular basement membrane was significantly different from control only in Grs II, IV, V and VI. Crystallization of granules in the juxtaglomerular cells was also observed in Cd and Pb treated birds. Administration of the three metals in combination caused marked changes in podocytes with fusion of secondary processes and no pedicle differentiation. The proximal tubule cells approximately (PT) accumulated lipid droplets, lysosomal bodies and membrane bound vacuoles in methylmercury treated birds. Lead exposed birds had a large number of secondary lysosomes and swollen mitochondria in PT cells. Cadmium administration caused degenerative changes in PT cells which included accumulation of lysosomal bodies containing degenerating organelles, lipid droplets and vacuoles containing myelin figures. Marked degenerative changes in PT cells and interstitial fibrosis was prominent when cadmium was concomitantly administered with the other metals.« less

Ectoderm-targeted overexpression of the glucocorticoid receptor induces hypohidrotic ectodermal dysplasia.

PubMed

Cascallana, Jose Luis; Bravo, Ana; Donet, Eva; Leis, Hugo; Lara, Maria Fernanda; Paramio, Jesús M; Jorcano, José L; Pérez, Paloma

2005-06-01

Hypohidrotic ectodermal dysplasia is a human syndrome defined by maldevelopment of one or more ectodermal-derived tissues, including the epidermis and cutaneous appendices, teeth, and exocrine glands. The molecular bases of this pathology converge in a dysfunction of the transcription factor nuclear factor of the kappa-enhancer in B cells (NF-kappaB), which is essential to epithelial homeostasis and development. A number of mouse models bearing disruptions in NF-kappaB signaling have been reported to manifest defects in ectodermal derivatives. In ectoderm-targeted transgenic mice overexpressing the glucocorticoid receptor (GR) [keratin 5 (K5)-GR mice], the NF-kappaB activity is greatly decreased due to functional antagonism between GR and NF-kappaB. Here, we report that K5-GR mice exhibit multiple epithelial defects in hair follicle, tooth, and palate development. Additionally, these mice lack Meibomian glands and display underdeveloped sweat and preputial glands. These phenotypic features appear to be mediated specifically by ligand-activated GR because the synthetic analog dexamethasone induced similar defects in epithelial morphogenesis, including odontogenesis, in wild-type mice. We have focused on tooth development in K5-GR mice and found that an inhibitor of steroid synthesis partially reversed the abnormal phenotype. Immunostaining revealed reduced expression of the inhibitor of kappaB kinase subunits, IKKalpha and IKKgamma, and diminished p65 protein levels in K5-GR embryonic tooth, resulting in a significantly reduced kappaB-binding activity. Remarkably, altered NF-kappaB activity elicited by GR overexpression correlated with a dramatic decrease in the protein levels of DeltaNp63 in tooth epithelia without affecting Akt, BMP4, or Foxo3a. Given that many of the 170 clinically distinct ectodermal dysplasia syndromes still remain without cognate genes, deciphering the molecular mechanisms of this mouse model with epithelial NF-kappaB and p63 dysfunction may provide important clues to understanding the basis of other ectodermal dysplasia syndromes.

Elevated utero/placental GR/NR3C1 is not required for the induction of parturition in the dog.

PubMed

Gram, Aykut; Trachsel, Alexandra; Boos, Alois; Kowalewski, Mariusz P

2016-10-01

The endocrine mechanisms that lead to initiation of parturition in dogs are still not fully understood. The prepartum luteolysis is associated with increased prostaglandin (PG) F2α secretion; however, there is no pregnancy- or parturition-related increase in estrogens. Moreover, unlike in other mammalian species, in the dog, increased peripartum levels of cortisol measured sporadically in maternal peripheral blood are not mandatory for normal parturition. Nevertheless, auto/paracrine effects of cortisol at the placental feto-maternal level cannot be excluded. Therefore, the aim of this study was to investigate the expression and localization of glucocorticoid receptor (GR/NR3C1) in canine utero/placental (Ut/Pl) units and uterine interplacental sites at selected time points during pregnancy (pre-implantation, post-implantation and mid-gestation), and at normal and antigestagen-induced parturition. The Ut/Pl expression of GR/NR3C1 did not change significantly from pre-implantation until mid-gestation; however, it was strongly induced during the prepartum luteolysis. Within the interplacental samples, expression of GR/NR3C1-mRNA was greater post-implantation than pre-implantation and did not change afterward, i.e. toward mid-gestation. Compartmentalization studies within the Ut/Pl units, involving placenta, endometrium and myometrium separately, performed at the prepartum luteolysis revealed the highest GR/NR3C1-mRNA levels in placenta compared with endometrium and myometrium. Interestingly, in antigestagen-treated mid-pregnancy dogs, Ut/Pl and interplacental GR/NR3C1-mRNA expression remained unaffected. At the cellular level, placental GR/NR3C1 was clearly detectable in placenta fetalis, i.e. in trophoblast cells. In conclusion, increased expression of GR/NR3C1 during normal parturition, but not following antigestagen-treatment, suggest that it is not required for initiating the signaling cascade of PG synthesis leading to the induction of parturition in the dog. © 2016 Society for Reproduction and Fertility.

Novel regulation of 25-hydroxyvitamin D3 24-hydroxylase (24(OH)ase) transcription by glucocorticoids: cooperative effects of the glucocorticoid receptor, C/EBP beta, and the Vitamin D receptor in 24(OH)ase transcription.

PubMed

Dhawan, Puneet; Christakos, Sylvia

2010-08-15

Glucocorticoid-induced bone loss has been proposed to involve direct effects on bone cells as well as alterations in calcium absorption and excretion. Since vitamin D is important for the maintenance of calcium homeostasis, in the present study the effects of glucocorticoids on vitamin D metabolism through the expression of 24(OH)ase, an enzyme involved in the catabolism of 1,25(OH)(2)D(3), were examined. Injection of vitamin D replete mice with dexamethasone (dex) resulted in a significant induction in 24(OH)ase mRNA in kidney, indicating a regulatory effect of glucocorticoids on vitamin D metabolism. Whether glucocorticoids can affect 24(OH)ase transcription is not known. Here we demonstrate for the first time a glucocorticoid receptor (GR) dependent enhancement of 1,25(OH)(2)D(3)-induced 24(OH)ase transcription. Dex treatment of GR and vitamin D receptor (VDR) transfected COS-7 cells and dex treatment of osteoblastic cells (in which VDR and GR are present endogenously) potentiated 1,25(OH)(2)D(3)-induced 24(OH)ase transcription. In addition, GR was found to cooperate with C/EBP beta to enhance VDR-mediated 24(OH)ase transcription. Using the rat 24(OH)ase promoter with the C/EBP site mutated, GR-mediated potentiation of 1,25(OH)(2)D(3)-induced 24(OH)ase transcription was inhibited. Immunoprecipitation indicated that that GR can interact with C/EBP beta and ChIP/re-ChIP analysis showed that C/EBP beta and GR bind simultaneously to the 24(OH)ase promoter. These findings indicate a novel mechanism whereby glucocorticoids can alter VDR-mediated 24(OH)ase transcription through functional cooperation between C/EBP beta and GR that results in an enhanced ability of C/EBP beta to cooperate with VDR in the regulation of 24(OH)ase. (c) 2010 Wiley-Liss, Inc.

A mannitol/sorbitol receptor stimulates dietary intake in Tribolium castaneum.

PubMed

Takada, Tomoyuki; Sato, Ryoichi; Kikuta, Shingo

2017-01-01

In insects, perception of chemical stimuli is involved in the acceptance or rejection of food. Gustatory receptors (Grs) that regulate external signals in chemosensory organs have been found in many insects. Tribolium castaneum, a major pest of stored products, possesses over 200 Gr genes. An expanded repertoire of Gr genes appears to be required for diet recognition in species that are generalist feeders; however, it remains unclear whether T. castaneum recognizes a suite of chemicals common to many products or whether its feeding is activated by specific chemicals, and whether its Grs are involved in feeding behavior. It is difficult to determine the food preferences of T. castaneum based on dietary intake due to a lack of appropriate methodology. This study established a novel dietary intake estimation method using gypsum, designated the TribUTE (Tribolium Urges To Eat) assay. For this assay, T. castaneum adults were fed a gypsum block without added organic compounds. Sweet preference was determined by adding sweeteners and measuring the amount of gypsum in the excreta. Mannitol was the strongest activator of T. castaneum dietary intake. In a Xenopus oocyte expression, TcGr20 was found to be responsible for mannitol and sorbitol responses, but not for responses to other tested non-volatile compounds. The EC50 values of TcGr20 for mannitol and sorbitol were 72.6 mM and 90.6 mM, respectively, suggesting that TcGr20 is a feasible receptor for the recognition of mannitol at lower concentrations. We used RNAi and the TribUTE assay to examine whether TcGr20 expression was involved in mannitol recognition. The amounts of excreta in TcGr20 dsRNA-injected adults decreased significantly, despite the presence of mannitol, compared to control adults. Taken together, our results indicate that T. castaneum adults recognized mannitol/sorbitol using the TcGr20 receptor, thereby facilitating the dietary intake of these compounds.

A mannitol/sorbitol receptor stimulates dietary intake in Tribolium castaneum

PubMed Central

Takada, Tomoyuki; Sato, Ryoichi

2017-01-01

In insects, perception of chemical stimuli is involved in the acceptance or rejection of food. Gustatory receptors (Grs) that regulate external signals in chemosensory organs have been found in many insects. Tribolium castaneum, a major pest of stored products, possesses over 200 Gr genes. An expanded repertoire of Gr genes appears to be required for diet recognition in species that are generalist feeders; however, it remains unclear whether T. castaneum recognizes a suite of chemicals common to many products or whether its feeding is activated by specific chemicals, and whether its Grs are involved in feeding behavior. It is difficult to determine the food preferences of T. castaneum based on dietary intake due to a lack of appropriate methodology. This study established a novel dietary intake estimation method using gypsum, designated the TribUTE (Tribolium Urges To Eat) assay. For this assay, T. castaneum adults were fed a gypsum block without added organic compounds. Sweet preference was determined by adding sweeteners and measuring the amount of gypsum in the excreta. Mannitol was the strongest activator of T. castaneum dietary intake. In a Xenopus oocyte expression, TcGr20 was found to be responsible for mannitol and sorbitol responses, but not for responses to other tested non-volatile compounds. The EC50 values of TcGr20 for mannitol and sorbitol were 72.6 mM and 90.6 mM, respectively, suggesting that TcGr20 is a feasible receptor for the recognition of mannitol at lower concentrations. We used RNAi and the TribUTE assay to examine whether TcGr20 expression was involved in mannitol recognition. The amounts of excreta in TcGr20 dsRNA-injected adults decreased significantly, despite the presence of mannitol, compared to control adults. Taken together, our results indicate that T. castaneum adults recognized mannitol/sorbitol using the TcGr20 receptor, thereby facilitating the dietary intake of these compounds. PMID:29023543

β-Carotene in Golden Rice is as good as β-carotene in oil at providing vitamin A to children.

PubMed

Tang, Guangwen; Hu, Yuming; Yin, Shi-an; Wang, Yin; Dallal, Gerard E; Grusak, Michael A; Russell, Robert M

2012-09-01

Golden Rice (GR) has been genetically engineered to be rich in β-carotene for use as a source of vitamin A. The objective was to compare the vitamin A value of β-carotene in GR and in spinach with that of pure β-carotene in oil when consumed by children. Children (n = 68; age 6-8 y) were randomly assigned to consume GR or spinach (both grown in a nutrient solution containing 23 atom% ²H₂O) or [²H₈]β-carotene in an oil capsule. The GR and spinach β-carotene were enriched with deuterium (²H) with the highest abundance molecular mass (M) at M(β-C)+²H₁₀. [¹³C₁₀]Retinyl acetate in an oil capsule was administered as a reference dose. Serum samples collected from subjects were analyzed by using gas chromatography electron-capture negative chemical ionization mass spectrometry for the enrichments of labeled retinol: M(retinol)+4 (from [²H₈]β-carotene in oil), M(retinol)+5 (from GR or spinach [²H₁₀]β-carotene), and M(retinol)+10 (from [¹³C₁₀]retinyl acetate). Using the response to the dose of [¹³C₁₀]retinyl acetate (0.5 mg) as a reference, our results (with the use of AUC of molar enrichment at days 1, 3, 7, 14, and 21 after the labeled doses) showed that the conversions of pure β-carotene (0.5 mg), GR β-carotene (0.6 mg), and spinach β-carotene (1.4 mg) to retinol were 2.0, 2.3, and 7.5 to 1 by weight, respectively. The β-carotene in GR is as effective as pure β-carotene in oil and better than that in spinach at providing vitamin A to children. A bowl of ~100 to 150 g cooked GR (50 g dry weight) can provide ~60% of the Chinese Recommended Nutrient Intake of vitamin A for 6-8-y-old children.

Generative Retrieval Improves Learning and Retention of Cardiac Anatomy Using Transesophageal Echocardiography.

PubMed

Kleiman, Amanda M; Forkin, Katherine T; Bechtel, Allison J; Collins, Stephen R; Ma, Jennie Z; Nemergut, Edward C; Huffmyer, Julie L

2017-05-01

Transesophageal echocardiography (TEE) is a valuable monitor for patients undergoing cardiac and noncardiac surgery as it allows for evaluation of cardiovascular compromise in the perioperative period. It is challenging for anesthesiology residents and medical students to learn to use and interpret TEE in the clinical environment. A critical component of learning to use and interpret TEE is a strong grasp of normal cardiovascular ultrasound anatomy. Fifteen fourth-year medical students and 15 post-graduate year (PGY) 1 and 2 anesthesiology residents without prior training in cardiac anesthesia or TEE viewed normal cardiovascular anatomy TEE video clips; participants were randomized to learning cardiac anatomy in generative retrieval (GR) and standard practice (SP) groups. GR participants were required to verbally identify each unlabeled cardiac anatomical structure within 10 seconds of the TEE video appearing on the screen. Then a correctly labeled TEE video clip was shown to the GR participant for 5 more seconds. SP participants viewed the same TEE video clips as GR but there was no requirement for SP participants to generate an answer; for the SP group, each TEE video image was labeled with the correctly identified anatomical structure for the 15 second period. All participants were tested for intermediate (1 week) and late (1 month) retention of normal TEE cardiovascular anatomy. Improvement of intermediate and late retention of TEE cardiovascular anatomy was evaluated using a linear mixed effects model with random intercepts and random slopes. There was no statistically significant difference in baseline score between GR (49% ± 11) and SP (50% ± 12), with mean difference (95% CI) -1.1% (-9.5, 7.3%). At 1 week following the educational intervention, GR (90% ± 5) performed significantly better than SP (82% ± 11), with mean difference (95% CI) 8.1% (1.9, 14.2%); P = .012. This significant increase in scores persisted in the late posttest session at one month (GR: 83% ± 12; SP: 72% ± 12), with mean difference (95% CI) 10.2% (1.3 to 19.1%); P = .026. Mixed effects analysis showed significant improvements in TEE cardiovascular anatomy over time, at 5.9% and 3.5% per week for GR and SP groups respectively (P = .0003), and GR improved marginally faster than SP (P = .065). Medical students and anesthesiology residents inexperienced in the use of TEE showed both improved learning and retention of basic cardiovascular ultrasound anatomy with the incorporation of GR into the educational experience.

Associations between DNA methylation of a glucocorticoid receptor promoter and acute stress responses in a large healthy adult population are largely explained by lifestyle and educational differences.

PubMed

de Rooij, Susanne R; Costello, Paula M; Veenendaal, Marjolein V E; Lillycrop, Karen A; Gluckman, Peter D; Hanson, Mark A; Painter, Rebecca C; Roseboom, Tessa J

2012-06-01

Glucocorticoids are the key regulators of the biological stress response and act by binding to glucocorticoid receptors (GR). Expression of GR is altered by DNA methylation. Methylation patterns in GR promoters have been shown to be highly variable between individuals, but little is known about the functional consequences of this variation for the acute stress response. The present study investigated associations between methylation status of the GR 1-C promoter and cortisol, cardiovascular and perceived stress responses to a psychosocial stress protocol in a large healthy adult population. A total of 725 overall healthy men and women, aged 55-60 years, participated in a standardized psychosocial stress protocol consisting of three different stressors. At different stages during the stress protocol, salivary cortisol levels, continuous blood pressure and heart rate (HR) levels as well as perceived stress were measured. Stress reactivity was calculated as the increase between basal and peak measurements. Methylation status of the GR 1-C promoter was assessed in DNA isolated from peripheral blood samples using a methylation sensitive PCR assay for 675 of the 725 participants. A decrease in methylation of the GR 1-C promoter was associated with a decrease in stress reactivity as indicated by lower cortisol and lower HR reactivity. A 1% decrease in GR 1-C methylation corresponded with a cortisol decrease by 0.14% (95% CI: 0.03-0.25, p=0.02) and an HR decrease by 0.10 bpm (0.03-0.16, p=0.003). Adjusting for sex, lifestyle and education largely abolished these associations. A decrease in methylation of the GR 1-C promoter was also associated with an increase in stress perception as indicated by higher perceived stress (0.03 points [0.00-0.06, p=0.05]), lower perceived performance (-0.03 points [-0.05 to -0.01], p=0.02), and lower perceived control (-0.03 points [-0.05 to 0.00], p=0.04). After adjusting for sex and educational level the associations were no longer statistically significant. GR 1-C methylation status was not associated with blood pressure responses to the stress protocol. Although effects were small, variation in methylation status in the GR 1-C promoter was associated with physical and perceived acute stress responses. Interestingly, these associations could largely be explained by differences in lifestyle and education. Copyright © 2011 Elsevier Ltd. All rights reserved.

The ability of laying pullets to negotiate two ramp designs as measured by bird preference and behaviour

PubMed Central

Weeks, Claire A.; Norman, Kate I.; Nicol, Christine J.

2017-01-01

Background Laying hens are often kept in barn or free-range systems where they must negotiate level changes in the house to access resources. However, collisions and resultant keel fractures are commonplace. Producers sometimes add ramps to make raised areas more accessible but designs vary and very little research has investigated bird preference or behaviour when using different ramp designs, or the effect of ramp design on falls and collisions. Methods Two ramp designs were studied in an experimental setting—a ramp made of plastic poultry slats (grid ramp, GR) and a ramp made of wooden rungs (ladder ramp, LR). Sixty-four young female hens were trained to move to a food reward and this was used to test their behavioural responses when first negotiating the two different ramps during individual tests. Both upward and downward transitions were studied. Ramp preference was also tested using a room that replicated a commercial single-tier system with both types of ramp available. Birds were placed in this room in groups of 16 for three days and their use of the ramps studied. Results A greater percentage of birds successfully completed (reached the reward bowl) on the GR than the LR during both upward (58% vs 37%) and downward (83% vs 73%) transitions, and a smaller percentage of birds made zero attempts to use the GR than the LR (upwards: 13% vs 56%, downwards: 8% vs 26%). When making a downward transition, more hesitation behaviours were seen (head orientations, stepping on the spot, moving away) for the LR. However, more head orientations were seen for the GR during the upward transition. Birds were more likely to abort attempts (an attempt began when a bird placed both feet on the ramp) to move up the GR than the LR. Birds took longer to negotiate the LR than the GR in both directions, and more pauses were seen during a successful upward transition on the LR. Birds were more likely to move down the GR by walking/running whereas birds tended to jump over the entire LR. More collisions with the food reward bowl were seen for the LR. In the group tests, birds preferred to use the GR, with more transitions seen at all timepoints. However, in these tests, birds preferred to rest on the LR with greater numbers of birds counted on this type of ramp during scan sampling at all timepoints. Discussion Behavioural results suggest that the GR was easier for the birds to use than the LR, particularly on the downward transition. The GR was also less likely to result in collisions. However, the upward transition may be more difficult on the GR for some birds, potentially because of the inability to pause on a level surface during the transition. The results suggest that the GR was preferred by pullets for moving between a raised area and the ground but the LR was preferred for resting. PMID:29177116

Functional Development of the Octenol Response in Aedes aegypti

DTIC Science & Technology

2013-03-07

and AgGr24 genes (Jones et al., 2007; Lu et al., 2007), the orthologs of the Drosophila melanogaster CO2 receptors Gr21a and Gr63a (Jones et al... genome with TopHat (Trapnell et al., 2009). Resulting sequence alignment files were uploaded into the Avadis NGS software (Strand Scientific...isolated following the manufacturer’s protocol and sent to the Genomic Services Lab at Hudson Alpha Institute for Biotechnology (Huntsville, Alabama

Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis | Center for Cancer Research

Cancer.gov

We demonstrate a novel tumor-promoting role of myeloid immune suppressor Gr+CD11b+ cells, which are evident in cancer patients and tumor-bearing animals. These cells constitute approximately 5% of total cells in tumors. Tumors coinjected with Gr+CD11b+ cells exhibited increased vascular density, vascular maturation, and decreased necrosis. These immune cells produce high

Analysis of the Glucocorticoid Receptor in Spontaneous and Drug-induced Steroid Resistant Mutants Isolated from the Human Leukemic Cell Line CEM-C7

DTIC Science & Technology

1991-01-04

be due to defects in GR function. However, the loss of GR function in x" S49 cells is paralleled by the loss of GR mRNA which is not seen in x’ OEM ...in the protein transcription factor IIIA from Xepopus oocytes. EMBO J. 4: 1609-1614. Milgrom. E.; Atger, M.; Baulieu, E.-E. 1973 Acidophilic

Should idiopathic facial aseptic granuloma be considered granulomatous rosacea? Report of three pediatric cases.

PubMed

Neri, Iria; Raone, Beatrice; Dondi, Arianna; Misciali, Cosimo; Patrizi, Annalisa

2013-01-01

Idiopathic facial aseptic granuloma (IFAG), or pyodermite froide du visage, is a skin disease reported only in children and characterized by painless red nodules usually located on the cheeks. Its etiology is still unclear, but some authors considered the possibility that IFAG might be included in the spectrum of granulomatous rosacea (GR). The histopathological features of IFAG and GR are quite similar, showing perifolliculitis, granulomas, folliculitis, and lymphocytes and plasmacells around epithelioid histiocytes. In the present article, we discuss three cases in which an association between a facial nodule, compatible with both IFAG and GR, and recurrent chalazia make us support the hypothesis that IFAG should be considered as GR. © 2012 Wiley Periodicals, Inc.

Reanalysis of the orbital period variations of two DLMR overcontact binaries: FG Hya and GR Vir

NASA Astrophysics Data System (ADS)

Zhang, Xu-Dong; Yu, Yun-Xia; Xiang, Fu-Yuan; Hu, Ke

2017-12-01

We investigate orbital period changes of two deep, low mass ratio (DLMR) overcontact W UMa-type binaries, FG Hya and GR Vir. It is found that the orbital period of FG Hya shows a cyclic change with a period of {P}{mod}=54.44 {yr}. The cyclic oscillation may be due to a third body in an eccentric orbit, while the orbital period of GR Vir shows a periodic variation with a period of {P}{mod}=28.56 {yr} and an amplitude of A = 0.0352 d. The periodic variation of GR Vir can be interpreted as a result of either the light-time effect of an unseen third body or the magnetic activity cycle.

Anti-glare LED lamps with adjustable illumination light field.

PubMed

Chen, Yung-Sheng; Lin, Chung-Yi; Yeh, Chun-Ming; Kuo, Chie-Tong; Hsu, Chih-Wei; Wang, Hsiang-Chen

2014-03-10

We introduce a type of LED light-gauge steel frame lamp with an adjustable illumination light field that does not require a diffusion plate. Base on the Monte Carlo ray tracing method, this lamp has a good glare rating (GR) of 17.5 at 3050 lm. Compared with the traditional LED light-gauge steel frame lamp (without diffusion plate), the new type has low GR. The adjustability of the illumination light field could improve the zebra effect caused by the inadequate illumination light field of the lamp. Meanwhile, we adopt the retinal image analysis to discuss the influence of GR on vision. High GR could reflect stray light on the retinal image, which will reduce vision clarity and hasten the feeling of eye fatigue.

Schottky barrier at graphene/metal oxide interfaces: insight from first-principles calculations

NASA Astrophysics Data System (ADS)

Cheng, Kai; Han, Nannan; Su, Yan; Zhang, Junfeng; Zhao, Jijun

2017-02-01

Anode materials play an important role in determining the performance of lithium ion batteries. In experiment, graphene (GR)/metal oxide (MO) composites possess excellent electrochemical properties and are promising anode materials. Here we perform density functional theory calculations to explore the interfacial interaction between GR and MO. Our result reveals generally weak physical interactions between GR and several MOs (including Cu2O, NiO). The Schottky barrier height (SBH) in these metal/semiconductor heterostructures are computed using the macroscopically averaged electrostatic potential method, and the role of interfacial dipole is discussed. The calculated SBHs below 1 eV suggest low contact resistance; thus these GR/MO composites are favorable anode materials for better lithium ion batteries.

Schottky barrier at graphene/metal oxide interfaces: insight from first-principles calculations.

PubMed

Cheng, Kai; Han, Nannan; Su, Yan; Zhang, Junfeng; Zhao, Jijun

2017-02-06

Anode materials play an important role in determining the performance of lithium ion batteries. In experiment, graphene (GR)/metal oxide (MO) composites possess excellent electrochemical properties and are promising anode materials. Here we perform density functional theory calculations to explore the interfacial interaction between GR and MO. Our result reveals generally weak physical interactions between GR and several MOs (including Cu2O, NiO). The Schottky barrier height (SBH) in these metal/semiconductor heterostructures are computed using the macroscopically averaged electrostatic potential method, and the role of interfacial dipole is discussed. The calculated SBHs below 1 eV suggest low contact resistance; thus these GR/MO composites are favorable anode materials for better lithium ion batteries.

Description of Alloretochus sigillatus new species with comments and new distributional records for Alloretochus peruanicus (Ephemeroptera, Caenidae, Brachycercinae).

PubMed

Molineri, C

2014-06-19

Alloretochus sigillatus sp. nov. is described from adults of both sexes and eggs from Bolivia and Ecuador. Diagnostic characters of this species include: large body size, ratio pedicel/scape 1.75, presence of posteromedian projection on metanotum, characteristic blackish marks on abdominal terga, presence of vestiges of posterolateral projections on abdomen segments IV-VI, male subgenital plate broadly emarginated posteriorly, ratios forceps length/subbasal width 8.9, female sternum IX produced distally reaching apex of segment X, tapering distally with rounded apex, egg with 4 costae in lateral half. Additional characters for all stages and SEM photographs of eggs are provided for Alloretochus peruanicus, with new records of its presence in Argentina, Bolivia, Peru and Colombia.

Combinatorial Effects of the Glucocorticoid Receptor and Krüppel-Like Transcription Factor 15 on Bovine Herpesvirus 1 Transcription and Productive Infection.

PubMed

El-Mayet, Fouad S; Sawant, Laximan; Thunuguntla, Prasanth; Jones, Clinton

2017-11-01

Bovine herpesvirus 1 (BoHV-1), an important bovine pathogen, establishes lifelong latency in sensory neurons. Latently infected calves consistently reactivate from latency following a single intravenous injection of the synthetic corticosteroid dexamethasone. The immediate early transcription unit 1 (IEtu1) promoter, which drives bovine ICP0 (bICP0) and bICP4 expression, is stimulated by dexamethasone because it contains two glucocorticoid receptor (GR) response elements (GREs). Several Krüppel-like transcription factors (KLF), including KLF15, are induced during reactivation from latency, and they stimulate certain viral promoters and productive infection. In this study, we demonstrate that the GR and KLF15 were frequently expressed in the same trigeminal ganglion (TG) neuron during reactivation and cooperatively stimulated productive infection and IEtu1 GREs in mouse neuroblastoma cells (Neuro-2A). We further hypothesized that additional regions in the BoHV-1 genome are transactivated by the GR or stress-induced transcription factors. To test this hypothesis, BoHV-1 DNA fragments (less than 400 bp) containing potential GR and KLF binding sites were identified and examined for transcriptional activation by stress-induced transcription factors. Intergenic regions within the unique long 52 gene (UL52; a component of the DNA primase/helicase complex), bICP4, IEtu2, and the unique short region were stimulated by KLF15 and the GR. Chromatin immunoprecipitation studies revealed that the GR and KLF15 interacted with sequences within IEtu1 GREs and the UL52 fragment. Coimmunoprecipitation studies demonstrated that KLF15 and the GR were associated with each other in transfected cells. Since the GR stimulates KLF15 expression, we suggest that these two transcription factors form a feed-forward loop that stimulates viral gene expression and productive infection following stressful stimuli. IMPORTANCE Bovine herpesvirus 1 (BoHV-1) is an important viral pathogen that causes respiratory disease and suppresses immune responses in cattle; consequently, life-threatening bacterial pneumonia can occur. Following acute infection, BoHV-1 establishes lifelong latency in sensory neurons. Reactivation from latency is initiated by the synthetic corticosteroid dexamethasone. Dexamethasone stimulates lytic cycle viral gene expression in sensory neurons of calves latently infected with BoHV-1, culminating in virus shedding and transmission. Two stress-induced cellular transcription factors, Krüppel-like transcription factor 15 (KLF15) and the glucocorticoid receptor (GR), cooperate to stimulate productive infection and viral transcription. Additional studies demonstrated that KLF15 and the GR form a stable complex and that these stress-induced transcription factors bind to viral DNA sequences, which correlates with transcriptional activation. The ability of the GR and KLF15 to synergistically stimulate viral gene expression and productive infection may be critical for the ability of BoHV-1 to reactivate from latency following stressful stimuli. Copyright © 2017 American Society for Microbiology.

Combinatorial Effects of the Glucocorticoid Receptor and Krüppel-Like Transcription Factor 15 on Bovine Herpesvirus 1 Transcription and Productive Infection

PubMed Central

El-mayet, Fouad S.; Sawant, Laximan; Thunuguntla, Prasanth

2017-01-01

ABSTRACT Bovine herpesvirus 1 (BoHV-1), an important bovine pathogen, establishes lifelong latency in sensory neurons. Latently infected calves consistently reactivate from latency following a single intravenous injection of the synthetic corticosteroid dexamethasone. The immediate early transcription unit 1 (IEtu1) promoter, which drives bovine ICP0 (bICP0) and bICP4 expression, is stimulated by dexamethasone because it contains two glucocorticoid receptor (GR) response elements (GREs). Several Krüppel-like transcription factors (KLF), including KLF15, are induced during reactivation from latency, and they stimulate certain viral promoters and productive infection. In this study, we demonstrate that the GR and KLF15 were frequently expressed in the same trigeminal ganglion (TG) neuron during reactivation and cooperatively stimulated productive infection and IEtu1 GREs in mouse neuroblastoma cells (Neuro-2A). We further hypothesized that additional regions in the BoHV-1 genome are transactivated by the GR or stress-induced transcription factors. To test this hypothesis, BoHV-1 DNA fragments (less than 400 bp) containing potential GR and KLF binding sites were identified and examined for transcriptional activation by stress-induced transcription factors. Intergenic regions within the unique long 52 gene (UL52; a component of the DNA primase/helicase complex), bICP4, IEtu2, and the unique short region were stimulated by KLF15 and the GR. Chromatin immunoprecipitation studies revealed that the GR and KLF15 interacted with sequences within IEtu1 GREs and the UL52 fragment. Coimmunoprecipitation studies demonstrated that KLF15 and the GR were associated with each other in transfected cells. Since the GR stimulates KLF15 expression, we suggest that these two transcription factors form a feed-forward loop that stimulates viral gene expression and productive infection following stressful stimuli. IMPORTANCE Bovine herpesvirus 1 (BoHV-1) is an important viral pathogen that causes respiratory disease and suppresses immune responses in cattle; consequently, life-threatening bacterial pneumonia can occur. Following acute infection, BoHV-1 establishes lifelong latency in sensory neurons. Reactivation from latency is initiated by the synthetic corticosteroid dexamethasone. Dexamethasone stimulates lytic cycle viral gene expression in sensory neurons of calves latently infected with BoHV-1, culminating in virus shedding and transmission. Two stress-induced cellular transcription factors, Krüppel-like transcription factor 15 (KLF15) and the glucocorticoid receptor (GR), cooperate to stimulate productive infection and viral transcription. Additional studies demonstrated that KLF15 and the GR form a stable complex and that these stress-induced transcription factors bind to viral DNA sequences, which correlates with transcriptional activation. The ability of the GR and KLF15 to synergistically stimulate viral gene expression and productive infection may be critical for the ability of BoHV-1 to reactivate from latency following stressful stimuli. PMID:28794031

Parathyroid Hormone Activates Phospholipase C (PLC)-Independent Protein Kinase C Signaling Pathway via Protein Kinase A (PKA)-Dependent Mechanism: A New Defined Signaling Route Would Induce Alternative Consideration to Previous Conceptions

PubMed Central

Tong, Guojun; Meng, Yue; Hao, Song; Hu, Shaoyu; He, Youhua; Yan, Wenjuan; Yang, Dehong

2017-01-01

Background Parathyroid hormone (PTH) is an effective anti-osteoporosis agent, after binding to its receptor PTHR1, several signaling pathways, including cAMP/protein kinase A (PKA) and phospholipase C (PLC)/protein kinase C (PKC), are initiated through G proteins; with the cAMP/PKA pathway as the major pathway. Earlier studies have reported that PTHR1 might also activate PKC via a PLC-independent mechanism, but this pathway remains unclear. Material/Methods In HEK293 cells, cAMP accumulation was measured with ELISA and PKC was measured with fluorescence resonance energy transfer (FRET) analysis using CKAR plasmid. In MC3T3-E1 cells, real-time PCR was performed to examine gene expressions. Then assays for cell apoptosis, cell differentiation, alkaline phosphatase activity, and mineralization were performed. Results The FRET analysis found that PTH(1–34), [G1,R19]PTH(1–34) (GR(1–34), and [G1,R19]PTH(1–28) (GR(1–28) were all activated by PKC. The PKC activation ability of GR(1–28) was blocked by cAMP inhibitor (Rp-cAMP) and rescued with the addition of active PKA-α and PKA-β. The PKC activation ability of GR(1–34) was partially inhibited by Rp-cAMP. In MC3T3-E1 cells, gene expressions of ALP, CITED1, NR4a2, and OSX that was regulated by GR(1–28) were significantly changed by the pan-PKC inhibitor Go6983. After pretreatment with Rp-cAMP, the gene expressions of ALP, CITED1, and OPG were differentially regulated by GR(1–28) or GR(1–34), and the difference was blunted by Go6983. PTH(1–34), GR(1–28), and GR(1–34) significantly decreased early apoptosis and augmented osteoblastic differentiation in accordance with the activities of PKA and PKC. Conclusions PLC-independent PKC activation induced by PTH could be divided into two potential mechanisms: one was PKA-dependent and associated with PTH(1–28); the other was PKA-independent and associated with PTH(29–34). We also found that PTH could activate PLC-independent PKC via PKA-dependent mechanisms. PMID:28424452

Clinical prognostic factors and grading system for rib fracture following stereotactic body radiation therapy (SBRT) in patients with peripheral lung tumors.

PubMed

Kim, Su Ssan; Song, Si Yeol; Kwak, Jungwon; Ahn, Seung Do; Kim, Jong Hoon; Lee, Jung Shin; Kim, Woo Sung; Kim, Sang-We; Choi, Eun Kyung

2013-02-01

Several studies reported rib fractures following stereotactic body radiation therapy (SBRT) for peripheral lung tumors. We tried to investigate risk factors and grading system for rib fractures after SBRT. Of 375 primary or metastatic lung tumors (296 patients) which were treated with SBRT at the Asan Medical Center (2006-2009), 126 lesions (118 patients) were adjacent to the chest-wall (<1cm) and followed-up with chest computed tomography (CT) for >6 months; these were investigated in the present retrospective study. Three to four fractional doses of 10-20 Gy were delivered to 85-90% iso-dose volume of the isocenter dose. Rib fracture grade was defined from follow-up CT scans as the appearance of a fracture line (Gr1), dislocation of the fractured rib by more than half the rib diameter (Gr2), or the appearance of adjacent soft tissue edema (Gr3). Chest wall pain was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Correlations between dose-volume data and the development of rib fracture were then analyzed. The Kaplan-Meier method, log-rank tests, and chi-square tests were used for statistical analysis. The median age of the patients was 69 years (range: 19-90). Over a median follow-up period of 22 months (range: 7-62), 48 cases of rib fracture were confirmed. Median time to rib fracture was 17 months (range: 4-52). The 2-year actuarial risk of rib fracture was 42.4%. Maximal grade was Gr1 (n=28), Gr2 (n=8), or Gr3 (n=15). The incidence of moderate to severe chest wall pain (CTCAE Gr ≥ 2) increased with maximal fracture grade (17.5% for Gr0-1 and 60.9% for Gr2-3; p<0.001). Multivariate analysis identified female gender, lateral location, and the dose to the 8cc of the chest wall as significant prognostic factors. Female gender and lateral tumor location were clinical risk factors for rib fracture in the present study. Efforts to decrease chest wall dose should be made to reduce the risk of the rib fracture, particularly in high-risk patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Spin foam models for quantum gravity

NASA Astrophysics Data System (ADS)

Perez, Alejandro

The definition of a quantum theory of gravity is explored following Feynman's path-integral approach. The aim is to construct a well defined version of the Wheeler-Misner- Hawking ``sum over four geometries'' formulation of quantum general relativity (GR). This is done by means of exploiting the similarities between the formulation of GR in terms of tetrad-connection variables (Palatini formulation) and a simpler theory called BF theory. One can go from BF theory to GR by imposing certain constraints on the BF-theory configurations. BF theory contains only global degrees of freedom (topological theory) and it can be exactly quantized á la Feynman introducing a discretization of the manifold. Using the path integral for BF theory we define a path integration for GR imposing the BF-to-GR constraints on the BF measure. The infinite degrees of freedom of gravity are restored in the process, and the restriction to a single discretization introduces a cut- off in the summed-over configurations. In order to capture all the degrees of freedom a sum over discretization is implemented. Both the implementation of the BF-to-GR constraints and the sum over discretizations are obtained by means of the introduction of an auxiliary field theory (AFT). 4-geometries in the path integral for GR are given by the Feynman diagrams of the AFT which is in this sense dual to GR. Feynman diagrams correspond to 2-complexes labeled by unitary irreducible representations of the internal gauge group (corresponding to tetrad rotation in the connection to GR). A model for 4-dimensional Euclidean quantum gravity (QG) is defined which corresponds to a different normalization of the Barrett-Crane model. The model is perturbatively finite; divergences appearing in the Barrett-Crane model are cured by the new normalization. We extend our techniques to the Lorentzian sector, where we define two models for four-dimensional QG. The first one contains only time-like representations and is shown to be perturbatively finite. The second model contains both time-like and space-like representations. The spectrum of geometrical operators coincide with the prediction of the canonical approach of loop QG. At the moment, the convergence properties of the model are less understood and remain for future investigation.

Air-particle abrasion on zirconia ceramic using different protocols: effects on biaxial flexural strength after cyclic loading, phase transformation and surface topography.

PubMed

Souza, Rodrigo O A; Valandro, Luiz F; Melo, Renata M; Machado, João P B; Bottino, Marco A; Ozcan, Mutlu

2013-10-01

This study evaluated the effect of different air-particle abrasion protocols on the biaxial flexural strength and structural stability of zirconia ceramics. Zirconia ceramic specimens (ISO 6872) (Lava, 3M ESPE) were obtained (N=336). The specimens (N=118, n=20 per group) were randomly assigned to one of the air-abrasion protocols: Gr1: Control (as-sintered); Gr2: 50 µm Al2O3 (2.5 bar); Gr3: 50 µm Al2O3 (3.5 bar); Gr4: 110 µm Al2O3(2.5 bar); Gr5: 110 µm Al2O3 (3.5 bar); Gr6: 30 µm SiO2 (2.5 bar) (CoJet); Gr7: 30 µm SiO2(3.5 bar); Gr8: 110 µm SiO2 (2.5 bar) (Rocatec Plus); and Gr9: 110 µm SiO2 (3.5 bar) (duration: 20 s, distance: 10 mm). While half of the specimens were tested immediately, the other half was subjected to cyclic loading in water (100,000 cycles; 50 N, 4 Hz, 37 °°C) prior to biaxial flexural strength test (ISO 6872). Phase transformation (t→m), relative amount of transformed monoclinic zirconia (FM), transformed zone depth (TZD) and surface roughness were measured. Particle type (p=0.2746), pressure (p=0.5084) and cyclic loading (p=0.1610) did not influence the flexural strength. Except for the air-abraded group with 110 µm Al2O3 at 3.5 bar, all air-abrasion protocols increased the biaxial flexural strength (MPa) (Controlnon-aged: 1,030 ± 153, Controlaged: 1,138 ± 138; Experimentalnon-aged: 1,307 ± 184-1,554 ± 124; Experimentalaged: 1,308 ± 118-1,451 ± 135) in both non-aged and aged conditions, respectively. Surface roughness (Ra) was the highest with 110 µm Al2O3(0.84 µm. FM values ranged from 0% to 27.21%, higher value for the Rocatec Plus (110 µm SiO2) and 110 µm Al2O3 groups at 3.5 bar pressure. TZD ranged between 0 and 1.43 µm, with the highest values for Rocatec Plus and 110 µm Al2O3 groups at 3.5 bar pressure. Copyright © 2013 Elsevier Ltd. All rights reserved.

Colloidal graphite/graphene nanostructures using collagen showing enhanced thermal conductivity.

PubMed

Bhattacharya, Soumya; Dhar, Purbarun; Das, Sarit K; Ganguly, Ranjan; Webster, Thomas J; Nayar, Suprabha

2014-01-01

In the present study, the exfoliation of natural graphite (GR) directly to colloidal GR/graphene (G) nanostructures using collagen (CL) was studied as a safe and scalable process, akin to numerous natural processes and hence can be termed "biomimetic". Although the exfoliation and functionalization takes place in just 1 day, it takes about 7 days for the nano GR/G flakes to stabilize. The predominantly aromatic residues of the triple helical CL forms its own special micro and nanoarchitecture in acetic acid dispersions. This, with the help of hydrophobic and electrostatic forces, interacts with GR and breaks it down to nanostructures, forming a stable colloidal dispersion. Surface enhanced Raman spectroscopy, X-ray diffraction, photoluminescence, fluorescence, and X-ray photoelectron spectroscopy of the colloid show the interaction between GR and CL on day 1 and 7. Differential interference contrast images in the liquid state clearly reveal how the GR flakes are entrapped in the CL fibrils, with a corresponding fluorescence image showing the intercalation of CL within GR. Atomic force microscopy of graphene-collagen coated on glass substrates shows an average flake size of 350 nm, and the hexagonal diffraction pattern and thickness contours of the G flakes from transmission electron microscopy confirm ≤ five layers of G. Thermal conductivity of the colloid shows an approximate 17% enhancement for a volume fraction of less than approximately 0.00005 of G. Thus, through the use of CL, this new material and process may improve the use of G in terms of biocompatibility for numerous medical applications that currently employ G, such as internally controlled drug-delivery assisted thermal ablation of carcinoma cells.

Complications of growth-sparing surgery in early onset scoliosis.

PubMed

Akbarnia, Behrooz A; Emans, John B

2010-12-01

Review of available literature, authors' opinion. To describe complications associated with growth-sparing surgical treatment of early onset scoliosis (EOS). EOS has many potential etiologies and is often associated with thoracic insufficiency syndrome. The growth of the spine, thorax, and lungs are interrelated, and severe EOS typically involves disturbance of the normal development of all 3. Severe EOS may be treated during growth with surgical techniques, intended to preserve growth while controlling deformity, the most common of which are spinal "growing rods" (GR) or "vertical expandable prosthetic titanium rib" (VEPTR). Although presently popular, there is minimal long-term data on the outcome of growth-sparing surgical techniques on EOS. Review. Potential adverse outcomes of GR or VEPTR treatment of EOS include failure to prevent progressive deformity or thoracic insufficiency syndrome, an unacceptably short or stiff spine or deformed thorax, increased family burden of care, and potentially negative psychological consequences from repeated surgical interventions. Neither technique reliably controls all deformity over the entirety of growth period. Infections are common to both GR and VEPTR. Rod breakage and spontaneous premature spinal fusion beneath rods are troublesome complications in GR, whereas drift of rib attachments and chest wall scarring are anticipated complications in VEPTR treatment. Indications for GR and VEPTR overlap, but thoracogenic scoliosis and severe upper thoracic kyphosis are best treated by VEPTR and GR, respectively. Surgeons planning treatment of EOS should anticipate the many complications common to growth-sparing surgery, share their knowledge with families, and use complications as one factor in the complex decision as to when and whether to initiate the repetitive surgeries associated with GR or VEPTR in the treatment of severe EOS.

High level of reduced glutathione contributes to detoxification of lipid peroxide-derived reactive carbonyl species in transgenic Arabidopsis overexpressing glutathione reductase under aluminum stress.

PubMed

Yin, Lina; Mano, Jun'ichi; Tanaka, Kiyoshi; Wang, Shiwen; Zhang, Meijuan; Deng, Xiping; Zhang, Suiqi

2017-10-01

Lipid peroxide-derived reactive carbonyl species (RCS), generated downstream of reactive oxygen species (ROS), are critical damage-inducing species in plant aluminum (Al) toxicity. In mammals, RCS are scavenged primarily by glutathione (reduced form of glutathione, GSH), but in plant Al stress, contribution of GSH to RCS detoxification has not been evaluated. In this study, Arabidopsis plants overexpressing the gene AtGR1 (accession code At3g24170), encoding glutathione reductase (GR), were generated, and their performance under Al stress was examined. These transgenic plants (GR-OE plants) showed higher GSH levels and GSH/GSSG (oxidized form of GSH) ratio, and an improved Al tolerance as they suffered less inhibition of root growth than wild-type under Al stress. Exogenous application of 4-hydroxy-2-nonenal, an RCS responsible for Al toxicity in roots, markedly inhibited root growth in wild-type plants. GR-OE plants suffered significantly smaller inhibition, indicating that the enhanced GSH level increased the capacity of RCS detoxification. The generation of H 2 O 2 due to Al stress in GR-OE plants was lower by 26% than in wild-type. Levels of various RCS, such as malondialdehyde, butyraldehyde, phenylacetaldehyde, (E)-2-heptenal and n-octanal, were suppressed by more than 50%. These results indicate that high levels of GSH and GSH/GSSG ratio by GR overexpression contributed to the suppression of not only ROS, but also RCS. Thus, the maintenance of GSH level by overexpressing GR reinforces dual detoxification functions in plants and is an efficient approach to enhance Al tolerance. © 2017 Scandinavian Plant Physiology Society.

Enhancement of ligand-dependent down-regulation of glucocorticoid receptor by lipopolysaccharide.

PubMed

Hirasawa, Noriyasu; Yashima, Kazushi; Ishihara, Kenji

2009-10-07

The inhibitory actions of glucocorticoids are often attenuated in inflamed tissues. The aim of the present study was to investigate whether the dexamethasone-induced downregulation of glucocorticoid receptor (GR) expression was enhanced by the stimulation with lipopolysaccharide (LPS). Various cells were stimulated with LPS (1microg/ml) for 30min and then treated with dexamethasone (1microM) for specified periods. The levels of GR and the phosphorylation at Ser211 were determined by Western blot. The effects of kinase inhibitors and a proteasome inhibitor on them were examined. The treatment of NCI-H292 cells with dexamethasone reduced the levels of GR, and the pretreatment with LPS accelerated the reduction. Such an enhancement by LPS of the dexamethasone-induced downregulation was observed in the respiratory epithelial cell lines BEAS-2B and A549, but not in the keratinocyte-like cell line HaCaT, the hematopoietic cell lines U937, THP-1 and Eol-1, or in hepatocytoma HepG2 cells. The treatment with dexamethasone and LPS apparently decreased GR levels in the lungs of BALB/c mice but not in the liver. In NCI-H292 cells, the LPS-enhanced downregulation of GR expression was recovered by the proteasome inhibitor MG-132. SP600125, SB203580 and roscovitine but not U0126 inhibited the LPS-induced enhancement of both the phosphorylation and the downregulation of GR. These findings suggested that the ligand-dependent downregulation of GR expression via the proteasome was apparent in the respiratory epithelial cells and enhanced by lipopolysaccharide via the activation of p38 MAP kinase, c-Jun N-terminal kinase and cyclin-dependent kinases.

The influence of combined oral contraceptives containing drospirenone on hypothalamic-pituitary-adrenocortical axis activity and glucocorticoid receptor expression and function in women with polycystic ovary syndrome.

PubMed

Macut, Djuro; Božić Antić, Ivana; Nestorov, Jelena; Topalović, Vladanka; Bjekić Macut, Jelica; Panidis, Dimitrios; Kastratović Kotlica, Biljana; Papadakis, Efstathios; Matić, Gordana; Vojnović Milutinović, Danijela

2015-01-01

Most women with PCOS have increased adrenal androgen production, enhanced peripheral metabolism of cortisol and elevation in urinary excretion of its metabolites. Increased cortisol clearance in PCOS is followed by a compensatory overdrive of the hypothalamic-pituitary-adrenocortical (HPA) axis. We hypothesized that oral contraceptives containing ethinylestradiol and drospirenone (EE-DRSP) could modulate glucocorticoid receptor (GR) expression and function and thus affect HPA axis activity in PCOS patients. We analyzed 12 women with PCOS (age 24.17±4.88 years; body mass index 22.05±3.97 kg/m²) treated for 12 months with EE-DRSP and 20 BMI matched controls. In all subjects testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), cortisol (basal and after dexamethasone), concentrations of GR protein, phospo-GR211 protein, number of GR per cell (B(max) and its equilibrium dissociation constant (K(D)) were measured. Before treatment, increased concentrations of testosterone and DHEAS (p<0.001, respectively), unaltered basal cortisol and an increased sensitivity (p<0.05) of the HPA axis to dexamethasone were observed in PCOS women in comparison to controls. After treatment, testosterone (p<0.01), DHEAS (p<0.05) and cortisol suppression after dexamethasone (p<0.01) were decreased in PCOS women. There were no changes in GR protein concentration, GR phosphorylation nor in the receptor functional parameters B(max) and K(D) in women with PCOS before and after the therapy, and in comparison to controls. Prolonged treatment with EE-DRSP in PCOS women decreased serum androgens and increased cortisol in the presence of decreased sensitivity of the HPA axis and did not exert changes in GR expression and function.

Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in Holocaust survivor offspring.

PubMed

Yehuda, Rachel; Daskalakis, Nikolaos P; Lehrner, Amy; Desarnaud, Frank; Bader, Heather N; Makotkine, Iouri; Flory, Janine D; Bierer, Linda M; Meaney, Michael J

2014-08-01

Differential effects of maternal and paternal posttraumatic stress disorder (PTSD) have been observed in adult offspring of Holocaust survivors in both glucocorticoid receptor sensitivity and vulnerability to psychiatric disorder. The authors examined the relative influences of maternal and paternal PTSD on DNA methylation of the exon 1F promoter of the glucocorticoid receptor (GR-1F) gene (NR3C1) in peripheral blood mononuclear cells and its relationship to glucocorticoid receptor sensitivity in Holocaust offspring. Adult offspring with at least one Holocaust survivor parent (N=80) and demographically similar participants without parental Holocaust exposure or parental PTSD (N=15) completed clinical interviews, self-report measures, and biological procedures. Blood samples were collected for analysis of GR-1F promoter methylation and of cortisol levels in response to low-dose dexamethasone, and two-way analysis of covariance was performed using maternal and paternal PTSD as main effects. Hierarchical clustering analysis was used to permit visualization of maternal compared with paternal PTSD effects on clinical variables and GR-1F promoter methylation. A significant interaction demonstrated that in the absence of maternal PTSD, offspring with paternal PTSD showed higher GR-1F promoter methylation, whereas offspring with both maternal and paternal PTSD showed lower methylation. Lower GR-1F promoter methylation was significantly associated with greater postdexamethasone cortisol suppression. The clustering analysis revealed that maternal and paternal PTSD effects were differentially associated with clinical indicators and GR-1F promoter methylation. This is the first study to demonstrate alterations of GR-1F promoter methylation in relation to parental PTSD and neuroendocrine outcomes. The moderation of paternal PTSD effects by maternal PTSD suggests different mechanisms for the intergenerational transmission of trauma-related vulnerabilities.

Effects of gramicidin-A on the adsorption of phospholipids to the air–water interface

PubMed Central

Biswas, Samares C.; Rananavare, Shankar B.; Hall, Stephen B.

2012-01-01

Prior studies suggest that the hydrophobic surfactant proteins, SP-B and SP-C, promote adsorption of the lipids in pulmonary surfactant to an air–water interface by stabilizing a negatively curved rate-limiting structure that is intermediate between bilayer vesicles and the surface film. This model predicts that other peptides capable of stabilizing negative curvature should also promote lipid adsorption. Previous reports have shown that under appropriate conditions, gramicidin-A (GrA) induces dioleoyl phosphatidylcholine (DOPC), but not dimyristoyl phosphatidylcholine (DMPC), to form the negatively curved hexagonal-II (HII) phase. The studies reported here determined if GrA would produce the same effects on adsorption of DMPC and DOPC that the hydrophobic surfactant proteins have on the surfactant lipids. Small angle X-ray scattering and 31P-nuclear magnetic resonance confirmed that at the particular conditions used to study adsorption, GrA induced DOPC to form the HII phase, but DMPC remained lamellar. Measurements of surface tension showed that GrA in vesicles produced a general increase in the rate of adsorption for both phospholipids. When restricted to the interface, however, in preexisting films, GrA with DOPC, but not with DMPC, replicated the ability of the surfactant proteins to promote adsorption of vesicles containing only the lipids. The correlation between the structural and functional effects of GrA with the two phospholipids, and the similar effects on adsorption of GrA with DOPC and the hydrophobic surfactant proteins with the surfactant lipids fit with the model in which SP-B and SP-C facilitate adsorption by stabilizing a rate-limiting intermediate with negative curvature. PMID:16242116

Clarithromycin expands CD11b+Gr-1+ cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and post-influenza bacterial pneumonia

PubMed Central

Fujii, Hideki; Yagi, Kazuma; Suzuki, Shoji; Hegab, Ahmed E.; Tasaka, Sadatomo; Nakamoto, Nobuhiro; Iwata, Satoshi; Honda, Kenya; Kanai, Takanori; Hasegawa, Naoki; Betsuyaku, Tomoko

2018-01-01

Macrolides are used to treat various inflammatory diseases owing to their immunomodulatory properties; however, little is known about their precise mechanism of action. In this study, we investigated the functional significance of the expansion of myeloid-derived suppressor cell (MDSC)-like CD11b+Gr-1+ cells in response to the macrolide antibiotic clarithromycin (CAM) in mouse models of shock and post-influenza pneumococcal pneumonia as well as in humans. Intraperitoneal administration of CAM markedly expanded splenic and lung CD11b+Gr-1+ cell populations in naïve mice. Notably, CAM pretreatment enhanced survival in a mouse model of lipopolysaccharide (LPS)-induced shock. In addition, adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice against LPS-induced lethality via increased IL-10 expression. CAM also improved survival in post-influenza, CAM-resistant pneumococcal pneumonia, with improved lung pathology as well as decreased interferon (IFN)-γ and increased IL-10 levels. Adoptive transfer of CAM-treated CD11b+Gr-1+ cells protected mice from post-influenza pneumococcal pneumonia. Further analysis revealed that the CAM-induced CD11b+Gr-1+ cell expansion was dependent on STAT3-mediated Bv8 production and may be facilitated by the presence of gut commensal microbiota. Lastly, an analysis of peripheral blood obtained from healthy volunteers following oral CAM administration showed a trend toward the expansion of human MDSC-like cells (Lineage−HLA-DR−CD11b+CD33+) with increased arginase 1 mRNA expression. Thus, CAM promoted the expansion of a unique population of immunosuppressive CD11b+Gr-1+ cells essential for the immunomodulatory properties of macrolides. PMID:29621339

Comparison of surface energy budgets and feedbacks to microclimate among different land use types in an agro-pastoral ecotone of northern China.

PubMed

Zhao, Wei; Hu, Zhongmin; Li, Shenggong; Guo, Qun; Liu, Zhengjia; Zhang, Leiming

2017-12-01

The biophysical effect of land use conversion plays a significant role in regulating climate change. Owing to albedo and evapotranspiration (ET) change, the effect of energy budget difference on land surface temperature (LST) is important but unclear among contrasting land use types, especially in temperate semi-arid regions. Based on moderate-resolution imaging spectroradiometer (MODIS) data, we compared the differences in albedo, ET, and LST between cropland and grassland (CR-GR), and between planted forest and grassland (PF-GR) in the Horqin Sandy Land of Inner Mongolia, an agro-pastoral ecotone of northern China. Our main objective was to explore the magnitude and direction of albedo and ET change during the growing season and, subsequently, to estimate the biophysical effects on LST as a result of land use and land cover change. Our results indicate no significant difference in mean monthly albedo for CR-GR and PF-GR. Cropland lost more water through ET and significantly decreased daytime LST compared with grassland from July to September, but no significant differences in ET and LST were observed for PF-GR in any month. The biophysical climate effects were more pronounced for CR-GR compared with PF-GR. The response of LST to the changes in energy budget confirmed that ET was the critical driving factor relative to albedo. Compared with grassland, cropland and planted forest tended to cool the land surface by 5.15°C and 1.51°C during the growing season, respectively, because of the biophysical effects. Our findings suggest the significance of local-scale biophysical effect on climate variation after land use conversion in semi-arid regions. Copyright © 2017 Elsevier B.V. All rights reserved.

Biomass Burning and the 2012 Greenland Ice Sheet (GrIS) melt

NASA Astrophysics Data System (ADS)

Choi, H. D.; Soja, A. J.; Polashenski, C.; Fairlie, T. D.; Winker, D. M.; Trepte, C. R.

2017-12-01

This study is the part of the Sunlight Absorption on the Greenland ice sheet Experiment (SAGE) project investigating the impact of light absorbing impurities (e.g., aerosols) on the Greenland Ice Sheet (GrIS). Satellite observations, [e.g. Oceansat-2 (OS2) and the Moderate-resolution Imaging Spectroradionmeter (MODIS)] discovered an unusually large melt event in July 2012. NASA sensors showed that nearly 98.6% of the GrIS experienced melting at or near surface [Nghiem et al., 2012]. In this study, we question the extent to which biomass burning derived aerosols enhanced melting across the GrIS. Random points [59 total, 13 coincident with snow pit sites and 46 gridded] are selected across the entire extent of the GrIS from April 1st to August 31st 2012, and then the NASA Langley Trajectory Model (LaTM) is used to simulate the transport of potentially smoke-filled air parcels backwards for 5 days form these points, evaluation the back trajectory for coincidence with active fire detections. The trajectory model is initialized for 24-hour sustained injection from each site, and air parcels are released from the surface to 2 km at 200m intervals. With the trajectory model outputs, we are able to identify trajectories that have coincidences with fires. We focus on events in April through July when the GrIS albedo was dramatically decreased. We also utilize Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) data to verify smoke-aerosol signatures in boreal regions based on the NASA LaTM results. The results of this study will help us better understand the transport of biomass burning plumes and black carbon deposition that could lead to enhanced GrIS melting.

In vivo gastric residence and gastroprotective effect of floating gastroretentive tablet of DA-9601, an extract of Artemisia asiatica, in beagle dogs

PubMed Central

Kim, Jeong Soo; Cha, Kwang Ho; Kang, Seung Yeob; Won, Donghan; Jang, Sun Woo; Son, Miwon; Son, Moon Ho; Choi, Ho Jung; Lee, Young Won; Kang, Myung Joo

2016-01-01

Objective DA-9601, an extract of Artemisia asiatica containing eupatilin and jaceosidin as active compounds, has been prescribed to treat gastritis in Asia. In recent times, sustained-release, floating gastroretentive (GR) tablets of DA-9601 are available on the market. In the present study, the physical properties and in vitro drug release profile, in vivo gastric residence time, and gastroprotective effect of GR tablet were compared to those of immediate release (IR) tablets of DA-9601. Method In vitro buoyancy behavior (floating lag time and duration) and release profile of eupatilin were assessed in acidic medium. The in vivo intragastric behaviors of the barium sulfate-loaded IR and GR tablets were evaluated in beagle dogs by radiographic studies. Local gastroprotective effect was compared in an experimentally induced gastric lesion in beagle dogs after oral administration of IR (three times per day) or GR (twice daily) tablets for 15 days. Results Upon contact with gastric juice, a low-density floating tablet (apparent density of 0.93 g/cm3) was buoyant on the medium and was upheld for 14 hours, providing sustained drug release profile, whereas the IR tablet disintegrated within 10 minutes, showing complete drug release within 2 hours. In vivo radiographic studies showed that the GR tablet was retained for >4 hours in the stomach. Both DA-9601 formulations remarkably alleviated gastric mucosal injury compared to placebo group, when observed by gastric endoscopy. Conclusion Twice-daily GR tablets exhibited a prolonged gastric residence time and a remarkable mucosal restoration effect in animal models. Therefore, the GR system of DA-9601 could be a substitute dosage form for the treatment of gastritis, while reducing the dosing frequency and thus improving patient compliance. PMID:27354765

Topological and Functional Characterization of an Insect Gustatory Receptor

PubMed Central

Zhang, Hui-Jie; Anderson, Alisha R.; Trowell, Stephen C.; Luo, A-Rong; Xiang, Zhong-Huai; Xia, Qing-You

2011-01-01

Insect gustatory receptors are predicted to have a seven-transmembrane structure and are distantly related to insect olfactory receptors, which have an inverted topology compared with G-protein coupled receptors, including mammalian olfactory receptors. In contrast, the topology of insect gustatory receptors remains unknown. Except for a few examples from Drosophila, the specificity of individual insect gustatory receptors is also unknown. In this study, the total number of identified gustatory receptors in Bombyx mori was expanded from 65 to 69. BmGr8, a silkmoth gustatory receptor from the sugar receptor subfamily, was expressed in insect cells. Membrane topology studies on BmGr8 indicate that, like insect olfactory receptors, it has an inverted topology relative to G protein-coupled receptors. An orphan GR from the bitter receptor family, BmGr53, yielded similar results. We infer, from the finding that two distantly related BmGrs have an intracellular N-terminus and an odd number of transmembrane spans, that this is likely to be a general topology for all insect gustatory receptors. We also show that BmGr8 functions independently in Sf9 cells and responds in a concentration-dependent manner to the polyalcohols myo-inositol and epi-inositol but not to a range of mono- and di-saccharides. BmGr8 is the first chemoreceptor shown to respond specifically to inositol, an important or essential nutrient for some Lepidoptera. The selectivity of BmGr8 responses is consistent with the known responses of one of the gustatory receptor neurons in the lateral styloconic sensilla of B. mori, which responds to myo-inositol and epi-inositol but not to allo-inositol. PMID:21912618

Enzalutamide inhibits proliferation of gemcitabine-resistant bladder cancer cells with increased androgen receptor expression.

PubMed

Kameyama, Koji; Horie, Kengo; Mizutani, Kosuke; Kato, Taku; Fujita, Yasunori; Kawakami, Kyojiro; Kojima, Toshio; Miyazaki, Tatsuhiko; Deguchi, Takashi; Ito, Masafumi

2017-01-01

Advanced bladder cancer is treated mainly with gemcitabine and cisplatin, but most patients eventually become resistance. Androgen receptor (AR) signaling has been implicated in bladder cancer as well as other types of cancer including prostate cancer. In this study, we investigated the expression and role of AR in gemcitabine-resistant bladder cancer cells and also the potential of enzalutamide, an AR inhibitor, as a therapeutic for the chemoresistance. First of all, we established gemcitabine-resistant T24 cells (T24GR) from T24 bladder cancer cells and performed gene expression profiling. Microarray analysis revealed upregulation of AR expression in T24GR cells compared with T24 cells. AR mRNA and protein expression was confirmed to be increased in T24GR cells, respectively, by quantitative RT-PCR and western blot analysis, which was associated with more potent AR transcriptional activity as measured by luciferase reporter assay. The copy number of AR gene in T24GR cells determined by PCR was twice as many as that of T24 cells. AR silencing by siRNA transfection resulted in inhibition of proliferation of T24GR cells. Cell culture in charcoal-stripped serum and treatment with enzalutamide inhibited growth of T24GR cells, which was accompanied by cell cycle arrest. AR transcriptional activity was found to be reduced in T24GR cells by enzalutamide treatment. Lastly, enzalutamide also inhibited cell proliferation of HTB5 bladder cancer cells that express AR and possess intrinsic resistance to gemcitabine. Our results suggest that enzalutamide may have the potential to treat patients with advanced gemcitabine-resistant bladder cancer with increased AR expression.

Regulation of the corticosteroid signalling system in rainbow trout HPI axis during confinement stress.

PubMed

Kiilerich, Pia; Servili, Arianna; Péron, Sandrine; Valotaire, Claudiane; Goardon, Lionel; Leguen, Isabelle; Prunet, Patrick

2018-03-01

This study aims to shed light on corticosteroid regulation of stress in teleost fish with focus on the corticosteroid signalling system. The role of the mineralocorticoid-like hormone 11-deoxycorticosterone (DOC) in fish is still enigmatic, as is the function of the mineralocorticoid receptor, MR. Low plasma DOC levels and ubiquitous tissue distribution of MR question the physiological relevance of the mineralocorticoid-axis. Furthermore, the particular purpose of each of the three corticosteroid receptors in fish, the glucocorticoid receptors, GR1 and GR2, and the MR, is still largely unknown. Therefore we investigate the regulation of cortisol and DOC in plasma and mRNA levels of MR, GR1 and GR2 in the HPI-axis tissues (hypothalamus, pituitary and interrenal gland) during a detailed confinement stress time-course. Here we show a sustained up-regulation of plasma DOC levels during a confinement stress time-course. However, the low DOC levels compared to cortisol measured in the plasma do not favour an activity of DOC through MR receptors. Furthermore, we show differential contribution of the CRs in regulation and control of HPI axis activity following confinement stress. Judged by the variation of mRNA levels negative feedback regulation of cortisol release occurs on the level of the pituitary via MR and on the level of the interrenal gland via GR2. Finally, asa significant effect of confinement stress on CR expressions was observed in the pituitary gland, we completed this experiment by demonstrating that corticosteroid receptors (GR1, GR2 and MR) are co-expressed in the ACTH cells located in the adenohypophysis. Overall, these data suggest the involvement of these receptors in the regulation of the HPI axis activity by cortisol. Copyright © 2017 Elsevier Inc. All rights reserved.

Dexamethasone-Mediated Changes in Adipose Triacylglycerol Metabolism Are Exaggerated, Not Diminished, in the Absence of a Functional GR Dimerization Domain

PubMed Central

Roohk, Donald J.; Mascharak, Smita; Khambatta, Cyrus; Leung, Ho; Hellerstein, Marc

2013-01-01

The glucocorticoid (GC) receptor (GR) has multiple effector mechanisms, including dimerization-mediated transactivation of target genes via DNA binding and transcriptional repression mediated by protein-protein interactions. Much attention has been focused on developing selective GR modulators that would dissociate adverse effects from therapeutic anti-inflammatory effects. The GRdim/dim mouse has a mutation in the dimerization domain of GR and has been shown to have attenuated transactivation with intact repression. To understand the role of GR dimerization-dependent targets in multiple tissues, we measured metabolic fluxes through several disease-relevant GC target pathways using heavy water labeling and mass spectrometry in wild-type and GRdim/dim mice administered the potent GC dexamethasone (DEX). Absolute triglyceride synthesis was increased in both wild-type and GRdim/dim mice by DEX in the inguinal and epididymal fat depots. GRdim/dim mice showed an exaggerated response to DEX in both depots. De novo lipogenesis was also greatly increased in both depots in response to DEX in GRdim/dim, but not wild-type mice. In contrast, the inhibitory effect of DEX on bone and skin collagen synthesis rates was greater in wild-type compared with GRdim/dim mice. Wild-type mice were more sensitive to DEX-dependent decreases in insulin sensitivity than GRdim/dim mice. Wild-type and GRdim/dim mice were equally sensitive to DEX-dependent decreases in muscle protein synthesis. Chronic elevation of GCs in GRdim/dim mice results in severe runting and lethality. In conclusion, some metabolic effects of GC treatment are exaggerated in adipose tissue of GRdim/dim mice, suggesting that selective GR modulators based on dissociating GR transactivation from repression should be evaluated carefully. PMID:23493372

Molecular characterization and expression analysis of a glycine-rich RNA-binding protein gene from Malus hupehensis Rehd.

PubMed

Wang, Shuncai; Wang, Rongchao; Liang, Dong; Ma, Fengwang; Shu, Huairui

2012-04-01

Members of the plant glycine-rich RNA-binding protein (GR-RBP) family play diverse roles in regulating RNA metabolism for various cellular processes. To understand better their function at the molecular level in stress responses, we cloned a GR-RBP gene, MhGR-RBP1, from Malus hupehensis. Its full-length cDNA is 558 bp long, with a 495-bp open reading frame, and it encodes 164 amino acids. The deduced amino acid sequence contains an RNA-recognition motif (RRM) at the amino terminal and a glycine-rich domain at the carboxyl terminal; these are highly homologous with those from other plant species. Multiple alignment and phylogenetic analyses show that the deduced protein is a novel member of the plant GR-RBP family. To characterize this gene, we also applied a model for predicting its homology of protein structure with other species. Both organ-specific and stress-related expression were detected by quantitative real-time PCR and semi-quantitative RT-PCR, indicating that MhGR-RBP1 is expressed abundantly in young leaves but weakly in roots and shoots. Transcript levels in the leaves were increased markedly by drought, hydrogen peroxide (H(2)O(2)), and mechanical wounding, slightly by salt stress. Furthermore, the transcript is initially up- and down-regulated rapidly within 24 h of abscisic acid (ABA) treatment. After 24 h of ABA and jasmonic acid (JA) treatments with different concentrations, the transcript levels of MhGR-RBP1 were significantly repressed. These results suggest that MhGR-RBP1 may be involved in the responses to abiotic stresses, H(2)O(2), ABA, or JA.

Inhibition of thioredoxin reductase but not of glutathione reductase by the major classes of alkylating and platinum-containing anticancer compounds.

PubMed

Witte, Anne-Barbara; Anestål, Karin; Jerremalm, Elin; Ehrsson, Hans; Arnér, Elias S J

2005-09-01

Mammalian thioredoxin reductase (TrxR) is important for cell proliferation, antioxidant defense, and redox signaling. Together with glutathione reductase (GR) it is the main enzyme providing reducing equivalents to many cellular processes. GR and TrxR are flavoproteins of the same enzyme family, but only the latter is a selenoprotein. With the active site containing selenocysteine, TrxR may catalyze reduction of a wide range of substrates, but can at the same time easily be targeted by electrophilic compounds due to the extraordinarily high reactivity of a selenolate moiety. Here we addressed the inhibition of the enzyme by major anticancer alkylating agents and platinum-containing compounds and we compared it to that of GR. We confirmed prior studies suggesting that the nitrosourea carmustine can inhibit both GR and TrxR. We next found, however, that nitrogen mustards (chlorambucil and melphalan) and alkyl sulfonates (busulfan) efficiently inhibited TrxR while these compounds, surprisingly, did not inhibit GR. Inhibitions were concentration and time dependent and apparently irreversible. Anticancer anthracyclines (daunorubicin and doxorubicin) were, in contrast to the alkylating agents, not inhibitors but poor substrates of TrxR. We also found that TrxR, but not GR, was efficiently inhibited by both cisplatin, its monohydrated complex, and oxaliplatin. Carboplatin, in contrast, could not inhibit any of the two enzymes. These findings lead us to conclude that representative compounds of the major classes of clinically used anticancer alkylating agents and most platinum compounds may easily target TrxR, but not GR. The TrxR inhibition should thereby be considered as a factor that may contribute to the cytotoxicity seen upon clinical use of these drugs.

In vivo gastric residence and gastroprotective effect of floating gastroretentive tablet of DA-9601, an extract of Artemisia asiatica, in beagle dogs.

PubMed

Kim, Jeong Soo; Cha, Kwang Ho; Kang, Seung Yeob; Won, Donghan; Jang, Sun Woo; Son, Miwon; Son, Moon Ho; Choi, Ho Jung; Lee, Young Won; Kang, Myung Joo

2016-01-01

DA-9601, an extract of Artemisia asiatica containing eupatilin and jaceosidin as active compounds, has been prescribed to treat gastritis in Asia. In recent times, sustained-release, floating gastroretentive (GR) tablets of DA-9601 are available on the market. In the present study, the physical properties and in vitro drug release profile, in vivo gastric residence time, and gastroprotective effect of GR tablet were compared to those of immediate release (IR) tablets of DA-9601. In vitro buoyancy behavior (floating lag time and duration) and release profile of eupatilin were assessed in acidic medium. The in vivo intragastric behaviors of the barium sulfate-loaded IR and GR tablets were evaluated in beagle dogs by radiographic studies. Local gastroprotective effect was compared in an experimentally induced gastric lesion in beagle dogs after oral administration of IR (three times per day) or GR (twice daily) tablets for 15 days. Upon contact with gastric juice, a low-density floating tablet (apparent density of 0.93 g/cm(3)) was buoyant on the medium and was upheld for 14 hours, providing sustained drug release profile, whereas the IR tablet disintegrated within 10 minutes, showing complete drug release within 2 hours. In vivo radiographic studies showed that the GR tablet was retained for >4 hours in the stomach. Both DA-9601 formulations remarkably alleviated gastric mucosal injury compared to placebo group, when observed by gastric endoscopy. Twice-daily GR tablets exhibited a prolonged gastric residence time and a remarkable mucosal restoration effect in animal models. Therefore, the GR system of DA-9601 could be a substitute dosage form for the treatment of gastritis, while reducing the dosing frequency and thus improving patient compliance.

Colloidal graphite/graphene nanostructures using collagen showing enhanced thermal conductivity

PubMed Central

Bhattacharya, Soumya; Dhar, Purbarun; Das, Sarit K; Ganguly, Ranjan; Webster, Thomas J; Nayar, Suprabha

2014-01-01

In the present study, the exfoliation of natural graphite (GR) directly to colloidal GR/graphene (G) nanostructures using collagen (CL) was studied as a safe and scalable process, akin to numerous natural processes and hence can be termed “biomimetic”. Although the exfoliation and functionalization takes place in just 1 day, it takes about 7 days for the nano GR/G flakes to stabilize. The predominantly aromatic residues of the triple helical CL forms its own special micro and nanoarchitecture in acetic acid dispersions. This, with the help of hydrophobic and electrostatic forces, interacts with GR and breaks it down to nanostructures, forming a stable colloidal dispersion. Surface enhanced Raman spectroscopy, X-ray diffraction, photoluminescence, fluorescence, and X-ray photoelectron spectroscopy of the colloid show the interaction between GR and CL on day 1 and 7. Differential interference contrast images in the liquid state clearly reveal how the GR flakes are entrapped in the CL fibrils, with a corresponding fluorescence image showing the intercalation of CL within GR. Atomic force microscopy of graphene-collagen coated on glass substrates shows an average flake size of 350 nm, and the hexagonal diffraction pattern and thickness contours of the G flakes from transmission electron microscopy confirm ≤ five layers of G. Thermal conductivity of the colloid shows an approximate 17% enhancement for a volume fraction of less than approximately 0.00005 of G. Thus, through the use of CL, this new material and process may improve the use of G in terms of biocompatibility for numerous medical applications that currently employ G, such as internally controlled drug-delivery assisted thermal ablation of carcinoma cells. PMID:24648728

Epidemiology of gingival recession and risk indicators in dental hospital population of Bhimavaram

PubMed Central

Manchala, S. Reddy; Vandana, K. L.; Mandalapu, N. B.; Mannem, S.; Dwarakanath, C. D.

2012-01-01

Objective: Gingival recession (GR) is a common manifestation in most populations, and is considered as an early sign of periodontal disease. GR is an intriguing condition where various factors play an important role in its etiology. Only few studies have been undertaken to assess the prevalence and risk factors for GR in patients visiting dental hospitals. The aim of this study is not only to estimate prevalence, severity, and extent of GR in hospital population, of Vishnu Dental College, Bhimavaram, Andhra Pradesh, India, but also to assess the potential risk factors for the same. Materials and Methods: In this study, 2837 patients were examined of which 627 were included into the study. The age range was 16-80 years. Subjects were interviewed using a structural questionnaire, and full mouth clinical examination was done to assess recession. Results: Of all subjects examined 45.6%, 16.2% of individuals and 13%, 4.8% of teeth per individual showed GR >3 mm. Prevalence and severity of recession was correlated with age. Recession was present but recession threshold ≥3 and ≥5 mm affected only small percentage of teeth in subjects younger than 45 years. Mandibular incisors showed the highest prevalence of GR ≥1 mm with 61% of teeth being affected. Smoking and presence of supragingival calculus were most significantly associated localized and generalized recession. Conclusion: Prevalence of periodontal disease is high among this population based on the presence of gingival recession in most the individuals. High prevalence of GR is significantly associated with supragingival calculus and smoking habits. This suggests a need to improve their periodontal condition through education, motivation, and improving their periodontal health. PMID:24478971

Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet

PubMed Central

Michailidou, Z.; Carter, R. N.; Marshall, E.; Sutherland, H. G.; Brownstein, D. G.; Owen, E.; Cockett, K.; Kelly, V.; Ramage, L.; Al-Dujaili, E. A. S.; Ross, M.; Maraki, I.; Newton, K.; Holmes, M. C.; Seckl, J. R.; Morton, N. M.; Kenyon, C. J.; Chapman, K. E.

2008-01-01

Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GRβgeo/+ mice were generated from embryonic stem (ES) cells with a gene trap integration of a β-galactosidase-neomycin phosphotransferase (βgeo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GRβgeo/+ mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin-aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GRβgeo/+ mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GRβgeo/+ mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet.—Michailidou, Z., Carter, R. N., Marshall, E., Sutherland, H. G., Brownstein, D. G., Owen, E., Cockett, K., Kelly, V., Ramage, L., Al-Dujaili, E. A. S., Ross, M., Maraki, I., Newton, K., Holmes, M. C., Seckl, J. R., Morton, N. M., Kenyon, C. J., Chapman, K. E. Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet. PMID:18697839

Glucocorticoid receptor ligand binding in monocytic cells using a microplate assay.

PubMed

Jansen, J; Uitdehaag, B; Koper, J W; van Den Berg, T K

1999-01-01

Glucocorticoids have profound effects on macrophage function and are widely used as anti-inflammatory drugs. Glucocorticoids receptor (GR) ligand binding capacity is a major determinant of cellular glucocorticoid sensitivity. The number and affinity of GR can be measured in a whole cell binding assay using (3)H-dexamethasone. Here, we describe a rapid and simple microplate assay for GR measurement using the human promonocytic cell line THP-1. Copyright 2000 S. Karger AG, Basel.

Computing Gröbner Bases within Linear Algebra

NASA Astrophysics Data System (ADS)

Suzuki, Akira

In this paper, we present an alternative algorithm to compute Gröbner bases, which is based on computations on sparse linear algebra. Both of S-polynomial computations and monomial reductions are computed in linear algebra simultaneously in this algorithm. So it can be implemented to any computational system which can handle linear algebra. For a given ideal in a polynomial ring, it calculates a Gröbner basis along with the corresponding term order appropriately.

Confirmation and mechanism of glyphosate resistance in tall windmill grass (Chloris elata) from Brazil.

PubMed

Brunharo, Caio Acg; Patterson, Eric L; Carrijo, Daniela R; de Melo, Marcel Sc; Nicolai, Marcelo; Gaines, Todd A; Nissen, Scott J; Christoffoleti, Pedro J

2016-09-01

Overreliance on glyphosate as a single tool for weed management in agricultural systems in Brazil has selected glyphosate-resistant populations of tall windmill grass (Chloris elata Desv.). Two C. elata populations, one glyphosate resistant (GR) and one glyphosate susceptible (GS), were studied in detail for a dose-response experiment and for resistance mechanism. The dose causing 50% reduction in dry weight was 620 g a.e. ha(-1) for GR and 114 g ha(-1) for GS, resulting in an R/S ratio of 5.4. GS had significantly higher maximum (14) C-glyphosate absorption into the treated leaf (51.3%) than GR (39.5%), a difference of 11.8% in maximum absorption. GR also retained more (14) C-glyphosate in the treated leaf (74%) than GS (51%), and GR translocated less glyphosate (27%) to other plant parts (stems, roots and root exudation) than GS (36%). There were no mutations at the Pro106 codon in the gene encoding 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). There was no difference in EPSPS genomic copy number or EPSPS transcription between GS and GR populations. Based on these data, reduced glyphosate absorption and increased glyphosate retention in the treated leaf contribute to glyphosate resistance in this C. elata population from Brazil. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Benchmark study on glyphosate-resistant cropping systems in the United States. Part 4: Weed management practices and effects on weed populations and soil seedbanks.

PubMed

Wilson, Robert G; Young, Bryan G; Matthews, Joseph L; Weller, Stephen C; Johnson, William G; Jordan, David L; Owen, Micheal D K; Dixon, Philip M; Shaw, David R

2011-07-01

Weed management in glyphosate-resistant (GR) maize, cotton and soybean in the United States relies almost exclusively on glyphosate, which raises criticism for facilitating shifts in weed populations. In 2006, the benchmark study, a field-scale investigation, was initiated in three different GR cropping systems to characterize academic recommendations for weed management and to determine the level to which these recommendations would reduce weed population shifts. A majority of growers used glyphosate as the only herbicide for weed management, as opposed to 98% of the academic recommendations implementing at least two herbicide active ingredients and modes of action. The additional herbicides were applied with glyphosate and as soil residual treatments. The greater herbicide diversity with academic recommendations reduced weed population densities before and after post-emergence herbicide applications in 2006 and 2007, particularly in continuous GR crops. Diversifying herbicides reduces weed population densities and lowers the risk of weed population shifts and the associated potential for the evolution of glyphosate-resistant weeds in continuous GR crops. Altered weed management practices (e.g. herbicides or tillage) enabled by rotating crops, whether GR or non-GR, improves weed management and thus minimizes the effectiveness of only using chemical tactics to mitigate weed population shifts. Copyright © 2011 Society of Chemical Industry.

Mass production of highly-porous graphene for high-performance supercapacitors

NASA Astrophysics Data System (ADS)

Amiri, Ahmad; Shanbedi, Mehdi; Ahmadi, Goodarz; Eshghi, Hossein; Kazi, S. N.; Chew, B. T.; Savari, Maryam; Zubir, Mohd Nashrul Mohd

2016-09-01

This study reports on a facile and economical method for the scalable synthesis of few-layered graphene sheets by the microwave-assisted functionalization. Herein, single-layered and few-layered graphene sheets were produced by dispersion and exfoliation of functionalized graphite in ethylene glycol. Thermal treatment was used to prepare pure graphene without functional groups, and the pure graphene was labeled as thermally-treated graphene (T-GR). The morphological and statistical studies about the distribution of the number of layers showed that more than 90% of the flakes of T-GR had less than two layers and about 84% of T-GR were single-layered. The microwave-assisted exfoliation approach presents us with a possibility for a mass production of graphene at low cost and great potentials in energy storage applications of graphene-based materials. Owing to unique surface chemistry, the T-GR demonstrates an excellent energy storage performance, and the electrochemical capacitance is much higher than that of the other carbon-based nanostructures. The nanoscopic porous morphology of the T-GR-based electrodes made a significant contribution in increasing the BET surface as well as the specific capacitance of graphene. T-GR, with a capacitance of 354.1 Fg-1 at 5 mVs-1 and 264 Fg-1 at 100 mVs-1, exhibits excellent performance as a supercapacitor.

The Application of Graphene and Its Derivatives to Energy Conversion, Storage, and Environmental and Biosensing Devices.

PubMed

Ali Tahir, Asif; Ullah, Habib; Sudhagar, Pitchaimuthu; Asri Mat Teridi, Mohd; Devadoss, Anitha; Sundaram, Senthilarasu

2016-06-01

Graphene (GR) and its derivatives are promising materials on the horizon of nanotechnology and material science and have attracted a tremendous amount of research interest in recent years. The unique atom-thick 2D structure with sp(2) hybridization and large specific surface area, high thermal conductivity, superior electron mobility, and chemical stability have made GR and its derivatives extremely attractive components for composite materials for solar energy conversion, energy storage, environmental purification, and biosensor applications. This review gives a brief introduction of GR's unique structure, band structure engineering, physical and chemical properties, and recent energy-related progress of GR-based materials in the fields of energy conversion (e.g., photocatalysis, photoelectrochemical water splitting, CO2 reduction, dye-sensitized and organic solar cells, and photosensitizers in photovoltaic devices) and energy storage (batteries, fuel cells, and supercapacitors). The vast coverage of advancements in environmental applications of GR-based materials for photocatalytic degradation of organic pollutants, gas sensing, and removal of heavy-metal ions is presented. Additionally, the use of graphene composites in the biosensing field is discussed. We conclude the review with remarks on the challenges, prospects, and further development of GR-based materials in the exciting fields of energy, environment, and bioscience. © 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Three-dimensionally porous graphene: A high-performance adsorbent for removal of albumin-bonded bilirubin.

PubMed

Ma, Chun Fang; Gao, Qiang; Xia, Kai Sheng; Huang, Zhi Yuan; Han, Bo; Zhou, Cheng Gang

2017-01-01

The development of bilirubin adsorbents with high adsorption efficiencies towards albumin-bonded bilirubin is still a considerable challenge. In this work, a three-dimensionally porous graphene (3D-pGR) has been fabricated through a simple carbon dioxide (CO 2 ) activation of thermally exfoliated graphite oxide (EGO). Intriguingly, the resultant 3D-pGR material showed hierarchically micro-meso-macroporous structure, high specific surface area of up to 843m 2 g -1 , and large pore volume as high as 2.71cm 3 g -1 . Besides, the large planar π-configuration structure of 3D-pGR made it possible to compete effectively with albumin for bilirubin binding. Taking advantages of these fantastic characteristics, the 3D-pGR was demonstrated to be extraordinarily efficient for bilirubin removal from a bovine serum albumin (BSA)-rich solution. Under optimized conditions, the maximum adsorption capacity of 3D-pGR for BSA-bonded bilirubin was up to 126.1mgg -1 , which is not only significantly higher than the adsorption capacities of currently available adsorbents towards albumin-bonded bilirubin, but also superior to those of many reported adsorbents towards free bilirubin. In addition, the hemolysis assay of 3D-pGR indicated that this material had negligible hemolysis effect. Findings from this study may open up important new possibilities for removal of protein-bonded toxins. Copyright © 2016 Elsevier B.V. All rights reserved.

Visible light photocatalytic H2-production activity of wide band gap ZnS nanoparticles based on the photosensitization of graphene

NASA Astrophysics Data System (ADS)

Wang, Faze; Zheng, Maojun; Zhu, Changqing; Zhang, Bin; Chen, Wen; Ma, Li; Shen, Wenzhong

2015-08-01

Visible light photocatalytic H2 production from water splitting is considered an attractive way to solve the increasing global energy crisis in modern life. In this study, a series of zinc sulfide nanoparticles and graphene (GR) sheet composites were synthesized by a two-step hydrothermal method, which used zinc chloride, sodium sulfide, and graphite oxide (GO) as the starting materials. The as-prepared ZnS-GR showed highly efficient visible light photocatalytic activity in hydrogen generation. The morphology and structure of the composites obtained by transmission electron microscope and x-ray diffraction exhibited a small crystallite size and a good interfacial contact between the ZnS nanoparticles and the two-dimensional (2D) GR sheet, which were beneficial for the photocatalysis. When the content of the GR in the catalyst was 0.1%, the ZG0.1 sample exhibited the highest H2-production rate of 7.42 μmol h-1 g-1, eight times more than the pure ZnS sample. This high visible-light photocatalytic H2 production activity is attributed to the photosensitization of GR. Irradiated by visible light, the electrons photogenerated from GR transfer to the conduction band of ZnS to participate in the photocatalytic process. This study presents the visible-light photocatalytic activity of wide bandgap ZnS and its application in H2 evolution.

A facile, branched DNA assay to quantitatively measure glucocorticoid receptor auto-regulation in T-cell acute lymphoblastic leukemia

PubMed Central

Schwartz, Jason R.; Sarvaiya, Purvaba J.; Leiva, Lily E.; Velez, Maria C.; Singleton, Tammuella C.; Yu, Lolie C.; Vedeckis, Wayne V.

2012-01-01

Glucocorticoid (GC) steroid hormones are used to treat acute lymphoblastic leukemia (ALL) because of their pro-apoptotic effects in hematopoietic cells. However, not all leukemia cells are sensitive to GC, and no assay to stratify patients is available. In the GC-sensitive T-cell ALL cell line CEM-C7, auto-up-regulation of RNA transcripts for the glucocorticoid receptor (GR) correlates with increased apoptotic response. This study aimed to determine if a facile assay of GR transcript levels might be promising for stratifying ALL patients into hormone-sensitive and hormone-resistant populations. The GR transcript profiles of various lymphoid cell lines and 4 bone marrow samples from patients with T-cell ALL were analyzed using both an optimized branched DNA (bDNA) assay and a real-time quantitative reverse transcription-polymerase chain reaction assay. There were significant correlations between both assay platforms when measuring total GR (exon 5/6) transcripts in various cell lines and patient samples, but not for a probe set that detects a specific, low abundance GR transcript (exon 1A3). Our results suggest that the bDNA platform is reproducible and precise when measuring total GR transcripts and, with further development, may ultimately offer a simple clinical assay to aid in the prediction of GC-sensitivity in ALL patients. PMID:22739263

A C-terminal HSP90 inhibitor restores glucocorticoid sensitivity and relieves a mouse allograft model of Cushing disease.

PubMed

Riebold, Mathias; Kozany, Christian; Freiburger, Lee; Sattler, Michael; Buchfelder, Michael; Hausch, Felix; Stalla, Günter K; Paez-Pereda, Marcelo

2015-03-01

One function of the glucocorticoid receptor (GR) in corticotroph cells is to suppress the transcription of the gene encoding proopiomelanocortin (POMC), the precursor of the stress hormone adrenocorticotropin (ACTH). Cushing disease is a neuroendocrine condition caused by partially glucocorticoid-resistant corticotroph adenomas that excessively secrete ACTH, which leads to hypercortisolism. Mutations that impair GR function explain glucocorticoid resistance only in sporadic cases. However, the proper folding of GR depends on direct interactions with the chaperone heat shock protein 90 (HSP90, refs. 7,8). We show here that corticotroph adenomas overexpress HSP90 compared to the normal pituitary. N- and C-terminal HSP90 inhibitors act at different steps of the HSP90 catalytic cycle to regulate corticotroph cell proliferation and GR transcriptional activity. C-terminal inhibitors cause the release of mature GR from HSP90, which promotes its exit from the chaperone cycle and potentiates its transcriptional activity in a corticotroph cell line and in primary cultures of human corticotroph adenomas. In an allograft mouse model, the C-terminal HSP90 inhibitor silibinin showed anti-tumorigenic effects, partially reverted hormonal alterations, and alleviated symptoms of Cushing disease. These results suggest that the pathogenesis of Cushing disease caused by overexpression of heat shock proteins and consequently misregulated GR sensitivity may be overcome pharmacologically with an appropriate HSP90 inhibitor.

UV light B-mediated inhibition of skin catalase activity promotes Gr-1+ CD11b+ myeloid cell expansion.

PubMed

Sullivan, Nicholas J; Tober, Kathleen L; Burns, Erin M; Schick, Jonathan S; Riggenbach, Judith A; Mace, Thomas A; Bill, Matthew A; Young, Gregory S; Oberyszyn, Tatiana M; Lesinski, Gregory B

2012-03-01

Skin cancer incidence and mortality are higher in men compared with women, but the causes of this sex discrepancy remain largely unknown. UV light exposure induces cutaneous inflammation and neutralizes cutaneous antioxidants. Gr-1(+)CD11b(+) myeloid cells are heterogeneous bone marrow-derived cells that promote inflammation-associated carcinogenesis. Reduced activity of catalase, an antioxidant present in the skin, has been associated with skin carcinogenesis. We used the outbred, immune-competent Skh-1 hairless mouse model of UVB-induced inflammation and non-melanoma skin cancer to further define sex discrepancies in UVB-induced inflammation. Our results demonstrated that male skin had relatively lower baseline catalase activity, which was inhibited following acute UVB exposure in both sexes. Further analysis revealed that skin catalase activity inversely correlated with splenic Gr-1(+)CD11b(+) myeloid cell percentage. Acute UVB exposure induced Gr-1(+)CD11b(+) myeloid cell skin infiltration, which was inhibited to a greater extent in male mice by topical catalase treatment. In chronic UVB studies, we demonstrated that the percentage of splenic Gr-1(+)CD11b(+) myeloid cells was 55% higher in male tumor-bearing mice compared with their female counterparts. Together, our findings indicate that lower skin catalase activity in male mice may at least in part contribute to increased UVB-induced generation of Gr-1(+)CD11b(+) myeloid cells and subsequent skin carcinogenesis.

Visible light photocatalytic H2-production activity of wide band gap ZnS nanoparticles based on the photosensitization of grapheme.

PubMed

Wang, Faze; Zheng, Maojun; Zhu, Changqing; Zhang, Bin; Chen, Wen; Ma, Li; Shen, Wenzhong

2015-08-28

Visible light photocatalytic H(2) production from water splitting is considered an attractive way to solve the increasing global energy crisis in modern life. In this study, a series of zinc sulfide nanoparticles and graphene (GR) sheet composites were synthesized by a two-step hydrothermal method, which used zinc chloride, sodium sulfide, and graphite oxide (GO) as the starting materials. The as-prepared ZnS-GR showed highly efficient visible light photocatalytic activity in hydrogen generation. The morphology and structure of the composites obtained by transmission electron microscope and x-ray diffraction exhibited a small crystallite size and a good interfacial contact between the ZnS nanoparticles and the two-dimensional (2D) GR sheet,which were beneficial for the photocatalysis. When the content of the GR in the catalyst was 0.1%, the ZG0.1 sample exhibited the highest H(2)-production rate of 7.42 μmol h(−1) g(−1), eight times more than the pure ZnS sample. This high visible-light photocatalytic H(2) production activity is attributed to the photosensitization of GR. Irradiated by visible light, the electrons photogenerated from GR transfer to the conduction band of ZnS to participate in the photocatalytic process. This study presents the visible-light photocatalytic activity of wide bandgap ZnS and its application in H(2) evolution.

DNA-templated synthesis of PtAu bimetallic nanoparticle/graphene nanocomposites and their application in glucose biosensor

PubMed Central

2014-01-01

In this paper, single-stranded DNA (ss-DNA) is demonstrated to functionalize graphene (GR) and to further guide the growth of PtAu bimetallic nanoparticles (PtAuNPs) on GR with high densities and dispersion. The obtained nanocomposites (PtAuNPs/ss-DNA/GR) were characterized by transmission electron microscopy (TEM), energy-dispersive X-ray spectrometer (EDS), and electrochemical techniques. Then, an enzyme nanoassembly was prepared by self-assembling glucose oxidase (GOD) on PtAuNP/ss-DNA/GR nanocomposites (GOD/PtAuNPs/ss-DNA/GR). The nanocomposites provided a suitable microenvironment for GOD to retain its biological activity. The direct and reversible electron transfer process between the active site of GOD and the modified electrode was realized without any extra electron mediator. Thus, the prepared GOD/PtAuNP/ss-DNA/GR electrode was proposed as a biosensor for the quantification of glucose. The effects of pH, applied potential, and temperature on the performance of the biosensor were discussed in detail and were optimized. Under optimal conditions, the biosensor showed a linearity with glucose concentration in the range of 1.0 to 1,800 μM with a detection limit of 0.3 μM (S/N = 3). The results demonstrate that the developed approach provides a promising strategy to improve the sensitivity and enzyme activity of electrochemical biosensors. PMID:24572068

Control of natural microorganisms in chamomile (Chamomilla recutita L.) by gamma ray and electron beam irradiation.

PubMed

Al-Bachir, Mahfouz

2017-01-01

Microbial contamination levels and corresponding sensitivities to gamma rays (GR) and elec- tron beam (EB) irradiation were tested in chamomile (Chamomile recutta L.). Chamomile powders were treated with 10 and 20 kGy by GR and EB, respectively. Microbiological and chemical analyses were performed on controls and treated samples immediately after irradiation, and after 12 months of storage. The control samples of chamomile exhibited rather high microbiological contamination, exceeding the levels of 4 log10 CFU g-1   (CFU - colony forming units) reported by national and international authorities as the maximum permissible total count level. Irradiation with GR and EB was found to cause a reduction in microbial contamination proportionate to the dose delivered. The sterilizing effect of EB on microorganisms was higher than the GR one. A dose of 10 kGy of GR and EB significantly (p < 0.05) reduced the total bacte- rial, total coliform and total fungal contamination. A dose of 20 kGy of GR significantly (p < 0.05) reduced the total bacterial and total fungal contamination, while a 20 kGy dose of EB reduced the initial bacterial, total coliform and total fungal contamination to below detection level when the analysis was carried out im- mediately after irradiation treatment or after 12 months of storage. The comparative study demonstrated that electron beam was more effective for decontamination of chamomile powder than gamma irradiation.

Digital photogrammetry and histomorphometric assessment of the effect of non-coherent light (light-emitting diode) therapy (λ640 ± 20 nm) on the repair of third-degree burns in rats.

PubMed

Neves, Silvana Maria Véras; Nicolau, Renata Amadei; Filho, Antônio Luiz Martins Maia; Mendes, Lianna Martha Soares; Veloso, Ana Maria

2014-01-01

Recent studies have demonstrated the efficacy of coherent light therapy from the red region of the electromagnetic spectrum on the tissue-healing process. This study analysed the effect of non-coherent light therapy (light-emitting diode-LED) with or without silver sulfadiazine (sulpha) on the healing process of third-degree burns. In this study, 72 rats with third-degree burns were randomly divided into six groups (n = 12): Gr1 (control), Gr2 (non-contact LED), Gr3 (contact LED), Gr4 (sulfadiazine), Gr5 (sulfadiazine + non-contact LED) and Gr6 (sulfadiazine + contact LED). The groups treated with LED therapy received treatment every 48 h (λ = 640 ± 20 nm, 110 mW, 16 J/cm(2); 41 s with contact and 680 s without contact). The digital photometric and histomorphometric analyses were conducted after the burn occurred. The combination of sulpha and LED (contact or non-contact) improved the healing of burn wounds. These results demonstrate that the combination of silver sulfadiazine with LED therapy (λ = 640 ± 20 nm, 4 J/cm(2), without contact) improves healing of third-degree burn wounds, significantly reduces the lesion area and increases the granulation tissue, increases the number of fibroblasts, promotes collagen synthesis and prevents burn infections by accelerating recovery.

Maternal licking regulates hippocampal glucocorticoid receptor transcription through a thyroid hormone–serotonin–NGFI-A signalling cascade

PubMed Central

Hellstrom, Ian C.; Dhir, Sabine K.; Diorio, Josie C.; Meaney, Michael J.

2012-01-01

Variations in parental care direct phenotypic development across many species. Variations in maternal pup licking/grooming (LG) in the rat regulate the development of individual differences in hypothalamic–pituitary–adrenal responses to stress. The adult offspring of mothers that show an increased frequency of pup LG have increased hippocampal glucocorticoid receptor (GR) expression and more modest pituitary–adrenal responses to stress. This parental effect is mediated by the epigenetic programming of a GR exon 1 promoter (exon 17) through the binding of the transcription factor nerve growth factor-inducible factor A (NGFI-A). In this paper, we report that: (i) the association of NGFI-A with the exon 17 GR promoter is dynamically regulated by mother–pup interactions; (ii) this effect is mimicked by artificial tactile stimulation comparable to that provided by pup LG; (iii) that serotonin (5-HT) induces an NGFI-A-dependent increase in GR transcription in hippocampal neurons and NGFI-A overexpression is sufficient for this effect; and (iv) that thyroid hormones and 5-HT are key mediators of the effects of pup LG and tactile stimulation on NGFI-A binding to the exon 17 GR promoter in hippocampus. These findings suggest that pup LG directly activates 5-HT systems to initiate intracellular signalling pathways in the hippocampus that regulate GR transcription. PMID:22826348

Role of Prefrontal Cortex Glucocorticoid Receptors in Stress and Emotion

PubMed Central

McKlveen, Jessica M.; Myers, Brent; Flak, Jonathan N.; Bundzikova, Jana; Solomon, Matia B.; Seroogy, Kim B.; Herman, James P.

2013-01-01

Background Stress-related disorders (e.g., depression) are associated with hypothalamic-pituitary-adrenocortical axis dysregulation and prefrontal cortex (PFC) dysfunction, suggesting a functional link between aberrant prefrontal corticosteroid signaling and mood regulation. Methods We used a virally mediated knockdown strategy (short hairpin RNA targeting the glucocorticoid receptor [GR]) to attenuate PFC GR signaling in the rat PFC. Adult male rats received bilateral microinjections of vector control or short hairpin RNA targeting the GR into the prelimbic (n = 44) or infralimbic (n = 52) cortices. Half of the animals from each injection group underwent chronic variable stress, and all were subjected to novel restraint. The first 2 days of chronic variable stress were used to assess depression- and anxiety-like behavior in the forced swim test and open field. Results The GR knockdown confined to the infralimbic PFC caused acute stress hyper-responsiveness, sensitization of stress responses after chronic variable stress, and induced depression-like behavior (increased immobility in the forced swim test). Knockdown of GR in the neighboring prelimbic PFC increased hypothalamic-pituitary-adrenocortical axis responses to acute stress and caused hyper-locomotion in the open field, but did not affect stress sensitization or helplessness behavior. Conclusions The data indicate a marked functional heterogeneity of glucocorticoid action in the PFC and highlight a prominent role for the infralimbic GR in appropriate stress adaptation, emotional control, and mood regulation. PMID:23683655

Glycyrrhizin restores the impaired IL-12 production in thermally injured mice.

PubMed

Utsunomiya, T; Kobayashi, M; Ito, M; Herndon, D N; Pollard, R B; Suzuki, F

2001-04-07

Mice 6 days after thermal injury (TI-mice) did not respond to lipopolysaccharide (LPS) stimulation for production of serum interleukin 12 (IL-12; 2 h after LPS stimulation, <20 pg/ml in TI-mice; 1091+/-162 pg/ml in normal mice). However, 2 h after LPS stimulation, 1456+/-118 pg/ml of IL-12 were demonstrated in sera of TI-mice previously treated with a 10 mg/kg i.p. dose of glycyrrhizin (GR). IL-12 was not induced by LPS in sera of normal mice inoculated with burn-associated type 2 T cells (IL-4/IL-10-producing CD8+CD11b+TCRgamma/delta+T cells isolated from spleens of TI-mice). However, IL-12 production was induced by LPS in sera of these mice previously treated with GR or a mixture of monoclonal antibodies (mAbs) for type 2 cytokines. Also, IL-12 production was induced by LPS in TI-mice inoculated with CD4+T cells from spleens of GR-treated normal mice (GR-CD4+T cells, 5x10(6)cells/mouse). Since GR-CD4+T cells have been shown to be antagonistic cells against production of type 2 cytokines by burn-associated type 2 T cells, these results indicate that IL-12 unresponsiveness shown in TI-mice is recovered by GR through the regulation of burn-associated type 2 T cell responses. Copyright 2001 Academic Press.

In vitro and in silico assessment of the structure-dependent binding of bisphenol analogues to glucocorticoid receptor.

PubMed

Zhang, Jie; Zhang, Tiehua; Guan, Tianzhu; Yu, Hansong; Li, Tiezhu

2017-03-01

Widespread use of bisphenol A (BPA) and other bisphenol analogues has attracted increasing attention for their potential adverse effects. As environmental endocrine-disrupting compounds (EDCs), bisphenols (BPs) may activate a variety of nuclear receptors, including glucocorticoid receptor (GR). In this work, the binding of 11 BPs to GR was investigated by fluorescence polarization (FP) assay in combination with molecular dynamics simulations. The human glucocorticoid receptor was prepared as a soluble recombinant protein. A fluorescein-labeled dexamethasone derivative (Dex-fl) was employed as tracer. Competitive displacement of Dex-fl from GR by BPs showed that the binding affinities of bisphenol analogues were largely dependent on their characteristic functional groups. In order to further understand the relationship between BPs structures and their GR-mediated activities, molecular docking was utilized to explore the binding modes at the atomic level. The results confirmed that structural variations of bisphenol analogues contributed to different interactions of BPs with GR, potentially causing distinct toxic effects. Comparison of the calculated binding energies vs. experimental binding affinities yielded a good correlation (R 2  = 0.8266), which might be helpful for the design of environmentally benign materials with reduced toxicities. In addition, the established FP assay based on GR exhibited the potential to offer an alternative to traditional methods for the detection of bisphenols.

Structural and functional diversity of CLAVATA3/ESR (CLE)-like genes from the potato cyst nematode Globodera rostochiensis.

PubMed

Lu, Shun-Wen; Chen, Shiyan; Wang, Jianying; Yu, Hang; Chronis, Demosthenis; Mitchum, Melissa G; Wang, Xiaohong

2009-09-01

Plant CLAVATA3/ESR-related (CLE) peptides have diverse roles in plant growth and development. Here, we report the isolation and functional characterization of five new CLE genes from the potato cyst nematode Globodera rostochiensis. Unlike typical plant CLE peptides that contain a single CLE motif, four of the five Gr-CLE genes encode CLE proteins with multiple CLE motifs. These Gr-CLE genes were found to be specifically expressed within the dorsal esophageal gland cell of nematode parasitic stages, suggesting a role for their encoded proteins in plant parasitism. Overexpression phenotypes of Gr-CLE genes in Arabidopsis mimicked those of plant CLE genes, and Gr-CLE proteins could rescue the Arabidopsis clv3-2 mutant phenotype when expressed within meristems. A short root phenotype was observed when synthetic GrCLE peptides were exogenously applied to roots of Arabidopsis or potato similar to the overexpression of Gr-CLE genes in Arabidopsis and potato hairy roots. These results reveal that G. rostochiensis CLE proteins with either single or multiple CLE motifs function similarly to plant CLE proteins and that CLE signaling components are conserved in both Arabidopsis and potato roots. Furthermore, our results provide evidence to suggest that the evolution of multiple CLE motifs may be an important mechanism for generating functional diversity in nematode CLE proteins to facilitate parasitism.

N-doped graphene-carbon nanotube hybrid networks attaching with gold nanoparticles for glucose non-enzymatic sensor.

PubMed

Jeong, Hun; Nguyen, Dang Mao; Lee, Min Sang; Kim, Hong Gun; Ko, Sang Cheol; Kwac, Lee Ku

2018-09-01

Herein, we successfully developed a novel three dimensional (3D) opened networks based on nitrogen doped graphene‑carbon nanotubes attaching with gold nanoparticles (N-GR-CNTs/AuNPs) to apply for non-enzymatic glucose determination. It was demonstrated that the N-GR-CNTs/AuNPs modified electrode exhibited good behavior for glucose detection with a long linear range of 2 μM to 19.6 mM, high sensitivity of 0.9824 μA·mM -1 ·cm -2 , low detection limit of 500 nM, and negligible interference effect. The high performance of the N-GR-CNTs/AuNPs based sensor was assumed due to the outstanding catalytic activity of AuNPs well dispersing on N-GR-CNTs networks, which exhibited as a perfect supporting scaffold due to the enhanced electrical conductivity and large surface area. The obtained results indicated that the N-GR-CNTs/AuNPs hybrid is highly promising for sensitive and selective detection of glucose in sensor application. Copyright © 2018 Elsevier B.V. All rights reserved.

Bone marrow-derived Gr1+ cells can generate a metastasis-resistant microenvironment via induced secretion of thrombospondin-1

PubMed Central

Catena, Raúl; Bhattacharya, Nandita; Rayes, Tina El; Wang, Suming; Choi, Hyejin; Gao, Dingcheng; Ryu, Seongho; Joshi, Natasha; Bielenberg, Diane; Lee, Sharrell B.; Haukaas, Svein A.; Gravdal, Karsten; Halvorsen, Ole J.; Akslen, Lars A.; Watnick, Randolph S.; Mittal, Vivek

2013-01-01

Metastatic tumors have been shown to establish permissive microenvironments for metastases via recruitment of bone marrow (BM)- derived cells. Here, we show that metastasis-incompetent tumors are also capable of generating such microenvironments. However, in these situations the otherwise pro-metastatic Gr1+ myeloid cells create a metastasis-refractory microenvironment via the induction of thrombospondin-1 (Tsp-1) by tumor-secreted prosaposin. (BM)-specific genetic deletion of Tsp-1 abolished the inhibition of metastasis, which was restored by BM transplant from Tsp-1+ donors. We also developed a 5-amino acid peptide from prosaposin as a pharmacological inducer of Tsp-1 in Gr1+ BM cells, which dramatically suppresses metastasis. These results provide mechanistic insights into why certain tumors are deficient in metastatic potential and implicate recruited Gr1+ myeloid cells as the main source of Tsp-1. The results underscore the plasticity of Gr1+ cells, which, depending on the context, promote or inhibit metastasis, and suggest that the peptide could be a potential therapeutic agent against metastatic cancer. PMID:23633432

Optimization of Chitosan Drying Temperature on The Quality and Quantity of Edible Film

NASA Astrophysics Data System (ADS)

Sri Wahyuni, Endah; Arifan, Fahmi

2018-02-01

Edible film is a thin layer (biodegradable) used to coat food and can be eaten. In addition edible film serves as a vapor transfer inhibitor, inhibits gas exchange, prevents aroma loss, prevents fat transfer, improves physical characteristics, and as an additive carrier. Edible film made of cassava starch, glycerol and chitosan. Cassava starch is used as raw material because it contains 80% starch. Glycerol serves as a plasticizer and chitosan serves to form films and membranes well. The purpose of this research is to know the characteristic test of edible film by using ANOVA analysis, where the variable of drying of the oven is temperature (70°C, 80°C, 90°C) and time for 3 hours and variables change chitosan (2 gr, 3 gr, 4 gr). The result of this research was obtained the most optimum for water content and water resistance in temperature variable 80 °C and chitosan 4 gr. The best edible films and bubbles on temperature variables are 80 °C and chitosan 4 gr.

Involvement of STH7 in light-adapted development in Arabidopsis thaliana promoted by both strigolactone and karrikin.

PubMed

Thussagunpanit, Jutiporn; Nagai, Yuko; Nagae, Miyu; Mashiguchi, Kiyoshi; Mitsuda, Nobutaka; Ohme-Takagi, Masaru; Nakano, Takeshi; Nakamura, Hidemitsu; Asami, Tadao

2017-02-01

Strigolactones (SLs) and karrikins (KARs) regulate photomorphogenesis. GR24, a synthetic SL and KAR 1 , a KAR, inhibit the hypocotyl elongation of Arabidopsis thaliana in a weak light. GR24 and KAR 1 up-regulate the expression of STH7, encoding a transcription factor belonging to the double B-box zinc finger subfamily. In this study, we used STH7-overexpressing (STH7ox) lines and functionally defective STH7 (STH7-SRDX) mutants to investigate roles of SLs and KARs in photomorphogenesis of Arabidopsis. Hypocotyl elongation of STH7-SRDX mutants was less sensitive to both GR24 and KAR 1 treatment than that of wild-type Arabidopsis under weak light conditions. Furthermore, the chlorophyll and anthocyanin content was increased in STH7ox lines when de-etiolated with light and GR24-treated plants had enhanced anthocyanin production. GR24 and KAR 1 treatment significantly increased the expression level of photosynthesis-related genes LHCB1 and rbcS. The results strongly suggest that SL and KAR induce photomorphogenesis of Arabidopsis in an STH7-dependent manner.

Electrochemical biosensor based on glucose oxidase encapsulated within enzymatically synthesized poly(1,10-phenanthroline-5,6-dione).

PubMed

Ciftci, Hakan; Oztekin, Yasemin; Tamer, Ugur; Ramanaviciene, Almira; Ramanavicius, Arunas

2014-11-01

This study is focused on the investigation of electrocatalytic effect of glucose oxidase (GOx) immobilized on the graphite rod (GR) electrode. The enzyme modified electrode was prepared by encapsulation of immobilized GOx within enzymatically formed poly(1,10-phenanthroline-5,6-dione) (pPD) film. The electrochemical responses of such enzymatic electrode (pPD/GOx/GR) vs. different glucose concentrations were examined chronoamperometrically in acetate-phosphate buffer solution (A-PBS), pH 6.0, under aerobic or anaerobic conditions. Amperometric signals of the pPD/GOx/GR electrode exhibited well-defined hyperbolic dependence upon glucose concentration. Amperometric signals at 100mM of glucose were 41.17 and 32.27 μA under aerobic and anaerobic conditions, respectively. Amperometric signals of the pPD/GOx/GR electrode decreased by 6% within seven days. The pPD/GOx/GR electrode showed excellent selectivity in the presence of dopamine and uric acid. Furthermore it had a good reproducibility and repeatability with standard deviation of 9.4% and 8.0%, respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

A facile and scalable method to prepare carbon nanotube-grafted-graphene for high performance Li-S battery

NASA Astrophysics Data System (ADS)

Wang, Q. Q.; Huang, J. B.; Li, G. R.; Lin, Z.; Liu, B. H.; Li, Z. P.

2017-01-01

A carbon nanotube-grafted-graphene (CNT-g-Gr) is developed for enhancements of electrical conduction and polysulfide (PS) absorption to improve rate performance and cycleability of lithium-sulfur battery. The CNT-g-Gr is prepared through CNT growth on Ni-deposited graphene sheet which is fabricated via pyrolysis of glucose in a molten salt. The obtained CNT-g-Gr shows much higher specific surface area and PS adsorption capability than graphene. The in-situ formed Ni nanoparticles on graphene sheet not only serve as the catalytic sites for CNT growth, but also function as the anchor-sites for polar PS absorption. The CNT-g-Gr contributes a superb PS adsorption capability arising from graphene and CNT absorbing weakly-polar PS species, and Ni nanoparticles absorbing the species with stronger polarity. The resultant Li-S battery with the CNT-g-Gr shows excellent cycleability and rate performance. A stable discharge capacity of 900 mAh g-1 (with low capacity degradation rate) and a rate capacity of 260 mAh g-1 at 30 C discharge rate have been achieved.

The enhancement of stress-related memory by glucocorticoids depends on synapsin-Ia/Ib

PubMed Central

Revest, J-M; Kaouane, N; Mondin, M; Le Roux, A; Rougé-Pont, F; Vallée, M; Barik, J; Tronche, F; Desmedt, A; Piazza, P V

2010-01-01

The activation of glucocorticoid receptors (GR) by glucocorticoids increases stress-related memory through the activation of the MAPK signaling pathway and the downstream transcription factor Egr-1. Here, using converging in vitro and in vivo approaches, respectively, GR-expressing cell lines, culture of hippocampal neurons, and GR genetically modified mice (GRNesCre), we identified synapsin-Ia/Ib as one of the effectors of the glucocorticoid signaling cascade. Stress and glucocorticoid-induced activation of the GR modulate synapsin-Ia/Ib through two complementary mechanisms. First, glucocorticoids driving Egr-1 expression increase the expression of synapsin-Ia/Ib, and second, glucocorticoids driving MAPK activation increase its phosphorylation. Finally, we showed that blocking fucosylation of synapsin-Ia/Ib in the hippocampus inhibits its expression and prevents the glucocorticoid-mediated increase in stress-related memory. In conclusion, our data provide a complete molecular pathway (GR/Egr-1/MAPK/Syn-Ia/Ib) through which stress and glucocorticoids enhance the memory of stress-related events and highlight the function of synapsin-Ia/Ib as molecular effector of the behavioral effects of stress. PMID:20368707

O-ribosyl-phosphate purine as a constant modified nucleotide located at position 64 in cytoplasmic initiator tRNAs(Met) of yeasts.

PubMed Central

Glasser, A L; Desgres, J; Heitzler, J; Gehrke, C W; Keith, G

1991-01-01

The unknown modified nucleotide G*, isolated from both Schizosaccharomyces pombe and Torulopsis utilis initiator tRNAs(Met), has been identified as an O-ribosyl-(1"----2')-guanosine-5"-phosphate, called Gr(p), by means of HPLC, UV-absorption, mass spectrometry and periodate oxidation procedures. By comparison with the previously published structure of Ar(p) isolated from Saccharomyces cerevisiae initiator tRNA(Met), the (1"----2')-glycosidic bond in Gr(p) has been postulated to have a beta-spatial conformation. The modified nucleotide Gr(p) is located at position 64 in the tRNA(Met) molecules, i.e. at the same position as Ar(p). Since we have also characterized Gr(p) in Candida albicans initiator tRNA(Met), the phosphoribosylation of purine 64 can be considered as a constant nucleotide modification in the cytoplasmic initiator tRNAs(Met) of all yeast species so far sequenced. Precise evidence for the presence of Gr(p) in initiator tRNAs(Met) of several plants is also reported. PMID:1656390

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

NASA Astrophysics Data System (ADS)

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.

ATP hydrolysis is essential for Bag-1M-mediated inhibition of the DNA binding by the glucocorticoid receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Wei, E-mail: hongwei@tijmu.edu.cn; Chen, Linfeng; Liu, Yunde

2009-12-04

The 70-kDa heat shock protein (Hsp70) is involved in providing the appropriate conformation of various nuclear hormone receptors, including the glucocorticoid receptor (GR). The Bcl-2 associated athanogene 1M (Bag-1M) is known to downregulate the DNA binding by the GR. Also, Bag-1M interacts with the ATPase domain of Hsp70 to modulate the release of the substrate from Hsp70. In this study, we demonstrate that ATP hydrolysis enhances Bag-1M-mediated inhibition of the DNA binding by the GR. However, the inhibitory effect of Bag-1M was abolished when the intracellular ATP was depleted. In addition, a Bag-1M mutant lacking the interaction with Hsp70 didmore » not influence the GR to bind DNA, suggesting the interaction of Bag-1M with Hsp70 in needed for its negative effect. These results indicate that ATP hydrolysis is essential for Bag-1M-mediated inhibition of the DNA binding by the GR and Hsp70 is a mediator for this process.« less

Ensemble average theory of gravity

NASA Astrophysics Data System (ADS)

Khosravi, Nima

2016-12-01

We put forward the idea that all the theoretically consistent models of gravity have contributions to the observed gravity interaction. In this formulation, each model comes with its own Euclidean path-integral weight where general relativity (GR) has automatically the maximum weight in high-curvature regions. We employ this idea in the framework of Lovelock models and show that in four dimensions the result is a specific form of the f (R ,G ) model. This specific f (R ,G ) satisfies the stability conditions and possesses self-accelerating solutions. Our model is consistent with the local tests of gravity since its behavior is the same as in GR for the high-curvature regime. In the low-curvature regime the gravitational force is weaker than in GR, which can be interpreted as the existence of a repulsive fifth force for very large scales. Interestingly, there is an intermediate-curvature regime where the gravitational force is stronger in our model compared to GR. The different behavior of our model in comparison with GR in both low- and intermediate-curvature regimes makes it observationally distinguishable from Λ CDM .

Mechanisms of Molecular Mimicry of Plant CLE Peptide Ligands by the Parasitic Nematode Globodera rostochiensis1[C][W

PubMed Central

Guo, Yongfeng; Ni, Jun; Denver, Robert; Wang, Xiaohong; Clark, Steven E.

2011-01-01

Nematodes that parasitize plant roots cause huge economic losses and have few mechanisms for control. Many parasitic nematodes infect plants by reprogramming root development to drive the formation of feeding structures. How nematodes take control of plant development is largely unknown. Here, we identify two host factors involved in the function of a receptor ligand mimic, GrCLE1, secreted by the potato cyst nematode Globodera rostochiensis. GrCLE1 is correctly processed to an active form by host plant proteases. Processed GrCLE1 peptides bind directly to the plant CLE receptors CLV2, BAM1, and BAM2. Involvement of these receptors in the ligand-mimicking process is also supported by the fact that the ability of GrCLE1 peptides to alter plant root development in Arabidopsis (Arabidopsis thaliana) is dependent on these receptors. Critically, we also demonstrate that GrCLE1 maturation can be entirely carried out by plant factors and that the availability of CLE processing activity may be essential for successful ligand mimicry. PMID:21750229

The influence of the concentration of Sr ions on the crystal and magnetic structures of Ba{sub 2} –{sub x}Sr{sub x}FeMoO{sub 6} double perovskites (x = 0–1.6)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turchenko, V. A., E-mail: turchenko@jinr.ru; Kalanda, N. A.; Kovalev, L. V.

2017-01-15

The crystal and magnetic structures of a solid solution of double perovskite Ba{sub 2–} {sub x}Sr{sub x}FeMoO{sub 6} (x = 0–1.6) have been investigated by neutron diffraction. The high-resolution diffraction patterns have provided precise information about the changes in the crystal and magnetic structures with an increase in the strontium content and data on the behavior of the sample microstructure. Replacement of barium with strontium leads to a change in the lattice symmetry from cubic (x = 0, sp. gr. Fm3̄m)) to tetragonal (x = 0.4, sp. gr. I4/m). At x = 1.0, the symmetry is either tetragonal (sp. gr.more » I4/m) or orthorhombic (sp. gr. Fmmm), and at x = 1.6 the symmetry becomes again tetragonal (sp. gr. I4/m). The values of the Curie temperature and microstrain increase with an increase in the strontium content.« less

Mechanisms of molecular mimicry of plant CLE peptide ligands by the parasitic nematode Globodera rostochiensis.

PubMed

Guo, Yongfeng; Ni, Jun; Denver, Robert; Wang, Xiaohong; Clark, Steven E

2011-09-01

Nematodes that parasitize plant roots cause huge economic losses and have few mechanisms for control. Many parasitic nematodes infect plants by reprogramming root development to drive the formation of feeding structures. How nematodes take control of plant development is largely unknown. Here, we identify two host factors involved in the function of a receptor ligand mimic, GrCLE1, secreted by the potato cyst nematode Globodera rostochiensis. GrCLE1 is correctly processed to an active form by host plant proteases. Processed GrCLE1 peptides bind directly to the plant CLE receptors CLV2, BAM1, and BAM2. Involvement of these receptors in the ligand-mimicking process is also supported by the fact that the ability of GrCLE1 peptides to alter plant root development in Arabidopsis (Arabidopsis thaliana) is dependent on these receptors. Critically, we also demonstrate that GrCLE1 maturation can be entirely carried out by plant factors and that the availability of CLE processing activity may be essential for successful ligand mimicry.

Depositing of CuS nanocrystals upon the graphene scaffold and their photocatalytic activities

NASA Astrophysics Data System (ADS)

Wang, Yongbin; Zhang, Lixin; Jiu, Hongfang; Li, Na; Sun, Yixin

2014-06-01

A series of copper sulfide nanocrystals/graphene nanocomposites (CuS/GR) with different weight ratios of GR were fabricated via a one-step hydrothermal approach by using dimethylsulfoxide (DMSO) as the source of sulfur and solvent. The as-prepared samples were studied by X-ray diffraction (XRD), UV-vis diffuse reflectance spectra (DRS), transmission scanning electron microscopy (TEM) and photoluminescence spectra (PL) are employed to determine the properties of the samples. The results show that the CuS nanocrystals with an average size of 16 nm almost overspread on the GR graphene scaffold. The samples exhibit excellent photocatalytic activities in degrading the methylene blue (MB) compared with pure CuS. This work shows that CuS/GR nanocomposites would be promising in dye wastewater treatment as Fenton-like reagents.

Long-term orbital period behaviour of low mass ratio contact binaries GR Vir and FP Boo

NASA Astrophysics Data System (ADS)

Ćetinkaya, Halil; Soydugan, Faruk

2017-02-01

In this study, we investigated orbital period variations of two low mass ratio contact binaries GR Vir and FP Boo based on published minima times. From the O-C analysis, it was found that FP Boo indicates orbital period decrease while the period of GR Vir is increasing. Mass transfer process was used to explain increase and decrease in the orbital periods. In the O-C diagrams of both systems periodic variations also exist. Cyclic changes can be explained as being the result of a light-travel time effect via a third component around the eclipsing binaries. In order to interpret of cyclic orbital period changes for GR Vir, which has late-type components, possible magnetic activity cycles of the components have been also considered.

The synergetic effect of MoS2 and graphene on Ag3PO4 for its ultra-enhanced photocatalytic activity in phenol degradation under visible light

NASA Astrophysics Data System (ADS)

Peng, Wen-Chao; Wang, Xi; Li, Xiao-Yan

2014-06-01

The photo-degradation of organic pollutants using solar light is an attractive chemical process for water pollution control. In this study, we synthesized a new composite material consisting of silver phosphate (Ag3PO4) sub-microcrystals grown on a layered molybdenum disulfide (MoS2) and graphene (GR) hybrid as a high-performance photocatalyst for the degradation of toxic organic pollutants. This composite photocatalyst was prepared via a simple two-step hydrothermal process that used sodium molybdate, thiourea and graphene oxide as precursors for the MoS2/GR hybrid and silver nitrate for the Ag3PO4 sub-microcrystals. The composite Ag3PO4-0.02(MoS2/0.005GR) was found to be the most effective catalyst for the photo-decomposition of 2,4-dichlorophenol under simulated solar light and visible light (λ >= 420 nm). The photocatalyst was also highly active for the degradation of nitrophenol and chlorophenol. The ultra photocatalytic activity of the novel catalyst arose from the synergetic effects of MoS2 and GR as cocatalysts in the composite. MoS2/GR nanosheets served as electron collectors for the interfacial electron transfer from Ag3PO4 to electron acceptors in the aqueous solution and thus enhanced the separation of the photo-generated electron-hole pairs and made the holes more available for organic oxidation. In addition, the presence of MoS2 and GR provided more active adsorption sites and allowed for the activation of dissolved O2 for organic degradation in water.The photo-degradation of organic pollutants using solar light is an attractive chemical process for water pollution control. In this study, we synthesized a new composite material consisting of silver phosphate (Ag3PO4) sub-microcrystals grown on a layered molybdenum disulfide (MoS2) and graphene (GR) hybrid as a high-performance photocatalyst for the degradation of toxic organic pollutants. This composite photocatalyst was prepared via a simple two-step hydrothermal process that used sodium molybdate, thiourea and graphene oxide as precursors for the MoS2/GR hybrid and silver nitrate for the Ag3PO4 sub-microcrystals. The composite Ag3PO4-0.02(MoS2/0.005GR) was found to be the most effective catalyst for the photo-decomposition of 2,4-dichlorophenol under simulated solar light and visible light (λ >= 420 nm). The photocatalyst was also highly active for the degradation of nitrophenol and chlorophenol. The ultra photocatalytic activity of the novel catalyst arose from the synergetic effects of MoS2 and GR as cocatalysts in the composite. MoS2/GR nanosheets served as electron collectors for the interfacial electron transfer from Ag3PO4 to electron acceptors in the aqueous solution and thus enhanced the separation of the photo-generated electron-hole pairs and made the holes more available for organic oxidation. In addition, the presence of MoS2 and GR provided more active adsorption sites and allowed for the activation of dissolved O2 for organic degradation in water. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01654h

Genetic influences on alcohol use behaviors have diverging developmental trajectories: a prospective study among male and female twins.

PubMed

Meyers, Jacquelyn L; Salvatore, Jessica E; Vuoksimaa, Eero; Korhonen, Tellervo; Pulkkinen, Lea; Rose, Richard J; Kaprio, Jaakko; Dick, Danielle M

2014-11-01

Both alcohol-specific genetic factors and genetic factors related to externalizing behavior influence problematic alcohol use. Little is known, however, about the etiologic role of these 2 components of genetic risk on alcohol-related behaviors across development. Prior studies conducted in a male cohort of twins suggest that externalizing genetic factors are important for predicting heavy alcohol use in adolescence, whereas alcohol-specific genetic factors increase in importance during the transition to adulthood. In this report, we studied twin brothers and sisters and brother-sister twin pairs to examine such developmental trajectories and investigate whether sex and cotwin sex effects modify these genetic influences. We used prospective, longitudinal twin data collected between ages 12 and 22 within the population-based FinnTwin12 cohort study (analytic n = 1,864). Our dependent measures of alcohol use behaviors included alcohol initiation (age 12), intoxication frequency (ages 14 and 17), and alcohol dependence criteria (age 22). Each individual's genetic risk of alcohol use disorders (AUD-GR) was indexed by his/her parents' and cotwin's DSM-IV Alcohol Dependence (AD) criterion counts. Likewise, each individual's genetic risk of externalizing disorders (EXT-GR) was indexed with a composite measure of parents' and cotwin's DSM-IV Conduct Disorder and Antisocial Personality Disorder criterion counts. EXT-GR was most strongly related to alcohol use behaviors during adolescence, while AUD-GR was most strongly related to alcohol problems in young adulthood. Further, sex of the twin and sex of the cotwin significantly moderated the associations between genetic risk and alcohol use behaviors across development: AUD-GR influenced early adolescent alcohol use behaviors in females more than in males, and EXT-GR influenced age 22 AD more in males than in females. In addition, the associations of AUD-GR and EXT-GR with intoxication frequency were greater among 14- and 17-year-old females with twin brothers. We found divergent developmental trajectories for alcohol-specific and externalizing behavior-related genetic influences on alcohol use behaviors; in early adolescence, genetic influences on alcohol use behaviors are largely nonspecific, and later in adolescence and young adulthood, alcohol-specific genetic influences on alcohol use are more influential. Importantly, within these overall trajectories, several interesting sex differences emerged. We found that the relationship between genetic risk and problematic drinking across development is moderated by the individual's sex and his/her cotwin's sex. AUD-GR influenced adolescent alcohol outcomes in females more than in males and by age 22, EXT-GR influenced AD criteria more for males than females. In addition, the association between genetic risk and intoxication frequency was greater among 14- and 17-year-old females with male cotwins. Copyright © 2014 by the Research Society on Alcoholism.

Nitrogen-doped graphene interpenetrated 3D Ni-nanocages: efficient and stable water-to-dioxygen electrocatalysts

NASA Astrophysics Data System (ADS)

Dhavale, Vishal M.; Gaikwad, Sachin S.; George, Leena; Devi, R. Nandini; Kurungot, Sreekumar

2014-10-01

Herein, we report the synthesis of a nitrogen-doped graphene (NGr) interpenetrated 3D Ni-nanocage (Ni-NGr) electrocatalyst by a simple water-in-oil (w/o) emulsion technique for oxidation of water to dioxygen. Correlation of adsorption of NGr and subsequent interpenetration through the specific surface plane of nickel particles as well as the concomitant interaction of N and C with Ni in the nano-regime has been investigated. Apart from the benefits of the synergistic interactions between Ni, N, and C, the overall integrity of the structure and its intra-molecular connectivity within the framework help in achieving better oxygen evolution characteristics at a significantly reduced overpotential. The engineered Ni-NGr nanocage displays a substantially low overpotential of ~290 mV at a practical current density of 20 mA cm-2 in 0.1 M KOH. In comparison, NGr and Ni-particles as separate entities give overpotentials of ~570 and ~370 mV under similar conditions. Moreover, the long term stability of Ni-NGr was investigated by anodic potential cycling for 500 cycles and an 8.5% increment in the overpotential at 20 mA cm-2 was observed. Additionally, a chronoamperometric test was performed for 15 h at 20 mA cm-2, which highlights the better sustainability of Ni-NGr under the actual operating conditions. Finally, the quantitative estimation of evolved oxygen was monitored by gas chromatography and was found to be 70 mmol h-1 g-1 of oxygen, which is constant in the second cycle as well.Herein, we report the synthesis of a nitrogen-doped graphene (NGr) interpenetrated 3D Ni-nanocage (Ni-NGr) electrocatalyst by a simple water-in-oil (w/o) emulsion technique for oxidation of water to dioxygen. Correlation of adsorption of NGr and subsequent interpenetration through the specific surface plane of nickel particles as well as the concomitant interaction of N and C with Ni in the nano-regime has been investigated. Apart from the benefits of the synergistic interactions between Ni, N, and C, the overall integrity of the structure and its intra-molecular connectivity within the framework help in achieving better oxygen evolution characteristics at a significantly reduced overpotential. The engineered Ni-NGr nanocage displays a substantially low overpotential of ~290 mV at a practical current density of 20 mA cm-2 in 0.1 M KOH. In comparison, NGr and Ni-particles as separate entities give overpotentials of ~570 and ~370 mV under similar conditions. Moreover, the long term stability of Ni-NGr was investigated by anodic potential cycling for 500 cycles and an 8.5% increment in the overpotential at 20 mA cm-2 was observed. Additionally, a chronoamperometric test was performed for 15 h at 20 mA cm-2, which highlights the better sustainability of Ni-NGr under the actual operating conditions. Finally, the quantitative estimation of evolved oxygen was monitored by gas chromatography and was found to be 70 mmol h-1 g-1 of oxygen, which is constant in the second cycle as well. Electronic supplementary information (ESI) available: An experimental procedure for the synthesis of GO, Gr, Ni-particles, and Ni-Gr. TEM images of Gr, NGr, and Ni-Gr. XPS of C 1s and O 1s of Ni-NGr. C 1s, O 1s and N 1s spectra of NGr. A comparative cyclic voltammogram of NGr and Ni-NGr. A Tafel plot, RRDE, HR-TEM image of Ni-NGr and the corresponding line profile showing the lattice spacing values, anodic scan of NGr. Comparative anodic scan of Ni-particles, Ni-Gr and Ni-NGr. CV of the Pt-electrode and capacitive CV. SEM elemental mapping and the mechanism of OER. See DOI: 10.1039/c4nr03578j

Cisplatin-Induced Conditioned Taste Aversion: Attenuation by Dexamethasone but not Zacopride or GR38032F

DTIC Science & Technology

1992-01-01

SR2-1 Cisplatin-induced conditioned taste aversion: ateuto by dexamethasone but not zacopride or GR38032F Nm I- Paul C Mele, John R. McDonough, David...to 5-H1’, receptor blockade. 5-HT., receptor antagonists; Zacopridc: GR38032F; Desamethasone: Cisplatin: Taste aversion (conditioned) I. Introductlon...intake) was used as the area known as the chemoreceptor trigger zone (Borri- index of the CTA. son, 1974). Moreover. the findings that rats, ferrets

Synthesis and characterization of nickel oxide/graphene sheet/graphene ribbon composite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lavanya, J.; Gomathi, N., E-mail: sivakumar.gomathi@gmail.com

2016-04-13

A novel and simple hydrothermal synthesis of nickel oxide (NiO)/graphene sheets (GNS)/graphene ribbon (GR) hybrid material is reported for the first time. The crystalline property and surface morphology of NiO/GNS/GR (NiO/HG) hybrid material is characterized by X-ray diffraction, Raman spectroscopy and Transmission electron spectroscopy. The fast electron transfer of GNS/GR along with NiO contributes an excellent electrochemical performance in the field of non-enzymatic glucose sensor.

Army Science Conference Proceedings Held in Orlando, Florida on June 22 - 25, 1992. Volume 1, Principal Authors A Through G.

DTIC Science & Technology

1992-06-25

Michael See Bryzik, Walter I 205 Reid, Robert H. Oral, Microencapsulated, CFA/II III 35 Vaccine Against E. coli Diarrheal Disease: Preclinical Evaluation...Cloning, Characterization, and III 179 Expression of Animal Toxin Genes for Vaccine Development Smith, Stan See Juhasz, Arpad II 159 Soicher, Haim...modeling predictions that were supported by test data. FWD AND AFT SHELLS LONGERONS T300 GR/934 EPOXYAND T300 GR/934 EPOXY(BASELINE) CORK HS (BASELINE) GR

Nitrite/Nitrate responses to endotoxin in calves.

PubMed

Hüsler, B R; Blum, J W

2001-10-01

Plasma concentrations and urinary excretions of nitrite plus nitrate (NOx) increase in heifers after endotoxin-induced nitric oxide synthase activation. The rise can be enhanced by administration of arginine, the substrate for the production of nitric oxide, whose effects may be modified by the iron status. In 10-week-old veal calves (six Simmental x Red Holstein) arginine (0.5 g/kg body weight for 6 h) was intravenously infused. At 2 h after the start of the infusions Escherichia coli endotoxin O26:B6 (2 microg/kg body weight) was intravenously injected. This caused a rise of rectal temperature, heart rate, respiration rate, and of urinary NOx excretion, but not of plasma NOx concentrations, in contrast to the experience with older cattle to which the same amounts of arginine were infused before and during endotoxin administration. In 8-week-old veal calves (18 Simmental x Red Holstein) the question of whether oral supplementation with arginine and iron modifies NOx responses to endotoxin (2 microg/kg) was also investigated. The calves were divided between three groups (GrA-, GirA+, GrC) and before endotoxin injections GrA- was fed 0.5 g arginine/kg for 4 days, GrA+ was fed 0.5 g arginine/kg for 4 days plus 80 mg iron/kg milk for 2 weeks, whereas GrC was not supplemented with arginine or iron. Iron supplementation increased plasma iron concentrations and arginine supplementation increased plasma arginine and urea concentrations and urinary urea excretion. Ensuing administration of endotoxin enhanced plasma tumour necrosis factor-alpha concentrations, rectal temperature, heart rate, and respiration rate, but not plasma NOx concentrations in GrC and GrA- and only transiently and slightly increased plasma NOx concentrations in GrA+ but did not affect urinary NOx excretions. In conclusion, the expected stimulation of NOx responses to endotoxin by intravenous arginine infusion appears to be much weaker in young veal calves than in older cattle. The NOx responses in young veal calves were not modified if arginine was orally administered and plasma NOx were barely enhanced by combined oral supplementation of arginine and iron.

Rapid corticosteroid-dependent regulation of mineralocorticoid receptor protein expression in rat brain.

PubMed

Kalman, Brian A; Spencer, Robert L

2002-11-01

Corticosteroid hormones regulate many aspects of neural function via mineralocorticoid receptors (MR) and glucocorticoid receptors (GR). Although GR expression is negatively regulated by endogenous corticosteroids, the autologous regulation of MR expression has been less well studied, partly due to limitations of receptor binding assays that cannot measure the ligand-activated form of MR. Using MR-reactive antibodies and Western blot, we examined relative MR protein expression in rat brain and its potential autoregulation by corticosteroids. We found that MR protein expression is autoregulated in a negative fashion by adrenal steroids. Compared with GR, we see a more rapid regulation of MR, such that there is a substantial increase in MR protein within 12 h after adrenalectomy, whereas GR levels show very little increase until more than 24 h after adrenalectomy. Also, in contrast to GR, which has been found to be regulated by both MR and GR, adrenalectomy-induced increase in MR was prevented by treatment with the MR selective agonist, aldosterone, but not the GR selective agonist, RU28362. Interestingly, acute treatment of adrenalectomized rats with corticosterone produced a significant decrease in whole-cell MR protein within 45 min, suggesting ligand-induced rapid degradation of MR. Chronic high levels of corticosterone also produced a significant decrease in MR protein levels below adrenal-intact rat levels. These results have important implications for previous studies that estimated the proportion of MR that are occupied in vivo by various circulating levels of corticosterone. Those studies compared available MR binding levels in adrenal-intact rats with 24-h adrenalectomized rats, with the assumption that there were no differences between the various conditions in total receptor expression. Those studies concluded that MR is nearly fully occupied by even the lowest circulating corticosterone levels. Given the 2- to 3-fold increase in MR protein that we have observed within 24 h after adrenalectomy, it is likely that those studies significantly overestimated the proportion of MR that were occupied by low basal corticosterone levels. These results support the prospect that MR as well as GR can participate in the transduction of phasic corticosteroid signals.

Breakfast replacement with a low-glycaemic response liquid formula in patients with type 2 diabetes: a randomised clinical trial.

PubMed

Stenvers, Dirk J; Schouten, Lydia J; Jurgens, Jordy; Endert, Erik; Kalsbeek, Andries; Fliers, Eric; Bisschop, Peter H

2014-08-28

Low-glycaemic index diets reduce glycated Hb (HbA1c) in patients with type 2 diabetes, but require intensive dietary support. Using a liquid meal replacement with a low glycaemic response (GR) may be an alternative dietary approach. In the present study, we investigated whether breakfast replacement with a low-GR liquid meal would reduce postprandial glycaemia and/or improve long-term glycaemia. In the present randomised, controlled, cross-over design, twenty patients with type 2 diabetes consumed either a breakfast replacement consisting of an isoenergetic amount of Glucerna SR or a free-choice breakfast for 3 months. Postprandial AUC levels were measured using continuous glucose measurement at home. After the 3-month dietary period, meal profiles and oral glucose tolerance were assessed in the clinical setting. The low-GR liquid meal replacement reduced the AUC of postprandial glucose excursions at home compared with a free-choice control breakfast (estimated marginal mean 141 (95 % CI 114, 174) v. estimated marginal mean 259 (95 % CI 211, 318) mmol × min/l; P= 0·0002). The low-GR liquid meal replacement also reduced glucose AUC levels in the clinical setting compared with an isoenergetic control breakfast (low GR: median 97 (interquartile range (IQR) 60-188) mmol × min/l; control: median 253 (IQR 162-386) mmol × min/l; P< 0·001). However, the 3-month low-GR liquid meal replacement did not affect fasting plasma glucose, HbA1c or lipid levels, and even slightly reduced oral glucose tolerance. In conclusion, the low-GR liquid meal replacement is a potential dietary approach to reduce postprandial glycaemia in patients with type 2 diabetes. However, clinical trials into the effects of replacing multiple meals on long-term glycaemia in poorly controlled patients are required before a low-GR liquid meal replacement can be adopted as a dietary approach to the treatment of type 2 diabetes.

Functional anatomy and ultrasound examination of the canine penis.

PubMed

Goericke-Pesch, Sandra; Hölscher, Catharina; Failing, Klaus; Wehrend, Axel

2013-07-01

The aim of this study was to identify the functional-anatomical structures of the canine penis during and after erection to demonstrate the respective changes to provide a basis for further examinations of pathological conditions like priapism. Additionally, a gray-scale analysis was performed to quantify results from the ultrasound examination. In total, 80 dogs were examined. In group (Gr.) A, 44 intact or castrated dogs were examined, and in Gr. B, 36 dogs were examined during erection and after complete detumescence of the penis. The following parameters were assessed: (1) using physical measurements: length of the Pars longa glandis [Plg] and length of the Bulbus glandis [Bg]; and (2) using ultrasound: total penile diameter, width of the erectile tissue of the Plg, diameter of the Corpus spongiosum [Cs] including the penile bone and urethra, vertical diameter, circumference of the penis, cross-sectional area, and area of the Cs including the urethra. The mentioned parameters could be assessed in all dogs of Gr. A and Gr. B with the only exception being the urethra that could be visualized using ultrasound in some dogs only and predominantly in the erected penis (Gr. B). Concomitantly, the erectile tissue of the Plg and the Cs was more heterogenous and hypo- to anechoic during erection compared with dogs in Gr. A and Gr. B after detumescence. Comparing the results in Gr. B, the length of the Plg and the Bg were decreased approximately 40.6% and 38.0%, the total width of the penis 40.5%, the total width of the erectile tissue of the Plg 48.0%, and the width of the Cs 15.6% during detumescence compared with erection. Comparing the decrease in size at the different locations (apex penis, middle of Plg, middle of Bg) for vertical diameter, total circumference, and cross-section area, it was largest at the Bg. B-mode ultrasound is a suitable tool to investigate not only the morpho-functional structures of the resting canine penis, but also of the erected and detumescent penis, and to investigate the underlying changes during erection and detumenscence. Copyright © 2013 Elsevier Inc. All rights reserved.

Abstinence from prolonged ethanol exposure affects plasma corticosterone, glucocorticoid receptor signaling and stress-related behaviors.

PubMed

Somkuwar, Sucharita S; Vendruscolo, Leandro F; Fannon, McKenzie J; Schmeichel, Brooke E; Nguyen, Tran Bao; Guevara, Jasmin; Sidhu, Harpreet; Contet, Candice; Zorrilla, Eric P; Mandyam, Chitra D

2017-10-01

Alcohol dependence is linked to dysregulation of the hypothalamic-pituitary-adrenal axis. Here, we investigated effects of repeated ethanol intoxication-withdrawal cycles (using chronic intermittent ethanol vapor inhalation; CIE) and abstinence from CIE on peak and nadir plasma corticosterone (CORT) levels. Irritability- and anxiety-like behaviors as well as glucocorticoid receptors (GR) in the medial prefrontal cortex (mPFC) were assessed at various intervals (2h-28d) after cessation of CIE. Results show that peak CORT increased during CIE, transiently decreased during early abstinence (1-11d), and returned to pre-abstinence levels during protracted abstinence (17-27d). Acute withdrawal from CIE enhanced aggression- and anxiety-like behaviors. Early abstinence from CIE reduced anxiety-like behavior. mPFC-GR signaling (indexed by relative phosphorylation of GR at Ser211) was transiently decreased when measured at time points during early and protracted abstinence. Further, voluntary ethanol drinking in CIE (CIE-ED) and CIE-naïve (ED) rats, and effects of CIE-ED and ED on peak CORT levels and mPFC-GR were investigated during acute withdrawal (8h) and protracted abstinence (28d). CIE-ED and ED increased peak CORT during drinking. CIE-ED and ED decreased expression and signaling of mPFC-GR during acute withdrawal, an effect that was reversed by systemic mifepristone treatment. CIE-ED and ED demonstrate robust reinstatement of ethanol seeking during protracted abstinence and show increases in mPFC-GR expression. Collectively, the data demonstrate that acute withdrawal from CIE produces robust alterations in GR signaling, CORT and negative affect symptoms which could facilitate excessive drinking. The findings also show that CIE-ED and ED demonstrate enhanced relapse vulnerability triggered by ethanol cues and these changes are partially mediated by altered GR expression in the mPFC. Taken together, transition to alcohol dependence could be accompanied by alterations in mPFC stress-related pathways that may increase negative emotional symptoms and increase vulnerability to relapse. Copyright © 2017 Elsevier Ltd. All rights reserved.

General Relativistic Precession in Small Solar System Bodies

NASA Astrophysics Data System (ADS)

Sekhar, Aswin; Werner, Stephanie; Hoffmann, Volker; Asher, David; Vaubaillon, Jeremie; Hajdukova, Maria; Li, Gongjie

2016-10-01

Introduction: One of the greatest successes of the Einstein's General Theory of Relativity (GR) was the correct prediction of the precession of perihelion of Mercury. The closed form expression to compute this precession tells us that substantial GR precession would occur only if the bodies have a combination of both moderately small perihelion distance and semi-major axis. Minimum Orbit Intersection Distance (MOID) is a quantity which helps us to understand the closest proximity of two orbits in space. Hence evaluating MOID is crucial to understand close encounters and collision scenarios better. In this work, we look at the possible scenarios where a small GR precession in argument of pericentre (ω) can create substantial changes in MOID for small bodies ranging from meteoroids to comets and asteroids.Analytical Approach and Numerical Integrations: Previous works have looked into neat analytical techniques to understand different collision scenarios and we use those standard expressions to compute MOID analytically. We find the nature of this mathematical function is such that a relatively small GR precession can lead to drastic changes in MOID values depending on the initial value of ω. Numerical integrations were done with package MERCURY incorporating the GR code to test the same effects. Numerical approach showed the same interesting relationship (as shown by analytical theory) between values of ω and the peaks/dips in MOID values. Previous works have shown that GR precession suppresses Kozai oscillations and this aspect was verified using our integrations. There is an overall agreement between both analytical and numerical methods.Summary and Discussion: We find that GR precession could play an important role in the calculations pertaining to MOID and close encounter scenarios in the case of certain small solar system bodies (depending on their initial orbital elements). Previous works have looked into impact probabilities and collision scenarios on planets from different small body populations. This work aims to find certain sub-sets of orbits where GR could play an interesting role. Certain parallels are drawn between the cases of asteroids, comets and small perihelion distance meteoroid streams.

Sense-encoded poly-GR dipeptide repeat proteins correlate to neurodegeneration and uniquely co-localize with TDP-43 in dendrites of repeat-expanded C9orf72 amyotrophic lateral sclerosis.

PubMed

Saberi, Shahram; Stauffer, Jennifer E; Jiang, Jie; Garcia, Sandra Diaz; Taylor, Amy E; Schulte, Derek; Ohkubo, Takuya; Schloffman, Cheyenne L; Maldonado, Marcus; Baughn, Michael; Rodriguez, Maria J; Pizzo, Don; Cleveland, Don; Ravits, John

2018-03-01

Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (C9 ALS). The main hypothesized pathogenic mechanisms are C9orf72 haploinsufficiency and/or toxicity from one or more of bi-directionally transcribed repeat RNAs and their dipeptide repeat proteins (DPRs) poly-GP, poly-GA, poly-GR, poly-PR and poly-PA. Recently, nuclear import and/or export defects especially caused by arginine-containing poly-GR or poly-PR have been proposed as significant contributors to pathogenesis based on disease models. We quantitatively studied and compared DPRs, nuclear pore proteins and C9orf72 protein in clinically related and clinically unrelated regions of the central nervous system, and compared them to phosphorylated TDP-43 (pTDP-43), the hallmark protein of ALS. Of the five DPRs, only poly-GR was significantly abundant in clinically related areas compared to unrelated areas (p < 0.001), and formed dendritic-like aggregates in the motor cortex that co-localized with pTDP-43 (p < 0.0001). While most poly-GR dendritic inclusions were pTDP-43 positive, only 4% of pTDP-43 dendritic inclusions were poly-GR positive. Staining for arginine-containing poly-GR and poly-PR in nuclei of neurons produced signals that were not specific to C9 ALS. We could not detect significant differences of nuclear markers RanGap, Lamin B1, and Importin β1 in C9 ALS, although we observed subtle nuclear changes in ALS, both C9 and non-C9, compared to control. The C9orf72 protein itself was diffusely expressed in cytoplasm of large neurons and glia, and nearly 50% reduced, in both clinically related frontal cortex and unrelated occipital cortex, but not in cerebellum. In summary, sense-encoded poly-GR DPR was unique, and localized to dendrites and pTDP43 in motor regions of C9 ALS CNS. This is consistent with new emerging ideas about TDP-43 functions in dendrites.

Sense-encoded poly-GR dipeptide repeat proteins correlate to neurodegeneration and uniquely co-localize with TDP-43 in dendrites of repeat expanded C9orf72 amyotrophic lateral sclerosis

PubMed Central

Saberi, Shahram; Stauffer, Jennifer E.; Jiang, Jie; Garcia, Sandra Diaz; Taylor, Amy E; Schulte, Derek; Ohkubo, Takuya; Schloffman, Cheyenne L.; Maldonado, Marcus; Baughn, Michael; Rodriguez, Maria J; Pizzo, Don; Cleveland, Don; Ravits, John

2018-01-01

Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (C9 ALS). The main hypothesized pathogenic mechanisms are C9orf72 haploinsufficiency and/or toxicity from one or more of bi-directionally transcribed repeat RNAs and their dipeptide repeat proteins (DPRs) poly-GP, poly-GA, poly-GR, poly-PR and poly-PA. Recently, nuclear import and/or export defects especially caused by arginine-containing poly-GR or poly-PR have been proposed as significant contributors to pathogenesis based on disease models. We quantitatively studied and compared DPRs, nuclear pore proteins and C9orf72 protein in clinically-related and clinically-unrelated regions of the central nervous system, and compared them to phosphorylated TDP-43 (pTDP-43), the hallmark protein of ALS. Of the five DPRs, only poly-GR was significantly abundant in clinically-related areas compared to unrelated areas (p<0.001), and formed dendritic-like aggregates in the motor cortex that co-localized with pTDP-43 (p<0.0001). While most poly-GR dendritic inclusions were pTDP-43-positive, only 4% of pTDP-43 dendritic inclusions were poly-GR-positive. Staining for arginine-containing poly-GR and poly-PR in nuclei of neurons produced signals that were not specific to C9 ALS. We could not detect significant differences of nuclear markers RanGap, Lamin B1, and Importin β1 in C9 ALS, although we observed subtle nuclear changes in ALS, both C9 and non-C9, compared to control. The C9orf72 protein itself was diffusely expressed in cytoplasm of large neurons and glia, and nearly 50% reduced, in both clinically-related frontal cortex and unrelated occipital cortex, but not in cerebellum. In summary, sense-encoded poly-GR DPR was unique, and localized to neurites and pTDP43 in motor regions of C9 ALS CNS. This is consistent with new emerging ideas about TDP-43 functions in dendrites. PMID:29196813

Reappraising the surgical approach on the perforated gastroduodenal ulcer: should gastric resection be abandoned?

PubMed

Kuwabara, Kazuaki; Matsuda, Shinya; Fushimi, Kiyohide; Ishikawa, Koichi B; Horiguchi, Hiromasa; Fujimori, Kenji

2011-10-01

Advancements in medical care for peptic ulcer disease (PUD) have reduced the need for invasive surgical procedures such as gastric resection (GR). Community-based PUD studies from a large sampling of PUD patients designed to analyze hospital resource use and outcomes after different surgical procedures have been rare. We aimed to exhaustively reappraise the risk factors and patient demographics that affect PUD patient recoveries after GR compared to those after simple closure (SC). We used a Japanese administrative database for 6 consecutive months each year between 2006 and 2010. The database included a total of 68,432 PUD patients; we analyzed 6,334 perforation cases and 3,148 cases of patients who underwent GR or SC. Study variables were demographics, comorbidities, characteristics of PUD, and operative day. Study outcomes that were analyzed included mortality, postoperative complications, ventilation administration, postoperative blood transfusions, length of stay, total charges, operating room (OR) time, and the postoperative fasting period (defined as the day of surgery to the day oral food intake was resumed.) To reduce selection bias in study procedures and to control the variation in hospital practice, a propensity score (PS) matching cohort analysis and a mixed linear regression model were used to assess the effects of GR on the outcomes. In 699 hospitals, 322 GRs and 2,826 SCs were observed. Younger age, duodenal ulcers, preexisting anemia and an operative day no more than 24hours were significant associated with the choice of SCs. No significant differences were observed in study outcomes after either GR or SC; more postoperative blood transfusions and longer OR times but shorter postoperative fasting periods were observed after GR. Longer OR times, ventilation and postoperative blood transfusion were significantly associated with mortality. Not GR but longer OR times use of ventilation and complications were the most significant indicators of increased resource use. There were no major significant differences in GR when compared to SC with regards to patient recoveries. Surgeons should obtain the skills and establish strategies to optimize either type of surgical procedure including minimizing OR time and establishing the best perioperative critical care. Peptic ulcer perforation; Simple closure; Gastric resection; Outcome; Resource use.

Evidence for smaller extents of the northwestern Greenland Ice Sheet and North Ice Cap during the Holocene

NASA Astrophysics Data System (ADS)

Kelly, M. A.; Osterberg, E. C.; Axford, Y.; Bigl, M.; Birkel, S. D.; Corbett, L. B.; Roy, E. P.; Thompson, J. T.; Whitecloud, S.

2013-12-01

The Greenland Ice Sheet (GrIS) and local glaciers on Greenland are responding dynamically to warming temperatures with widespread retreat. GRACE satellite data (e.g., Kahn et al., 2010) and the Petermann Glacier calving events document the recent expansion of ice loss into northwestern Greenland. To improve the ability to estimate future ice loss in a warming climate, we are developing records of the response of the northwestern Greenlandic cryosphere to Holocene climatic conditions, with a focus on past warm periods. Our ongoing research includes analyses of glacial geology, sub-fossil vegetation, lake sediment cores, chironomid assemblages and ice cores combined with glaciological modeling. To constrain past ice extents that were as small as, or smaller than, at present, we recovered sub-fossil vegetation exposed at the receding margins of the GrIS and North Ice Cap (NIC) in the Nunatarssuaq region (~76.7°N, 67.4°W) and of the GrIS near Thule (~76.5°N, 68.7°W). We present vegetation types and radiocarbon ages of 30 plant samples collected in August 2012. In the Nunatarssuaq region, five ages of in situ (rooted) vegetation including Polytrichum moss, Saxifraga nathorstii and grasses located <5 m outboard of the GrIS margin are ~120-200 cal yr BP (range of medians of the 2-sigma calibrated age ranges). Nine ages of in situ Polytrichum, Saxifraga oppositafolia and grasses from ~1-5 m inboard of the NIC margin (excavated from beneath ice) range from ~50 to 310 cal yr BP. The growth of these plants occurred when the GrIS and NIC were at least as small as at present and their ages suggest that ice advances occurred in the last 50-120 yrs. In addition to the in situ samples, we collected plants from well-preserved ground material exposed along shear planes in the GrIS margins. In Nunatarssuaq, two Polytrichum mosses rooted in ground material and exposed along a shear plane in the GrIS margin date to 4680 and 4730 cal yr BP. Near Thule, three ages of Salix arctica rooted in ground material and exposed along a shear plane in the GrIS are ~170-390 cal yr BP. Four ages of plant fragments within ice in a shear plane in the NIC margin are ~600-950 cal yr BP. Since these organic remains have been transported from beneath the GrIS and NIC, respectively, they indicate times of smaller than present ice extents. Together these plants provide evidence that the northwestern GrIS was smaller than at present at ~4600-4800 and ~170-390 cal yr BP. Advance to the modern GrIS extent was likely underway at of after ~170 cal yr BP. NIC was smaller than at present at ~600-950 cal yr. Our ongoing research is investigating the climatic conditions during these times and the relationship of these restricted ice extents to those documented elsewhere on Greenland as well as on Baffin Island.

Hybridized polymer matrix composites

NASA Technical Reports Server (NTRS)

London, A.

1981-01-01

Design approaches and materials are described from which are fabricated pyrostatic graphite/epoxy (Gr/Ep) laminates that show improved retention of graphite particulates when subjected to burning. Sixteen hybridized plus two standard Gr/Ep laminates were designed, fabricated, and tested in an effort to eliminate the release of carbon (graphite) fiber particles from burned/burning, mechanically disturbed samples. The term pyrostatic is defined as meaning mechanically intact in the presence of fire. Graphite particulate retentive laminates were constructed whose constituent materials, cost of fabrication, and physical and mechanical properties were not significantly different from existing Gr/Ep composites. All but one laminate (a Celion graphite/bis-maleimide polyimide) were based on an off-the-shelf Gr/Ep, the AS-1/3501-5A system. Of the 16 candidates studied, four thin (10-ply) and four thick (50-ply) hybridized composites are recommended.

Beyond δ: Tailoring marked statistics to reveal modified gravity

NASA Astrophysics Data System (ADS)

Valogiannis, Georgios; Bean, Rachel

2018-01-01

Models which attempt to explain the accelerated expansion of the universe through large-scale modifications to General Relativity (GR), must satisfy the stringent experimental constraints of GR in the solar system. Viable candidates invoke a “screening” mechanism, that dynamically suppresses deviations in high density environments, making their overall detection challenging even for ambitious future large-scale structure surveys. We present methods to efficiently simulate the non-linear properties of such theories, and consider how a series of statistics that reweight the density field to accentuate deviations from GR can be applied to enhance the overall signal-to-noise ratio in differentiating the models from GR. Our results demonstrate that the cosmic density field can yield additional, invaluable cosmological information, beyond the simple density power spectrum, that will enable surveys to more confidently discriminate between modified gravity models and ΛCDM.

Deformation of extremal black holes from stringy interactions

NASA Astrophysics Data System (ADS)

Chen, Baoyi; Stein, Leo C.

2018-04-01

Black holes are a powerful setting for studying general relativity and theories beyond GR. However, analytical solutions for rotating black holes in beyond-GR theories are difficult to find because of the complexity of such theories. In this paper, we solve for the deformation to the near-horizon extremal Kerr metric due to two example string-inspired beyond-GR theories: Einstein-dilaton-Gauss-Bonnet and dynamical Chern-Simons theory. We accomplish this by making use of the enhanced symmetry group of NHEK and the weak-coupling limit of EdGB and dCS. We find that the EdGB metric deformation has a curvature singularity, while the dCS metric is regular. From these solutions, we compute orbital frequencies, horizon areas, and entropies. This sets the stage for analytically understanding the microscopic origin of black hole entropy in beyond-GR theories.

Scintigraphic assessment of indium-111-labeled granulocyte splenic pooling: A new approach to inflammatory bowel disease activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loreal, O.; Moisan, A.; Bretagne, J.F.

1990-09-01

We have conducted a prospective study into the sensitivity and the specificity of the fall in splenic activity (FSA) as an index of activity in inflammatory bowel disease (IBD). FSA was measured on scintiscans obtained at 3 and 24 hr postinjection of indium-111-labeled granulocytes. One hundred and twenty-two scans were acquired in 96 patients who were divided into six groups: Gr. I = normal volunteers (n = 10); Gr. II = inflammatory rheumatism (n = 10); Gr. III = abscesses (n = 17); Gr. IV = ulcerative colitis (UC: n = 23); Gr. V = colonic Crohn's disease (CCD: nmore » = 22); and Gr. VI = ileal Crohn's disease (ICD: n = 14). FSA for Groups I and II was constantly below 10%, but it was increased in the other four groups (abscesses: 39% +/- 12%; UC: 35% +/- 13.5%; CCD: 23.7% +/- 14.7%; ICD: 21.5% +/- 11.7%). There was a significant correlation between fecal excretion of 111In (FEI) and FSA in patients with IBD (UC: r = 0.71, p less than 0.001; CCD: r = 0.74, p less than 0.001; ICD: r = 0.43, p less than 0.001). FSA was followed in 16 patients with IBD after medical treatment and there was a significant correlation between variations in FSA and in FEI (r = 0.879, p less than 0.001). FSA is a very sensitive although nonspecific index of disease activity in IBD and may replace FEI in the assessment of IBD activity.« less

Population structure of microbial communities associated with two deep, anaerobic, alkaline aquifers.

PubMed Central

Fry, N K; Fredrickson, J K; Fishbain, S; Wagner, M; Stahl, D A

1997-01-01

Microbial communities of two deep (1,270 and 316 m) alkaline (pH 9.94 and 8.05), anaerobic (Eh, -137 and -27 mV) aquifers were characterized by rRNA-based analyses. Both aquifers, the Grande Ronde (GR) and Priest rapids (PR) formations, are located within the Columbia River Basalt Group in south-central Washington, and sulfidogenesis and methanogenesis characterize the GR and PR formations, respectively. RNA was extracted from microorganisms collected from groundwater by ultrafiltration through hollow-fiber membranes and hybridized to taxon-specific oligonucleotide probes. Of the three domains, Bacteria dominated both communities, making up to 92.0 and 64.4% of the total rRNA from the GR and PR formations, respectively. Eucarya comprised 5.7 and 14.4%, and Archaea comprised 1.8% and 2.5%, respectively. The gram-positive target group was found in both aquifers, 11.7% in GR and 7.6% in PR. Two probes were used to target sulfate- and/or metal-reducing bacteria within the delta subclass of Proteobacteria. The Desulfobacter groups was present (0.3%) only in the high-sulfate groundwater (GR). However, comparable hybridization to a probe selective for the desulfovibrios and some metal-reducing bacteria was found in both aquifers, 2.5 and 2.9% from the GR and PR formations, respectively. Selective PCR amplification and sequencing of the desulfovibrio/metal-reducing group revealed a predominance of desulfovibrios in both systems (17 of 20 clones), suggesting that their environmental distribution is not restricted by sulfate availability. PMID:9097447

Population structure of microbial communities associated with two deep, anaerobic, alkaline aquifers.

PubMed

Fry, N K; Fredrickson, J K; Fishbain, S; Wagner, M; Stahl, D A

1997-04-01

Microbial communities of two deep (1,270 and 316 m) alkaline (pH 9.94 and 8.05), anaerobic (Eh, -137 and -27 mV) aquifers were characterized by rRNA-based analyses. Both aquifers, the Grande Ronde (GR) and Priest rapids (PR) formations, are located within the Columbia River Basalt Group in south-central Washington, and sulfidogenesis and methanogenesis characterize the GR and PR formations, respectively. RNA was extracted from microorganisms collected from groundwater by ultrafiltration through hollow-fiber membranes and hybridized to taxon-specific oligonucleotide probes. Of the three domains, Bacteria dominated both communities, making up to 92.0 and 64.4% of the total rRNA from the GR and PR formations, respectively. Eucarya comprised 5.7 and 14.4%, and Archaea comprised 1.8% and 2.5%, respectively. The gram-positive target group was found in both aquifers, 11.7% in GR and 7.6% in PR. Two probes were used to target sulfate- and/or metal-reducing bacteria within the delta subclass of Proteobacteria. The Desulfobacter groups was present (0.3%) only in the high-sulfate groundwater (GR). However, comparable hybridization to a probe selective for the desulfovibrios and some metal-reducing bacteria was found in both aquifers, 2.5 and 2.9% from the GR and PR formations, respectively. Selective PCR amplification and sequencing of the desulfovibrio/metal-reducing group revealed a predominance of desulfovibrios in both systems (17 of 20 clones), suggesting that their environmental distribution is not restricted by sulfate availability.

Recruitment of bone marrow CD11b+Gr-1+ cells by polymeric nanoparticles for antigen cross-presentation

NASA Astrophysics Data System (ADS)

Yang, Ya-Wun; Luo, Wen-Hui

2017-03-01

The objective of this study was to investigate the function of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on the activation of antigen-specific CD8+ T cell responses via the CD11b+Gr-1+ myeloid subpopulations in murine bone marrow (BM). PLGA NPs containing ovalbumin (OVA) were fabricated by the double-emulsion method. The CD11b+Gr-1lowLy-6Chigh and CD11b+Gr-1highLy-6Clow subsets from mice bone marrow were sorted and treated with the PLGA/OVA NPs, followed by co-culture with the carboxyfluorescein succinimidyl ester (CFSE)-labelled OT-I CD8+ cells. Co-culture of OT-I CD8+ T cells with PLGA/OVA NPs-primed CD11b+Gr-1+ subsets upregulated the expression of IL-2, TNF-α, INF-γ, granzyme B, and perforin, resulting in proliferation of CD8+ T cells and differentiation into effector cytotoxic T lymphocytes (CTLs). In vivo proliferation of CFSE-labelled OT-I CD8+ cells in response to OVA was also obtained in the animals immunized with PLGA/OVA NPs. The results presented in this study demonstrate the ability of polymeric NPs to recruit two CD11b+Gr-1+ myeloid subsets for effective presentation of exogenous antigen to OT-I CD8+ T cells in the context of major histocompatibility complex (MHC) class I, leading to an induction of antigen-specific cell proliferation and differentiation into effector cells.

A novel Laccase Biosensor based on Laccase immobilized Graphene-Cellulose Microfiber Composite modified Screen-Printed Carbon Electrode for Sensitive Determination of Catechol

PubMed Central

Palanisamy, Selvakumar; Ramaraj, Sayee Kannan; Chen, Shen-Ming; Yang, Thomas C. K.; Yi-Fan, Pan; Chen, Tse-Wei; Velusamy, Vijayalakshmi; Selvam, Sonadevi

2017-01-01

In the present work, we demonstrate the fabrication of laccase biosensor to detect the catechol (CC) using laccase immobilized on graphene-cellulose microfibers (GR-CMF) composite modified screen printed carbon electrode (SPCE). The direct electrochemical behavior of laccase was investigated using laccase immobilized different modified SPCEs, such as GR/SPCE, CMF/SPCE and GR-CMF/SPCE. Compared with laccase immobilized GR and CMF modified SPCEs, a well-defined redox couple of CuI/CuII for laccase was observed at laccase immobilized GR-CMF composite modified SPCE. Cyclic voltammetry results show that the as-prepared biosensor has 7 folds higher catalytic activity with lower oxidation potential towards CC than SPCE modified with GR-CMF composite. Under optimized conditions, amperometric i-t method was used for the quantification of CC, and the amperometric response of the biosensor was linear over the concertation of CC ranging from 0.2 to 209.7 μM. The sensitivity, response time and the detection limit of the biosensor for CC is 0.932 μMμA−1 cm−2, 2 s and 0.085 μM, respectively. The biosensor has high selectivity towards CC in the presence of potentially active biomolecules and phenolic compounds. The biosensor also accessed for the detection of CC in different water samples and shows good practicality with an appropriate repea. PMID:28117357

Changes in Greenland ice bed conditions inferred from seismology

NASA Astrophysics Data System (ADS)

Toyokuni, Genti; Takenaka, Hiroshi; Takagi, Ryota; Kanao, Masaki; Tsuboi, Seiji; Tono, Yoko; Childs, Dean; Zhao, Dapeng

2018-04-01

Basal conditions of the Greenland Ice Sheet (GrIS) are a key research topic in climate change studies. The recent construction of a seismic network has provided a new opportunity for direct, real-time, and continuous monitoring of the GrIS. Here we use ambient noise surface wave data from seismic stations all over Greenland for a 4.5-year period to detect changes in Rayleigh-wave phase velocity between seismic station pairs. We observe clear seasonal and long-term velocity changes for many pairs, and propose a plausible mechanism for these changes. Dominant factors driving the velocity changes might be seasonal and long-term pressurization/depressurization of the GrIS and shallow bedrock by air and ice mass loading/unloading. However, heterogeneity of the GrIS basal conditions might impose strong regionalities on the results. An interesting feature is that, even at adjacent two station pairs in the inland GrIS, one pair shows velocity decrease while another shows velocity increase as a response to the high air and snow pressure. The former pair might be located on a thawed bed that decreases velocity by increased meltwater due to pressure melting, whereas the latter pair might be located on a frozen bed that increases velocity by compaction of ice and shallow bedrock. The results suggest that surface waves are very sensitive to the GrIS basal conditions, and further observations will contribute to a more direct and quantitative estimation of water balance in the Arctic region.

Degradation of Mcl-1 by granzyme B: implications for Bim-mediated mitochondrial apoptotic events.

PubMed

Han, Jie; Goldstein, Leslie A; Gastman, Brian R; Froelich, Christopher J; Yin, Xiao-Ming; Rabinowich, Hannah

2004-05-21

Recent studies have suggested that in the absence of Bid, granzyme B (GrB) can utilize an unknown alternative pathway to mediate mitochondrial apoptotic events. The current study has elucidated just such a pathway for GrB-mediated mitochondrial apoptotic alterations. Two Bcl-2 family members have been identified as interactive players in this newly discovered mitochondrial response to GrB: the pro-survival protein Mcl-1L and the pro-apoptotic protein, Bim. Expression of Mcl-1L, which localizes mainly to the outer mitochondrial membrane, decreases significantly in cells subjected to CTL-free cytotoxicity mediated by a combination of GrB and replication-deficient adenovirus. The data suggest that Mcl-1L is a substrate for GrB and for caspase-3, but the two enzymes appear to target different cleavage sites. The cleavage pattern of endogenous Mcl-1L resembles that of in vitro translated Mcl-1L subjected to similar proteolytic activity. Co-immunoprecipitation experiments performed with endogenous as well as with in vitro translated proteins suggest that Mcl-1L is a high affinity binding partner of the three isoforms of Bim (extra-long, long, and short). Bim, a BH3-only protein, is capable of mediating the release of mitochondrial cytochrome c, and this activity is inhibited by the presence of exogenous Mcl-1L. The findings presented herein imply that Mcl-1L degradation by either GrB or caspase-3 interferes with Bim sequestration by Mcl-1L.

Constructing the quantum Hall system on the Grassmannians Gr2(CN)

NASA Astrophysics Data System (ADS)

Ballı, F.; Behtash, A.; Kürkçüoğlu, S.; Ünal, G.

2015-04-01

In this talk, we give the formulation of Quantum Hall Effects (QHEs) on the complex Grassmann manifolds Gr2(CN). We set up the Landau problem in Gr2(CN), solve it using group theoretical techniques and provide the energy spectrum and the eigenstates in terms of the SU(N) Wigner D-functions for charged particles on Gr2(CN) under the influence of abelian and non-abelian background magnetic monopoles or a combination of these thereof. For the simplest case of Gr2(C4) we provide explicit constructions of the single and many- particle wavefunctions by introducing the Plucker coordinates and show by calculating the two-point correlation function that the lowest Landau level (LLL) at filling factor v = 1 forms an incompressible fluid. Finally, we heuristically identify a relation between the U(1) Hall effect on Gr2(C4) and the Hall effect on the odd sphere S5, which is yet to be investigated in detail, by appealing to the already known analogous relations between the Hall effects on CP3 and CP7 and those on the spheres S4 and S8, respectively. The talk is given by S. Kürkçüoğlu at the Group 30 meeting at Ghent University, Ghent, Belgium in July 2014 and based on the article by F.Ballı, A.Behtash, S. Kürkçüoğlu, G.Ünal [1].