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Sample records for activated gamma delta

  1. Circulating gamma delta T cells are activated and depleted during progression of high-grade gliomas: Implications for gamma delta T cell therapy of GBM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glioblastoma multiforme (GBM) remains frustratingly impervious to any existing therapy. We have previously shown that GBM is sensitive to recognition and lysis by ex vivo activated gamma delta T cells, a minor subset of lymphocytes that innately recognize autologous stress-associated target antigens...

  2. Mycobacterium tuberculosis induces apoptosis in gamma/delta T lymphocytes from patients with advanced clinical forms of active tuberculosis.

    PubMed Central

    Duarte, R; Kindlelán, J M; Carracedo, J; Sánchez-Guijo, P; Ramírez, R

    1997-01-01

    Antigens from inactivated Mycobacterium tuberculosis H37Ra induce activation in a subpopulation of gamma/delta (gamma/delta) T lymphocytes in a manner that resembles that of superantigens from alpha/beta T cells. After culture in vitro with H37Ra proteins, gamma/delta T lymphocytes from patients with advanced clinical forms of active tuberculosis (ACF-TBC) display cytotoxic activity against homotypic target cells exposed to H37Ra. Cytotoxicity by gamma/delta T lymphocytes from ACF-TBC patients occurs in a range similar to that observed in healthy subjects. Following activation, H37Ra-stimulated gamma/delta T lymphocytes from healthy subjects did proliferate in the presence of exogenous recombinant human interleukin 2. However, under the same conditions, gamma/delta T lymphocytes from ACF-TBC patients not only did not proliferate but died by apoptosis. These results suggest that in gamma/delta T lymphocytes from patients with ACF-TBC, antigens from M. tuberculosis may induce cell activation that leads to apoptotic cell death. PMID:9008275

  3. Clonal expansions of activated gamma/delta T cells in recent-onset multiple sclerosis.

    PubMed Central

    Shimonkevitz, R; Colburn, C; Burnham, J A; Murray, R S; Kotzin, B L

    1993-01-01

    Multiple sclerosis (MS) is a chronic disease characterized by focal demyelination of the white matter of the brain and spinal cord. Central nervous system damage appears to be mediated by infiltrating T lymphocytes and macrophages, and a central role for autoreactive CD4+ T cells has been proposed. However, the initial immune events that lead to the chronic process of MS remain unidentified. We now present evidence that a subset of T lymphocytes bearing gamma/delta T-cell antigen receptors has been activated in patients with recent-onset disease. Cells recovered from the cerebrospinal fluid of subjects with MS were cultured for short periods of time in medium supplemented with T-cell growth factors. Expansions of V delta 1 and V delta 2 T-cell receptor-bearing lymphocytes were found only in cell populations obtained from subjects with recent-onset disease. Similar populations were not expanded in subjects with chronic MS or other neurological diseases. Junctional region sequencing showed the expanded gamma/delta T cells to be oligoclonal in nature, suggestive of specific stimulation by antigen. These results reveal a fundamental difference in the immunopathogenesis of acute vs. chronic disease and provide additional insight into the autoimmune nature of MS. PMID:8430106

  4. Role of the mononuclear phagocyte as an antigen-presenting cell for human gamma delta T cells activated by live Mycobacterium tuberculosis.

    PubMed Central

    Boom, W H; Chervenak, K A; Mincek, M A; Ellner, J J

    1992-01-01

    gamma delta T cells, both human and murine, have been found to be highly responsive to mycobacterial antigens. However, the role and function of gamma delta T cells in the immune response to Mycobacterium tuberculosis remain largely unknown. In earlier studies, we demonstrated that monocytes infected with live M. tuberculosis were particularly effective inducers of human peripheral blood gamma delta T cells. The present studies were performed to further characterize the interaction between human mononuclear phagocytes, gamma delta T cells, and live M. tuberculosis, in comparison with CD4+ T cells. First, we found that resting gamma delta T cells expanded in vitro by live M. tuberculosis were specific for M. tuberculosis, and that heat killing and washing the mycobacteria removed the antigen(s) for gamma delta T cells. In contrast, the heat-killed mycobacteria retained significant antigenicity for CD4+ T cells. Second, live M. tuberculosis-expanded gamma delta T cells from healthy tuberculin-positive donors did not respond significantly to the antigens in M. tuberculosis culture filtrate, including the 65- and 71-kDa mycobacterial heat shock proteins. Third, the activation of gamma delta T cells by live mycobacteria was dependent on antigen-presenting cells, and mononuclear phagocytes were found to be very efficient antigen-presenting cells both for resting peripheral blood gamma delta T cells and for activated expanded gamma delta T cells. The mononuclear phagocyte carried the necessary costimulatory factors necessary for gamma delta T-cell proliferation. Fourth, the antigen repertoire and HLA requirements for CD4+ memory T cells and those for gamma delta T cells appear to be quite distinct from each other. CD4+ T cells recognized both soluble protein antigens and whole organisms in a class II major histocompatibility complex-restricted manner, whereas gamma delta T cells appeared to recognize only constituents associated with the whole organism and were not

  5. Rapid and transient activation of gamma/delta T cells to interferon gamma production, NK cell-like killing and antigen processing during acute virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gamma/delta T cells are the majority peripheral blood T cells in young cattle. The role of gamma/delta T cells in innate responses against infection with foot-and-mouth disease virus (FMDV) was analyzed on 5 consecutive days following infection. Before infection, bovine gamma/delta T cells expressed...

  6. Novel time-dependent vascular actions of {delta}{sup 9}-tetrahydrocannabinol mediated by peroxisome proliferator-activated receptor gamma

    SciTech Connect

    O'Sullivan, Saoirse E. . E-mail: Saoirse.o'sullivan@nottingham.ac.uk; Tarling, Elizabeth J.; Bennett, Andrew J.; Kendall, David A.; Randall, Michael D.

    2005-11-25

    Cannabinoids have widespread effects on the cardiovascular system, only some of which are mediated via G-protein-coupled cell surface receptors. The active ingredient of cannabis, {delta}{sup 9}-tetrahydrocannabinol (THC), causes acute vasorelaxation in various arteries. Here we show for the first time that THC also causes slowly developing vasorelaxation through activation of peroxisome proliferator-activated receptors gamma (PPAR{gamma}). In vitro, THC (10 {mu}M) caused time-dependent vasorelaxation of rat isolated arteries. Time-dependent vasorelaxation to THC was similar to that produced by the PPAR{gamma} agonist rosiglitazone and was inhibited by the PPAR{gamma} antagonist GW9662 (1 {mu}M), but not the cannabinoid CB{sub 1} receptor antagonist AM251 (1 {mu}M). Time-dependent vasorelaxation to THC requires an intact endothelium, nitric oxide, production of hydrogen peroxide, and de novo protein synthesis. In transactivation assays in cultured HEK293 cells, THC-activated PPAR{gamma}, transiently expressed in combination with retinoid X receptor {alpha} and a luciferase reporter gene, in a concentration-dependent manner (100 nM-10 {mu}M). In vitro incubation with THC (1 or 10 {mu}M, 8 days) stimulated adipocyte differentiation in cultured 3T3L1 cells, a well-accepted property of PPAR{gamma} ligands. The present results provide strong evidence that THC is a PPAR{gamma} ligand, stimulation of which causes time-dependent vasorelaxation, implying some of the pleiotropic effects of cannabis may be mediated by nuclear receptors.

  7. Dynamics of circulating gamma delta T cell activity in an immunocompetent mouse model of high-grade glioma

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human gamma delta T cells are potent effectors against glioma cell lines in vitro and in human/mouse xenograft models of glioblastoma, however, this effect has not been investigated in an immunocompetent mouse model. In this report, we established GL261 intracranial gliomas in syngeneic WT C57BL/6 m...

  8. Unlike PPAR{gamma}, PPAR{alpha} or PPAR{beta}/{delta} activation does not promote human monocyte differentiation toward alternative macrophages

    SciTech Connect

    Bouhlel, Mohamed Amine; Brozek, John; Derudas, Bruno; Zawadzki, Christophe; Jude, Brigitte; Staels, Bart; Chinetti-Gbaguidi, Giulia

    2009-08-28

    Macrophages adapt their response to micro-environmental signals. While Th1 cytokines promote pro-inflammatory M1 macrophages, Th2 cytokines promote an 'alternative' anti-inflammatory M2 macrophage phenotype. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors expressed in macrophages where they control the inflammatory response. It has been shown that PPAR{gamma} promotes the differentiation of monocytes into anti-inflammatory M2 macrophages in humans and mice, while a role for PPAR{beta}/{delta} in this process has been reported only in mice and no data are available for PPAR{alpha}. Here, we show that in contrast to PPAR{gamma}, expression of PPAR{alpha} and PPAR{beta}/{delta} overall does not correlate with the expression of M2 markers in human atherosclerotic lesions, whereas a positive correlation with genes of lipid metabolism exists. Moreover, unlike PPAR{gamma}, PPAR{alpha} or PPAR{beta}/{delta} activation does not influence human monocyte differentiation into M2 macrophages in vitro. Thus, PPAR{alpha} and PPAR{beta}/{delta} do not appear to modulate the alternative differentiation of human macrophages.

  9. Gamma delta T cells are activated by polysaccharide K (PSK) and contribute to the anti-tumor effect of PSK

    PubMed Central

    Inatsuka, Carol; Yang, Yi; Gad, Ekram; Rastetter, Lauren; Disis, Mary L.

    2013-01-01

    Polysaccharide K (PSK) is a widely used mushroom extract that has shown anti-tumor and immunomodulatory effects in both preclinical and clinical studies. Therefore, it is important to understand the mechanism of actions of PSK. We recently reported that PSK can activate toll-like receptor 2 and enhances the function of NK cells. The current study was undertaken to study the effect of PSK on gamma delta (γδ) T cells, another important arm of the innate immunity. In vitro experiments using mouse splenocytes showed that γδ T cells produce IFN-γ after treatment with PSK and have up-regulated expression of CD25, CD69, and CD107a. To investigate whether the effect of PSK on γδ T cells is direct or indirect, purified γδ T cells were cultured either alone or together with bone marrow-derived DC in a co-culture or trans-well system and then stimulated with PSK. Results showed that direct cell-to-cell contact between γδ T cells and DC is required for optimal activation of γδ T cells. There was also reciprocal activation of DC by PSK-activated γδ T cells, as demonstrated by higher expression of costimulatory molecules and enhanced production of IL-12 by DC in the presence of γδ T cells. PSK can also co-stimulate γδ T cells with anti-TCR and anti-CD3 stimulation, in the absence of DC. Finally, in vivo treatment with PSK activates γδ T cells among the tumor infiltrating lymphocytes, and depleting γδ T cells during PSK treatment attenuated the anti-tumor effect of PSK. All together, these results demonstrated that γδ T cells are activated by PSK and contribute to the anti-tumor effect of PSK. PMID:23685781

  10. Association between peroxisome proliferator-activated receptor-alpha, delta, and gamma polymorphisms and risk of coronary heart disease

    PubMed Central

    Qian, Yufeng; Li, Peiwei; Zhang, Jinjie; Shi, Yu; Chen, Kun; Yang, Jun; Wu, Yihua; Ye, Xianhua

    2016-01-01

    Abstract Objectives: Risk of coronary heart disease (CHD) has been suggested to be associated with polymorphisms of peroxisome proliferator-activated receptors (PPARs), while the results were controversial. We aimed to systematically assess the association between PPAR polymorphisms and CHD risk. Methods: A case–control study with 446 subjects was conducted to evaluate the association between CHD risk and C161T polymorphism, which was of our special interest as this polymorphism showed different effects on risks of CHD and acute coronary syndrome (ACS). Meta-analyses were conducted to assess all PPAR polymorphisms. Either a fixed- or a random-effects model was adopted to estimate overall odds ratios (ORs). Results: In the case–control study, T allele carriers of C161T polymorphism were not significantly associated with CHD risk (Odds ratio (OR) = 0.74, 95% confidence interval (CI) 0.47–1.15, P = 0.19), while T allele carriers showed higher risk of ACS (OR = 1.63, 95% CI 1.00–2.65, P = 0.048). The meta-analysis indicated that compared with CC homozygous, T allele carriers had lower CHD risk (OR = 0.69, 95% CI 0.59–0.82, P < 0.001) but higher ACS risk (OR = 1.43, 95% CI 1.09–1.87, P = 0.010). Three other polymorphisms were also found to be significantly associated with CHD risk under dominant model: PPAR-alpha intron 7G/C polymorphism (CC+GC vs GG, OR 1.42, 95% CI 1.13–1.78, P = 0.003), L162V polymorphism (VV+LV vs LL, OR 0.74, 95% CI 0.56–0.97, P = 0.031), and PPAR-delta +294T/C polymorphism (CC+TC vs TT, OR 1.51, 95% CI 1.12–2.05, P = 0.007). Conclusions: The results suggested that PPAR-alpha intron 7G/C and L162V, PPAR-delta +294T/C and PPAR-gamma C161T polymorphisms could affect CHD susceptibility, and C161T polymorphism might have different effects on CHD and ACS. PMID:27512842

  11. Activating and propagating polyclonal gamma delta T cells with broad specificity for malignancies

    PubMed Central

    Deniger, Drew C.; Maiti, Sourindra N.; Mi, Tiejuan; Switzer, Kirsten C.; Ramachandran, Vijaya; Hurton, Lenka V.; Ang, Sonny; Olivares, Simon; Rabinovich, Brian A.; Huls, Helen; Lee, Dean A.; Bast, Robert C.; Champlin, Richard E.; Cooper, Laurence J.N.

    2014-01-01

    Purpose To activate and propagate populations of γδT cells expressing polyclonal repertoire of γ and δ TCR chains for adoptive immunotherapy for cancer, which has yet to be achieved. Experimental Design Clinical-grade artificial antigen presenting cells (aAPC) derived from K562 tumor cells were used as irradiated feeders to activate and expand human γδT cells to clinical scale. These cells were tested for proliferation, TCR expression, memory phenotype, cytokine secretion, and tumor killing. Results γδT cell proliferation was dependent upon CD137L expression on aAPC and addition of exogenous IL-2 and IL-21. Propagated γδT cells were polyclonal as they expressed Vδ1, Vδ2, Vδ3, Vδ5, Vδ7, and Vδ8 with Vγ2, Vγ3, Vγ7, Vγ8, Vγ9, Vγ10, and Vγ11 TCR chains. Interferon-γ production by Vδ1, Vδ2, and Vδ1negVδ2neg subsets was inhibited by pan-TCRγδantibody when added to co-cultures of polyclonal γδT cells and tumor cell lines. Polyclonal γδT cells killed acute and chronic leukemia, colon, pancreatic, and ovarian cancer cell lines, but not healthy autologous or allogeneic normal B cells. Blocking antibodies demonstrated that polyclonal γδT cells mediated tumor cell lysis through combination of DNAM1, NKG2D, and TCRγδ. The adoptive transfer of activated and propagated γδT cells expressing polyclonal versus defined Vδ TCR chains imparted a hierarchy (polyclonal>Vδ1>Vδ1negVδ2neg>Vδ2) of survival of mice with ovarian cancer xenografts. Conclusions Polyclonal γδT cells can be activated and propagated with clinical-grade aAPC and demonstrate broad anti-tumor activities, which will facilitate the implementation of γδT cell cancer immunotherapies in humans. PMID:24833662

  12. Anti-Leukemia Activity of In Vitro-Expanded Human Gamma Delta T Cells in a Xenogeneic Ph+ Leukemia Model

    PubMed Central

    Siegers, Gabrielle M.; Felizardo, Tania C.; Mathieson, A. Mark; Kosaka, Yoko; Wang, Xing-Hua; Medin, Jeffrey A.; Keating, Armand

    2011-01-01

    Gamma delta T cells (GDTc) lyse a variety of hematological and solid tumour cells in vitro and in vivo, and are thus promising candidates for cellular immunotherapy. We have developed a protocol to expand human GDTc in vitro, yielding highly cytotoxic Vgamma9/Vdelta2 CD27/CD45RA double negative effector memory cells. These cells express CD16, CD45RO, CD56, CD95 and NKG2D. Flow cytometric, clonogenic, and chromium release assays confirmed their specific cytotoxicity against Ph+ cell lines in vitro. We have generated a fluorescent and bioluminescent Ph+ cell line, EM-2eGFPluc, and established a novel xenogeneic leukemia model. Intravenous injection of EM-2eGFPluc into NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice resulted in significant dose-dependent bone marrow engraftment; lower levels engrafted in blood, lung, liver and spleen. In vitro-expanded human GDTc injected intraperitoneally were found at higher levels in blood and organs compared to those injected intravenously; GDTc survived at least 33 days post-injection. In therapy experiments, we documented decreased bone marrow leukemia burden in mice treated with GDTc. Live GDTc were found in spleen and bone marrow at endpoint, suggesting the potential usefulness of this therapy. PMID:21304898

  13. Effect of monolayer surface pressure on the activities of phosphoinositide-specific phospholipase C-beta 1, -gamma 1, and -delta 1.

    PubMed

    Boguslavsky, V; Rebecchi, M; Morris, A J; Jhon, D Y; Rhee, S G; McLaughlin, S

    1994-03-15

    Three isoforms of phospholipase C, either PLC-beta 1, PLC-gamma 1, or PLC-delta 1, were added to the aqueous subphase beneath phospholipid monolayers formed at an air-solution interface, and the initial rate of hydrolysis of phosphatidylinositol 4,5-bisphosphate was measured after addition of 10 microM free Ca2+. The monolayers were formed from mixtures of phosphatidylcholine (65% PC), phosphatidylserine (33% PS), and phosphatidylinositol 4,5-biphosphate (2% PIP2). Increasing the surface pressure of the monolayer, pi, from 15 to 25 mN/m decreases the rate of hydrolysis 16-, 13-, and 5-fold for PLC-beta 1, PLC-gamma 1, and PLC-delta 1, respectively. The simplest interpretation of these results is that a portion of each of the enzymes of area Ap must insert into the monolayer, doing work pi Ap, prior to hydrolysis of PIP2; binding studies with simple model compounds of known cross-sectional area are consistent with this interpretation. Removing the monovalent acidic lipid PS from the monolayer decreases the initial rates of hydrolysis of PIP2 about 3-fold for each PLC isoform, which suggests that negative electrostatic surface potentials increase the PLC activity. PMID:8130216

  14. Production of interferon-gamma and tumour necrosis factor-alpha by human T-cell clones expressing different forms of the gamma delta receptor.

    PubMed Central

    Christmas, S E; Meager, A

    1990-01-01

    Panels of human T-cell clones bearing the gamma delta T-cell receptor (TcR) were obtained from peripheral blood and decidual tissue and maintained in the presence of interleukin-2 (IL-2). TcR V gamma and V delta gene expression was determined in 40 TcR delta 1+ clones using the gamma delta T-cell subset markers Ti gamma A and delta TCS1, in conjunction with Southern blot analysis using TcR J gamma and J delta probes. gamma delta T-cell clones, together with control alpha beta T-cell clones derived from the same lymphocyte populations, were stimulated with phytohaemagglutinin (PHA) and their ability to produce interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) tested using specific ELISA. Many clones representative of the major peripheral V gamma 9/V delta 2J1 subset produced high amounts of both cytokines and mean levels were not significantly different from those produced by alpha beta T-cell clones. Panels of clones expressing V gamma 9 and V delta 2J1 produced significantly higher levels of TNF-alpha than clones not expressing V delta 2J1 and those expressing V delta 1J1. There was no relationship between levels of IFN-gamma and TNF-alpha produced by individual gamma delta T-cell clones and also no relationship between their non-major histocompatibility complex (MHC)-restricted cytotoxic activity and levels of either cytokine. There was a significant tendency for gamma delta T-cell clones to produce more TNF-alpha than IFN-gamma in comparison to alpha beta T-cell clones. The significance of these findings is discussed in the light of the reported differences in distribution in vivo of V delta 1J1+ and V delta 2J1+ cells. Images Figure 1 PMID:2126252

  15. Growth kinetics of gamma-prime precipitates in a directionally solidified eutectic, gamma/gamma-prime-delta

    NASA Technical Reports Server (NTRS)

    Tewari, S. N.

    1976-01-01

    A directionally solidified eutectic alloy (DSEA), of those viewed as potential candidates for the next generation of aircraft gas turbine blade materials, is studied for the gamma-prime growth kinetics, in the system Ni-Nb-Cr-Al, specifically: Ni-20 w/o Nb-6 w/o Cr-2.5 w/o Al gamma/gamma-prime-delta DSEA. Heat treatment, polishing and etching, and preparation for electron micrography are described, and the size distribution of gamma-prime phase following various anneals is plotted, along with gamma-prime growth kinetics in this specific DSEA, and the cube of gamma-prime particle size vs anneal time. Activation energies and coarsening kinetics are studied.

  16. Human gamma delta T-cell recognition of Yersinia enterocolitica.

    PubMed Central

    Young, J L; Goodall, J C; Beacock-Sharp, H; Gaston, J S

    1997-01-01

    We have studied the human gamma delta T-cell response to Yersinia enterocolitica, a facultative intracellular bacterium which causes gastroenteritis and, particularly in human leucocyte antigen (HLA)-B27+ individuals, reactive arthritis (ReA). A marked proliferation of that cytotoxic gamma delta T cells is seen when Yersinia-infected lymphoblastoid cell lines or fixed intact Yersinia are added to cultures of mononuclear cells derived from the synovial fluid of ReA patients or from the peripheral blood of healthy donors. In contrast, heat-inactivated Yersinia fail to stimulate the gamma delta T-cell response. The gamma delta T-cell lines generated killed both autologous and allogeneic infected cell lines. Interestingly, a T-cell line generated from synovial fluid mononuclear cells (SFMC) killed infected autologous cell lines and a cell line matched for HLA-B27 less well than infected allogeneic target cells. gamma delta T-cell clones isolated from this line were found to express V gamma 9V delta 2 T-cell receptor (TCR) and also killed infected mismatched cells more efficiently than autologous targets. Moreover, from experiments using major histocompatability complex (MHC)-deficient cell lines, it was apparent that target cell recognition was MHC independent. Our results suggest that gamma delta T cells can be involved in immunity to Yersinia enterocolitica and should be taken into account when considering immunopathological mechanisms leading to reactive arthritis. PMID:9378487

  17. Dual antigenic recognition by cloned human gamma delta T cells.

    PubMed Central

    Holoshitz, J; Vila, L M; Keroack, B J; McKinley, D R; Bayne, N K

    1992-01-01

    The function of gamma delta T cells is still elusive. The nature of the antigens that they recognize and the mode of presentation of these antigens are largely unknown. The majority of human peripheral gamma delta T cells bear a V gamma 9/V delta 2 T cell receptor, and display nonclonal reactivity to mycobacteria, without restriction by MHC. It is unknown whether these cells have clonal antigenic specificity as well. Here we describe rheumatoid arthritis-derived V gamma 9/V delta 2 T cell clones, displaying dual antigenic recognition: a nonclonal, MHC-unrestricted recognition of mycobacteria, and a clonal recognition of a short tetanus toxin peptide presented by HLA-DRw53, a nonpolymorphic class II MHC molecule associated with susceptibility to rheumatoid arthritis. This is the first evidence that V gamma 9/V delta 2 T cells can recognize nominal antigenic peptides presented by class II MHC molecules. These results suggest that much like alpha beta T cells, V gamma 9/V delta 2 cells may contribute to the immune response against foreign antigens in an antigen-specific and MHC-restricted manner. The reactivity of these gamma delta T cells to mycobacteria may represent a superantigen-like phenomenon. PMID:1345917

  18. Indanylacetic acid derivatives carrying 4-thiazolyl-phenoxy tail groups, a new class of potent PPAR alpha/gamma/delta pan agonists: synthesis, structure-activity relationship, and in vivo efficacy.

    PubMed

    Rudolph, Joachim; Chen, Libing; Majumdar, Dyuti; Bullock, William H; Burns, Michael; Claus, Thomas; Dela Cruz, Fernando E; Daly, Michelle; Ehrgott, Frederick J; Johnson, Jeffrey S; Livingston, James N; Schoenleber, Robert W; Shapiro, Jeffrey; Yang, Ling; Tsutsumi, Manami; Ma, Xin

    2007-03-01

    Compounds that simultaneously activate the three peroxisome proliferator-activated receptor (PPAR) subtypes alpha, gamma, and delta hold potential to address the adverse metabolic and cardiovascular conditions associated with diabetes and the metabolic syndrome. We recently identified the indanylacetic acid moiety as a well-tunable PPAR agonist head group. Here we report the synthesis and structure-activity relationship (SAR) studies of novel aryl tail group derivatives that led to a new class of potent PPAR pan agonists. While most of the tail group modifications imparted potent PPAR delta agonist activity, improvement of PPAR alpha and gamma activity required the introduction of new heterocyclic substituents that were not known in the PPAR literature. Systematic optimization led to the discovery of 4-thiazolyl-phenyl derivatives with potent PPAR alpha/gamma/delta pan agonistic activity. The lead candidate from this series was found to exhibit excellent ADME properties and superior therapeutic potential compared to known PPAR gamma activating agents by favorably modulating lipid levels in hApoA1 mice and hyperlipidemic hamsters, while normalizing glucose levels in diabetic rodent models. PMID:17274610

  19. Diffusion welding of a directionally solidified gamma/gamma prime - delta eutectic alloy

    NASA Technical Reports Server (NTRS)

    Moore, T. J.

    1977-01-01

    Hot-press diffusion welding parameters were developed for a directionally solidified, gamma/gamma prime-delta eutectic alloy. Based on metallography, a good diffusion weld was achieved at 1100 C under 34.5 MPa (5 ksi) pressure for 1 hour. In addition, a dissimilar metal weld between gamma/gamma prime-delta and IN-100 was successfully made at 1100 C under 20.7 MPa (3 ksi) pressure for 1 hour.

  20. V delta 1 gene usage, interleukin-2 receptors and adhesion molecules on gamma delta+ T cells in inflammatory diseases of the nervous system.

    PubMed

    Mix, E; Fiszer, U; Olsson, T; Fredrikson, S; Kostulas, V; Söderström, M; Link, H

    1994-01-01

    This study investigates the expression of T cell receptor V delta 1 chain, interleukin-2 receptor alpha-chain (CD25) and adhesion molecules ICAM-1 (CD54), LFA-1 (CD11a/18) and CD44 on gamma delta+ T cells by three-color flow cytometry on cerebrospinal fluid (CSF) and blood cells in patients with multiple sclerosis (MS), other inflammatory neurological diseases (OIND) and other neurological diseases (OND). Of gamma delta + T cells in CSF and blood, 20-40% belonged to the 'epithelial' V delta 1 subtype. MS patients had the lowest levels in both CSF and blood, but the differences between the patient groups were not significant. The activation markers CD25 and CD54 were expressed by only a small proportion of gamma delta+ T cells and in a minority of patients. Although the occurrence of CD25+ and CD54+ gamma delta+ T cells was somewhat higher in CSF than in blood and in inflammatory diseases than in controls, the small numbers of CD25+ and CD54+ gamma delta+ T cells preclude establishing differences amongst compartments and patient groups. The adhesion molecules CD11a/18 and CD44 were constitutively expressed on all T cells. Therefore, we compared the relative antigen density per cell as measured by the relative fluorescence index (RFI) between CSF and blood, between the patient groups and between gamma delta+ and total T cells. The only difference encountered was a slightly higher expression of adhesion molecules on gamma delta+ compared to total T cells, with preference to MS patients. In conclusion, the V delta 1+ subtype of gamma delta+ T cells does not dominate in the CSF compartment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7507498

  1. A model for the Delta(1600) resonance and gamma N -> Delta(1600) transition

    SciTech Connect

    G. Ramalho, K. Tsushima

    2010-10-01

    A covariant spectator constituent quark model is applied to study the gamma N -> Delta(1600) transition. Two processes are important in the transition: a photon couples to the individual quarks of the Delta(1600) core (quark core), and a photon couples to the intermediate pion-baryon states (pion cloud). While the quark core contributions are estimated assuming Delta(1600) as the first radial excitation of Delta(1232), the pion cloud contributions are estimated based on an analogy with the gamma N -> Delta(1232) transition. To estimate the pion cloud contributions in the gamma N -> Delta(1600) transition, we include the relevant intermediate states, pi-N, pi-Delta, pi-N(1440) and pi-Delta(1600). Dependence on the four-momentum transfer squared, Q2, is predicted for the magnetic dipole transition form factor, GM*(Q2), as well as the helicity amplitudes, A_1/2(Q2) and A_3/2(Q2). The results at Q2=0 are compared with the existing data.

  2. Model for the {Delta}(1600) resonance and {gamma}N{yields}{Delta}(1600) transition

    SciTech Connect

    Ramalho, G.; Tsushima, K.

    2010-10-01

    A covariant spectator constituent quark model is applied to study the {gamma}N{yields}{Delta}(1600) transition. Two processes are important in the transition: a photon couples to the individual quarks of the {Delta}(1600) core (quark core), and a photon couples to the intermediate pion-baryon states (pion cloud). While the quark core contributions are estimated assuming {Delta}(1600) as the first radial excitation of {Delta}(1232), the pion cloud contributions are estimated based on an analogy with the {gamma}N{yields}{Delta}(1232) transition. To estimate the pion cloud contributions in the {gamma}N{yields}{Delta}(1600) transition, we include the relevant intermediate states, {pi}N, {pi}{Delta}, {pi}N(1440) and {pi}{Delta}(1600). Dependence on the four-momentum transfer squared, Q{sup 2}, is predicted for the magnetic dipole transition form factor, G{sub M}*(Q{sup 2}), as well as the helicity amplitudes, A{sub 1/2}(Q{sup 2}) and A{sub 3/2}(Q{sup 2}). The results at Q{sup 2}=0 are compared with the existing data.

  3. Pathogenic anti-DNA autoantibody-inducing T helper cell lines from patients with active lupus nephritis: isolation of CD4-8- T helper cell lines that express the gamma delta T-cell antigen receptor.

    PubMed Central

    Rajagopalan, S; Zordan, T; Tsokos, G C; Datta, S K

    1990-01-01

    The antigen responsible for autoimmunization in systemic lupus erythematosus is unknown. In spite of this obstacle, we show that T helper (Th) cell lines that are functionally relevant to this disease can be established in vitro. We derived a total of 396 interleukin 2-dependent T-cell lines from the in vivo activated T cells of five patients with lupus nephritis. Only 59 (approximately 15%) of these lines had the ability to selectively augment the production of pathogenic anti-DNA autoantibodies that were IgG in class, cationic in charge, specific for native DNA, and clonally restricted in spectrotype. Forty-nine of these autoantibody-inducing Th lines were CD4+ and expressed the alpha beta T-cell receptor (TCR). The other 10 were CD4-8- (double negative), 3 expressing the alpha beta TCR and 7 expressing the gamma delta TCR. All of the autoantibody-inducing Th lines responded to some endogenous antigen presented by autologous B cells. The autoreactive responses of the CD4+ Th lines were restricted to HLA class II antigens, whereas those of the double-negative cells were not. Endogenous heat shock or stress proteins of the HSP60 family that were expressed by the lupus patients' B cells were involved in stimulating an autoreactive proliferation of the gamma delta Th cells. These studies demonstrate a novel helper activity of certain gamma delta T cells in a spontaneous autoimmune response. Images PMID:2144899

  4. Delta- and gamma-tocotrienol isomers are potent in inhibiting inflammation and endothelial activation in stimulated human endothelial cells

    PubMed Central

    Muid, Suhaila; Froemming, Gabriele R. Anisah; Rahman, Thuhairah; Ali, A. Manaf; Nawawi, Hapizah M.

    2016-01-01

    Background Tocotrienols (TCTs) are more potent antioxidants than α-tocopherol (TOC). However, the effectiveness and mechanism of the action of TCT isomers as anti-atherosclerotic agents in stimulated human endothelial cells under inflammatory conditions are not well established. Aims 1) To compare the effects of different TCT isomers on inflammation, endothelial activation, and endothelial nitric oxide synthase (eNOS). 2) To identify the two most potent TCT isomers in stimulated human endothelial cells. 3) To investigate the effects of TCT isomers on NFκB activation, and protein and gene expression levels in stimulated human endothelial cells. Methods Human umbilical vein endothelial cells were incubated with various concentrations of TCT isomers or α-TOC (0.3–10 µM), together with lipopolysaccharides for 16 h. Supernatant cells were collected and measured for protein and gene expression of cytokines (interleukin-6, or IL-6; tumor necrosis factor-alpha, or TNF-α), adhesion molecules (intercellular cell adhesion molecule-1, or ICAM-1; vascular cell adhesion molecule-1, or VCAM-1; and e-selectin), eNOS, and NFκB. Results δ-TCT is the most potent TCT isomer in the inhibition of IL-6, ICAM-1, VCAM-1, and NFκB, and it is the second potent in inhibiting e-selectin and eNOS. γ-TCT isomer is the most potent isomer in inhibiting e-selectin and eNOS, and it is the second most potent in inhibiting is IL-6, VCAM-1, and NFκB. For ICAM-1 protein expression, the most potent is δ-TCT followed by α-TCT. α- and β-TCT inhibit IL-6 at the highest concentration (10 µM) but enhance IL-6 at lower concentrations. γ-TCT markedly increases eNOS expression by 8–11-fold at higher concentrations (5–10 µM) but exhibits neutral effects at lower concentrations. Conclusion δ- and γ-TCT are the two most potent TCT isomers in terms of the inhibition of inflammation and endothelial activation whilst enhancing eNOS, possibly mediated via the NFκB pathway. Hence, there is a

  5. Martensitic nature of {delta} {yields} {gamma} allotropic transformation in plutonium

    SciTech Connect

    Lopez, P.C.; Cost, J.R.; Axler, K.M.

    1996-09-01

    Isothermal and isoplethal studies using differential scanning calorimetry have been conducted to characterize the allotropic transformations of plutonium. The {delta}-{gamma} transformation (upon cooling) was observed to have a classic martensitic nature. The work described herein is the first quantitative study of this phenomena in plutonium.

  6. Interaction between Calpain 5, Peroxisome proliferator-activated receptor-gamma and Peroxisome proliferator-activated receptor-delta genes: a polygenic approach to obesity

    PubMed Central

    Sáez, María E; Grilo, Antonio; Morón, Francisco J; Manzano, Luis; Martínez-Larrad, María T; González-Pérez, Antonio; Serrano-Hernando, Javier; Ruiz, Agustín; Ramírez-Lorca, Reposo; Serrano-Ríos, Manuel

    2008-01-01

    Context Obesity is a multifactorial disorder, that is, a disease determined by the combined effect of genes and environment. In this context, polygenic approaches are needed. Objective To investigate the possibility of the existence of a crosstalk between the CALPAIN 10 homologue CALPAIN 5 and nuclear receptors of the peroxisome proliferator-activated receptors family. Design Cross-sectional, genetic association study and gene-gene interaction analysis. Subjects The study sample comprise 1953 individuals, 725 obese (defined as body mass index ≥ 30) and 1228 non obese subjects. Results In the monogenic analysis, only the peroxisome proliferator-activated receptor delta (PPARD) gene was associated with obesity (OR = 1.43 [1.04–1.97], p = 0.027). In addition, we have found a significant interaction between CAPN5 and PPARD genes (p = 0.038) that reduces the risk for obesity in a 55%. Conclusion Our results suggest that CAPN5 and PPARD gene products may also interact in vivo. PMID:18657264

  7. Clinical Applications of Gamma Delta T Cells with Multivalent Immunity

    PubMed Central

    Deniger, Drew C.; Moyes, Judy S.; Cooper, Laurence J. N.

    2014-01-01

    γδ T cells hold promise for adoptive immunotherapy because of their reactivity to bacteria, viruses, and tumors. However, these cells represent a small fraction (1–5%) of the peripheral T-cell pool and require activation and propagation to achieve clinical benefit. Aminobisphosphonates specifically expand the Vγ9Vδ2 subset of γδ T cells and have been used in clinical trials of cancer where objective responses were detected. The Vγ9Vδ2 T cell receptor (TCR) heterodimer binds multiple ligands and results in a multivalent attack by a monoclonal T cell population. Alternatively, populations of γδ T cells with oligoclonal or polyclonal TCR repertoire could be infused for broad-range specificity. However, this goal has been restricted by a lack of applicable expansion protocols for non-Vγ9Vδ2 cells. Recent advances using immobilized antigens, agonistic monoclonal antibodies (mAbs), tumor-derived artificial antigen presenting cells (aAPC), or combinations of activating mAbs and aAPC have been successful in expanding gamma delta T cells with oligoclonal or polyclonal TCR repertoires. Immobilized major histocompatibility complex Class-I chain-related A was a stimulus for γδ T cells expressing TCRδ1 isotypes, and plate-bound activating antibodies have expanded Vδ1 and Vδ2 cells ex vivo. Clinically sufficient quantities of TCRδ1, TCRδ2, and TCRδ1negTCRδ2neg have been produced following co-culture on aAPC, and these subsets displayed differences in memory phenotype and reactivity to tumors in vitro and in vivo. Gamma delta T cells are also amenable to genetic modification as evidenced by introduction of αβ TCRs, chimeric antigen receptors, and drug-resistance genes. This represents a promising future for the clinical application of oligoclonal or polyclonal γδ T cells in autologous and allogeneic settings that builds on current trials testing the safety and efficacy of Vγ9Vδ2 T cells. PMID:25566249

  8. 15-Deoxy-{Delta}{sup 12,14}-prostaglandin J{sub 2} enhanced the anti-tumor activity of camptothecin against renal cell carcinoma independently of topoisomerase-II and PPAR{gamma} pathways

    SciTech Connect

    Yamamoto, Yasuhiro; Fujita, Megumi; Koma, Hiromi; Yamamori, Motohiro; Nakamura, Tsutomu; Okamura, Noboru; Yagami, Tatsurou

    2011-07-08

    Highlights: {yields} A topoisomerase-I inhibitor, camptothecin, exhibited synergistically toxicity with 15d-PGJ{sub 2}. {yields} The combination of 15d-PGJ{sub 2} and a topoisomerase-II inhibitor, doxorubicine, did not cause synergistic cell growth inhibition. {yields} A PPAR{gamma} antagonist did not prevent Caki-2 from undergoing 15d-PGJ{sub 2}-induced cytotoxicity. {yields} The treatment of camptothecin combined with 15d-PGJ{sub 2} activated caspase-3 more than the separate treatment. -- Abstract: Renal cell carcinoma (RCC) is chemoresistant cancer. Although several clinical trials were conducted to explore effective medications, the chemoresistance of RCC has not yet been conquered. An endogenous ligand for peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}), 15-deoxy-{Delta}{sup 12,14}-prostaglandin J{sub 2} (15d-PGJ{sub 2}), induces apoptosis in RCC. Here, we examined synergistic effects of several carcinostatics on the anti-tumor activity of 15d-PGJ{sub 2} in Caki-2 cell line by MTT assay. A topoisomerase-I inhibitor, camptothecin (CPT), exhibited synergistically toxicity with 15d-PGJ{sub 2}, but neither 5-fluorouracil nor cisplatin did. The combination of 15d-PGJ{sub 2} and a topoisomerase-II inhibitor, doxorubicine, did not cause synergistic cell growth inhibition. The synergistic effect of topoisomerase-I and II inhibitors was not also detected. A PPAR{gamma} antagonist, GW9662, did not prevent Caki-2 from undergoing 15d-PGJ{sub 2}-induced cytotoxicity. The treatment of CPT combined with 15d-PGJ{sub 2} activated caspase-3 more than the separate treatment. These results suggest that 15d-PGJ{sub 2} exhibited the anti-tumor activity synergistically with CPT independent of topoisomerase-II and PPAR{gamma}.

  9. Morphological instability of {delta}-ferrite/{gamma}-austenite interphase boundary in low carbon steels

    SciTech Connect

    Yin, H.; Emi, T.; Shibata, H.

    1999-03-31

    The dynamic behavior of the {delta}-ferrite/{gamma}-austenite interphase boundary during {delta}/{gamma} transformations was observed in situ with a confocal scanning laser microscope. The morphological instability and the growth of the finger pattern of the {delta}/{gamma} interphase boundary were mainly focused on and studied in this work. It was found that the incoherent {delta}/{gamma} interphase boundaries were always unstable with finger-like morphology during {delta} {yields} {gamma} transformation, which developed along {delta}-GBs at low supercoolings (< 7 K) and even into the {delta}-matrix at higher supercoolings for the transformation. At the same time, the finger spacing was measured and analyzed by using the classical constitutional supercooling and instability theories, which show good agreement between the observations and theories.

  10. Role of IL-7 in the shaping of the pulmonary gamma delta T cell repertoire.

    PubMed

    Hayes, S M; Sirr, A; Jacob, S; Sim, G K; Augustin, A

    1996-04-15

    Gamma delta T cells bearing the canonical fetal-type V gamma 6/V delta 1 rearrangements are the predominant gamma delta T cells in the lungs of adult mice. In contrast, these V gamma 6/V delta 1 T cells are virtually absent in the pulmonary epithelia of nude mice. The intraepithelial dominance of gamma delta T cells that express this particular TCR is thought to result from a preferred thymic pathway of gene rearrangement and not from TCR-mediated positive selection. We now show that gamma delta T cell precursors in the lung epithelium of both euthymic and athymic neonatal mice generate this rearrangement in situ. In athymic mice, these clonotypes do not survive, but can be rescued in vitro and in vivo by the lymphokine IL-7. PMID:8609389

  11. gamma* p ---> Delta form-factors in QCD

    SciTech Connect

    V. M. Belyaev; A. V. Radyushkin

    1995-05-01

    We use local quark-hadron duality to estimate the purely nonperturbative soft contribution to the {gamma}*p {yields} {Delta} form factors. Our results are in agreement with existing experimental data. We predict that the ratio G*{sub E}(Q{sup 2})/G*{sub M}(Q{sup 2}) is small for all accessible Q{sup 2}, in contrast to the perturbative QCD expectations that G*{sub E}(Q{sup 2}) {yields} -G*{sub M}(Q{sup 2}).

  12. ACTIVATION OF MOUSE AND HUMAN PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPAR ALPHA, GAMMA, BETA DELTA) BY PERFLUOROOCTANOIC ACID (PFOA) AND PERFLUOROOCTANE SULFONATE (PFOS)

    EPA Science Inventory

    This study evaluates the potential for perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) to activate peroxisome proliferator-activated receptors (PPARs), using a transient transfection cell assay. Cos-1 cells were cultured in DMEM with fetal bovine serum (FBS) in ...

  13. Studies of LDL oxidation following alpha-, gamma-, or delta-tocotrienyl acetate supplementation of hypercholesterolemic humans.

    PubMed

    O'Byrne, D; Grundy, S; Packer, L; Devaraj, S; Baldenius, K; Hoppe, P P; Kraemer, K; Jialal, I; Traber, M G

    2000-11-01

    In vitro tocotrienols (T3s) have potent vitamin E antioxidant activity, but unlike tocopherols can inhibit cholesterol synthesis by suppressing 3-hydroxy-3-methyl-glutarylCoA (HMG-CoA) reductase. Because hypercholesterolemia is a major risk factor for coronary artery disease and oxidative modification of low-density lipoprotein (LDL) may be involved in atherogenesis, we investigated whether daily supplements of placebo, or alpha-, gamma-, or delta- (alpha-, gamma-, or delta-) tocotrienyl acetates would alter serum cholesterol or LDL oxidative resistance in hypercholesterolemics in a double-blind placebo controlled study. Subjects were randomly assigned to receive placebo (n = 13), alpha- (n = 13), gamma- (n = 12), or delta- (n = 13) tocotrienyl acetate supplements (250 mg/d). All subjects followed a low-fat diet for 4 weeks, then took supplements with dinner for the following 8 weeks while still continuing diet restrictions. Plasma alpha- and gamma-tocopherols were unchanged by supplementation. Plasma T3s were undetectable initially and always in the placebo group. Following supplementation in the respective groups plasma concentrations were: alpha-T3 0.98 +/- 0.80 micromol/l, gamma-T3 0.54 +/- 0.45 micromol/l, and delta-T3 0.09 +/- 0.07 micromol/l. Alpha-T3 increased in vitro LDL oxidative resistance (+22%, p <.001) and decreased its rate of oxidation (p <. 01). Neither serum or LDL cholesterol nor apolipoprotein B were significantly decreased by tocotrienyl acetate supplements. This study demonstrates that: (i) tocotrienyl acetate supplements are hydrolyzed, absorbed, and detectable in human plasma; (ii) tocotrienyl acetate supplements do not lower cholesterol in hypercholesterolemic subjects on low-fat diets; and (iii) alpha-T3 may be potent in decreasing LDL oxidizability. PMID:11063909

  14. V gamma 9 V delta 2 T cell cytotoxicity against tumor cells is enhanced by monoclonal antibody drugs--rituximab and trastuzumab.

    PubMed

    Tokuyama, Hirotake; Hagi, Tomomi; Mattarollo, Stephen R; Morley, Jacqueline; Wang, Qiao; So, Hang-Fai; Fai-So, Hang; Moriyasu, Fuminori; Nieda, Mie; Nicol, Andrew J

    2008-06-01

    V gamma 9 V delta 2 T cells exert potent cytotoxicity toward various tumor cells and adoptive transfer of V gamma 9 V delta 2 T cells is an attractive proposition for cell based immunotherapy. V gamma 9 V delta 2 T cells expanded in the presence of Zoledronate and IL-2 express CD16 (Fc gamma RIII), which raises the possibility that V gamma 9 V delta 2 T cells could be used in conjunction with tumor targeting monoclonal antibody drugs to increase antitumor cytotoxicity by antibody dependent cellular cytotoxicity (ADCC). Cytotoxic activity against CD20-positive B lineage lymphoma or chronic lymphocytic leukemia (CLL) and HER2-positive breast cancer cells was assessed in the presence of rituximab and trastuzumab, respectively. Cytotoxicity of V gamma 9 V delta 2 T cells against CD20-positive targets was higher when used in combination with rituximab. Similarly, V gamma 9 V delta 2 T cells used in combination with trastuzumab resulted in greater cytotoxicity against HER2-positive cells in comparison with either agent alone and this effect was restricted to the CD16(+)V gamma 9 V delta 2 T cell population. Our results show that CD16(+)V gamma 9 V delta 2 T cells recognize monoclonal antibody coated tumor cells via CD16 and exert ADCC similar to that observed with NK cells, even when target cells are relatively resistant to monoclonal antibodies or V gamma 9 V delta 2 T cells alone. Combination therapy involving ex vivo expanded CD16(+)V gamma 9 V delta 2 T cells and monoclonal antibodies may enhance the clinical outcomes for patients treated with monoclonal antibody therapy. PMID:18307255

  15. Delta XTE Launch Activities (Scrub #2)

    NASA Technical Reports Server (NTRS)

    1995-01-01

    This NASA Kennedy Space Center video presents Delta XTE (X-Ray Timing Explorer) launch activities on 12/11/95. The launch was rescheduled for next weekend due to out of limit upper level wind conditions.

  16. CCL20, (gamma)(delta) T cells, and IL-22 in corneal epithelial healing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    After corneal epithelial abrasion, leukocytes and platelets rapidly enter the corneal stroma, and CCR6 (+) IL-17(+) gamma delta T cells migrate into the epithelium. Gamma delta T-cell-deficient (TCRd(-/-)) mice have significantly reduced inflammation and epithelial wound healing. Epithelial CCL20 mR...

  17. T cell receptor gamma and delta rearrangements in hematologic malignancies. Relationship to lymphoid differentiation.

    PubMed Central

    Griesinger, F; Greenberg, J M; Kersey, J H

    1989-01-01

    We have studied recombinatorial events of the T cell receptor delta and gamma chain genes in hematopoietic malignancies and related these to normal stages of lymphoid differentiation. T cell receptor delta gene recombinatorial events were found in 91% of acute T cell lymphoblastic leukemia, 68% of non-T, non-B lymphoid precursor acute lymphoblastic leukemia (ALL) and 80% of mixed lineage acute leukemias. Mature B-lineage leukemias and acute nonlymphocytic leukemias retained the T-cell receptor delta gene in the germline configuration. The incidence of T cell receptor gamma and delta was particularly high in CD10+CD19+ non-T, non-B lymphoid precursor ALL. In lymphoid precursor ALL, T cell receptor delta was frequently rearranged while T cell receptor gamma was in the germline configuration. This suggests that TCR delta rearrangements may precede TCR gamma rearrangements in lymphoid ontogeny. In T-ALL, only concordant T cell receptor delta and gamma rearrangements were observed. Several distinct rearrangements were defined using a panel of restriction enzymes. Most of the rearrangements observed in T-ALL represented joining events of J delta 1 to upstream regions. In contrast, the majority of rearrangements in lymphoid precursor ALL most likely represented D-D or V-D rearrangements, which have been found to be early recombinatorial events of the TCR delta locus. We next analyzed TCR delta rearrangements in five CD3+TCR gamma/delta+ ALL and cell lines. One T-ALL, which demonstrated a different staining pattern with monoclonal antibodies against the products of the TCR gamma/delta genes than the PEER cell line, rearranges J delta 1 to a currently unidentified variable region. Images PMID:2547833

  18. Heat treating of a lamellar eutectic alloy /gamma/gamma prime + delta/

    NASA Technical Reports Server (NTRS)

    Tewari, S. N.; Dreshfield, R. L.

    1976-01-01

    Eutectic superalloys are being developed at several laboratories for application as aircraft gas turbine airfoils. One such alloy gamma/gamma prime + delta was subjected to several heat treatments to determine if its mechanical properties could be improved. It was found that by partially dissolving the gamma prime at 1210 C and then aging at 900 C, the tensile strength can be increased about 12 per cent at temperatures up to 900 C. At 1040 C, no change in tensile strength was observed. Times to rupture were measured between 760 and 1040 C and were essentially the same or greater than for as-grown material. Tensile and rupture ductility of the alloy were reduced by heat treatment.

  19. Tissue distribution of human gamma delta T cells: no evidence for general epithelial tropism.

    PubMed Central

    Vroom, T M; Scholte, G; Ossendorp, F; Borst, J

    1991-01-01

    In man and mice only a small proportion of T cells in the peripheral lymphoid compartment express the gamma delta T cell receptor (TCR). In mice, however, gamma delta T cells comprise the predominant population at particular epithelial sites--in epidermis and epithelia of intestine, reproductive organs, and tongue. The distribution of gamma delta T cells in normal human tissues was investigated, paying particular attention to epithelial layers. In all lymphatic organs and in epithelia of a wide variety of non-lymphatic organs, including the respiratory tract, male and female reproductive organs and tongue, gamma delta T cells constituted less than 5% of total T cells, with the remainder expressing TCR alpha beta. The only exception was the intestine, where gamma delta T cells were preferentially situated in the columnar epithelium of the crypts, rather than in the lamina propria. It is concluded, therefore, that human gamma delta T cells do not display a general epithelial tropism and are, in terms of relative numbers, no more able than alpha beta T cells to carry out continuous surveillance of the immune system against infection or transformation in epithelia. gamma delta T cells may, however, have a specialised function in the epithelium of the intestinal tract. Images PMID:1838746

  20. Fatigue crack propagation behaviour of unidirectionally solidified gamma/gamma-prime-delta eutectic alloys. [Ni-Nb-Al alloys

    NASA Technical Reports Server (NTRS)

    Bretz, P. E.; Hertzberg, R. W.

    1979-01-01

    Fatigue crack propagation studies were carried out on unidirectionally solidified gamma/gamma-prime-delta (Ni-Nb-Al) alloys over an aluminum content range of 1.5-2.5% by weight. The variation of Al content of as-grown alloys did not significantly affect the crack growth behavior of these eutectic composites. The results indicate that the addition of Al to the eutectic dramatically improved the FCP behavior. The gamma/gamma-prime-delta alloy exhibited crack growth rates for a given stress intensity range that are an order of magnitude lower than those for the gamma-delta alloy. It is suggested that this difference in FCP behavior can be explained on the basis of stacking fault energy considerations. Extensive delaminations at the crack tip were also revealed, which contributed to the superior fatigue response. Delamination was predominantly intergranular in nature.

  1. Empowering gamma delta T cells with antitumor immunity by dendritic cell-based immunotherapy

    PubMed Central

    Van Acker, Heleen H; Anguille, Sébastien; Van Tendeloo, Viggo F; Lion, Eva

    2015-01-01

    Gamma delta (γδ) T cells are the all-rounders of our immune-system with their major histocompatibility complex-unrestricted cytotoxicity, capacity to secrete immunosti-mulatory cytokines and ability to promote the generation of tumor antigen-specific CD8+ and CD4+ T cell responses. Dendritic cell (DC)-based vaccine therapy has the prospective to harness these unique features of the γδ T cells in the fight against cancer. In this review, we will discuss our current knowledge on DC-mediated γδ T cell activation and related opportunities for tumor immunologists. PMID:26405575

  2. Transverse tensile and stress rupture properties of gamma/gamma prime-delta directionally solidified eutectic

    NASA Technical Reports Server (NTRS)

    Gray, H. H.

    1976-01-01

    Tensile and stress rupture properties were determined primarily at 760 C for specimens oriented at various angles (0 deg, 10 deg, 45 deg, and 90 deg) from the solidification direction of bars and/or slabs of the Ni-20Cb-6Cr-2.5A (gamma/gamma prime-delta) eutectic. Threaded-head specimens yielded longer rupture lives with significantly less scatter than did tapered-head specimens. Miniature specimens are suitable for determining traverse tensile and rupture properties of 1.2 centimeter diameter bar stock. The 300 hour rupture stress at 760 C for specimens oriented at 10 deg from the solidification direction was reduced from 740 to 460 MPa, and to 230 MPa for material oriented at either 45 deg or 90 deg.

  3. Disruption of epithelial gamma delta T cell repertoires by mutation of the Syk tyrosine kinase.

    PubMed Central

    Mallick-Wood, C A; Pao, W; Cheng, A M; Lewis, J M; Kulkarni, S; Bolen, J B; Rowley, B; Tigelaar, R E; Pawson, T; Hayday, A C

    1996-01-01

    Chimeric mice in which lymphocytes are deficient in the Syk tyrosine kinase have been created. Compared with Syk-positive controls, mice with Syk -/- lymphocytes display substantial depletion of intraepithelial gamma delta T cells in the skin and gut, with developmental arrest occurring after antigen receptor gene rearrangement. In this dependence on Syk, subsets of intraepithelial gamma delta T cells are similar to B cells, but distinct from splenic gamma delta T cells that develop and expand in Syk-deficient mice. The characteristic associations of certain T-cell receptor V gamma/V delta gene rearrangements with specific epithelia are also disrupted by Syk deficiency. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:8790395

  4. Gamma delta T cell receptor gene expression by muscle-infiltrating lymphocytes in the idiopathic inflammatory myopathies.

    PubMed Central

    O'Hanlon, T P; Messersmith, W A; Dalakas, M C; Plotz, P H; Miller, F W

    1995-01-01

    Autoreactive alpha beta T cells have been implicated as playing a primary pathogenic role in a group of diseases characterized by chronic muscle inflammation known as the idiopathic inflammatory myopathies (IIM). gamma delta T cells, a distinct and enigmatic class of T cells, play a less certain role in a variety of human autoimmune diseases including the IIM. In an attempt to understand the significance of gamma delta T cells in the IIM, we utilized a sensitive polymerase chain reaction (PCR) technique to evaluate gamma delta T cell receptor (TCR) gene expression in 45 muscle biopsies obtained from 42 IIM patients (17 polymyositis, 12 dermatomyositis, and 13 inclusion body myositis). gamma delta TCR gene expression was not detected in 36 specimens, the majority of muscle biopsies surveyed. gamma delta TCR gene expression by muscle-infiltrating lymphocytes was detected among nine clinically heterogeneous patients. We further analysed the junctional sequence composition of the V gamma 3 and V delta 1 transcripts, whose expression was prominent among gamma delta positive patients. DNA sequence analysis of V gamma 3 amplification products from two patients revealed the presence of several productively rearranged transcripts with amino acid sequence similarities within the V gamma 3-N-J gamma junctional domain. No amino acid sequence similarities were evident within the V delta-N-D delta-N-J delta region of V delta 1 transcripts amplified from four patients, although a distinct and dominant clonotype was detected from each patient. Our cumulative data suggest that unlike alpha beta T cells, gamma delta T cells do not play a prominent pathologic role in the IIM. In fact, the sporadic nature of gamma delta TCR gene expression detected among these patients implies that gamma delta T cell infiltration, when it occurs, is a secondary event perhaps resulting from non-specific inflammatory processes. Images Fig. 1 PMID:7774065

  5. Analysis of T cells bearing different isotypic forms of the gamma/delta T cell receptor in patients with systemic autoimmune diseases.

    PubMed

    Gerli, R; Agea, E; Bertotto, A; Tognellini, R; Flenghi, L; Spinozzi, F; Velardi, A; Grignani, F

    1991-10-01

    The expression of gamma/delta T cell receptor (TCR) on peripheral blood CD3+ cells circulating in 74 patients with different systemic autoimmune diseases was evaluated. There was a significant increase in the gamma/delta T cell number only in patients with primary Sjögren's syndrome (SS) and in untreated patients with systemic lupus erythematosus (SLE). Unlike healthy subjects, a subgroup of patients with SLE and SS displayed a marked increase in gamma/delta T cells. Immunosuppressive treatment of patients with active SLE led to a normalization of the gamma/delta T cell number. Analysis of surface phenotype showed that when patient gamma/delta T cells were expanded in the peripheral blood, they were not activated but bore "memory" markers. In addition, they preferentially expressed the disulfide linked form of the TCR, except in progressive systemic sclerosis where the nondisulfide form was displayed. Serial determinations in single patients demonstrated that the gamma/delta T cell increase is a persistent immunological feature in these patient subgroups. PMID:1837314

  6. T lymphocytes bearing the gamma delta T cell receptor are susceptible to steroid-induced programmed cell death.

    PubMed

    Spinozzi, F; Agea, E; Bistoni, O; Travetti, A; Migliorati, G; Moraca, R; Nicoletti, I; Riccardi, C; Paoletti, F P; Vaccaro, R

    1995-05-01

    The mechanisms by which glucocorticoids suppress immune responses have not yet been clearly defined. In steroid-sensitive pathological conditions, an increase in gamma delta T cells can occur in certain untreated systemic autoimmune disorders and seems to be a peristent feature in most cases of systemic lupus erythematosus (SLE). Our previously published data demonstrated that immunosuppressive therapy normalized this expanded SLE T cell subset in parallel with clinical remission of the symptoms. To establish how corticosteroid treatment determines the disappearance of peripheral blood gamma delta T lymphocytes, circulating alpha beta and gamma delta T lymphocytes from seven SLE subjects with active disease and seven healthy individuals were cultured in the presence or absence of 10(-7) M Dexamethasone (DEX). Cell suspensions were then analysed for DNA fragmentation, characteristic of apoptotic cell death, by a new cytofluorimetric method. Conventional agarose-gel electrophoresis on the same T cell populations was carried out for comparison. Regular follow-ups for 6 months revealed in vivo steroid treatment determined a dramatic fall in SLE blood gamma delta T cells, and in vitro experiments seem to indicate that DEX-triggered apoptotic signals are confined to the double negative (CD4-CD8-) gamma delta T cell subpopulation which disappears after in vivo immunosuppressive therapy. Clinical and pathological remission of some autoimmune diseases is often obtained by corticosteroids. Our results offer new insights on the mechanisms through these hormones exert their potent inhibitory activities on immune system cells postulated to play a role in the generation of autoimmune responses. PMID:7725070

  7. Genetics Home Reference: activated PI3K-delta syndrome

    MedlinePlus

    ... Health Conditions activated PI3K-delta syndrome activated PI3K-delta syndrome Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Activated PI3K-delta syndrome is a disorder that impairs the immune ...

  8. Phosphoinositide 3-kinase gamma/delta inhibition limits infarct size after myocardial ischemia/reperfusion injury.

    PubMed

    Doukas, John; Wrasidlo, Wolfgang; Noronha, Glenn; Dneprovskaia, Elena; Fine, Richard; Weis, Sara; Hood, John; Demaria, Anthony; Soll, Richard; Cheresh, David

    2006-12-26

    Although phosphoinositide 3-kinases (PI3Ks) play beneficial pro-cell survival roles during tissue ischemia, some isoforms (gamma and delta) paradoxically contribute to the inflammation that damages these same tissues upon reperfusion. We therefore considered the possibility that selectively inhibiting proinflammatory PI3K isoforms during the reperfusion phase could ultimately limit overall tissue damage seen in ischemia/reperfusion injuries such as myocardial infarction. Panreactive and isoform-restricted PI3K inhibitors were identified by screening a novel chemical family; molecular modeling studies attributed isoform specificity based on rotational freedom of substituent groups. One compound (TG100-115) identified as a selective PI3K gamma/delta inhibitor potently inhibited edema and inflammation in response to multiple mediators known to participate in myocardial infarction, including vascular endothelial growth factor and platelet-activating factor; by contrast, endothelial cell mitogenesis, a repair process important to tissue survival after ischemic damage, was not disrupted. In rigorous animal MI models, TG100-115 provided potent cardioprotection, reducing infarct development and preserving myocardial function. Importantly, this was achieved when dosing well after myocardial reperfusion (up to 3 h after), the same time period when patients are most accessible for therapeutic intervention. In conclusion, by targeting pathologic events occurring relatively late in myocardial damage, we have identified a potential means of addressing an elusive clinical goal: meaningful cardioprotection in the postreperfusion time period. PMID:17172449

  9. A delta T-cell receptor deleting element transgenic reporter construct is rearranged in alpha beta but not gamma delta T-cell lineages.

    PubMed Central

    Shutter, J; Cain, J A; Ledbetter, S; Rogers, M D; Hockett, R D

    1995-01-01

    T cells can be divided into two groups on the basis of the expression of either alpha beta or gamma delta T-cell receptors (TCRs). Because the TCR delta chain locus lies within the larger TCR alpha chain locus, control of the utilization of these two receptors is important in T-cell development, specifically for determination of T-cell type: rearrangement of the alpha locus results in deletion of the delta coding segments and commitment to the alpha beta lineage. In the developing thymus, a relative site-specific recombination occurs by which the TCR delta chain gene segments are deleted. This deletion removes all D delta, J delta, and C delta genes and occurs on both alleles. This delta deletional mechanism is evolutionarily conserved between mice and humans. Transgenic mice which contain the human delta deleting elements and as much internal TCR delta chain coding sequence as possible without allowing the formation of a complete delta chain gene were developed. Several transgenic lines showing recombinations between deleting elements within the transgene were developed. These lines demonstrate that utilization of the delta deleting elements occurs in alpha beta T cells of the spleen and thymus. These recombinations are rare in the gamma delta population, indicating that the machinery for utilization of delta deleting elements is functional in alpha beta T cells but absent in gamma delta T cells. Furthermore, a discrete population of early thymocytes containing delta deleting element recombinations but not V alpha-to-J alpha rearrangements has been identified. These data are consistent with a model in which delta deletion contributes to the implementation of a signal by which the TCR alpha chain locus is rearranged and expressed and thus becomes an alpha beta T cell. PMID:8524269

  10. Delta diagram based test for the Halphen (A and B) and the Gamma distributions

    NASA Astrophysics Data System (ADS)

    El Adlouni, Salaheddine; Bobée, Bernard

    2014-05-01

    The most used statistical distributions to fit extreme value data in hydrology, can be regrouped in three classes: class C of regularly varying distributions and class D of sub exponential distributions, depending on their tail behaviour. The Halphen distributions (Halphen type A (HA) and Halphen type B (HB)) have both the Gamma (G2) distribution as limiting case and all these three distributions belong to the class D and can be displayed in the (Delta1 = ln(A/G); Delta2 = ln(G/H)) moment ratio diagram based on Geometric (G), Arithmetic (A) and Harmonic (H) means. In this study, a statistical test for discriminating between HA, HB and the Gamma distribution is developed. The methodology is based on Monte Carlo simulation for (1) the determination of the confidence regions around the Gamma curve for each fixed couple (Delta1 , Delta2) and (2) the study of the power of the proposed test for both alternatives HA and HB distributions and comparison with the Likelihood Ratio Test (LRT). Results showed that the test is powerful especially for high values of skewness and is far better than the LRT. This test will be included, shortly, in Decision Support System (DSS) of the HYFRAN-PLUS software. Key words: Halphen distributions, Gamma distribution, Heavy tailed distribution, Monte Carlo simulation, (Delta1 , Delta2) diagram, power of the test, HYFRAN-PLUS.

  11. Effect of thermal cycling in a Mach 0.3 burner rig on properties and structure of directionally solidified gamma/gamma prime - delta eutectic

    NASA Technical Reports Server (NTRS)

    Gray, H. R.; Sanders, W. A.

    1975-01-01

    Tensile and stress rupture properties at 1040 C of a thermally cycled gamma/gamma prime - delta eutectic were essentially equivalent to the as-grown properties. Tensile strength and rupture life at 760 C appeared to decrease slightly by thermal cycling. Thermal cycling resulted in gamma prime coarsening and Widmanstatten delta precipitation in the gamma phase. An unidentified precipitate, presumably gamma prime, was observed within the delta phase. The eutectic alloy exhibited a high rate of oxidation-erosion weight loss during thermal cycling in the Mach 0.3 burner rig.

  12. Functional effects on the acetylcholine receptor of multiple mutations of gamma Asp174 and delta Asp180.

    PubMed

    Martin, M D; Karlin, A

    1997-09-01

    Residues gamma Asp174 and delta Asp180, previously implicated in the binding of acetylcholine (ACh) by the mouse muscle ACh receptor, were each mutated to nine other residues, Asn, Glu, Thr, Ala, Cys, His, Val, Tyr, and Lys. The effects of the mutations on ACh-induced current was determined on surface receptors containing wild-type alpha and beta subunits and mutant gamma and delta subunits. The mutations increased the concentration of ACh eliciting half-maximal current (EC50) by factors from 22 for the Glu mutant to 660 for the Lys mutant. Analysis of the effects in terms of the difference in the accessible surface areas of the mutant and wild-type side chains and the difference in side-chain charges indicated that, per binding site, Delta DeltaG0 for activation was a sum of 10 cal mol-1 A-2 of change in side-chain accessible surface area and of 0.95 kcal mol-1 positive step-1 in side-chain charge, equivalent to 1 mol of charge falling through 42 mV. The effects on the concentration of ACh (IC50, ACh) and of d-tubocurarine (IC50,dTC) causing half-maximal retardation of alpha-bungarotoxin binding were determined on complexes containing wild-type alpha and beta subunits and either mutant gamma or mutant delta subunit. The effects on IC50,ACh correlated well with the effects on EC50, with a similar magnitude for the influence of side-chain charge on the free energy of binding (in this case to the desensitized state) and on the electrostatic potential at the binding site. The effects on IC50,dTC were in all cases less than the effects on IC50,ACh, and the two sets of effects were poorly correlated. In line with the higher ACh affinity and lower d-tubocurarine affinity of the alpha-delta binding site compared to the alpha-gamma binding site, mutations of delta Asp180 had a greater effect on IC50,ACh than did the same mutations of gamma Asp174, and vice versa for effects on IC50,dTC. Consequently, all mutations decreased the asymmetry in the binding properties of the

  13. Close correlation between Daudi and mycobacterial antigen recognition by human gamma delta T cells and expression of V9JPC1 gamma/V2DJC delta-encoded T cell receptors.

    PubMed

    Davodeau, F; Peyrat, M A; Hallet, M M; Gaschet, J; Houde, I; Vivien, R; Vie, H; Bonneville, M

    1993-08-01

    Recent studies have demonstrated that a large fraction of human gamma delta PBL recognize Ag of prokaryotic and eukaryotic origins, respectively found in hydrosoluble mycobacterial extracts and on the Daudi Burkitt's lymphoma cells. The structural basis of the recognition of these Ag have been presently studied in detail, through analysis of a large panel of thymus- and peripheral blood-derived gamma delta T-cell clones. Our results suggest that Daudi and mycobacteria-reactive gamma delta subsets are strictly overlapping and hence that gamma delta T-cell responses against these two Ag are closely related. Daudi cells and mycobacteria were recognized by V gamma 9+V delta 2+, but not by V gamma 9+V delta 2-, V gamma 9-V delta 2+, or V gamma 9-V delta 2- PBL clones. However, not all V gamma 9+V delta 2+ clones were reactive and, in particular: 1) the proportion of Ag-reactive lymphocytes was much lower among thymus- than PBL-derived clones (respectively 24/36 vs 72/73); 2) none of the V gamma 9+V delta 2+ clones expressing a V9J2C2 gamma chain (n = 4) were reactive to Daudi or mycobacteria, indicating that expression of a disulfide-linked TCR is probably a prerequisite for recognition of these Ag; and 3) among V gamma 9+V delta 2+ clones bearing disulfide-linked TCR, almost all (50/53) clones expressing a V9JPC1 gamma chain were reactive, whereas a large fraction (6/10) of those expressing a V9J1C1 gamma chain were weakly or nonreactive. Together, these observations suggest that germline residues specific to V gamma 9, V delta 2, and J gamma P elements directly contribute to recognition of Daudi and mycobacterial Ag. Furthermore, these findings may provide an explanation for coordinate use of these gene elements by a large fraction of gamma delta PBL, through peripheral selection events mediated by ligands identical or structurally related to the above Ag. PMID:8393042

  14. T-cell receptor gamma--delta lymphocytes and Eimeria vermiformis infection.

    PubMed Central

    Rose, M E; Hesketh, P; Rothwell, L; Gramzinski, R A

    1996-01-01

    The role of T-cell receptor gamma--delta T lymphocytes in coccidiosis was examined by determining the course of infection with Eimeria vermiformis in BALB/c mice depleted of gamma--delta lymphocytes by treatment with GL3 monoclonal antibody. The replication of the parasite in primary infections was not greatly, or consistently, affected by this treatment, and there was no correlation between the extent of depletion of small intestinal intraepithelial lymphocytes and the number of oocysts produced. The resistance of immunized mice to challenge was not compromised by depletion of intraintestinal epithelial lymphocytes when their depletion was effected at the time of primary infection and/or administration of the challenge inoculum. Thus, T-cell receptor gamma--delta T lymphocytes do not appear to be crucial to the establishment, or the control, of primary infection with E. vermiformis and are not principal mediators of the solid immunity to challenge that this infection induces. PMID:8890252

  15. Pioneer 10 observations of the Beta Cephei stars Gamma Pegasi and Delta Ceti

    NASA Technical Reports Server (NTRS)

    Peters, Geraldine J.; Ogawa, H. S.; Judge, K. S.; Judge, D. L.

    1987-01-01

    The results of analyzing broad-band Pioneer 10 photometric observations of the low-amplitude pulsating Beta Cephei stars Gamma Pegasi and Delta Ceti are reported. Periods and light curve amplitudes of 3.649 + or - 0.020 hr, 0.05 + or - 0.02 mag for Gamma Peg and 3.869 + or - 0.020 hr, 0.13 + or - 0.02 mag for Delta Ceti are obtained; a power spectrum analysis of the data reveals no other periods. No evidence is found for a phase shift between the light curve maxima in the UV and visible regions. The observed amplitudes combined with published visual and near-UV data suggest a flux and temperature variability of about 200 solar luminosities and 250 K for Gamma Peg and about 600 solar luminosities and 450 K for Delta Cet. These results are compared with others obtained with satellite and ground-based instrumentation.

  16. Extraction and interpretation of gammaN-->Delta form factors within a dynamical model

    SciTech Connect

    B. Juliá-Díaz, T.-S. H. Lee, T. Sato, and L. C. Smith

    2007-01-01

    Within the dynamical model of Refs. [Phys. Rev. C54, 2660 (1996); C63, 055201 (2001)], we perform an analysis of recent data of pion electroproduction reactions at energies near the {Delta}(1232) resonance. We discuss possible interpretations of the extracted bare and dressed {gamma} N {yields} {Delta} form factors in terms of relativistic constituent quark models and Lattice QCD calculations. Possible future developments are discussed.

  17. The dual peroxisome proliferator-activated receptor alpha/delta agonist GFT505 exerts anti-diabetic effects in db/db mice without peroxisome proliferator-activated receptor gamma-associated adverse cardiac effects.

    PubMed

    Hanf, Rémy; Millatt, Lesley J; Cariou, Bertrand; Noel, Benoit; Rigou, Géraldine; Delataille, Philippe; Daix, Valérie; Hum, Dean W; Staels, Bart

    2014-11-01

    We report here the efficacy and safety of GFT505, a novel liver-targeted peroxisome proliferator-activated receptor alpha/delta (PPARα/δ) agonist, in the db/db mouse model of diabetes. Mice were treated with vehicle, GFT505, PPARγ agonist rosiglitazone or dual-PPARα/γ agonist aleglitazar for up to 8 weeks. All compounds comparably reduced fasting glycaemia and HbA1c and improved insulin sensitivity. The glucose-lowering effect of GFT505 was associated with decreased hepatic gluconeogenesis, correlating with reduced expression of gluconeogenic genes. In contrast with the PPARγ-activating drugs, treatment with GFT505 did not affect heart weight and did not increase plasma adiponectin concentrations. This absence of cardiac effects of GFT505 was confirmed after 12 months of administration in cynomolgus monkeys, by the absence of echocardiographic and histological findings. Moreover, long-term GFT505 administration to monkeys induced no change in haematological parameters or in bone marrow differential cell counts. Compared to PPARγ-activating drugs, the dual-PPARα/δ agonist GFT505 therefore shows an improved benefit/risk ratio, treating multiple features of type 2 diabetes without inducing the cardiac side-effects associated with PPARγ activation. PMID:25212694

  18. Expression of the alpha/beta and gamma/delta T-cell receptors in 57 cases of peripheral T-cell lymphomas. Identification of a subset of gamma/delta T-cell lymphomas.

    PubMed Central

    Gaulard, P.; Bourquelot, P.; Kanavaros, P.; Haioun, C.; Le Couedic, J. P.; Divine, M.; Goossens, M.; Zafrani, E. S.; Farcet, J. P.; Reyes, F.

    1990-01-01

    Fifty-seven cases of peripheral T-cell lymphoma were studied for cell expression of the T-cell receptor (TCR) chains, using monoclonal antibodies specific for the beta chain (beta F1) of the alpha/beta TCR, and for the delta chain (anti-TCR delta-1) of the gamma/delta TCR. Three different patterns were demonstrated: in 39 cases (69%), the phenotype (CD3+beta F1+TCR delta-1-) was that of most normal T cells. A second pattern was found on six cases (10%), which were of CD3+beta F1-TCR delta-1+ phenotype, and in which DNA analysis showed a clonal rearrangement of the delta locus in the five cases studied. It is suggested that these cases are the neoplastic counterpart of the small subpopulation of normal T cells that express gamma delta receptor. It is of considerable interest that these gamma delta lymphomas had unusual clinicopathologic presentations, as one case corresponded to a lethal midline granuloma and the five others to hepatosplenic lymphomas with a sinusal/sinusoidal infiltration in spleen, marrow, and liver. The fact that the distribution of the neoplastic gamma delta cells in the splenic red pulp resembles that of normal gamma delta cells reinforces the concept of a preferential homing of gamma delta T cells to this tissue. A third pattern (CD3 +/- beta F1-TCR delta-1-) was seen in 12 cases (21%), in which, by contrast to normal post-thymic T cells, no evidence of either alpha beta or gamma delta T cell receptor was found. Images Figure 1 Figure 2 Figure 2 Figure 3 PMID:1698028

  19. Increased numbers of T lymphocytes with gamma delta-positive antigen receptors in a subgroup of individuals with pulmonary sarcoidosis.

    PubMed Central

    Balbi, B; Moller, D R; Kirby, M; Holroyd, K J; Crystal, R G

    1990-01-01

    Individuals with sarcoidosis were evaluated for preferential usage of T cells with the gamma delta-positive (+) type of T cell antigen receptor. Compared with normal subjects (n = 19), the group with sarcoidosis had increased numbers of CD3+ alpha beta-negative (-) T cells in the blood (normal, 58 +/- 12 cells/microliters; sarcoid, 192 +/- 45 cells/microliters, P less than 0.05) and in the epithelial lining fluid of the lung (normal, 78 14 cells/microliters; sarcoid, 240 +/- 60 cells/microliters, P less than 0.04) and a concomitant elevated number of blood and lung CD3+ gamma delta+ T cells, owing to a striking increase in the number of CD3+ gamma delta+ T cells in a subgroup (7 of 20) of sarcoid individuals. The elevated numbers of sarcoid blood gamma delta+ T lymphocytes were mostly Ti gamma A+ and delta TCS1-, a pattern also seen in normal individuals, consistent with the majority of gamma delta+ T cells expressing one gamma-chain variable region, V gamma 9. The observation of an increase in the total gamma delta+ T cell numbers in a sarcoid subgroup suggests that various specific stimuli may trigger the expansion of different T cell subpopulations within different groups of individuals with sarcoidosis. Images PMID:2110187

  20. Microstructural changes caused by thermal treatment and their effects on mechanical properties of a gamma/gamma prime - delta eutectic alloy

    NASA Technical Reports Server (NTRS)

    Tewari, S. N.; Dreshfield, R. L.

    1976-01-01

    Microstructural changes due to thermal treatments of a directionally solidified gamma/gamma'-delta eutectic alloy were investigated. Aging treatments of 8 to 48 hours and ranging from 750 to 1120 C were given to the alloy in both its as directionally solidified condition and after gamma' solutioning. Aging resulted in gamma' coarsening gamma precipitates in delta, and delta and gamma'' precipitates in delta. The tensile strength was increased about 12 percent at temperatures up to 900 C by a heat treatment. Times to rupture were essentially the same or greater than for as directionally solidified material. Tensile and rupture ductility in the growth direction of the alloy were reduced by the heat treatment.

  1. Human peripheral gamma delta T cells recognize hsp60 molecules on Daudi Burkitt's lymphoma cells.

    PubMed

    Kaur, I; Voss, S D; Gupta, R S; Schell, K; Fisch, P; Sondel, P M

    1993-03-01

    Studies with the use of polyclonal rabbit antiserum reactive with 60-kDa heat shock proteins (hsp60) suggested that hsp60-related molecules could be found on the surface of Daudi cells and were involved in their recognition by certain human gamma delta T cells. The present study confirms this finding by using a mAb specifically recognizing hsp60. This mAb can block outgrowth of human gamma delta T cells in response to stimulation with Daudi and in response to an extract of the mycobacteria H37Ra. This anti-hsp60 mAb stains the surface of Daudi cells, but does not stain either Raji or EBV-transformed B cells, cells which do not stimulate gamma delta T cell outgrowth. Anti-hsp60 mAb could immunoprecipitate a 60-kDa molecule from the H37Ra extract but was unable to precipitate this 60-kDa molecule if the mAb was first absorbed on Daudi cells. This mAb also precipitated a 60-kDa molecule from the surface of Daudi cells which shows an electrophoretic mobility pattern consistent with hsp60. These experiments demonstrate that human gamma delta T cells recognize hsp60-related epitopes on the surface of Daudi cells and within mycobacterial extracts. PMID:8094731

  2. The role of gamma delta T cells in immunity to Mycobacterium bovis infection in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accumulating evidence suggests that gamma delta (gd) T cells play a critical role in the early response to M. bovis and may be key in bridging innate and adaptive immunity following infection. In vitro, gd T cells proliferate and produce robust amounts of IFNy in response to complex, protein and no...

  3. Gamma delta T cells recognize a microbial encoded B Cell antigen to initiate a rapid antigen-specific Interleukin-17 response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gamma delta T cells contribute uniquely to host immune defense, but the way in which they do so remains an enigma. Here we show that an algae protein, phycoerythrin (PE) is recognized by gamma delta T cells from mice, bovine and humans and binds directly to specific gamma delta T cell antigen recept...

  4. Nanoparticles of superconducting {gamma}-Mo{sub 2}N and {delta}-MoN

    SciTech Connect

    Gomathi, A.; Sundaresan, A.; Rao, C.N.R.

    2007-01-15

    We have been able to prepare nanoparticles ({approx}4 nm diameter) of cubic {gamma}-Mo{sub 2}N by a simple procedure involving the reaction of MoCl{sub 5} with urea at 873 K. The nanoparticles show a superconducting transition around 6.5 K. The {gamma}-Mo{sub 2}N nanoparticles are readily transformed to nanoparticles of {delta}-MoN with a slightly larger diameter on heating in a NH{sub 3} atmosphere at 573 K. Phase-pure {delta}-MoN obtained by this means shows a superconducting transition around 5 K. - Graphical abstract: TEM image of the {gamma}-Mo{sub 2}N particles with the inset showing the resistivity of the sample as a function of temperature.

  5. Directional solidification and {delta}/{gamma} solid state transformation in Fe-3% Ni alloy

    SciTech Connect

    Vandyoussefi, M.; Kerr, H.W.; Kurz, W.

    1997-10-01

    Directional growth experiments were carried out to study the solidification behavior of {delta}-Fe and the {delta}-{gamma} solid state transformation in Fe-Ni alloys containing about 3 at.% Ni. Depending on the growth conditions, the solid-liquid interface morphology ranged from planar to cellular. In the solid state transformation, {gamma} grew from {delta} phase as plate like cells with small tip radii at low growth rates but as wider cells with flat interface at a velocity of 30 {micro}m/s. Volume diffusion-controlled plane front and dendritic growth models were applied to both transformations. This was possible as the diffusion coefficient of Ni in the parent {delta} phase is much larger than that of forming {gamma} phase. Good agreement was obtained between theory and experimental observations. The flat-tipped cells in the solid state transformations at a velocity of 30 {micro}m/s showed little overall change in composition, similar to a massive transformation. This composition-invariant transformation is consistent with a plane front growing with solute partitioning at the limit of absolute stability.

  6. Synergy between suppressor of Hairless and Notch in regulation of Enhancer of split m gamma and m delta expression.

    PubMed Central

    Eastman, D S; Slee, R; Skoufos, E; Bangalore, L; Bray, S; Delidakis, C

    1997-01-01

    The Notch signaling pathway is known to regulate cell fate decisions in a variety of organisms from worms to humans. Although several components of the pathway have been characterized, the actual mechanism and molecular results of signaling remain elusive. We have examined the role of the Notch signaling pathway in the transcriptional regulation of two Drosophila Enhancer of split [E(spl)] genes, whose gene products have been shown to be downstream players in the pathway. Using a reporter assay system in Drosophila tissue culture cells, we have observed a significant induction of E(spl) m gamma and m delta expression after cotransfection with activated Notch. Characterization of the 5' regulatory regions of these two genes led to the identification of a number of target sites for the Suppressor of Hairless [Su(H)] protein, a transcription factor activated by Notch signaling. We show that Notch-inducible expression of E(spl) m gamma and m delta both in cultured cells and in vivo is dependent on functional Su(H). Although overexpression of Su(H) augments the level of induction of the reporter genes by activated Notch, Su(H) alone is insufficient to produce high levels of transcriptional activation. Despite the synergy observed between activated Notch and Su(H), the former affects neither the nuclear localization nor the DNA binding activity of the latter. PMID:9271437

  7. Neurotropic Gamma-Delta T-Cell Lymphoma With CD30-Positive Lymphoid Infiltrates.

    PubMed

    Gammon, Bryan; Gammon, Benjamin R; Kim, Youn H; Kim, Jinah

    2016-09-01

    Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a clonal proliferation of gamma-delta T cells with a cytotoxic phenotype that is typically characterized by an aggressive clinical course with ulcerative plaques or subcutaneous nodules. In this report, the authors describe a patient who developed an ulcerated tumor on the left upper extremity and painful papules and nodules on the right lower extremity. Interestingly, several of the papulonodules on the right lower extremity underwent spontaneous involution. A skin biopsy of the papulonodular lesion demonstrated a superficial and deep perivascular interstitial infiltrate with a population of pleomorphic enlarged CD30-positive T cells. These enlarged lymphocytes lacked expression of TCR beta, CD4, CD8, and the pan T-cell antigen CD7, but were positive for TCR gamma, supporting the diagnosis of PCGD-TCL. The patient rapidly developed pain and severe weakness in the left upper limb and MRI revealed extensive neurolymphomatosis of the left brachial plexus. The patient was treated with chemotherapy with complete remission achieved. Unfortunately, her response was transient and the patient relapsed and ultimately died due to her disease. In this article, the authors describe an extraordinary case of a CD30-positive PCGD-TCL to expand the histopathological spectrum of CD30-positive and gamma-delta-positive lymphoproliferative disorders. PMID:27391454

  8. Role of gamma delta T cells in inflammatory bowel disease.

    PubMed

    Kühl, Anja A; Loddenkemper, Christoph; Westermann, Jürgen; Hoffmann, Jörg C

    gammadelta T cells have previously been shown to play a protective role in various animal models of chronic inflammation (e.g., experimental autoimmune encephalomyelitis, collagen-induced arthritis, and non-obese diabetes). This immunoregulatory potential is exerted by synthesizing various anti-inflammatory cytokines and growth factors (e.g., transforming growth factor-beta). As the normal balance between inflammatory and regulatory cytokines is perturbed in inflammatory bowel disease (IBD) a protective effect of gammadelta T cells seems likely. This notion is supported by our finding of increased mortality of rats with 2,4,6-trinitrobenzene sulfonic acid-induced colitis following gammadelta T cell depletion. In contrast, no effect was observed after depletion of gammadelta T cells in a Crohn's disease animal model with terminal ileitis (TNF(DeltaARE) mice). Therefore, future studies must further define where in the intestinal immune system gammadelta T cells exert their protective function and how this can be used in the treatment of IBD. PMID:12571419

  9. Relationship between the lattice constant of {Upsilon} phase and the content of {delta} phase, {gamma}{double_prime} and {gamma}{prime} phases in Inconel 718

    SciTech Connect

    Liu, W.C.; Xiao, F.R.; Yao, M.; Chen, Z.L.; Jiang, Z.Q.; Wang, S.G.

    1997-07-01

    Inconel 718, a Nb-modified nickel-base superalloy has been widely used in gas turbine and related applications due to its good mechanical properties and structural stability at elevated temperatures ({approximately}650 C). The mechanical properties of Inconel 718 depended on the austenite grain size and the size, morphology and content of {delta} phase, {gamma}{double_prime} and {gamma}{prime} phases. In a previous study, the {delta} phase content in Inconel 718 was measured by X-ray diffraction techniques. However, it was difficult to measure the content of {gamma}{double_prime} and {gamma}{prime} phases. M.G. Burke and M.K. Miller determined the composition of the {Upsilon} matrix by using analytical electron microscopy and atom probe field ion microscopy. Their results indicated that the composition of the {Upsilon} matrix changed due to the formation of the various precipitates. The variation in the composition of the {Upsilon} matrix affected the lattice constant of {Upsilon} phase, then the content of {delta} phase, {gamma}{double_prime} and {gamma}{prime} phases was thought to be associated with the lattice constant of {Upsilon} phase. In this paper, the lattice constant of {Upsilon} phase and the content of {delta} phase in Inconel 718 aged at 910 C for different times after cold rolling are measured by X-ray diffraction techniques. The lattice constant of {Upsilon} phase as a function of the content of {delta} phase, {gamma}{double_prime} and {gamma}{prime} phases is derived.

  10. Amplitude Variability in gamma Dor and delta Sct Stars Observed by Kepler

    SciTech Connect

    Guzik, Joyce Ann; Kosak, Mary Katherine; Bradley, Paul Andrew; Jackiewicz, Jason

    2015-08-17

    The NASA Kepler spacecraft data revealed a large number of new multimode nonradially pulsating gamma Dor and delta Sct variable stars. The Kepler high-precision long time-series photometry makes it possible to study amplitude variations of the frequencies, and recent literature on amplitude and frequency variations in nonradially pulsating variables is summarized. Several methods are applied to study amplitude variability in about a dozen gamma Doradus or delta Scuti candidate variable stars observed for several quarters as part of the Kepler Guest Observer program. The magnitude and timescale of the amplitude variations are discussed, along with the presence or absence of correlations between amplitude variations for different frequencies of a given star. Proposed causes of amplitude spectrum variability that will require further investigation are also discussed.

  11. Lactones 12. Enzymatic lactonization of gamma, delta-epoxy esters by the apple fruit and Jerusalem artichoke bulb.

    PubMed

    Olejniczak, Teresa; Mironowicz, Agnieszka; Wawrzeńczyk, Czesław

    2003-06-01

    The enzymatic lactonization of three acyclic gamma, delta-epoxy esters (ethyl 3,7-dimethyl-4,5-epoxyoctanoate, ethyl 3,7,7-trimethyl-4,5-epoxyoctanoate, and ethyl 3,3,7-trimethyl-4,5-epoxyoctanoate) by apple fruit (Malus silvestris) and Jerusalem artichoke bulb (Helianthus tuberosus L.) was investigated. The substrates were transformed into a mixture of isomeric delta-hydroxy-gamma-lactones and gamma-hydroxy-delta-lactones. The gamma-lactones (yields ranging from 45-70%) predominated over delta-lactones (yields ranging from 8-40%). The composition of the product mixture depended on the structure of substrate as well as the biocatalyst. The enzymatic system in these biocatalysts also exhibited diastereoselectivity and enantioselectivity. PMID:12818229

  12. Insights into the Relationship between Toll Like Receptors and Gamma Delta T Cell Responses

    PubMed Central

    Dar, Asif Amin; Patil, Rushikesh Sudam; Chiplunkar, Shubhada Vivek

    2014-01-01

    The tumor microenvironment is an important aspect of cancer biology that contributes to tumor initiation, tumor progression and responses to therapy. The composition and characteristics of the tumor microenvironment vary widely and are important in determining the anti-tumor immune response. Successful immunization requires activation of both innate and adaptive immunity. Generally, immune system is compromised in patients with cancer due to immune suppression, loss of tumor antigen expression and dysfunction of antigen presenting cells (APC). Thus, therapeutic immunization leading to cancer regression remains a significant challenge. Certain cells of the immune system, including dendritic cells (DCs) and gamma delta (γδ) T cells are capable of driving potent anti-tumor responses. The property of MHC-unrestricted cytotoxicity, high potential of cytokine release, tissue tropism and early activation in infections and malignant disease makes γδ T cells as an emerging candidate for immunotherapy. Various strategies are being developed to enhance anti-tumor immune responses of γδ T cells and DCs one of them is the use of novel adjuvants like toll like receptors (TLR) agonists, which enhance γδ T cell function directly or through DC activation, which has ability to prime γδ T cells. TLR agonists are being used clinically either alone or in combination with tumor antigens and has shown initial success in both enhancing immune responses and eliciting anti-tumor activity. TLR activated γδ T cells and DCs nurture each other’s activation. This provides a potent base for first line of defense and manipulation of the adaptive response against pathogens and cancer. The available data provides a strong rationale for initiating combinatorial therapy for the treatment of diseases and this review will summarize the application of adjuvants (TLRs) for boosting immune response of γδ T cells to treat cancer and infectious diseases and their use in combinatorial therapy

  13. Novel primary thymic defect with T lymphocytes expressing gamma delta T cell receptor.

    PubMed

    Geisler, C; Pallesen, G; Platz, P; Odum, N; Dickmeiss, E; Ryder, L P; Svejgaard, A; Plesner, T; Larsen, J K; Koch, C

    1989-07-01

    Flow cytometric analysis of the peripheral blood mononuclear cells in a six year old girl with a primary cellular immune deficiency showed a normal fraction of CD3 positive T cells. Most (70%) of the CD3 positive cells, however, expressed the gamma delta and not the alpha beta T cell receptor. Immunoprecipitation and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that most of the gamma delta T cell receptors existed as disulphide-linked heterodimers. Proliferative responses to mitogens were severely reduced, but specific antibody responses after vaccination could be detected. A thymic biopsy specimen showed severe abnormalities of both the thymic lymphoid and epithelial component with abortive medullary differentiation and almost an entire lack of Hassall's corpuscles. This patient represents a case of primary immune deficiency syndrome not previously described. Thymic deficiency associated with a high proportion of T cells expressing the gamma delta T cell receptor has been described in nude mice, and it is suggested that the immune deficiency of this patient may represent a human analogue. PMID:2527256

  14. Primary central nervous system gamma delta cytotoxic T-cell lymphoma.

    PubMed

    Mooney, Kelly L; Choy, Winward; Woodard, Joslyn; Xian, Rena R; Deal, Taylor M; Kendle, Ryan F; Said, Jonathan; Grody, Wayne; Yang, Isaac

    2016-04-01

    Primary T-cell lymphomas of the central nervous system (CNS) are uncommon, but aggressive and increasing in incidence. We describe a rare case of T-cell lymphoma in a cerebellar location, to our knowledge the first reported case demonstrating gamma/delta receptor expression. Additionally, we elaborate on key diagnostic features and review all nine patients with primary CNS lymphoma of cytotoxic T-cell phenotype reported in the literature. A 26-year-old female medical student presented with a 6week history of nausea, vomiting and dizziness. MRI revealed a 2cm cerebellar mass. The tumor was subtotally resected, and pathologic examination of a subtotal resection specimen demonstrated peripheral T-cell lymphoma, not otherwise specified, with a gamma/delta cytotoxic T-cell phenotype. She subsequently started high dose methotrexate and cytarabine. We report a unique case of primary CNS gamma delta CD8+ T-cell lymphoma lineage in a young female patient. While these are rare entities, it is an important differential diagnosis to consider. Therapy should be tailored to the patient, and involves resection with adjuvant chemotherapy, radiotherapy or autologous stem-cell based treatments. PMID:26804925

  15. HYBRID {gamma} DORADUS-{delta} SCUTI PULSATORS: NEW INSIGHTS INTO THE PHYSICS OF THE OSCILLATIONS FROM KEPLER OBSERVATIONS

    SciTech Connect

    Grigahcene, A.; Monteiro, M. J. P. F. G.; Antoci, V.; Handler, G.; Houdek, G.; Balona, L.; Catanzaro, G.; Daszynska-Daszkiewicz, J.; Guzik, J. A.; Kurtz, D. W.; Marconi, M.; Ripepi, V.; Moya, A.; Suarez, J.-C.; Uytterhoeven, K.; Brown, T. M.; Christensen-Dalsgaard, J.; Gilliland, R. L.; Jenkins, J. M.

    2010-04-20

    Observations of the pulsations of stars can be used to infer their interior structure and test theoretical models. The main-sequence {gamma} Doradus (Dor) and {delta} Scuti (Sct) stars with masses 1.2-2.5 M {sub sun} are particularly useful for these studies. The {gamma} Dor stars pulsate in high-order g-modes with periods of order 1 day, driven by convective blocking at the base of their envelope convection zone. The {delta} Sct stars pulsate in low-order g- and p-modes with periods of order 2 hr, driven by the {kappa} mechanism operating in the He II ionization zone. Theory predicts an overlap region in the Hertzsprung-Russell diagram between instability regions, where 'hybrid' stars pulsating in both types of modes should exist. The two types of modes with properties governed by different portions of the stellar interior provide complementary model constraints. Among the known {gamma} Dor and {delta} Sct stars, only four have been confirmed as hybrids. Now, analysis of combined Quarter 0 and Quarter 1 Kepler data for hundreds of variable stars shows that the frequency spectra are so rich that there are practically no pure {delta} Sct or {gamma} Dor pulsators, i.e., essentially all of the stars show frequencies in both the {delta} Sct and the {gamma} Dor frequency range. A new observational classification scheme is proposed that takes into account the amplitude as well as the frequency and is applied to categorize 234 stars as {delta} Sct, {gamma} Dor, {delta} Sct/{gamma} Dor or {gamma} Dor/{delta} Sct hybrids.

  16. Antinociceptive activity of Delta9-tetrahydrocannabinol non-ionic microemulsions.

    PubMed

    Lazzari, P; Fadda, P; Marchese, G; Casu, G L; Pani, L

    2010-06-30

    Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the major psychoactive constituent of Cannabis sativa L., has been widely studied for its potential pharmaceutical application in the treatment of various diseases and disturbs. This sparingly soluble terpeno-phenolic compound is not easy to handle and to be formulated in pharmaceutical preparations. The aim of this work was to develop a stable aqueous Delta(9)-THC formulation acceptable for different ways of administration, and to evaluate the therapeutic properties of the new Delta(9)-THC based preparation for pain treatment. Due to the thermodynamic stability and advantages of microemulsion based systems, the study was focused on the identification of aqueous microemulsion based systems containing Delta(9)-THC. Oil in water Delta(9)-THC microemulsions were individuated through phase diagrams construction, using the non-ionic surfactant Solutol HS15, being this surfactant acceptable for parenteral administration in human. A selected microemulsion samples containing 0.2 wt% of Delta(9)-THC, stable up to 52 degrees C, was successfully assayed on animal models of pain. Significant antinociceptive activity has been detected by both intraperitoneal and intragastric administration of the new Delta(9)-THC pharmaceutical preparation. The effect has been highlighted in shorter time if compared to a preparation of the same active principle based on previously reported conventional preparation. PMID:20399844

  17. Analysis of gamma delta V region usage in normal and diseased human intestinal biopsies and peripheral blood by polymerase chain reaction (PCR) and flow cytometry.

    PubMed Central

    Bucht, A; Söderström, K; Esin, S; Grunewald, J; Hagelberg, S; Magnusson, I; Wigzell, H; Grönberg, A; Kiessling, R

    1995-01-01

    The intestinal population of gamma delta T cell receptor (TCR)-bearing cells was characterized with regard to V delta and V gamma subtype expression. For this purpose, we utilized V gene-specific PCR of mRNA prepared from intestinal biopsies. Predominant expression of the V delta 1 subtype was demonstrated in the small intestine of patients with coeliac disease and in the inflamed colon of patients with inflammatory bowel diseases (IBD: ulcerative colitis and Crohn's disease) as well as in colon biopsies taken from macroscopically normal areas of colon. Although intestinal gamma delta T cells preferentially expressed V delta 1, other V delta transcripts could be detected, of which V delta 2 and V delta 5 were commonly expressed. Analysis of biopsies from mesenteric lymph nodes demonstrated a V delta repertoire similar to the mucosa. In peripheral blood on the other hand, high expression of both V delta 2 and V delta 1 was found. The predominant expression of V delta 1 transcripts in the intestinal mucosa of IBD patients correlated well with protein cell surface expression as analysed by flow cytometry using V delta 1- and V delta 2-specific antibodies. Selective expansion of gamma delta T cells could not be demonstrated within the inflamed mucosa as shown by mRNA analysis and flow cytometry. Instead, IBD patients demonstrated a decreased proportion of TCR gamma delta-carrying T cells in the inflamed mucosa compared with macroscopically normal area of colon. On the other hand, a significantly increased percentage of T cells bearing the gamma delta TCR was found in peripheral blood of patients with Crohn's disease compared with healthy individuals, indicating that local mucosal inflammation may influence the circulating gamma delta T cell population. Images Fig. 1 PMID:7813110

  18. Gamma/delta intraepithelial lymphocytes in the mouse small intestine.

    PubMed

    Ogata, Masaki; Itoh, Tsunetoshi

    2016-09-01

    Although many studies of intraepithelial lymphocytes (IELs) have been reported, most of them have focused on αβ-IELs; little attention has been paid to γδ-IELs. The function of γδ-IELs remains largely unclear. In this article, we briefly review a number of reports on γδ-IELs, especially those in the small intestine, along with our recent studies. We found that γδ-IELs are the most abundant (comprising >70 % of the) IELs in the duodenum and the jejunum, implying that it is absolutely necessary to investigate the function(s) of γδ-IELs when attempting to delineate the in vivo defense system of the small intestine. Intraperitoneal injection of anti-CD3 mAb stimulated the γδ-IELs and caused rapid degranulation of them. Granzyme B released from their granules induced DNA fragmentation of duodenal and jejunal epithelial cells (paracrine) and of the IELs themselves (autocrine). However, perforin (Pfn) was not detected, and DNA fragmentation was induced even in Pfn-knockout mice; our system was therefore found to present a novel type of in vivo Pfn-independent DNA fragmentation. We can therefore consider γδ-IELs to be a novel type of large granular lymphocyte without Pfn. Fragmented DNA was repaired in the cells, indicating that DNA fragmentation alone cannot be regarded as an unambiguous marker of cell death or apoptosis. Finally, since the response was so rapid and achieved without the need for accessory cells, it seems that γδ-IELs respond readily to various stimuli, are activated only once, and die 2-3 days after activation in situ without leaving their site. Taken together, these results suggest that γδ-IELs are not involved in the recognition of specific antigen(s) and are not involved in the resulting specific killing or exclusion of the relevant antigen(s). PMID:27056578

  19. Hepatosplenic gamma-delta T-cell lymphoma.

    PubMed

    Ferreri, Andrés J M; Govi, Silvia; Pileri, Stefano A

    2012-08-01

    Hepatosplenic T-cell lymphoma (HSTL) is a rare and aggressive extranodal lymphoma derived mostly from cytotoxic γδ T-cells. The peak incidence is in adolescents and young adults, and is more common in males. Up to 20% of HSTL arise in the setting of chronic immune suppression, most commonly solid organ transplantation or prolonged antigenic stimulation. Patients present with systemic symptoms (fever), abdominal pain, weakness, and marked hepatosplenomegaly in the absence of lymphadenopathy. Patients usually manifest marked thrombocytopenia, often with anaemia and leucopenia, a leukemic phase, and bone marrow involvement in 80% of cases. Lactate dehydrogenase levels are usually markedly elevated. HSTL exhibits a marked chemoresistance to currently used regimens, a rapidly progressive behavior, and dismal prognosis. Patients with post-transplant HSTL exhibit an especially poor outcome. Standard treatment has yet to be established. Anthracycline-based chemotherapy is associated with a satisfactory response in two thirds of patients, but poor long-term results. Complete remission is extremely uncommon, and most patients die from lymphoma within two years of diagnosis. A prognostic correlation between outcome and degree of thrombocytopenia has been reported. Relapsing disease is usually chemorefractory and fast growing, and patients' performance status and clinical conditions are poor. These aspects, as well as the lack of drugs with proven activity against HSTL, render salvage treatment almost impossible. A few cases of HSTL successfully treated with autologous or allogeneic stem-cell transplantation have been reported. The use of 2'-deoxycoformycin and other targeted therapies, such as alemtuzumab, anti-γδ TCR monoclonal antibodies, and anti-CD44 therapy, have shown promising results in anecdotal reports. PMID:22047938

  20. Unitary model for the {gamma}p {yields} {gamma}{pi}{sup 0}p reaction and the magnetic dipole moment of the {Delta}{sup +}(1232)

    SciTech Connect

    W.T. Chiang; Marc Vanderhaeghen; S.N. Yang; D. Drechsel

    2004-09-01

    Radiative pion photoproduction in the {Delta}(1232) resonance region is studied with the aim to access the {Delta}{sup +}(1232) magnetic dipole moment. We present a unitary model of the {gamma}p {yields} {gamma}{pi}N ({pi}N) = ({pi}{sup 0}p, {pi}{sup +}n) reactions, where the {pi}N rescattering is included in an on-shell approximation. In this model, the low energy theorem which couples the {gamma}p {yields} {gamma}{pi}N process in the limit of a soft final photon to the {gamma}p {yields} {pi}N process is exactly satisfied. We study the sensitivity of the {gamma}p {yields} {gamma}{pi}{sup 0}p process at higher values of the final photon energy to the {Delta}{sup +}(1232) magnetic dipole moment. We compare our results with existing data and give predictions for forthcoming measurements of angular and energy distributions. It is found that the photon asymmetry and a helicity cross section are particularly sensitive to the {Delta}{sup +} magnetic dipole moment.

  1. T-cell alpha beta + and gamma delta + deficient mice display abnormal but distinct phenotypes toward a natural, widespread infection of the intestinal epithelium.

    PubMed Central

    Roberts, S J; Smith, A L; West, A B; Wen, L; Findly, R C; Owen, M J; Hayday, A C

    1996-01-01

    Vertebrate immune systems contain T cells bearing either alpha beta or gamma delta T-cell antigen receptors (TCRs). alpha beta T cells perform all well-characterized T-cell effector functions, while the biological functions of gamma delta + cells remain unclear. Of particular interest is the role of gamma delta + cells during epithelial infections, since gamma delta + cells are commonly abundant within epithelia. Eimeria spp. are intracellular protozoa that infect epithelia of most vertebrates, causing coccidiosis. This study shows that in response to Eimeria vermiformis, mice lacking alpha beta T cells display defects in protective immunity, while mice lacking gamma delta + cells display exaggerated intestinal damage, apparently due to a failure to regulate the consequences of the alpha beta T cell response. An immuno-downregulatory role during infection, and during autoimmune disease, may be a general one for gamma delta + cells. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8876213

  2. Pharmacokinetics and bioavailability of alpha-, gamma- and delta-tocotrienols under different food status.

    PubMed

    Yap, S P; Yuen, K H; Wong, J W

    2001-01-01

    We have investigated the pharmacokinetics and bioavailability of alpha-, gamma- and delta-tocotrienols under fed and fasted conditions in eight healthy volunteers. The volunteers were administered a single oral dose of mixed tocotrienols (300 mg) under fed or fasted conditions. The bioavailability of tocotrienols under the two conditions was compared using the parameters peak plasma concentration (Cmax), time to reach peak plasma concentration (Tmax) and total area under the plasma concentration-time curve (AUC(o-infinity)). A statistically significant difference was observed between the fed and fasted logarithmic transformed values of Cmax (P < 0.01) and AUC(0-infinity) (P < 0.01) for all three tocotrienols. In addition, the 90% confidence intervals for the ratio of the logarithmic transformed AUC(0-infinity) values of alpha-, gamma- and delta-tocotrienols under the fed state over those of the fasted state were found to lie between 2.24-3.40, 2.05-4.09 and 1.59-3.81, respectively, while those of the Cmax were between 2.28-4.39, 2.31-5.87 and 1.52-4.05, respectively. However, no statistically significant difference was observed between the fed and fasted Tmax values of the three homologues. The mean apparent elimination half-life (t(1/2)) of alpha-, gamma- and delta-tocotrienols was estimated to be 4.4, 4.3 and 2.3 h, respectively, being between 4.5- to 8.7-fold shorter than that reported for alpha-tocopherol. No statistically significant difference was observed between the fed and fasted t(1/2) values. The mean apparent volume of distribution (Vd/f) values under the fed state were significantly smaller than those of the fasted state, which could be attributed to increased absorption of the tocotrienols in the fed state. PMID:11206194

  3. Dual regulation of the {delta}Np63 transcriptional activity by {delta}Np63 in human nasopharyngeal carcinoma cell

    SciTech Connect

    Chu, W.-K.; Lee, K.-C.; Chow, S.-E.; Chen, J.-K. . E-mail: jkc508@mail.cgu.edu.tw

    2006-04-21

    p63 splicing variants lacking NH{sub 2}-terminal transactivating domain, known as {delta}Np63, are thought to antagonize p53 and p63 functions and are suggested to play roles in keratinocyte differentiation. Here, we show that {delta}Np63 has a dual-regulatory effect on the activity of its own promoter in NPC-076 cell. Down-regulation of the transcriptional activity is observed when {delta}Np63 is present in low levels. In contrast, up-regulation of {delta}Np63 transcriptional activity is observed when {delta}Np63 is expressed at higher levels. The down-regulation effect is abolished when the p53-binding site of the {delta}Np63 promoter is mutated. In sharp contrast, similar mutation does not affect the up-regulation of the {delta}Np63 transcriptional activity under the same experimental conditions. Further study shows that the up-regulation is correlated with the activation of the STAT3, as the blockade of STAT3 nuclear translocation abolishes the up-regulation by {delta}Np63. Thus, {delta}Np63 exerts a bidirectional regulation of the {delta}Np63 transcriptional activity in NPC-076 cell.

  4. Neuroblastoma killing properties of V-delta 2 and V-delta2 negative gamma delta T cells following expansion by artificial antigen presenting cells

    PubMed Central

    Fisher, Jonathan P.H.; Yan, Mengyong; Heuijerjens, Jennifer; Carter, Lisa; Abolhassani, Ayda; Frosch, Jennifer; Wallace, Rebecca; Flutter, Barry; Capsomidis, Anna; Hubank, Mike; Klein, Nigel; Callard, Robin; Gustafsson, Kenth; Anderson, John

    2015-01-01

    Purpose The majority of circulating human γδT lymphocytes are of the Vγ9Vδ2 lineage, and have TCR specificity for non-peptide phosphoantigens. Previous attempts to stimulate and expand these cells have therefore focussed on stimulation using ligands of the Vγ9Vδ2 receptor, whilst relatively little is known about variant blood γδT subsets and their potential role in cancer immunotherapy. Experimental Design To expand the full repertoire of γδT without bias towards specific T cell receptors, we made use of artificial antigen presenting cells loaded with an anti gamma delta T cell receptor antibody that promoted unbiased expansion of the γδT repertoire. Expanded cells from adult blood donors were sorted into 3 populations expressing respectively Vδ2 TCR chains (Vδ2+), Vδ1 chains (Vδ1+) and TCR of other delta chain subtypes (Vδ1negVδ2neg) Results Both freshly isolated and expanded cells showed heterogeneity of differentiation markers, with a less differentiated phenotype in the Vδ1 and Vδ1negVδ2neg populations. Expanded cells were largely of an effector memory phenotype although there were higher numbers of less differentiated cells in the Vδ1+ and Vδ1negVδ2neg populations. Using neuroblastoma tumor cells and the anti-GD2 therapeutic monoclonal antibody ch14.18 as a model system, all three populations showed clinically relevant cytotoxicity. Whilst killing by expanded Vδ2 cells was predominantly antibody dependent and proportionate to upregulated CD16, Vδ1 cells killed by antibody independent mechanisms. Conclusions In conclusion we have demonstrated that polyclonal expanded populations of γδT cells are capable of both antibody dependent and independent effector functions in neuroblastoma. PMID:24893631

  5. gamma. -hexachlorocyclohexane (. gamma. -HCH) activates washed rabbit platelets

    SciTech Connect

    Lalau-Keraly, C.; Delautier, D.; Benveniste, J.; Puiseux-Dao, S.

    1986-03-01

    In guinea-pig macrophages, ..gamma..-HCH triggers activation of the phosphatidylinositol cycle and Ca/sup 2 +/ mobilization. Since these two biochemical events are also involved in platelet activation, the authors examined the effects of ..gamma..-HCH on washed rabbit platelets. Release of /sup 14/C-serotonin (/sup 14/C-5HT) and ATP from platelets prelabelled with /sup 14/C-5HT was measured simultaneously with aggregation. ..gamma..-HCH induced shape-change, aggregation and release reaction of platelets. Maximal aggregation (89 arbitrary units, AU), was observed using 170 ..mu..M ..gamma..-HCH, and was associated with 38.1 +/- 6.9% and 161 +/- 48 nM for /sup 14/C-5HT and ATP release respectively (mean +/- 1 SD, n=3). Using 80 ..mu..M ..gamma..-HCH yielded 18 AU, 12.8 +/- 1.0% and 27 +/- 14 nM for aggregation, C-5HT and ATP release respectively (n=3). No effect was observed with 40 ..mu.. M ..gamma..-HCH. Aspirin (ASA), a cyclooxygenase blocker, did not affect ..gamma..-HCH-induced platelet activation. Apyrase (APY), an ADP scavenger, inhibited by 90% aggregation induced by 170 ..mu..M ..gamma..-HCH and slightly inhibited (15%) the /sup 14/C-5HT release. In the presence of both ASA and APY, 96% inhibition of aggregation and 48% inhibition of /sup 14/C-5HT release were observed. Thus, ..gamma..-HCH induced platelet activation in a dose-dependent manner ADP, but not cyclooxygenase-dependent arachidonate metabolites, is involved in ..gamma..-HCH-induced aggregation, whereas, both appear to play a role in ..gamma..-HCH-induced release reaction.

  6. B(s) Mixing, Delta Gamma(s) and CP Violation at the Tevatron

    SciTech Connect

    Di Giovanni, Gian Piero; /Paris U., VI-VII

    2008-05-01

    The authors discuss the results from the Tevatron experiments on mixing and CP violation in the B{sub s}{sup 0}-{bar B}{sub s}{sup 0} system, with particular emphasis to the updated measurements of the decay-width difference {Delta}{Lambda}{sub s} and the first measurement of the CP-violating phase {beta}{sub s} using flavor tagging information. They also briefly review the charge asymmetry measurements in semileptonic B{sub s}{sup 0} decays and in B{sup {+-}} {yields} J/{psi}K{sup {+-}} decays.

  7. Dihydropyrimidinone positive modulation of delta-subunit-containing gamma-aminobutyric acid type A receptors, including an epilepsy-linked mutant variant.

    PubMed

    Lewis, Ryan W; Mabry, John; Polisar, Jason G; Eagen, Kyle P; Ganem, Bruce; Hess, George P

    2010-06-15

    Gamma-aminobutyric acid type A receptors (GABA(A) receptors) are ligand-gated chloride channels that play a central role in signal transmission within the mammalian central nervous system. Compounds that modulate specific GABA(A) receptor subtypes containing the delta-subunit are scarce but would be valuable research tools and starting points for potential therapeutic agents. Here we report a class of dihydropyrimidinone (DHPM) heterocycles that preferentially potentiate peak currents of recombinant GABA(A) receptor subtypes containing the delta-subunit expressed in HEK293T cells. Using the three-component Biginelli reaction, 13 DHPMs with structural features similar to those of the barbiturate phenobarbital were synthesized; one DHPM used (monastrol) is commercially available. An up to approximately 3-fold increase in the current from recombinant alpha1beta2delta receptors was observed with the DHPM compound JM-II-43A or monastrol when co-applied with saturating GABA concentrations, similar to the current potentiation observed with the nonselective potentiating compounds phenobarbital and tracazolate. No agonist activity was observed for the DHPMs at the concentrations tested. A kinetic model was used in conjunction with dose-dependent measurements to calculate apparent dissociation constant values for JM-II-43A (400 muM) and monastrol (200 microM) at saturating GABA concentrations. We examined recombinant receptors composed of combinations of subunits alpha1, alpha4, alpha5, alpha6, beta2, beta3, gamma2L, and delta with JM-II-43A to demonstrate the preference for potentiation of delta-subunit-containing receptors. Lastly, reduced currents from receptors containing the mutated delta(E177A) subunit, described by Dibbens et al. [(2004) Hum. Mol. Genet. 13, 1315-1319] as a heritable susceptibility allele for generalized epilepsy with febrile seizures plus, are also potentiated by these DHPMs. PMID:20450160

  8. Valence quark contribution for the gamma N -> Delta quadrupole transition extracted from lattice QCD

    SciTech Connect

    Ramalho, Gilberto; Haderer De La Pena S, Maria

    2009-01-01

    Starting with a spectator quark model developed for the nucleon (N) and the Delta in the physical pion mass region, we extend the predictions of the reaction gamma N -> Delta to the lattice QCD regime. The quark model includes S and D waves in the quark-diquark wavefunctions. Within this framework it is the D-wave part in the Delta wavefunction that generates nonzero valence contributions for the quadrupole form factors of the transition. Those contributions are however insufficient to explain the physical data, since the pion cloud contributions dominate. To separate the two effects we apply the model to the lattice regime in a region where the pion cloud effects are negligible, and adjust the D-state parameters directly to the lattice data. This process allows us to obtain a better determination of the D-state contributions. Finally, by adding a simple parametrization of the pion cloud we establish the connection between the experimental data and the lattice da

  9. Near-midnight observations of nitric oxide delta- and gamma-band chemiluminescence

    NASA Technical Reports Server (NTRS)

    Tennyson, P. D.; Feldman, P. D.; Hartig, G. F.; Henry, R. C.

    1986-01-01

    Chemiluminescent nightglow emission of the nitric oxide delta and gamma bands was measured from a sounding rocket launched on April 27, 1981, near local midnight. The integrated band emission rates for this near zenith observation above 205 km were less than 10 Rayleighs. The solar zenith angle was 127 deg. The branching ratio from the C2Pi state to the A2Sigma(+) state of NO was determined from comparison of the total emission rate of the delta band system to that of the gamma band system and found to be 0.30 + or - 0.06. The branching ratios within each of the band systems were found to be consistent with previous theoretical and experimental determinations. The vertical atomic nitrogen distribution, derived with the use of a model atmosphere, was found to have a peak density of 2.0 x 10 to the 7th atoms/cu cm at an altitude of 205 km. The analysis of these data indicate the presence of residual NO emission above 270 km at local midnight on the order of 1 Rayleigh of total band emission.

  10. The p({gamma}, {pi}{sup 0}) reaction in the {Delta}(1232) region

    SciTech Connect

    Davidson, R.M.; Gutenberg, J.; Mukhopadhyay, N.C.

    1993-04-01

    Linearly polarized photons from the Laser Electron Gamma Source (LEGS) have been used by Blanpied et al. to study the p({gamma}, {pi}{sup 0}) reaction, looking for the E2 transition amplitude in the nucleon to Delta(1232) excitation. These authors contrast their measured cross-section ratio d{sigma}{parallel}/d{sigma}{perpendicular}, with expectations of earlier analyses, by the authors and Wittman (DMW), by Nozawa et al. (NBL), and using the multipoles of Behrends and Donnachie directly, and find {open_quotes}large discrepancies{close_quotes} among them. Here the authors clarify these discrepancies. The crucial difference between DMW and NBL calculations is the inclusion of the u-channel {Delta} contribution in DMW, omitted in NBL. The authors find for a fair, though not perfect, agreement with the new data: E{sub 1+}{sup {pi}}{sup 0} {r_arrow}2.1E{sub 1+}{sup {pi}}{sup 0}, keeping other multipoles fixed.

  11. DELTAE

    SciTech Connect

    Ward, W.C.; Swift, G.W. )

    1993-11-01

    In thermoacoustic engines and refrigerators, and in many simple acoustic systems, a one dimensional wave equation determines the spatial dependence of the acoustic pressure and velocity. DELTAE numerically integrates such wave equations in the acoustic approximation, in gases or liquids, in user-defined geometries. Boundary conditions can include conventional acoustic boundary conditions of geometry and impedance, as well as temperature and thermal power in thermoacoustic systems. DELTAE can be used easily for apparatus ranging from simple duct networks and resonators to thermoacoustic engines refrigerators and combinations thereof. It can predict how a given apparatus will perform, or can allow the user to design an apparatus to achieve desired performance. DELTAE views systems as a series of segments; twenty segment types are supported. The purely acoustic segments include ducts and cones, and lumped impedances including compliances, series impedances, and endcaps. Electroacoustics tranducer segments can be defined using either frequency-independent coefficients or the conventional parameters of loudspeaker-style drivers: mass, spring constant, magnetic field strength, etc. Tranducers can be current driven, voltage driven, or connected to an electrical load impedance. Thermoacoustic segment geometries include parallel plates, circular and rectangular pores, and pin arrays. Side branches can be defined with fixed impedances, frequency-dependent radiation impedances, or as an auxiliary series of segments of any types. The user can select working fluids from among air, helium, neon, argon, hydrogen, deuterium, carbon dioxide, nitrogen, helium-argon mixtures, helium-xenon mixtures, liquid sodium, and eutectic sodium-potassium. Additional fluids and solids can be defined by the user.

  12. delta 9-(16 alpha-/sup 125/I)iodo-19-nortestosterone: a gamma-emitting photoaffinity label for the progesterone receptor

    SciTech Connect

    Lamb, D.J.; Bullock, D.W.; Hoyte, R.M.; Hochberg, R.B.

    1988-05-01

    We have synthesized 16 alpha-iodo-4,9-estradien-17 beta-ol-3-one (delta 9-16 alpha-iodo-19-nortestosterone (delta 9-INT)) labeled with 125I (delta 9-(16 alpha-125I)INT) to provide a new gamma-emitting photoaffinity ligand for the progesterone receptor that has many advantages over the currently available (3H)R5020. We have characterized the interaction of delta 9-(16 alpha-125I)INT with the rabbit uterine progesterone receptor and have demonstrated the usefulness of this compound for studies of receptor structure. The binding of 2 nM (3H)progesterone to receptor in rabbit uterine cytosol was specifically competed for by 19-nortestosterone, 16 alpha-iodo-19-nortestosterone, and delta 9-INT. Scatchard analysis demonstrated that delta 9-(16 alpha-125I)INT and (3H)progesterone estimated the same number of binding sites in rabbit uterine cytosol, with a Kd for delta 9-(16 alpha-125I)INT of about 2.7 nM. The binding of delta 9-(16 alpha-125I)INT was inhibited by both progesterone and R5020, whereas testosterone, estradiol, and 5 alpha-dihydrotestosterone were ineffective. In cytosol, delta 9-(16 alpha-125I)INT covalently labeled the same mol wt receptor forms as (3H)R5020. Although the efficiency of cross-linking was similar for (3H)R5020 (3%) and delta 9-(16 alpha-125I)INT (4%), the radioactivity was 10-fold greater due to the higher specific activity of delta 9-(16 alpha-125I)INT and the lack of sample quench. The use of delta 9-(16 alpha-125I)INT greatly increases the sensitivity and efficiency of the photoaffinity labeling technique; it will provide a valuable tool for further studies of the progesterone receptor, allowing the detection of receptor in dilute cytosol after gel electrophoresis under denaturing conditions.

  13. The role of peroxisome-proliferator-activating receptor gamma agonists: rosiglitazone and 15-deoxy-delta12,14-prostaglandin J2 in chronic experimental cyclosporine A-induced nephrotoxicity.

    PubMed

    Korolczuk, A; Maciejewski, M; Smolen, A; Dudka, J; Czechowska, G; Widelska, I

    2014-12-01

    Cyclosporine A(CsA) is an immunosuppressor frequently used in the transplant surgery and in the treatment of autoimmune diseases. The therapeutic benefits of CsA are often limited by it's main side effect-nephrotoxicity. Mechanisms of chronic CsA- induced renal damage include: activation of renin-angiotensin-aldosterone system, upregulation of transforming growth factor beta (TGF-β), oxidative stress. This study was undertaken to investigate the protective effect of the peroxisome-proliferator-activated receptors gamma (PPARs-γ) agonists: rosiglitazone and 15-deoxy-Δ12,14-prostaglandin J2 (PGDJ2), against CsA-induced kidney injury in male Wistar rats. CsA was administered subcutaneously at a dose of 15 mg/kg/day for 28 days. Both PPAR-γ agonists were given for 28 days 0.5 hour before the administration of CsA. Rosiglitazone was administered orally at a dose of 8 mg/kg/day and PGDJ2 was given intraperitoneally at a dose of 30 μg/kg/day. CsA induced renal failure was evidenced by increased serum levels of urea, uric acid and creatinine. Serum concentrations of GSH and GSSG, lipid peroxidation products as well as NAD+/NADH, NADP+/NADPH and ADP/ATP ratios showed, that CsA induced oxidative stress and evoked an imbalanced red-ox state in the kidney. Light and electron microscope studies showed degenerative changes within renal tubules with damage to their mitochondria, interstitial fibrosis and arteriolopathy. Immunohistochemical expression of profibrotic TGF-β was assessed. The biochemical and morphological changes induced by CsA were limited by administration of both rosiglitazone and PGDJ2. Ultrastructural examination of renal tubular epithelial cells showed marked improvement within mitochondria. Our results indicate that both PPAR-γ agonists used in the experiment may play an important role in protecting against CsA-induced damage in the kidney. PMID:25554991

  14. Agonist-dependent single channel current and gating in alpha4beta2delta and alpha1beta2gamma2S GABAA receptors.

    PubMed

    Keramidas, Angelo; Harrison, Neil L

    2008-02-01

    The family of gamma-aminobutyric acid type A receptors (GABA(A)Rs) mediates two types of inhibition in the mammalian brain. Phasic inhibition is mediated by synaptic GABA(A)Rs that are mainly comprised of alpha(1), beta(2), and gamma(2) subunits, whereas tonic inhibition is mediated by extrasynaptic GABA(A)Rs comprised of alpha(4/6), beta(2), and delta subunits. We investigated the activation properties of recombinant alpha(4)beta(2)delta and alpha(1)beta(2)gamma(2S) GABA(A)Rs in response to GABA and 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3(2H)-one (THIP) using electrophysiological recordings from outside-out membrane patches. Rapid agonist application experiments indicated that THIP produced faster opening rates at alpha(4)beta(2)delta GABA(A)Rs (beta approximately 1600 s(-1)) than at alpha(1)beta(2)gamma(2S) GABA(A)Rs (beta approximately 460 s(-1)), whereas GABA activated alpha(1)beta(2)gamma(2S) GABA(A)Rs more rapidly (beta approximately 1800 s(-1)) than alpha(4)beta(2)delta GABA(A)Rs (beta < 440 s(-1)). Single channel recordings of alpha(1)beta(2)gamma(2S) and alpha(4)beta(2)delta GABA(A)Rs showed that both channels open to a main conductance state of approximately 25 pS at -70 mV when activated by GABA and low concentrations of THIP, whereas saturating concentrations of THIP elicited approximately 36 pS openings at both channels. Saturating concentrations of GABA elicited brief (<10 ms) openings with low intraburst open probability (P(O) approximately 0.3) at alpha(4)beta(2)delta GABA(A)Rs and at least two "modes" of single channel bursting activity, lasting approximately 100 ms at alpha(1)beta(2)gamma(2S) GABA(A)Rs. The most prevalent bursting mode had a P(O) of approximately 0.7 and was described by a reaction scheme with three open and three shut states, whereas the "high" P(O) mode ( approximately 0.9) was characterized by two shut and three open states. Single channel activity elicited by THIP in alpha(4)beta(2)delta and alpha(1)beta(2)gamma(2S) GABA

  15. Feasibility study of tungsten as a diffusion barrier between nickel-chromium-aluminum and Gamma/Gamma prime - Delta eutectic alloys

    NASA Technical Reports Server (NTRS)

    Young, S. G.; Zellars, G. R.

    1978-01-01

    Coating systems proposed for potential use on eutectic alloy components in high-temperature gas turbine engines were studied with emphasis on deterioration of such systems by diffusion. A 1-mil thick W sheet was placed between eutectic alloys and a NiCrAl layer. Layered test specimens were aged at 1100 C for as long as long as 500 hours. Without the W barrier, the delta phase of the eutectic deteriorated by diffusion of Nb into the NiCrAl. Insertion of the W barrier stopped the diffusion of Nb from delta. Chromium diffusion from the NiCrAl into the gamma/gamma prime phase of the eutectic was greatly reduced by the barrier. However, the barrier thickness decreased with time; and W diffused into both the NiCrAl and the eutectic. When the delta platelets were alined parallel to the NiCrAl layer, rather than perpendicular, diffusion into the eutectic was reduced.

  16. HtrA3 is regulated by 15-deoxy-{Delta}12,14-prostaglandin J2 independently of PPAR{gamma} in clear cell renal cell carcinomas

    SciTech Connect

    Theoleyre, Sandrine; Mottier, Stephanie; Masson, Damien; Denis, Marc G.

    2010-04-09

    Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) ligands have been shown to possess anti-proliferative effects in many types of cancer. In clear cell renal cell carcinoma (CCRCC), the targets involved in these effects are not known. In this study, we demonstrated that, in CCRCC cell lines, the endogenous PPAR{gamma} ligand 15-deoxy-{Delta}12,14-prostaglandin J2 (15dPGJ2) induces the expression, both at the mRNA and the protein levels, of the HtrA3 gene. This gene belongs to the High-Temperature Requirement Factor A family of serine proteases that repress signaling by TGF-{beta} family members and inhibit cell migration. Rosiglitazone or ciglitazone, synthetic PPAR{gamma} agonists, did not induce HtrA3 expression, and the PPAR{gamma} antagonist GW9662 did not prevent 15dPGJ2 induction, suggesting that the up-regulation of HtrA3 by 15dPGJ2 is independent of PPAR{gamma}. The MEK/ERK inhibitor PD98059 dramatically repressed HtrA3 induction. Altogether, these data indicate that 15dPGJ2 is able to stimulate the expression of HtrA3 through an indirect mechanism involving the MEK/ERK pathway but independent of PPAR{gamma}. Our results provide a better understanding of the mechanisms involved in the regulation of HtrA3, a potential tumor suppressor gene.

  17. Gamma-delta T cell responses in subclinical and clinical stages of Bovine Mycobacterium Avium Paratuberculosis infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The early immune response to Mycobacterium avium subsp. paratuberculosis (MAP) in cattle is characterized by a Th1-like immune response effective in controlling bacterial proliferation during the subclinical stage of infection. In young calves nearly 60% of circulating lymphocytes are gamma delta T ...

  18. Oxidative stability of crude mid-oleic sunflower oils from seeds with high gamma and delta tocopherol levels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sunflower oil typically has a tocopherol profile that consists primarily of alpha-tocopherol - usually 95% of the total tocopherol content. Gamma-, delta-tocopherols are better antioxidants in vitro than alpha-tocopherol. Therefore, the oxidative stability of sunflower oil could possibly be enhanc...

  19. Gamma delta T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gamma delta T cells are resident in adipose tissue and increase during diet-induced obesity. Their possible contribution to the inflammatory response that accompanies diet-induced obesity was investigated in mice after a 5-10 week high milk fat diet. The high milk fat diet resulted in significant in...

  20. Effect of thermal cycling in a Mach 0.3 burner rig on properties and structure of directionally solidified gamma/gamma prime-delta eutectic

    NASA Technical Reports Server (NTRS)

    Gray, H. R.; Sanders, W. A.

    1976-01-01

    An experimental study was carried out to evaluate the effect of cyclic thermal exposures on the mechanical properties of a gamma/gamma prime-delta eutectic alloy parallel to the growth direction. The alloy had a nominal composition by weight of Ni-20 Nb-6 Cr-2.5 Al and was directionally solidified at 3 cm/hr in a furnace with a thermal gradient of at least 200 C/cm. Bars of the alloy were exposed in a Mach 0.3 burner rig and cycled 300 times between 1100 and 425 C. Oxidation-erosion characteristics of the alloy were determined by weight loss measurements at 300-cycle intervals. After cyclic exposure, stress rupture and tensile tests were performed at both 760 and 1040 C. Microstructural changes from cyclic exposure were determined. Thermal cycling resulted in gamma prime coarsening and Widmanstaetten delta precipitation in the gamma phase. An unidentified precipitate, presumably gamma prime, was observed within the delta phase. These microstructural changes did not affect the mechanical properties of the eutectic. High oxidation-erosion weight loss rate was observed.

  1. Bovine WC1- gamma delta T-cells incubated with IL-15 express the natural cytotoxicity receptor CD335 (NKp46) and produce IFN-gamma in response to exogenous IL-12 and IL-18

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The gamma delta T-cells of ruminants are believed to participate in innate immunity and have been described with regulatory and cytotoxic functions. Here we describe a subset of CD3+ TcRr1+ Wc1- CD8+ CD2+ gamma delta T-cells expressing CD335 (NKp46), classically associated with CD3- NK cells, as a c...

  2. Differential chemokine and cytokine production by neonatal bovine gamma delta T-cell subsets in response to viral toll-like receptor agonists and in vivo respiratory syncytial virus infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gamma delta T cells have recently been shown to respond to stimulation via toll like receptors (TLR). Bovine gamma delta T cells express TLR3 and TLR7, endosomal receptors that are key for the recognition of viruses such as bovine respiratory syncytial virus (BRSV); however, responses of gamma delta...

  3. T helper cell recognition of muscle acetylcholine receptor in myasthenia gravis. Epitopes on the gamma and delta subunits.

    PubMed Central

    Manfredi, A A; Protti, M P; Dalton, M W; Howard, J F; Conti-Tronconi, B M

    1993-01-01

    We tested the response of CD4+ cells and/or total lymphocytes from the blood of 22 myasthenic patients and 10 healthy controls to overlapping synthetic peptides, 20 residues long, to screen the sequence of the gamma and delta subunits of human muscle acetylcholine receptor (AChR). The gamma subunit is part of the AChR expressed in embryonic muscle and is substituted in the AChRs of most adult muscles by an epsilon subunit. The delta subunit is present in both embryonic and adult AChRs. Adult extrinsic ocular muscles, which are preferentially and sometimes uniquely affected by myasthenic symptoms, and thymus, which has a still obscure but important role in the pathogenesis of myasthenia gravis, express the embryonic gamma subunit. Anti-AChR CD4+ responses were more easily detected after CD8+ depletion. All responders recognized epitopes on both the gamma and delta subunits and had severe symptoms. In four patients the CD4+ cell response was tested twice, when the symptoms were severe and during a period of remission. Consistently, the response was only detectable, or larger, when the patients were severely affected. Images PMID:7688757

  4. Increased frequency of {gamma}{delta} T cells in cerebrospinal fluid and peripheral blood of patients with multiple sclerosis: Reactivity, cytotoxicity, and T cell receptor V gene rearrangements

    SciTech Connect

    Stinissen, P.; Vandevyver, C.; Medaer, R.

    1995-05-01

    Infiltrating {gamma}{delta} T cells are potentially involved in the central nervous system demyelination in multiple sclerosis (MS). To further study this hypothesis, we analyzed the frequency and functional properties of {gamma}{delta} T cells in peripheral blood (PB) and paired cerebrospinal fluid (CSF) of patients with MS and control subjects, including patients with other neurologic diseases (OND) and healthy individuals. The frequency analysis was performed under limiting dilution condition using rIL-2 and PHA. After PHA stimulation, a significantly increased frequency of {gamma}{delta} T cells was observed in PB and in CSF of MS patients as compared with PB and CSF of patients with OND. The frequency was represented equally in OND patients and normal individuals. Similarly, the IL-2-responsive {gamma}{delta} T cells occurred at a higher frequency in PB of MS than of control subjects. Forty-three percent of the {gamma}{delta} T cell clones isolates from PB and CSF of MS patients responded to heat shock protein (HSP70) but not HSP65, whereas only 2 of 30 control {gamma}{delta} T cell clones reacted to the HSP. The majority of the {gamma}{delta} T cell clones were able to induce non-MHC-restricted cytolysis of Daudi cells. All clones displayed a substantial reactivity to bacterial superantigens staphylococcal enterotoxin B and toxic shock syndrome toxin-1, irrespective of their {gamma}{delta} V gene usage. Furthermore, the {gamma}{delta} T cell clones expressed predominantly TCRDV2 and GV2 genes, whereas the clones derived from CSF of MS patients expressed either DV1 or DV2 genes. The obtained {gamma}{delta} clones, in general, represented rather heterogeneous clonal origins, even though a predominant clonal origin was found in a set of 10 {gamma}{delta} clones derived from one patient with MS. The present study provides new evidence supporting a possible role of {gamma}{delta} T cells in the secondary inflammatory processes in MS. 39 refs., 5 figs., 4 tabs.

  5. IL-4 is able to reverse the CD2-mediated negative apoptotic signal to CD4-CD8- alpha beta and/or gamma delta T lymphocytes.

    PubMed

    Spinozzi, F; Nicoletti, I; Agea, E; Belia, S; Moraca, R; Migliorati, G; Riccardi, C; Grignani, F; Bertotto, A

    1995-11-01

    Activation of immature thymocytes or transformed T lymphocytes via T-cell receptor (TCR)/CD3 signalling can induce programmed cell death (apoptosis). Recent data indicate that anti-CD3/TCR monoclonal antibodies (mAb) also trigger apoptosis in activated (but not resting) mature peripheral blood T lymphocytes. Here we report that triggering of resting CD4-CD8-TCR alpha beta+ and/or TCR gamma delta+ via the alternative CD2-dependent activation pathway is able to induce programmed cell death. A pair of mitogenic anti-CD2 mAb provoked a dramatic rise in [Ca2+]i that was almost entirely sustained by extracellular fluxes, and the inhibition of membrane [Ca2+/Mg2+] ATPase. The resulting endonuclease activation was able to induce DNA fragmentation, as revealed by propidium iodide staining and gel electrophoresis. Induction of apoptosis was prevented by the presence of interleukin-4 (IL-4) as well as by endonuclease inactivation with 100 microM ZnCl2, but enhanced by the contemporary block of protein kinase C. Thus it seems that in resting T lymphocytes the strong calcium signal delivered by the alternative CD2 activation pathway may act as a negative apoptotic signal in both alpha beta and gamma delta T cells with low (non-major histocompatibility complex restricted) antigenic affinity, so limiting the extension of polyclonal T-cell growth. PMID:8550074

  6. Depletion of IFN-gamma, CD8+ or Tcr gamma delta+ cells in vivo during primary infection with an enteric parasite (Trichostrongylus colubriformis) enhances protective immunity.

    PubMed

    McClure, S J; Davey, R J; Lloyd, J B; Emery, D L

    1995-12-01

    In order to examine the role of CD8+ and WCI+ T cells and of IFN-gamma in the development of protective immunity against infection with the enteric nematode parasite Trichostrongylus colubriformis in sheep, mAb were administered during induction of the immune response to deplete or neutralize these components. Protection against the primary and challenge infections were assessed by faecal egg count and total worm count. Prolonged administration of mAb recognizing IFN-gamma and CD8+ resulted in significantly increased protection during the 6-week primary infection. CD8+ cells were depleted from blood but not intestinal mucosa. After injection of mAb (CC15) recognizing the surface antigen WCI, WCI+ and T cell receptor (Tcr) gamma delta+ cells were depleted from blood but not from enteric mucosa, and protection against challenge, although variable, was increased by up to 88%. It appears that CD8+ and WCI+/gamma delta+ cells and IFN-gamma all retard the potential development of naturally-acquired immunity against the parasite. PMID:8713478

  7. Gamma source for active interrogation

    DOEpatents

    Leung, Ka-Ngo; Lou, Tak Pui; Barletta, William A.

    2009-09-29

    A cylindrical gamma generator includes a coaxial RF-driven plasma ion source and target. A hydrogen plasma is produced by RF excitation in a cylindrical plasma ion generator using an RF antenna. A cylindrical gamma generating target is coaxial with the ion generator, separated by plasma and extraction electrodes which has many openings. The plasma generator emanates ions radially over 360.degree. and the cylindrical target is thus irradiated by ions over its entire circumference. The plasma generator and target may be as long as desired.

  8. Gamma source for active interrogation

    SciTech Connect

    Leung, Ka-Ngo; Lou, Tak Pui; Barletta, William A.

    2012-10-02

    A cylindrical gamma generator includes a coaxial RF-driven plasma ion source and target. A hydrogen plasma is produced by RF excitation in a cylindrical plasma ion generator using an RF antenna. A cylindrical gamma generating target is coaxial with the ion generator, separated by plasma and extraction electrodes which has many openings. The plasma generator emanates ions radially over 360.degree. and the cylindrical target is thus irradiated by ions over its entire circumference. The plasma generator and target may be as long as desired.

  9. Quaternary and quinary modifications of eutectic superalloys strengthened by delta Ni3Cb lamellae and gamma prime Ni3Al precipitates

    NASA Technical Reports Server (NTRS)

    Lemkey, F. D.; Mccarthy, G. P.

    1975-01-01

    By means of a compositional and heat treatment optimization program based on the quaternary gamma/gamma prime-delta, a tantalum modified gamma/gamma prime-delta alloy with improved shear and creep strength combined with better cyclic oxidation resistance was identified. Quinary additions, quaternary adjustments, and heat treatment were investigated. The tantalum modified gamma/gamma prime-delta alloy possessed a slightly higher liquidus temperature and exhibited rupture strength exceeding NASA VIA by approximately three and one-half Larson-Miller parameters (C = 20) above 1000 C. Although improvements in longitudinal mechanical properties were achieved, the shear and transverse strength property goals of the program were not met and present a continuing challenge to the alloy metallurgist.

  10. Sex differences, gamma activity and schizophrenia.

    PubMed

    Slewa-Younan, S; Gordon, E; Williams, L; Haig, A R; Goldberg, E

    2001-03-01

    This study explores the possibility that the more favourable clinical prognosis in females with schizophrenia may be associated with their greater network interconnectedness, which is possibly reflected in enhanced "Gamma" (40 Hz) electrical brain activity. An auditory "oddball" task was administered to 35 patients with schizophrenia and 35 age and sex matched controls (25 males and 10 females). Peak Gamma amplitude (from a time series of Gamma activity averaged for 40 target stimuli, as well as the immediately preceding 40 background tones) was examined across 19 sites. Peak Gamma activity occurred 250 to 450 ms in targets and 350 to 550 ms in backgrounds. Multiple within and between group MANOVAs were undertaken analysing both Peak Gamma amplitude (microvolts) and latency (milliseconds). Within-group, the control males showed a pattern of earlier Gamma latency in the right compared with the left hemisphere (F(1, 33)=3.70, p<.06), while control females exhibited delayed latency frontally compared with the posterior region (F(1, 33)=6.25, p<.04). This male lateralization finding and the anterior/posterior gradient in females is consistent with Goldberg's model. The patient group however, failed to show this male lateralized and female frontal-posterior pattern of Gamma activity, suggesting suboptimal network integration in the patient group, in both males and females. PMID:11328687

  11. Amplitude Spectrum Variability in gamma Dor and delta Sct Pulsating Variable Stars Observed by the NASA Kepler Spacecraft

    NASA Astrophysics Data System (ADS)

    Guzik, Joyce Ann; Kosak, Katie; Bradley, Paul A.; Jackiewicz, Jason

    2015-08-01

    The NASA Kepler spacecraft data has revealed a large number of new multimode nonradially pulsating gamma Dor and delta Sct variable stars. The Kepler high precision long time-series photometry makes it possible to study amplitude variations of the frequencies. We summarize recent literature on amplitude and frequency variations in nonradially pulsating variables. We apply several methods, including those we have developed, and the wavelet technique of the VStar software (http://www.aavso.org/vstar-overview), to study amplitude variability in about a dozen gamma Doradus or delta Scuti candidate variable stars observed for several quarters as part of the Kepler Guest Observer program. We discuss the magnitude and timescale of the amplitude variations, and the presence or absence of correlations between amplitude variations for different frequencies of a given star. We discuss proposed causes of amplitude spectrum variability that will require further investigation.

  12. Amino acids of the Murchison meteorite. II - Five carbon acyclic primary beta-, gamma-, and delta-amino alkanoic acids

    NASA Technical Reports Server (NTRS)

    Cronin, J. R.; Pizzarello, S.; Yuen, G. U.

    1985-01-01

    The five-carbon acyclic primary beta, gamma, and delta amino alkanoic acids of the Murchison meteorite are studied using gas chromatography-mass spectrometry and ion exchange chromatography. The chromatograms reveal that alpha is the most abundant monoamino alkanoic acid followed by gamma and beta, and an exponential increase in the amount of amino acid is observed as the carbon number increases in the homologous series. The influence of frictional heating, spontaneous thermal decomposition, and radiation of the synthesis of amino acids is examined. The data obtained support an amino acid synthesis process involving random combination of single-carbon precursors.

  13. Gamma Delta (γδ) T Cells and Their Involvement in Behçet's Disease

    PubMed Central

    Hasan, Md. Samiul; Bergmeier, Lesley Ann; Petrushkin, Harry; Fortune, Farida

    2015-01-01

    Behçet's disease (BD) is a multisystem inflammatory disorder characterized by orogenital ulcerations, ocular manifestations, arthritis, and vasculitis. The disease follows a relapsing-remitting course and its pathogenesis is unknown. Genetic predisposition and immune-dysregulation involving gamma delta (γδ) T cells are reported to have a role. γδ T cells are atypical T cells, which represent a small proportion of total lymphocytes. They have features of both innate and adaptive immunity and express characteristics of conventional T cells, natural killer cells, and myeloid antigen presenting cells. These unconventional T cells are found in the inflammatory BD lesions and have been suggested to be responsible for inducing and/or maintaining the proinflammatory environment characteristic of the disease. Over the last 20 years there has been much interest in the role of γδ T cells in BD. We review the literature and discuss the roles that γδ T cells may play in BD pathogenesis. PMID:26539557

  14. A case of hepatosplenic gamma-delta T-cell lymphoma with a transient response to fludarabine and alemtuzumab.

    PubMed

    Mittal, S; Milner, B J; Johnston, P W; Culligan, D J

    2006-06-01

    Hepatosplenic gamma-delta T-cell lymphoma is a rare, usually fatal lymphoma and available literature on management is sparse. Allografting is probably the only curative option. We describe a further case with a dramatic, though transient response to Fludarabine and Alemtuzumab combination, following a failure of conventional chemotherapy. Given the dreadful prognosis with conventional chemotherapy, it is a regimen worth pursuing as a disease reduction strategy prior to allograft where appropriate. PMID:16548918

  15. Eutectic superalloys strengthened by aligned delta, Ni3Cb lamellae, gamma-prime, Ni3Al precipitates and reduced interlamellar spacing.

    NASA Technical Reports Server (NTRS)

    Lemkey, F. D.; Thompson, E. R.

    1973-01-01

    Monovariant eutectic alloys, located on the liquidus trough between the binary eutectic gamma, Ni - delta, Ni3Cb and the ternary eutectic gamma, Ni - gamma-prime, Ni3Al - delta, Ni3Cb, were identified which permitted the production of aligned lamellae within a nickel solid solution matrix containing the precipitate gamma-prime. These alloys exhibited great insensitivity in their composite microstructures to solidification parameters such as growth rate temperature gradient, and were found to be remarkably uniform in composition along their length.

  16. Non-random migration of CD4+, CD8+ and gamma delta+T19+ lymphocytes through peripheral lymph nodes.

    PubMed Central

    Witherden, D A; Kimpton, W G; Washington, E A; Cahill, R N

    1990-01-01

    The experiments described in this paper have examined the migration of three fluorochrome-labelled T-lymphocyte subsets (CD4+, CD8+ and gamma delta+T19+) on a single passage from blood to lymph, through prescapular lymph nodes. Lymphocytes obtained from prescapular efferent lymph were labelled in vitro with fluorochrome and returned to the blood of the same animal. Over the next 2 days, lymph was continuously monitored and the cells in all collections, including the one used for intravenous infusion, were phenotyped and analysed by flow cytometry. Significant differences in the subset ratios between the infused, starting population and the recirculated population indicated that CD4+ and gamma delta+T19+ lymphocytes are extracted by a resting lymph node at the same rate and that both are extracted at a faster rate than CD8+ lymphocytes. The results presented here also suggest that a unique subset of gamma delta+T19+ lymphocytes may be present in blood that does not recirculate through peripheral lymph nodes. PMID:2115500

  17. Delta-6 desaturase from borage converts linoleic acid to gamma-linolenic acid in HEK293 cells.

    PubMed

    Chen, Qing; Nimal, Jonathan; Li, Wanli; Liu, Xia; Cao, Wenguang

    2011-07-01

    Gamma-linolenic acid (GLA, 18:3 n6) is an essential polyunsaturated fatty acid of the omega-6 family and is found to be effective in prevention and/or treatment of various health problems. In this study, we evaluated the possibility of increasing γ-linolenic acid contents in mammalian cells using the delta-6 gene from Borago officinalis. The borage Δ6-desaturase gene (sDelta-6) was codon-optimized and introduced into HEK293 cells by lipofectin transfection. Co-expression of GFP with sDelta-6 and RT-PCR analysis indicated that sDelta-6 could be expressed in mammalian cells. Subsequently, the heterologous expression of borage Δ6-desaturase was evaluated by fatty acid analysis. Total cellular lipid analysis of transformed cells fed with linoleic acid (LA 18:2 n6) as a substrate showed that the expression of sDelta-6 resulted in an 228-483% (p<0.05) increase of GLA when compared with that in the control cells. The highest conversion efficiency of LA into GLA in sDelta-6(+) cells was 6.9 times higher than that in the control group (11.59% vs. 1.69%; p<0.05). Our present work demonstrated that the sDelta-6 gene from borage could be functionally expressed in mammalian cells, and could convert LA into GLA. Furthermore, this study may pave the way to generate transgenic livestock that can synthesise GLA. PMID:21679695

  18. The production of alpha/beta and gamma/delta double negative (DN) T-cells and their role in the maintenance of pregnancy.

    PubMed

    Chapman, John C; Chapman, Fae M; Michael, Sandra D

    2015-01-01

    The ability of the thymus gland to convert bone marrow-derived progenitor cells into single positive (SP) T-cells is well known. In this review we present evidence that the thymus, in addition to producing SP T-cells, also has a pathway for the production of double negative (DN) T-cells. The existence of this pathway was noted during our examination of relevant literature to determine the cause of sex steroid-induced thymocyte loss. In conducting this search our objective was to answer the question of whether thymocyte loss is the end product of a typical interaction between the reproductive and immune systems, or evidence that the two systems are incompatible. We can now report that "thymocyte loss" is a normal process that occurs during the production of DN T-cells. The DN T-cell pathway is unique in that it is mediated by thymic mast cells, and becomes functional following puberty. Sex steroids initiate the development of the pathway by binding to an estrogen receptor alpha located in the outer membrane of the mast cells, causing their activation. This results in their uptake of extracellular calcium, and the production and subsequent release of histamine and serotonin. Lymphatic vessels, located in the subcapsular region of the thymus, respond to the two vasodilators by undergoing a substantial and preferential uptake of gamma/delta and alpha/beta DN T- cells. These T- cells exit the thymus via efferent lymphatic vessels and enter the lymphatic system.The DN pathway is responsible for the production of three subsets of gamma/delta DN T-cells and one subset of alpha/beta DN T-cells. In postpubertal animals approximately 35 % of total thymocytes exit the thymus as DN T-cells, regardless of sex. In pregnant females, their levels undergo a dramatic increase. Gamma/delta DN T-cells produce cytokines that are essential for the maintenance of pregnancy. PMID:26164866

  19. Opposite role of delta 1- and delta 2-opioid receptors activated by endogenous or exogenous opioid agonists on the endogenous cholecystokinin system: further evidence for delta-opioid receptor heterogeneity.

    PubMed

    Noble, F; Fournie-Zaluski, M C; Roques, B P

    1996-12-01

    Using the mouse caudate-putamen, where delta-opioid receptor subtypes have been shown to regulate adenylyl cyclase activity, we show in this study that endogenous enkephalins inhibit enzyme activity through activation of delta 1- and delta 2-opioid receptors. Thus, naltriben or 7-benzylidenenaltrexone as well as the delta-selective antagonist naltrindole (mixed delta 1 and delta 2 antagonist) antagonized inhibition of adenylyl cyclase activity induced by methionine- or leucine-enkephalin, while the micro-antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) was without effect. Furthermore, we have previously shown that activation of delta-opioid receptors increases cholecystokinin release in the central nervous system, resulting in a potentiation of micro-opioid antinociceptive responses, and the respective role of delta 1- and delta 2-opioid receptors in this facilitatory effect has now been evaluated. Activation of delta 2-opioid receptors, either by endogenous enkephalins protected from catabolism by the complete enkephalin-degrading enzyme inhibitor N-((R,S)-2-benzyl-3((S)(2-amino-4-methyl-thio) butyldithio)-1-oxopropyl)-L-phenyl-alanine benzyl ester (RB 101), or by the delta 2-selective agonist Tyr-D-Ser(O-tert-butyl)-Gly-Phe-Leu-Thr(O-tert-butyl) (BUBU), potentiated micro-opioid antinociceptive responses in the hot-plate test in mice. This effect was antagonized by a selective cholecystokinin-A antagonist. Activation of delta 1-opioid receptors by endogenous opioid peptides decreased the micro-opioid responses. These results suggest that stimulation of delta 2-opioid receptors potentiates micro-opioid analgesia in the hot-plate test in mice through an increase in endogenous cholecystokinin release, while activation of delta 1-opioid receptors could decrease it. Thus, the pre-existing physiological balance between opioid and cholecystokinin systems seems to be modulated in opposite directions depending on whether delta 1- or delta 2-opioid receptors are

  20. The gamma N ---> Delta transition in chiral effective-field theory.

    SciTech Connect

    Vladimir Pascalutsa; Marc Vanderhaeghen

    2006-04-27

    We describe the pion electroproduction processes in the {Delta}(1232)-resonance region within the framework of chiral effective-field theory. By studying the observables of pion electroproduction in a next-to-leading order calculation we are able to make predictions and draw conclusions on the properties of the N {yields} {Delta} electromagnetic form factors.

  1. Isoforms of p38MAPK gamma and delta contribute to differentiation of human AML cells induced by 1,25-dihydroxyvitamin D3

    PubMed Central

    Zhang, Jing; Harrison, Jonathan S; Studzinski, George P.

    2010-01-01

    Inhibition of p38MAPK alpha/beta is known to enhance 1,25-dihydroxyvitamin (1,25D)-induced monocytic differentiation, but the detailed mechanism of this effect was not clear. We now show that the enhancement of differentiation becomes apparent with slow kinetics (12-24h). Interestingly, the inhibition of p38MAPK alpha/beta by their selective inhibitor SB202190 (SB) leads to an upregulated expression of p38MAPK isoforms gamma and delta in 1,25D-treated AML cells, in cell lines and in primary culture. Although the expression and activating phosphorylations of p38MAPK alpha are also increased by an exposure of the cells to SB, its kinase activity is blocked by SB, as shown by reduced levels of phosphorylated Hsp27, a downstream target of p38MAPK alpha. A positive role of p38MAPKs in 1,25D-induced differentiation is shown by the inhibition of differentiation by antisense oligonucleotides to all p38MAPK isoforms. Other principal branches of MAPK pathways showed early (6h) activation of MEK/ERK by SB, followed by activation of JNK1/2 pathway and enhanced expression and/or activation of PU.1, ATF-2 differentiation-related transcription factors. Taken together with previous reports, the results indicate that 1,25D-induced differentiation is enhanced by the activation of at least three branches of MAPK pathways (ERK1/2; p38MAPK gamma/delta; JNK1/2). This activation may result from the removal of feedback inhibition of an upstream regulator of those pathways, when p38MAPK alpha and beta are inhibited by SB. PMID:20804750

  2. Role of the thymus in the generation of skin-homing alpha beta and gamma delta virgin T cells.

    PubMed

    Washington, E A; Kimpton, W G; Holder, J E; Cahill, R N

    1995-03-01

    Current models of lymphocyte traffic suggest that homing specificities of T cells to tissues such as skin are generated outside the thymus as a result of activation of naive T cells by antigen in lymph nodes. Virgin T cells are thought to home to high endothelial venules in lymph nodes, but are thought to be unable to home to extra-lymphoid tissues such as skin. We used the technique of in situ labeling of the thymus with fluorescein isothiocyanate to examine the homing specificities of authentically naive T cells in vivo, immediately after their export from the thymus. We report that homing specificities for skin as well as lymph node are imprinted on T cells inside the thymus, independent of antigen. We also show that both alpha beta and gamma delta emigrant T cells exhibit homing patterns to skin and lymph nodes which are identical to those of mature T cells. Our findings demonstrate a key role for the thymus in the induction of skin-homing specificities on T cells indicating that skin-homing specificities of T cells are not generated solely outside the thymus as a result of the activation of virgin T cells by antigen. The migration of thymic emigrants to extra-lymphoid tissues within a few hours of leaving the thymus may have implications for mechanisms of peripheral self-tolerance. This pathway provides an opportunity for direct virgin T cell interactions with self components only expressed in the periphery at a time when emigrants may be more susceptible to tolerance induction than mature circulating T cells. PMID:7535700

  3. Delta, theta, beta, and gamma brain oscillations index levels of auditory sentence processing.

    PubMed

    Mai, Guangting; Minett, James W; Wang, William S-Y

    2016-06-01

    A growing number of studies indicate that multiple ranges of brain oscillations, especially the delta (δ, <4Hz), theta (θ, 4-8Hz), beta (β, 13-30Hz), and gamma (γ, 30-50Hz) bands, are engaged in speech and language processing. It is not clear, however, how these oscillations relate to functional processing at different linguistic hierarchical levels. Using scalp electroencephalography (EEG), the current study tested the hypothesis that phonological and the higher-level linguistic (semantic/syntactic) organizations during auditory sentence processing are indexed by distinct EEG signatures derived from the δ, θ, β, and γ oscillations. We analyzed specific EEG signatures while subjects listened to Mandarin speech stimuli in three different conditions in order to dissociate phonological and semantic/syntactic processing: (1) sentences comprising valid disyllabic words assembled in a valid syntactic structure (real-word condition); (2) utterances with morphologically valid syllables, but not constituting valid disyllabic words (pseudo-word condition); and (3) backward versions of the real-word and pseudo-word conditions. We tested four signatures: band power, EEG-acoustic entrainment (EAE), cross-frequency coupling (CFC), and inter-electrode renormalized partial directed coherence (rPDC). The results show significant effects of band power and EAE of δ and θ oscillations for phonological, rather than semantic/syntactic processing, indicating the importance of tracking δ- and θ-rate phonetic patterns during phonological analysis. We also found significant β-related effects, suggesting tracking of EEG to the acoustic stimulus (high-β EAE), memory processing (θ-low-β CFC), and auditory-motor interactions (20-Hz rPDC) during phonological analysis. For semantic/syntactic processing, we obtained a significant effect of γ power, suggesting lexical memory retrieval or processing grammatical word categories. Based on these findings, we confirm that scalp EEG

  4. A new formulation of Gamma Delta Tocotrienol has superior bioavailability compared to existing Tocotrienol-Rich Fraction in healthy human subjects.

    PubMed

    Meganathan, Puvaneswari; Jabir, Rafid Salim; Fuang, Ho Gwo; Bhoo-Pathy, Nirmala; Choudhury, Roma Basu; Taib, Nur Aishah; Nesaretnam, Kalanithi; Chik, Zamri

    2015-01-01

    Gamma and delta tocotrienols are isomers of Vitamin E with established potency in pre-clinical anti-cancer research. This single-dose, randomized, crossover study aimed to compare the safety and bioavailability of a new formulation of Gamma Delta Tocotrienol (GDT) in comparison with the existing Tocotrienol-rich Fraction (TRF) in terms of gamma and delta isomers in healthy volunteers. Subjects were given either two 300 mg GDT (450 mg γ-T3 and 150 mg δ-T3) capsules or four 200 mg TRF (451.2 mg γ-T3 &102.72 mg δ-T3) capsules and blood samples were taken at several time points over 24 hours. Plasma tocotrienol concentrations were determined using HPLC method. The 90% CI for gamma and delta tocotrienols for the ratio of log-transformation of GDT/TRF for Cmax and AUC0-∞ (values were anti-logged and expressed as a percentage) were beyond the bioequivalence limits (106.21-195.46, 154.11-195.93 and 52.35-99.66, 74.82-89.44 respectively). The Wilcoxon Signed Rank Test for Tmax did not show any significant difference between GDT and TRF for both isomers (p > 0.05). No adverse events were reported during the entire period of study. GDT was found not bioequivalent to TRF, in terms of AUC and Cmax. Gamma tocotrienol in GDT showed superior bioavailability whilst delta tocotrienol showed less bioavailability compared to TRF. PMID:26323969

  5. Applications and development of communication models for the touchstone GAMMA and DELTA prototypes

    NASA Technical Reports Server (NTRS)

    Seidel, Steven R.

    1993-01-01

    The goal of this project was to develop models of the interconnection networks of the Intel iPSC/860 and DELTA multicomputers to guide the design of efficient algorithms for interprocessor communication in problems that commonly occur in CFD codes and other applications. Interprocessor communication costs of codes for message-passing architectures such as the iPSC/860 and DELTA significantly affect the level of performance that can be obtained from those machines. This project addressed several specific problems in the achievement of efficient communication on the Intel iPSC/860 hypercube and DELTA mesh. In particular, an efficient global processor synchronization algorithm was developed for the iPSC/860 and numerous broadcast algorithms were designed for the DELTA.

  6. IP receptor-dependent activation of PPAR{gamma} by stable prostacyclin analogues

    SciTech Connect

    Falcetti, Emilia; Flavell, David M.; Staels, Bart; Tinker, Andrew; Haworth, Sheila G.; Clapp, Lucie H. . E-mail: l.clapp@ucl.ac.uk

    2007-09-07

    Stable prostacyclin analogues can signal through cell surface IP receptors or by ligand binding to nuclear peroxisome proliferator-activated receptors (PPARs). So far these agents have been reported to activate PPAR{alpha} and PPAR{delta} but not PPAR{gamma}. Given PPAR{gamma} agonists and prostacyclin analogues both inhibit cell proliferation, we postulated that the IP receptor might elicit PPAR{gamma} activation. Using a dual luciferase reporter gene assay in HEK-293 cells stably expressing the IP receptor or empty vector, we found that prostacyclin analogues only activated PPAR{gamma} in the presence of the IP receptor. Moreover, the novel IP receptor antagonist, RO1138452, but not inhibitors of the cyclic AMP pathway, prevented activation. Likewise, the anti-proliferative effects of treprostinil observed in IP receptor expressing cells, were partially inhibited by the PPAR{gamma} antagonist, GW9662. We conclude that PPAR{gamma} is activated through the IP receptor via a cyclic AMP-independent mechanism and contributes to the anti-growth effects of prostacyclin analogues.

  7. Gamma delta T cell responses associated with the development of tuberculosis in health care workers.

    PubMed

    Ordway, Diane J; Pinto, Luisa; Costa, Leonor; Martins, Marta; Leandro, Clara; Viveiros, Miguel; Amaral, Leonard; Arroz, Maria J; Ventura, Fernando A; Dockrell, Hazel M

    2005-03-01

    This study evaluated T cell immune responses to purified protein derivative (PPD) and Mycobacterium tuberculosis (Mtb) in health care workers who remained free of active tuberculosis (HCWs w/o TB), health care workers who went on to develop active TB (HCWs w/TB), non-health care workers who were TB free (Non-HCWs) and tuberculosis patients presenting with minimal (Min TB) or advanced (Adv TB) disease. Peripheral blood mononuclear cells (PBMC) were stimulated with Mtb and PPD and the expression of T cell activation markers CD25+ and HLA-DR+, intracellular IL-4 and IFN-gamma production and cytotoxic responses were evaluated. PBMC from HCWs who developed TB showed decreased percentages of cells expressing CD8+CD25+ in comparison to HCWs who remained healthy. HCWs who developed TB showed increased gammadelta TCR+ cell cytotoxicity and decreased CD3+gammadelta TCR- cell cytotoxicity in comparison to HCWs who remained healthy. PBMC from TB patients with advanced disease showed decreased percentages of CD25+CD4+ and CD25+CD8+ T cells that were associated with increased IL-4 production in CD8+ and gammadelta TCR+ phenotypes, in comparison with TB patients presenting minimal disease. TB patients with advanced disease showed increased gammadelta TCR+ cytotoxicity and reduced CD3+gammadelta TCR- cell cytotoxicity. Our results suggest that HCWs who developed TB show an early compensatory mechanism involving an increase in lytic responses of gammadelta TCR+ cells which did not prevent TB. PMID:15708307

  8. Gamma rays from active galactic nuclei

    NASA Technical Reports Server (NTRS)

    Kazanas, Demosthenes

    1990-01-01

    The general properties of Active Galactic Nuclei (AGN) and quasars are reviewed with emphasis on their continuum spectral emission. Two general classes of models for the continuum are outlined and critically reviewed in view of the impending GRO (Gamma Ray Observatory) launch and observations. The importance of GRO in distinguishing between these models and in general in furthering the understanding of AGN is discussed. The very broad terms the status of the current understanding of AGN are discussed.

  9. Gamma Band Activity in the Reticular Activating System

    PubMed Central

    Urbano, Francisco J.; Kezunovic, Nebojsa; Hyde, James; Simon, Christen; Beck, Paige; Garcia-Rill, Edgar

    2012-01-01

    This review considers recent evidence showing that cells in three regions of the reticular activating system (RAS) exhibit gamma band activity, and describes the mechanisms behind such manifestation. Specifically, we discuss how cells in the mesopontine pedunculopontine nucleus (PPN), intralaminar parafascicular nucleus (Pf), and pontine subcoeruleus nucleus dorsalis (SubCD) all fire in the beta/gamma band range when maximally activated, but no higher. The mechanisms behind this ceiling effect have been recently elucidated. We describe recent findings showing that every cell in the PPN have high-threshold, voltage-dependent P/Q-type calcium channels that are essential, while N-type calcium channels are permissive, to gamma band activity. Every cell in the Pf also showed that P/Q-type and N-type calcium channels are responsible for this activity. On the other hand, every SubCD cell exhibited sodium-dependent subthreshold oscillations. A novel mechanism for sleep–wake control based on well-known transmitter interactions, electrical coupling, and gamma band activity is described. The data presented here on inherent gamma band activity demonstrates the global nature of sleep–wake oscillation that is orchestrated by brainstem–thalamic mechanism, and questions the undue importance given to the hypothalamus for regulation of sleep–wakefulness. The discovery of gamma band activity in the RAS follows recent reports of such activity in other subcortical regions like the hippocampus and cerebellum. We hypothesize that, rather than participating in the temporal binding of sensory events as seen in the cortex, gamma band activity manifested in the RAS may help stabilize coherence related to arousal, providing a stable activation state during waking and paradoxical sleep. Most of our thoughts and actions are driven by pre-conscious processes. We speculate that continuous sensory input will induce gamma band activity in the RAS that could participate in the processes of

  10. Ganges-Brahmaputra Delta: Balance of Subsidence, Sea level and Sedimentation in a Tectonically-Active Delta (Invited)

    NASA Astrophysics Data System (ADS)

    Steckler, M. S.; Goodbred, S. L.; Akhter, S. H.; Seeber, L.; Reitz, M. D.; Paola, C.; Nooner, S. L.; DeWolf, S.; Ferguson, E. K.; Gale, J.; Hossain, S.; Howe, M.; Kim, W.; McHugh, C. M.; Mondal, D. R.; Petter, A. L.; Pickering, J.; Sincavage, R.; Williams, L. A.; Wilson, C.; Zumberge, M. A.

    2013-12-01

    Bangladesh is vulnerable to a host of short and long-term natural hazards - widespread seasonal flooding, river erosion and channel avulsions, permanent land loss from sea level rise, natural groundwater arsenic, recurrent cyclones, landslides and huge earthquakes. These hazards derive from active fluvial processes related to the growth of the delta and the tectonics at the India-Burma-Tibet plate junctions. The Ganges and Brahmaputra rivers drain 3/4 of the Himalayas and carry ~1 GT/y of sediment, 6-8% of the total world flux. In Bangladesh, these two great rivers combine with the Meghna River to form the Ganges-Brahmaputra-Meghna Delta (GBMD). The seasonality of the rivers' water and sediment discharge is a major influence causing widespread flooding during the summer monsoon. The mass of the water is so great that it causes 5-6 cm of seasonal elastic deformation of the delta discerned by our GPS data. Over the longer-term, the rivers are also dynamic. Two centuries ago, the Brahmaputra River avulsed westward up to 100 km and has since captured other rivers. The primary mouth of the Ganges has shifted 100s of km eastward from the Hooghly River over the last 400y, finally joining the Brahmaputra in the 19th century. These avulsions are influenced by the tectonics of the delta. On the east side of Bangladesh, the >16 km thick GBMD is being overridden by the Burma Arc where the attempted subduction of such a thick sediment pile has created a huge accretionary prism. The foldbelt is up to 250-km wide and its front is buried beneath the delta. The main Himalayan thrust front is <100 km north, but adjacent to the GBMD is the Shillong Massif, a 300-km long, 2-km high block of uplifted Indian basement that is overthrusting and depressing GBMD sediments to the south. The overthrusting Shillong Massif may represent a forward jump of the Himalayan front to a new plate boundary. This area ruptured in a ~M8 1897 earthquake. Subsidence from the tectonics and differential

  11. Carburization and heat treatment to cause carbide precipitation in gamma/gamma prime-delta eutectic alloys

    NASA Technical Reports Server (NTRS)

    Tewari, S. N.; Dreshfield, R. L.

    1977-01-01

    In an attempt to improve their longitudinal shear strength, several directionally solidified eutectic alloy compositions with minor element modifications were pact, carburized, and heat treated to provide selective carbide precipitation at the cell and grain boundaries. The directionally solidified Ni-17.8 Nb-6Cr-2.5Al-3Ta (weight percent) alloy was selected for the shear strength evaluation because it showed the shallowest delta-denuded zone at the carburized surface. The carburization-carbide precipitation treatment, however, did not appear to improve the longitudinal shear strength of the alloy.

  12. The role of bovine gamma delta T cells and their WC1 co-receptor in response to bacterial pathogens and promoting vaccine efficacy: A model for cattle and humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gamma deltaT cells are critical to immune surveillance and protection since they are found as resident cells in many organs and tissues, including in humans and ruminants, and circulate at substantial numbers in the blood. It is known that gamma delta T cells contribute to cellular immunity and pro...

  13. Human placental DNA polymerase delta: identification of a 170-kilodalton polypeptide by activity staining and immunoblotting

    SciTech Connect

    Lee, M.Y.W.T.; Toomey, N.L.

    1987-02-24

    DNA polymerase delta was isolated from human placenta and identified as such on the basis of its association with a 3'- to 5'-exonuclease activity. The association of the polymerase and exonuclease activities was maintained throughout purification and attempted separations by physical or electrophoretic methods. Moreover, ratios of the two activities remained constant during the purification steps, and both activities were inhibited by aphidicolin, oxidized glutathione, and n-ethylmaleimide. The purified enzyme had an estimated molecular weight of 172,000, on the basis of a Stokes radius of 53.6 A and a sedimentation coefficient of 7.8 S. On sodium dodecyl sulfate (SDS) gel electrophoresis, polymerase delta preparations contained a band of ca. 170 kilodaltons (kDa) as well as several smaller polypeptides. The 170-kDa polypeptide was identified as the largest polypeptides component in the preparation possessing DNA polymerase activity by an activity staining procedure following gel electrophoresis in the presence of SDS. Western blotting of DNA polymerase delta with polyclonal antisera also revealed a single 170-kDa immunoreactive polypeptide. Monoclonal antibodies to KB cell polymerase ..cap alpha.. inhibited placental polymerase ..cap alpha.. but did not inhibit DNA polymerase delta, while the murine polyclonal antisera to polymerase delta inhibited delta but not ..cap alpha... These findings establish the existence of DNA polymerase delta in a human tissue and support the view that both its polymerase and its exonuclease activities may be associated with a single protein.

  14. Delta ferrite in the weld metal of reduced activation ferritic martensitic steel

    NASA Astrophysics Data System (ADS)

    Sam, Shiju; Das, C. R.; Ramasubbu, V.; Albert, S. K.; Bhaduri, A. K.; Jayakumar, T.; Rajendra Kumar, E.

    2014-12-01

    Formation of delta(δ)-ferrite in the weld metal, during autogenous bead-on-plate welding of Reduced Activation Ferritic Martensitic (RAFM) steel using Gas Tungsten Arc Welding (GTAW) process, has been studied. Composition of the alloy is such that delta-ferrite is not expected in the alloy; but examination of the weld metal revealed presence of delta-ferrite in the weld metal. Volume fraction of delta-ferrite is found to be higher in the weld interface than in the rest of the fusion zone. Decrease in the volume fraction of delta-ferrite, with an increase in preheat temperature or with an increase in heat input, is observed. Results indicate that the cooling rate experienced during welding affects the volume fraction of delta-ferrite retained in the weld metal and variation in the delta-ferrite content with cooling rate is explained with variation in the time that the weld metal spends in various temperature regimes in which delta-ferrite is stable for the alloy during its cooling from the liquid metal to the ambient temperature. This manuscript will discuss the effect of welding parameters on formation of delta-ferrite and its retention in the weld metal of RAFM steel.

  15. Monitoring rice farming activities in the Mekong Delta region

    NASA Astrophysics Data System (ADS)

    Nguyen, S. T.; Chen, C. F.; Chen, C. R.; Chiang, S. H.; Chang, L. Y.; Khin, L. V.

    2015-12-01

    Half of the world's population depends on rice for survival. Rice agriculture thus plays an important role in the developing world's economy. Vietnam is one of the largest rice producers and suppliers on earth and more than 80% of the exported rice was produced from the Mekong Delta region, which is situated in the southwestern Vietnam and encompasses approximately 40,000 km2. Changes in climate conditions could likely trigger the increase of insect populations and rice diseases, causing the potential loss of rice yields. Monitoring rice-farming activities through crop phenology detection can provide policymakers with timely strategies to mitigate possible impacts on the potential yield as well as rice grain exports to ensure food security for the region. The main objective of this study is to develop a logistic-based algorithm to investigate rice sowing and harvesting activities from the multi-temporal Moderate Resolution Imaging Spectroradiometer (MODIS)-Landsat fusion data. We processed the data for two main cropping seasons (i.e., winter-spring and summer-autumn seasons) through a three-step procedure: (1) MODIS-Landsat data fusion, (2) construction of the time-series enhanced vegetation index 2 (EVI2) data, (3) rice crop phenology detection. The EVI2 data derived from the fusion results between MODIS and Landsat data were compared with that of Landsat data indicated close correlation between the two datasets (R2 = 0.93). The time-series EVI2 data were processed using the double logistic method to detect the progress of sowing and harvesting activities in the region. The comparisons between the estimated sowing and harvesting dates and the field survey data revealed the root mean squared error (RMSE) values of 8.4 and 5.5 days for the winter-spring crop and 9.4 and 12.8 days for the summer-autumn crop, respectively. This study demonstrates the effectiveness of the double logistic-based algorithm for rice crop monitoring from temporal MODIS-Landsat fusion data

  16. Pedunculopontine Gamma Band Activity and Development

    PubMed Central

    Garcia-Rill, Edgar; Luster, Brennon; Mahaffey, Susan; MacNicol, Melanie; Hyde, James R.; D’Onofrio, Stasia M.; Phillips, Cristy

    2015-01-01

    This review highlights the most important discovery in the reticular activating system in the last 10 years, the manifestation of gamma band activity in cells of the reticular activating system (RAS), especially in the pedunculopontine nucleus, which is in charge of waking and rapid eye movement (REM) sleep. The identification of different cell groups manifesting P/Q-type Ca2+ channels that control waking vs. those that manifest N-type channels that control REM sleep provides novel avenues for the differential control of waking vs. REM sleep. Recent discoveries on the development of this system can help explain the developmental decrease in REM sleep and the basic rest-activity cycle. PMID:26633526

  17. Pedunculopontine Gamma Band Activity and Development.

    PubMed

    Garcia-Rill, Edgar; Luster, Brennon; Mahaffey, Susan; MacNicol, Melanie; Hyde, James R; D'Onofrio, Stasia M; Phillips, Cristy

    2015-01-01

    This review highlights the most important discovery in the reticular activating system in the last 10 years, the manifestation of gamma band activity in cells of the reticular activating system (RAS), especially in the pedunculopontine nucleus, which is in charge of waking and rapid eye movement (REM) sleep. The identification of different cell groups manifesting P/Q-type Ca(2+) channels that control waking vs. those that manifest N-type channels that control REM sleep provides novel avenues for the differential control of waking vs. REM sleep. Recent discoveries on the development of this system can help explain the developmental decrease in REM sleep and the basic rest-activity cycle. PMID:26633526

  18. Auroral recombination of N and O - A possible source for emission in the gamma and delta bands of NO

    NASA Technical Reports Server (NTRS)

    Wofsy, S. C.; Mcelroy, M. B.

    1977-01-01

    Radiative recombination of N and O provides a significant source for auroral emission in the gamma and delta bands of NO with selective population of vibrational levels in the A 2 Sigma(+) and C 2 Pi states. This mechanism may account for emissions detected near 2150 A. Models are derived for the auroral ionosphere and include estimates for the concentrations of N and NO. The concentration of NO is estimated to have a value of about 100 million per cu cm near 140 km in an IBC III aurora. The corresponding density for N is about 50 million per cu cm, and the concentration ratio NO(+)/O2(+) has a value of about 5.5.

  19. Q2 Dependence of Quadrupole Strength in the gamma*p-->Delta+(1232) --> p pi0 Transition

    SciTech Connect

    Burkert, Volker; Joo, Kyungseon; Smith, Lee; Minehart, Ralph; et. Al.

    2002-03-06

    Models of baryon structure predict a small quadrupole deformation of the nucleon due to residual tensor forces between quarks or distortions from the pion cloud. Sensitivity to quark versus pion degrees of freedom occurs through the Q{sup 2} dependence of the magnetic (M{sub 1+}), electric (E{sub 1+}), and scalar (S{sub 1+}) multipoles in the {gamma}*p {yields} {Delta}{sup +}(1232) {yields} p{pi}{sup 0} transition. New precision measurements of the ratios E{sub 1+}/M{sub 1+} and S{sub 1+}/M{sub 1+} are reported here over the range Q{sup 2} = 0.4-1.8 GeV{sup 2}. Results are best described by recent unitary models in which the pion cloud plays a dominant role.

  20. Q2 Dependence of quadrupole strength in the gamma*p --> Delta(+)(1232) --> p pi(0) transition.

    PubMed

    Joo, K; Smith, L C; Burkert, V D; Minehart, R; Aznauryan, I G; Elouadrhiri, L; Stepanyan, S; Adams, G S; Amaryan, M J; Anciant, E; Anghinolfi, M; Armstrong, D S; Asavapibhop, B; Audit, G; Auger, T; Avakian, H; Barrow, S; Bagdasaryan, H; Battaglieri, M; Beard, K; Bektasoglu, M; Bertozzi, W; Bianchi, N; Biselli, A S; Boiarinov, S; Bonner, B E; Brooks, W K; Calarco, J R; Capitani, G P; Carman, D S; Carnahan, B; Cole, P L; Coleman, A; Cords, D; Corvisiero, P; Crabb, D; Crannell, H; Cummings, J; De Sanctis, E; De Vita, R; Degtyarenko, P V; Demirchyan, R A; Denizli, H; Dennis, L C; Deppman, A; Dharmawardane, K V; Dhuga, K S; Djalali, C; Dodge, G E; Doughty, D; Dragovitsch, P; Dugger, M; Dytman, S; Eckhause, M; Efremenko, Y V; Egiyan, H; Egiyan, K S; Farhi, L; Feuerbach, R J; Ficenec, J; Fissum, K; Forest, T A; Funsten, H; Gai, M; Gavrilov, V B; Gilad, S; Gilfoyle, G P; Giovanetti, K L; Girard, P; Griffioen, K A; Guidal, M; Guillo, M; Gyurjyan, V; Hancock, D; Hardie, J; Heddle, D; Heisenberg, J; Hersman, F W; Hicks, K; Hicks, R S; Holtrop, M; Hyde-Wright, C E; Ito, M M; Jenkins, D; Kelley, J H; Khandaker, M; Kim, K Y; Kim, W; Klein, A; Klein, F J; Klusman, M; Kossov, M; Kuang, Y; Kuhn, S E; Laget, J M; Lawrence, D; Longhi, A; Loukachine, K; Lucas, M; Major, R W; Manak, J J; Marchand, C; Matthews, S K; McAleer, S; McNabb, J W C; Mecking, B A; Mestayer, M D; Meyer, C A; Mirazita, M; Miskimen, R; Muccifora, V; Mueller, J; Mutchler, G S; Napolitano, J; Niculescu, G; Niczyporuk, B; Niyazov, R A; Ohandjanyan, M S; Opper, A; Patois, Y; Peterson, G A; Philips, S; Pivnyuk, N; Pocanic, D; Pogorelko, O; Polli, E; Preedom, B M; Price, J W; Qin, L M; Raue, B A; Reolon, A R; Riccardi, G; Ricco, G; Ripani, M; Ritchie, B G; Ronchetti, F; Rossi, P; Rowntree, D; Rubin, P D; Salgado, C W; Sanzone, M; Sapunenko, V; Sargsyan, M; Schumacher, R A; Sharabian, Y G; Shaw, J; Shuvalov, S M; Skabelin, A; Smith, E S; Smith, T; Sober, D I; Spraker, M; Stoler, P; Taiuti, M; Taylor, S; Tedeschi, D; Thompson, R; Todor, L; Tung, T Y; Vineyard, M F; Vlassov, A; Weller, H; Weinstein, L B; Welsh, R; Weygand, D P; Whisnant, S; Witkowski, M; Wolin, E; Yegneswaran, A; Yun, J; Zhou, Z; Zhao, J

    2002-03-25

    Models of baryon structure predict a small quadrupole deformation of the nucleon due to residual tensor forces between quarks or distortions from the pion cloud. Sensitivity to quark versus pion degrees of freedom occurs through the Q2 dependence of the magnetic (M1+), electric (E1+), and scalar (S1+) multipoles in the gamma*p-->Delta(+)-->p pi(0) transition. We report new experimental values for the ratios E(1+)/M(1+) and S(1+)/M(1+) over the range Q2 = 0.4-1.8 GeV2, extracted from precision p(e,e(')p)pi(0) data using a truncated multipole expansion. Results are best described by recent unitary models in which the pion cloud plays a dominant role. PMID:11909446

  1. Specific recognition of mycobacterial protein and peptide antigens by gamma-delta T cell subsets following infection with virulent Mycobacterium bovis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Promoting effective immunity to Mycobacterium tuberculosis complex pathogens is a challenge that is of interest to the fields of human and veterinary medicine alike. We report that gamma delta T cells from virulent Mycobacterium bovis-infected cattle respond specifically and directly to complex, pro...

  2. Functional characterization of T cells bearing the gamma/delta T-cell receptor in patients with primary Sjögren's syndrome.

    PubMed

    Gerli, R; Agea, E; Muscat, C; Bertotto, A; Ercolani, R; Bistoni, O; Bini, P; Spinozzi, F; Venanzi, F

    1993-01-01

    High percentages of gamma/delta+ T cells in the peripheral blood of a subgroup of patients with primary Sjögren's syndrome (SS) were found. This allowed us to purify and analyze them without their being previously expanded in vitro, and to investigate, therefore, the role of these cells in the pathological immune response which characterizes such systemic autoimmune disorders. The results showed poor proliferation of patient gamma/delta+ T cells in response to anti-CD3, due not to macrophage-dependent suppression but to defective interleukin 2 (IL-2) synthesis. Despite the defective proliferation patient gamma/delta+ cells, unlike those of the normal controls, provided a helper effect in inducing B cells to secrete immunoglobulins (Ig), particularly when they were preincubated with IL-2. The relative increase in a gamma/delta+ T cell subset which, although it secretes low levels of IL-2, is able to provide help for B-cell Ig synthesis, suggests that this T-cell subpopulation may be functional in vivo and may be involved in the pathological immune response encountered in pSS. PMID:8353984

  3. Chronic stimulation of cultured neuronal networks boosts low-frequency oscillatory activity at theta and gamma with spikes phase-locked to gamma frequencies

    NASA Astrophysics Data System (ADS)

    Leondopulos, Stathis S.; Boehler, Michael D.; Wheeler, Bruce C.; Brewer, Gregory J.

    2012-04-01

    Slow wave oscillations in the brain are essential for coordinated network activity but have not been shown to self-organize in vitro. Here, the development of dissociated hippocampal neurons into an active network with oscillations on multi-electrode arrays was evaluated in the absence and presence of chronic external stimulation. Significant changes in signal power were observed in the range of 1-400 Hz with an increase in amplitude during bursts. Stimulation increased oscillatory activity primarily in the theta (4-11 Hz) and slow gamma (30-55 Hz) bands. Spikes were most prominently phase-locked to the slow gamma waves. Notably, the dissociated network self-organized to exhibit sustained delta, theta, beta and gamma oscillations without input from cortex, thalamus or organized pyramidal cell layers.

  4. Quantitative conformationally sampled pharmacophore for delta opioid ligands: reevaluation of hydrophobic moieties essential for biological activity.

    PubMed

    Bernard, Denzil; Coop, Andrew; MacKerell, Alexander D

    2007-04-19

    Recent studies have indicated several therapeutic applications for delta opioid agonists and antagonists. To exploit the therapeutic potential of delta opioids developing a structural basis for the activity of ligands at the delta opioid receptor is essential. The conformationally sampled pharmacophore (CSP) method (Bernard et al. J. Am. Chem. Soc. 2003, 125, 3103-3107) is extended here to obtain quantitative models of delta opioid ligand efficacy and affinity. Quantification is performed via overlap integrals of the conformational space sampled by ligands with respect to a reference compound. Iterative refinement of the CSP model identified hydrophobic groups other than the traditional phenylalanine residues as important for efficacy and affinity in DSLET and ICI 174 864. The obtained models for a structurally diverse set of peptidic and nonpeptidic delta opioid ligands offer good predictions with R2 values>0.9, and the predicted efficacy for a set of test compounds was consistent with the experimental values. PMID:17367120

  5. Modification by SUMOylation Controls Both the Transcriptional Activity and the Stability of Delta-Lactoferrin

    PubMed Central

    Escobar-Ramirez, Adelma; Vercoutter-Edouart, Anne-Sophie; Mortuaire, Marlène; Huvent, Isabelle; Hardivillé, Stephan; Hoedt, Esthelle; Lefebvre, Tony; Pierce, Annick

    2015-01-01

    Delta-lactoferrin is a transcription factor, the expression of which is downregulated or silenced in case of breast cancer. It possesses antitumoral activities and when it is re-introduced in mammary epithelial cancer cell lines, provokes antiproliferative effects. It is posttranslationally modified and our earlier investigations showed that the O-GlcNAcylation/phosphorylation interplay plays a major role in the regulation of both its stability and transcriptional activity. Here, we report the covalent modification of delta-lactoferrin with the small ubiquitin-like modifier SUMO-1. Mutational and reporter gene analyses identified five different lysine residues at K13, K308, K361, K379 and K391 as SUMO acceptor sites. The SUMOylation deficient M5S mutant displayed enhanced transactivation capacity on a delta-lactoferrin responsive promoter, suggesting that SUMO-1 negatively regulates the transactivation function of delta-lactoferrin. K13, K308 and K379 are the main SUMO sites and among them, K308, which is located in a SUMOylation consensus motif of the NDSM-like type, is a key SUMO site involved in repression of delta-lactoferrin transcriptional activity. K13 and K379 are both targeted by other posttranslational modifications. We demonstrated that K13 is the main acetylation site and that favoring acetylation at K13 reduced SUMOylation and increased delta-lactoferrin transcriptional activity. K379, which is either ubiquitinated or SUMOylated, is a pivotal site for the control of delta-lactoferrin stability. We showed that SUMOylation competes with ubiquitination and protects delta-lactoferrin from degradation by positively regulating its stability. Collectively, our results indicate that multi-SUMOylation occurs on delta-lactoferrin to repress its transcriptional activity. Reciprocal occupancy of K13 by either SUMO-1 or an acetyl group may contribute to the establishment of finely regulated mechanisms to control delta-lactoferrin transcriptional activity. Moreover

  6. A new formulation of Gamma Delta Tocotrienol has superior bioavailability compared to existing Tocotrienol-Rich Fraction in healthy human subjects

    PubMed Central

    Meganathan, Puvaneswari; Jabir, Rafid Salim; Fuang, Ho Gwo; Bhoo-Pathy, Nirmala; Choudhury, Roma Basu; Taib, Nur Aishah; Nesaretnam, Kalanithi; Chik, Zamri

    2015-01-01

    Gamma and delta tocotrienols are isomers of Vitamin E with established potency in pre-clinical anti-cancer research. This single-dose, randomized, crossover study aimed to compare the safety and bioavailability of a new formulation of Gamma Delta Tocotrienol (GDT) in comparison with the existing Tocotrienol-rich Fraction (TRF) in terms of gamma and delta isomers in healthy volunteers. Subjects were given either two 300 mg GDT (450 mg γ-T3 and 150 mg δ-T3) capsules or four 200 mg TRF (451.2 mg γ-T3 & 102.72 mg δ-T3) capsules and blood samples were taken at several time points over 24 hours. Plasma tocotrienol concentrations were determined using HPLC method. The 90% CI for gamma and delta tocotrienols for the ratio of log-transformation of GDT/TRF for Cmax and AUC0–∞ (values were anti-logged and expressed as a percentage) were beyond the bioequivalence limits (106.21–195.46, 154.11–195.93 and 52.35–99.66, 74.82–89.44 respectively). The Wilcoxon Signed Rank Test for Tmax did not show any significant difference between GDT and TRF for both isomers (p > 0.05). No adverse events were reported during the entire period of study. GDT was found not bioequivalent to TRF, in terms of AUC and Cmax. Gamma tocotrienol in GDT showed superior bioavailability whilst delta tocotrienol showed less bioavailability compared to TRF. PMID:26323969

  7. Delta activity from amygdala in squirrel monkeys (Saimiri sciureus): influence of social and environmental context.

    PubMed

    Lloyd, R L; Kling, A S

    1991-04-01

    A previous study reported that power in the delta band of the amygdala is selectively elevated when primates are exposed to affectively ladened stimuli (Kling, Steklis, & Deutsch, 1979). Radiotelemetric recordings suggested that this elevation was greatest when the animal was confronted with conspecific behaviors that could be interpreted as "ambiguous." In the present study, a specific elevation of delta activity was observed when the animal was placed in an environment in which uncued shock had previously been received, in relation to environments in which shock had always been cued. This occurred even though the conditioned stimulus or unconditioned stimulus (or both) was not presented. A specific elevation in delta activity also occurred when a conspecific was present, in relation to when the animal was alone. Finally, recordings in an environment in which shock training had previously occurred showed a striking lateralization of delta activity in the right amygdala but not in the cortex. At other times, no lateralization was observed. PMID:2043270

  8. Rapid induction of microsomal delta 12(omega 6)-desaturase activity in chilled Acanthamoeba castellanii.

    PubMed

    Jones, A L; Lloyd, D; Harwood, J L

    1993-11-15

    The activity of microsomal delta 12-desaturase in Acanthamoeba castellanii was increased after growing cultures were chilled from the optimal growth temperature (30 degrees C) to 15 degrees C. This increase was detectable in microsomes isolated from organisms subjected to only 10 min chilling. The mechanism of induction was investigated. The increase in activity on chilling was greatly reduced when protein synthesis was blocked before the temperature shift. Thus the major mechanism for the induction of delta 12-desaturase is increased protein synthesis. delta 12-Desaturase activity was higher when assayed at 20 degrees C than when assayed at 30 degrees C, but these changes were not due to the increased solubility of O2 at 20 degrees C. The major substrate of delta 12-desaturase was found to be 1-acyl-2-oleoyl phosphatidylcholine. PMID:8250841

  9. [Expression of Mortierella isabellina delta6-fatty acid desaturase gene in gamma-linolenic acid production in transgenic tobacco].

    PubMed

    Li, Ming-Chun; Liu, Li; Hu, Guo-Wu; Xing, Lai-Jun

    2003-03-01

    Gamma-linolenic acid (GLA, C18:3delta6.9.12) is nutritional and important polyunsaturated fatty acid in human and animal diets. GLA play an important role in hormone regulation and fatty acid metabolization. Furthermore it is also the biological precursor of a group of molecules, including prostaglandins, leukotrienes and thromboxanes. Vast majority of oilseed crops do not produce GLA, but linoleic acid (LA, C18:2delta9.12) as its substrate. GLA is only produced by a small number of oilseed plants such as evening promrose ( Oenotheera spp.), borage (Borago officinalis) and etc. delta6-fatty acid desaturase (D6D) is the rate-limiting enzyme in the production of GLA. It can convert from linoleic acid to linolenic acid. To produce GLA in tobacco, plant expression vector was first constructed. To facilitate preparation of plant expression constructs, flanking Xba I and Bgl II restriction enzyme sites were added to the coding region of clone pTMICL6 by PCR amplification. pTMICL6 contains delta6-fatty acid desaturase gene cloned from Mortierella isabellina which is an oil-producing fugus. The PCR product was purified and subcloned into the plant expression vector pGA643 to generate the recombinant vector pGAMICL6 which contains the ORF of the D6D gene of Mortierella isabellina, together with regulatory elements consisting of the cauliflower mosaic virus 35S promoter and the nopaline synthase (nos) termination sequence. The plasmid pGAMICL6 was transformed into Agrobacterium tumefaciens strain LBA4404 by method of freeze thawing of liquid nitrogen. Transformants were selected by plating on YEB medium plates containing kanamycin and streptomycin and grown overnight at 28 degrees C, then transformants were further identified by PCR. The positive transformant containing the plant expression vector pGAMICL6 was transformed into tobacco ( Nicotiana tabacum cv. Xanthi) via Agrobacterium infection. Transgenic plants were selected on 100 microg/mL kanamycin. Plants were

  10. IL-1 beta-dependent regulation of C/EBP delta transcriptional activity.

    PubMed

    Svotelis, Amy; Doyon, Geneviève; Bernatchez, Gérald; Désilets, Antoine; Rivard, Nathalie; Asselin, Claude

    2005-03-11

    We have previously shown that the transcription factor C/EBP delta is involved in the intestinal inflammatory response. C/EBP delta regulates several inflammatory response genes, such as haptoglobin, in the rat intestinal epithelial cell line IEC-6 in response to IL-1. However, the different C/EBP delta domains involved in IL-1 beta-mediated transcriptional activation and the kinases implicated have not been properly defined. To address this, we determined the role of the p38 MAP kinase in the regulation of C/EBP delta transcriptional activity. The IL-1-dependent induction of the acute phase protein gene haptoglobin in IEC-6 cells was decreased in response to the p38 MAP kinase inhibitor SB203580, as determined by Northern blot. Transcriptional activity of C/EBP delta was repressed by the specific inhibitor of the p38 MAP kinase, as assessed by transient transfection assays. Mutagenesis studies and transient transfection assays revealed an important domain for transcriptional activation between amino acids 70 and 108. This domain overlapped with a docking site for the p38 MAP kinase, between amino acids 75 and 85, necessary to insure C/EBP delta phosphorylation. Deletion of this domain led to a decrease in basal transcriptional activity of C/EBP delta and in p300-dependent transactivation, as assessed by transient transfection assays, and in IL-1-dependent haptoglobin induction. This unusual arrangement of a kinase docking site within a transactivation domain may functionally be important for the regulation of C/EBP delta transcriptional activity. PMID:15694370

  11. COMMD1 regulates the delta epithelial sodium channel ({delta}ENaC) through trafficking and ubiquitination

    SciTech Connect

    Chang, Tina; Ke, Ying; Ly, Kevin; McDonald, Fiona J.

    2011-08-05

    Highlights: {yields} The COMM domain of COMMD1 mediates binding to {delta}ENaC. {yields} COMMD1 reduces the cell surface population of {delta}ENaC. {yields} COMMD1 increases the population of {delta}ENaC-ubiquitin. {yields} Both endogenous and transfected {delta}ENaC localize with COMMD1 and transferrin suggesting they are located in early/recycling endosomes. -- Abstract: The delta subunit of the epithelial sodium channel ({delta}ENaC) is a member of the ENaC/degenerin family of ion channels. {delta}ENaC is distinct from the related {alpha}-, {beta}- and {gamma}ENaC subunits, known for their role in sodium homeostasis and blood pressure control, as {delta}ENaC is expressed in brain neurons and activated by external protons. COMMD1 (copper metabolism Murr1 domain 1) was previously found to associate with and downregulate {delta}ENaC activity. Here, we show that COMMD1 interacts with {delta}ENaC through its COMM domain. Co-expression of {delta}ENaC with COMMD1 significantly reduced {delta}ENaC surface expression, and led to an increase in {delta}ENaC ubiquitination. Immunocytochemical and confocal microscopy studies show that COMMD1 promoted localization of {delta}ENaC to the early/recycling endosomal pool where the two proteins were localized together. These results suggest that COMMD1 downregulates {delta}ENaC activity by reducing {delta}ENaC surface expression through promoting internalization of surface {delta}ENaC to an intracellular recycling pool, possibly via enhanced ubiquitination.

  12. Delta XTE Launch Activities and Scrub (Anomaly) at Cape Canaveral Air Station Complex 17

    NASA Technical Reports Server (NTRS)

    1995-01-01

    This NASA Kennedy Space Center video presents launch activities of the Delta X-ray Timing Explorer and scrub aboard a McDonnell Douglas Delta II rocket from Complex 17. The primary objective of the Delta XTE is to study time variability and broadband spectral phenomena in the X-ray emission from astronomical sources. XTE is designed for a required lifetime of two years with a goal of five years and will be inserted into a low-Earth circular orbit at an altitude of 600 km. The launch was postponed due to unfavorable wind conditions aloft.

  13. Genistein potentiates wild-type and delta F508-CFTR channel activity.

    PubMed

    Hwang, T C; Wang, F; Yang, I C; Reenstra, W W

    1997-09-01

    Effects of genistein on wild-type (wt) and delta F508-cystic fibrosis transmembrane conductance regulator (CFTR) were studied in NIH/3T3 cells stably transfected with wt or mutant CFTR cDNA. As measured by I- efflux, half-maximal concentration of agonist (K1/2) for forskolin-dependent activation was greater for delta F508-CFTR than wt-CFTR. Genistein decreased the K1/2 for both forms of the channel and increased the maximal activity of delta F508-CFTR by 3.7-fold. In cell-attached patches, 10 microM forskolin induced minimal delta F508-CFTR activity with characteristic prolonged closed times (estimated time constant, > 30 s). Genistein increased the forskolin-induced macroscopic currents of wt-CFTR and delta F508-CFTR by 3- and 19-fold, respectively. Variance analysis suggested that in the presence of forskolin and genistein the open probabilities (Po) of wt- and delta F508-CFTR were identical. In single-channel studies, at maximal adenosine 3',5'-cyclic monophosphate (cAMP) stimulation, genistein increased the Po of wt-CFTR by prolonging the open time, but, at submaximal cAMP stimulation, the Po was increased by prolonging the open time and shortening the closed time. In excised patches with CFTR channels preactivated in the cell-attached mode, genistein increased ATP-dependent wt- and delta F508-CFTR current about twofold by prolonging the open time. Our results thus suggest that phosphorylation-dependent activation of delta F508-CFTR is defective and that genistein corrects this defect at least in part by binding to the CFTR protein. PMID:9316420

  14. Linking rapid erosion of the Mekong River delta to human activities.

    PubMed

    Anthony, Edward J; Brunier, Guillaume; Besset, Manon; Goichot, Marc; Dussouillez, Philippe; Nguyen, Van Lap

    2015-01-01

    As international concern for the survival of deltas grows, the Mekong River delta, the world's third largest delta, densely populated, considered as Southeast Asia's most important food basket, and rich in biodiversity at the world scale, is also increasingly affected by human activities and exposed to subsidence and coastal erosion. Several dams have been constructed upstream of the delta and many more are now planned. We quantify from high-resolution SPOT 5 satellite images large-scale shoreline erosion and land loss between 2003 and 2012 that now affect over 50% of the once strongly advancing >600 km-long delta shoreline. Erosion, with no identified change in the river's discharge and in wave and wind conditions over this recent period, is consistent with: (1) a reported significant decrease in coastal surface suspended sediment from the Mekong that may be linked to dam retention of its sediment, (2) large-scale commercial sand mining in the river and delta channels, and (3) subsidence due to groundwater extraction. Shoreline erosion is already responsible for displacement of coastal populations. It is an additional hazard to the integrity of this Asian mega delta now considered particularly vulnerable to accelerated subsidence and sea-level rise, and will be exacerbated by future hydropower dams. PMID:26446752

  15. Linking rapid erosion of the Mekong River delta to human activities

    PubMed Central

    Anthony, Edward J.; Brunier, Guillaume; Besset, Manon; Goichot, Marc; Dussouillez, Philippe; Nguyen, Van Lap

    2015-01-01

    As international concern for the survival of deltas grows, the Mekong River delta, the world’s third largest delta, densely populated, considered as Southeast Asia’s most important food basket, and rich in biodiversity at the world scale, is also increasingly affected by human activities and exposed to subsidence and coastal erosion. Several dams have been constructed upstream of the delta and many more are now planned. We quantify from high-resolution SPOT 5 satellite images large-scale shoreline erosion and land loss between 2003 and 2012 that now affect over 50% of the once strongly advancing >600 km-long delta shoreline. Erosion, with no identified change in the river’s discharge and in wave and wind conditions over this recent period, is consistent with: (1) a reported significant decrease in coastal surface suspended sediment from the Mekong that may be linked to dam retention of its sediment, (2) large-scale commercial sand mining in the river and delta channels, and (3) subsidence due to groundwater extraction. Shoreline erosion is already responsible for displacement of coastal populations. It is an additional hazard to the integrity of this Asian mega delta now considered particularly vulnerable to accelerated subsidence and sea-level rise, and will be exacerbated by future hydropower dams. PMID:26446752

  16. Linking rapid erosion of the Mekong River delta to human activities

    NASA Astrophysics Data System (ADS)

    Anthony, Edward J.; Brunier, Guillaume; Besset, Manon; Goichot, Marc; Dussouillez, Philippe; Nguyen, Van Lap

    2015-10-01

    As international concern for the survival of deltas grows, the Mekong River delta, the world’s third largest delta, densely populated, considered as Southeast Asia’s most important food basket, and rich in biodiversity at the world scale, is also increasingly affected by human activities and exposed to subsidence and coastal erosion. Several dams have been constructed upstream of the delta and many more are now planned. We quantify from high-resolution SPOT 5 satellite images large-scale shoreline erosion and land loss between 2003 and 2012 that now affect over 50% of the once strongly advancing >600 km-long delta shoreline. Erosion, with no identified change in the river’s discharge and in wave and wind conditions over this recent period, is consistent with: (1) a reported significant decrease in coastal surface suspended sediment from the Mekong that may be linked to dam retention of its sediment, (2) large-scale commercial sand mining in the river and delta channels, and (3) subsidence due to groundwater extraction. Shoreline erosion is already responsible for displacement of coastal populations. It is an additional hazard to the integrity of this Asian mega delta now considered particularly vulnerable to accelerated subsidence and sea-level rise, and will be exacerbated by future hydropower dams.

  17. Quantitative expression patterns of peroxisome proliferator-activated receptor-{beta}/{delta} (PPAR{beta}/{delta}) protein in mice

    SciTech Connect

    Girroir, Elizabeth E.; Hollingshead, Holly E.; He Pengfei; Zhu Bokai; Perdew, Gary H.; Peters, Jeffrey M.

    2008-07-04

    The expression patterns of PPAR{beta}/{delta} have been described, but the majority of these data are based on mRNA data. To date, there are no reports that have quantitatively examined the expression of PPAR{beta}/{delta} protein in mouse tissues. In the present study, a highly specific PPAR{beta}/{delta} antibody was developed, characterized, and used to examine tissue expression patterns of PPAR{beta}/{delta}. As compared to commercially available anti-PPAR{beta}/{delta} antibodies, one of six polyclonal anti-PPAR{beta}/{delta} antibodies developed was significantly more effective for immunoprecipitation of in vitro-translated PPAR{beta}/{delta}. This antibody was used for quantitative Western blot analysis using radioactive detection methods. Expression of PPAR{beta}/{delta} was highest in colon, small intestine, liver, and keratinocytes as compared to other tissues including heart, spleen, skeletal muscle, lung, brain, and thymus. Interestingly, PPAR{beta}/{delta} expression was localized in the nucleus and RXR{alpha} can be co-immunoprecipitated with nuclear PPAR{beta}/{delta}. Results from these studies demonstrate that PPAR{beta}/{delta} expression is highest in intestinal epithelium, liver, and keratinocytes, consistent with significant biological roles in these tissues.

  18. Gamma Band Activity in the RAS-intracellular mechanisms

    PubMed Central

    Garcia-Rill, E.; Kezunovic, N.; D’Onofrio, S.; Luster, B.; Hyde, J.; Bisagno, V.; Urbano, F.J.

    2014-01-01

    Gamma band activity participates in sensory perception, problem solving, and memory. This review considers recent evidence showing that cells in the reticular activating system (RAS) exhibit gamma band activity, and describes the intrinsic membrane properties behind such manifestation. Specifically, we discuss how cells in the mesopontine pedunculopontine nucleus (PPN), intralaminar parafascicular nucleus (Pf), and pontine Subcoeruleus nucleus dorsalis (SubCD) all fire in the gamma band range when maximally activated, but no higher. The mechanisms involve high threshold, voltage-dependent P/Q-type calcium channels or sodium-dependent subthreshold oscillations. Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions. We address three necessary next steps resulting from these discoveries, an intracellular mechanism responsible for maintaining gamma band activity based on persistent G-protein activation, separate intracellular pathways that differentiate between gamma band activity during waking vs during REM sleep, and an intracellular mechanism responsible for the dysregulation in gamma band activity in schizophrenia. These findings open several promising research avenues that have not been thoroughly explored. What are the effects of sleep or REM sleep deprivation on these RAS mechanisms? Are these mechanisms involved in memory processing during waking and/or during REM sleep? Does gamma band processing differ during waking vs REM sleep after sleep or REM sleep deprivation? PMID:24309750

  19. Rapid progression of primary cutaneous gamma-delta T-cell lymphoma with an initial indolent clinical presentation.

    PubMed

    Alexander, Riley E; Webb, Alden R; Abuel-Haija, Mohammad; Czader, Magdalena

    2014-10-01

    Primary cutaneous gamma-delta T-cell lymphoma (CGD-TCL) is a rare cutaneous T-cell lymphoma characterized by a rapidly progressive clinical course and a poor prognosis. We report a case of a 52-year-old man with a 10-year history of erythematous nodules and a rapid terminal progression diagnosed as CGD-TCL. Biopsies taken at the time of progression showed a dense lymphocytic infiltrate involving the subcutaneous adipose tissue and deep dermis. One of the biopsies displayed much more limited involvement by CGD-TCL that was nearly identical to the biopsies of the erythematous lesions 10 years before. In conclusion, this case demonstrates a case of CGD-TCL presenting as a longstanding indolent disease with a rapid terminal progression. The indolent clinical course and histological heterogeneity make diagnosing this entity during the initial stage extremely challenging. This case underscores a diverse clinical presentations and a need to consider CGD-TCL in patients showing subcutaneous lesions with an indolent clinical course. PMID:25247673

  20. Fluorescence of the gamma, epsilon, and delta systems of nitric oxide - Polarization and use of calculated intensities for spectrometer calibration.

    NASA Technical Reports Server (NTRS)

    Poland, H. M.; Broida, H. P.

    1971-01-01

    Results of a study in which fluorescence of the gamma system of nitric oxide was obtained by excitation from both the 2144 A line of ionized cadmium and a continuum source. Individual rotational lines of the 2144 A excited fluorescence spectrum were found to be partially polarized and to have polarizations of differ ing sign. Measured relative vibrational band intensities from line and continuum excitation were compared to calculated Franck-Condon factors. Those Franck-Condon factors based on a single potential for the two spin states of the X super pi state agreed better with measured values than those based on separate potentials for the two spin states. Calculated intensities of the v prime = 3 progression were used to calibrate the instrument response in the wavelength region from 2000 to 2500 A and were checked with measured intensities of the v prime = 0.1, and 2 progressions. Fluorescence of the epsilon and delta bands obtained with continuum lamp excitation also were compared to calculated intensities.

  1. Sequential development of intraepithelial gamma delta and alpha beta T lymphocytes expressing CD8 alpha beta in neonatal rat intestine: requirement for the thymus.

    PubMed

    Helgeland, L; Brandtzaeg, P; Rolstad, B; Vaage, J T

    1997-12-01

    Previous studies in congenitally athymic nude rats have suggested that the thymus is important for the development of intestinal T cells. Here we have examined the effect of the nude mutation on intraepithelial lymphocyte (IEL) development from the perinatal period. By immunohistochemistry it was shown that CD3(-)CD8 alpha alpha + putative IEL precursors colonized the epithelium of both normal and athymic neonatal rats. Mature T cells, however, did not develop in athymic neonates. In normal rats, gamma delta T cells were present at birth and alpha beta T cells appeared within 8 days of postnatal life. At this age, the composition and relative number of intraepithelial T cells were similar to that in normal adult rats, with the exception that most neonatal T-cell receptor-gamma delta + and -alpha beta + IEL expressed CD8 beta. By contrast, extrathymic T-cell maturation in the gut of congenitally athymic rats occurred slowly, as CD3+ IEL did not appear until 4-6 months of age. These intraepithelial T cells displayed variable phenotypes and appeared to be induced by environmental antigens as they were not found in isolator-kept old nudes. In conclusion, the present results indicate that the major colonization of the gut epithelium with gamma delta and alpha beta T cells expressing CD8 alpha beta takes place perinatally and requires the presence of the thymus. The developmental relationship between these neonatal T cells and more immature CD3- CD8 alpha alpha +/- IEL remains elusive. PMID:9497485

  2. The impact of agricultural activities on water quality in oxbow lakes in the Mississippi Delta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the Mississippi Delta, agricultural activity is a major source of nonpoint source (NPS) pollutants. Sediment, nutrients and pesticides have been considered as priority NPS pollutants and greatly affect the water quality in this area. The impacts of agricultural activities on water quality in oxbo...

  3. Regulation of delta-aminolevulinate synthase activity during the development of oxidative stress.

    PubMed

    Kaliman, P A; Barannik, T V

    1999-06-01

    Activities of rat liver delta-aminolevulinate synthetase (delta-ALAS), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PDH), GSH content in the liver, and the absorption spectrum of blood serum were investigated after CoCl2, HgCl2, or beta-adrenoblocker (propranolol) injection and after CoCl2 and propranolol co-administration. Inhibition of the activity of the key heme biosynthesis enzyme delta-ALAS was most pronounced and prolonged during the first hours after CoCl2 and CoCl2 plus propranolol injections; this was associated with accumulation of Co2+--protoporphyrin-containing products of hemolysis. Inhibition of delta-ALAS after propranolol injection is not mediated by hemolysis. A decrease in GSH content precedes the induction of heme biosynthesis only in the case of HgCl2 administration, and this was associated with inhibition of GR and G6PDH. The decreased GSH content during the first hours after injection of propranolol and co-administration of CoCl2 and propranolol was not followed by increase in delta-ALAS activity 24 h after the injection. The mechanisms of the increase in the free heme content in the liver during the early stages of oxidative stress and the regulation of the key heme biosynthesis enzyme are discussed. PMID:10395986

  4. Hepatosplenic gamma-delta T-cell lymphoma: clinicopathological features and treatment

    PubMed Central

    Falchook, G. S.; Vega, F.; Dang, N. H.; Samaniego, F.; Rodriguez, M. A.; Champlin, R. E.; Hosing, C.; Verstovsek, S.; Pro, B.

    2009-01-01

    Background: Hepatosplenic T-cell lymphoma (HSTCL) is a rare peripheral T-cell lymphoma; treatment with standard anthracycline-containing chemotherapy regimens has been disappointing, and an optimal treatment strategy for this patient population has not yet been determined. Methods: We identified 15 cases of pathologically confirmed HSTCL in the institution's database. Clinical characteristics and treatment results were reviewed. Results: Complete responses (CRs) were achieved in 7 of 14 patients who received chemotherapy. Achievement of CR was followed by hematopoietic stem-cell transplantation in three patients. Median duration of CR was 8 months (range 2 to 32+ months) with four patients currently alive and in CR at 5, 8, 12, and 32 months, respectively. Median overall survival (OS) was 11 months (range 2 to 36+ months). Patients who achieved a CR had a median OS of 13 months, compared with 7.5 months in patients who did not achieve a CR. Risk factors associated with worse outcome included male gender, failure to achieve a CR, history of immunocompromise, and absence of a T-cell receptor gene rearrangement in the gamma chain. Conclusion: A better understanding of the pathophysiology of HSTCL and new therapeutic strategies are needed. PMID:19237479

  5. Enhanced gamma-ray activity from the Crab nebula

    NASA Astrophysics Data System (ADS)

    Buehler, R.; Ciprini, S.

    2016-01-01

    Preliminary LAT analysis indicates enhanced gamma-ray activity from the Crab nebula. The daily-averaged gamma-ray emission (E > 100 MeV) from the direction of the Crab Nebula has surpassed 4.0 x 10^-6 ph cm^-2 s^-1 five times in the last 12 days.

  6. Cortical delta activity reflects reward prediction error and related behavioral adjustments, but at different times.

    PubMed

    Cavanagh, James F

    2015-04-15

    Recent work has suggested that reward prediction errors elicit a positive voltage deflection in the scalp-recorded electroencephalogram (EEG); an event sometimes termed a reward positivity. However, a strong test of this proposed relationship remains to be defined. Other important questions remain unaddressed: such as the role of the reward positivity in predicting future behavioral adjustments that maximize reward. To answer these questions, a three-armed bandit task was used to investigate the role of positive prediction errors during trial-by-trial exploration and task-set based exploitation. The feedback-locked reward positivity was characterized by delta band activities, and these related EEG features scaled with the degree of a computationally derived positive prediction error. However, these phenomena were also dissociated: the computational model predicted exploitative action selection and related response time speeding whereas the feedback-locked EEG features did not. Compellingly, delta band dynamics time-locked to the subsequent bandit (the P3) successfully predicted these behaviors. These bandit-locked findings included an enhanced parietal to motor cortex delta phase lag that correlated with the degree of response time speeding, suggesting a mechanistic role for delta band activities in motivating action selection. This dissociation in feedback vs. bandit locked EEG signals is interpreted as a differentiation in hierarchically distinct types of prediction error, yielding novel predictions about these dissociable delta band phenomena during reinforcement learning and decision making. PMID:25676913

  7. Diversity in junctional sequences associated with the common human V gamma 9 and V delta 2 gene segments in normal blood and lung compared with the limited diversity in a granulomatous disease

    PubMed Central

    1990-01-01

    The T cell receptor (TCR) junctional regions (N regions) of the common human V gamma 9 and V delta 2 gene segments were sequenced from the blood and lung of normal individuals (195 transcripts) and a group of individuals with sarcoidosis (220 transcripts), a granulomatous disease in which increased numbers of V gamma 9+ gamma/delta + T cells are often observed. In normal individuals, the vast majority (86%) of blood V gamma 9 transcripts used the J gamma P gene segment. In contrast to this restriction of J region usage, there was a large diversity of the junctional region, with less than 20% of blood V gamma 9 junctional regions showing identical sequences for any one normal individual. For the blood V delta 2 transcripts in normal individuals, there was restriction of J region usage, with 93% using J delta 1. The junctional regions were even more diverse than for V gamma 9, with a unique sequence observed in each transcript examined. Compared with blood, sequences from the normal lung showed a small increase in identical junctional regions, particularly in one individual where 46% of V gamma 9 transcripts examined were identical, suggesting a response of some gamma/delta T cells to antigens found in the lung in the normal state. In marked contrast to normals, some individuals with sarcoidosis had large numbers of V gamma 9 transcripts, as well as V delta 2 transcripts, sharing identical sequences. For V gamma 9 blood transcripts, two individuals showed 84 and 56% of junctional region sequences to be identical, respectively. Similarly, blood V delta 2 transcripts showed 43, 33, and 25% identical junctional region sequences in three individuals. In the sarcoid patient with the most striking over-representation of blood V gamma 9 junctional sequences, lung V gamma 9 transcripts showed increased (67%) use of the same junctional region sequence as in blood. This limited diversity of TCR junctional regions among some individuals with sarcoidosis suggests a response from

  8. Characteristics of the somatic hypermutation in the Camelus dromedarius T cell receptor gamma (TRG) and delta (TRD) variable domains.

    PubMed

    Ciccarese, Salvatrice; Vaccarelli, Giovanna; Lefranc, Marie-Paule; Tasco, Gianluca; Consiglio, Arianna; Casadio, Rita; Linguiti, Giovanna; Antonacci, Rachele

    2014-10-01

    In previous reports, we had shown in Camelus dromedarius that diversity in T cell receptor gamma (TRG) and delta (TRD) variable domains can be generated by somatic hypermutation (SHM). In the present paper, we further the previous finding by analyzing 85 unique spleen cDNA sequences encoding a total of 331 mutations from a single animal, and comparing the properties of the mutation profiles of dromedary TRG and TRD variable domains. The transition preference and the significant mutation frequency in the AID motifs (dgyw/wrch and wa/tw) demonstrate a strong dependence of the enzymes mediating SHM in TRG and TRD genes of dromedary similar to that of immunoglobulin genes in mammals. Overall, results reveal no asymmetry in the motifs targeting, i.e. mutations are equally distributed among g:c and a:t base pairs and replacement mutations are favored at the AID motifs, whereas neutral mutations appear to be more prone to accumulate in bases outside of the motifs. A detailed analysis of clonal lineages in TRG and TRD cDNA sequences also suggests that clonal expansion of mutated productive rearrangements may be crucial in shaping the somatic diversification in the dromedary. This is confirmed by the fact that our structural models, computed by adopting a comparative procedure, are consistent with the possibility that, irrespective of where (in the CDR-IMGT or in FR-IMGT) the diversity was generated by mutations, both clonal expansion and selection seem to be strictly related to an enhanced structural stability of the γδ subunits. PMID:24836674

  9. V{delta}1 T cell receptor binds specifically to MHC I chain related A: Molecular and biochemical evidences

    SciTech Connect

    Zhao Jianqing; Huang Jie; Chen Hui; Cui Lianxian; He Wei . E-mail: heweiimu@public.bta.net.cn

    2006-01-06

    Human MHC class I chain-related A (MICA) is a tumor-associated antigen that can be recognized by V{delta}1 subset of tumor-infiltrating {gamma}{delta} T cells. We previously reported that immobilized recombinant MICA protein could induce the proliferation of tumor-infiltrating V{delta}1 {gamma}{delta} T cells in vitro. But there has been no direct evidence showing the engagement of {gamma}{delta} T cell receptors (TCR) of the induced cells with MICA. In the current investigation, we show that MICA induces specific cytolytic activity of the expanded {gamma}{delta} T cells. We expressed the coupled V domains from the MICA-induced T cells as a single polypeptide chain V{delta}V{gamma} TCR ({gamma}{delta} scTCR). Such scTCR can specifically bind MICA of HeLa cells. Direct interaction of {gamma}{delta} scTCRs with in vitro expressed MICA was monitored using an IAsys biosensor. We found that the V{delta}1 scTCR can specifically bind to immobilized MICA molecule and MICA{alpha}1{alpha}2 domains are responsible for the binding reaction.

  10. Step-based translation of physical activity guidelines in the Lower Mississippi Delta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine how many steps/day equate to current moderate-to-vigorous physical activity (MVPA) guidelines in a population from the Lower Mississippi Delta (LMD) of the United States, 58 overweight adults wore an Actigraph accelerometer (GT3X) for up to two weeks. Minutes/day in MVPA was a good pred...

  11. Comparative Gamma Delta T Cell Immunology: A Focus on Mycobacterial Disease in Cattle

    PubMed Central

    Plattner, Brandon L.; Hostetter, Jesse M.

    2011-01-01

    A theme among many pathogenic mycobacterial species affecting both humans and animals is a prolonged asymptomatic or latent period that can last years to decades. The mechanisms that favor progression to active disease are not well understood. Pathogen containment is often associated with an effective cell-mediated or T-helper 1 immune profile. With certain pathogenic mycobacteria, such as Mycobacterium avium subspecies paratuberculosis, a shift to active clinical disease is associated with loss of T-helper 1 immunity and development of an ineffective humoral or T-helper 2 immune response. Recently γδ T cells have been shown to play a role early in mycobacterial infections and have been hypothesized to influence disease outcome. The purpose of this paper is to compare recent advancements in our understanding of γδ T cells in humans, cattle, and mice and to discuss roles of γδ T cells in host response to mycobacterial infection. PMID:21647391

  12. Targeting gamma delta T cells for cancer immunotherapy: bench to bedside

    PubMed Central

    Gogoi, Dimpu; Chiplunkar, Shubhada V.

    2013-01-01

    γδ T lymphocytes represent a minor subset of peripheral blood in humans (<10%). γδ T cells expressing Vγ9Vδ2 T cell receptor recognise the endogenous pool of isopentenyl pyrophosphate (IPP) that is overproduced in cancer cells as a result of dysregulated mevalonate pathway. Aminobisphosphonates increase the endogenous pool of IPP in cells by blocking the enzyme farnesyl pyrophosphate synthase (FPPS) of the mevalonate pathway. Activated γδ T cells release copious amounts of interferon (IFN)-γ and tumour necrosis factor (TNF)-α and exhibit potent anti-tumour activity. Combination of γδ T cells with therapeutic monoclonal antibodies can efficiently mediate antibody dependent cellular cytotoxicity against tumours. These features makes γδ T cells attractive mediator of cancer immunotherapy. We review here, the basic properties and importance of γδ T cells in tumour immunity, and highlight the key advances in anti-tumour effector functions of γδ T cells achieved over the last few years and also summarize the results of the clinical trials that have been done till date. Future immunotherapeutic approach utilizing γδ T cells holds considerable promise for treatment of different types of cancer. PMID:24434328

  13. Analysis of tumor-infiltrating gamma delta T cells in rectal cancer

    PubMed Central

    Rong, Liang; Li, Ke; Li, Rui; Liu, Hui-Min; Sun, Rui; Liu, Xiao-Yan

    2016-01-01

    AIM: To investigate the regulatory effect of Vδ1 T cells and the antitumor activity of Vδ2 T cells in rectal cancer. METHODS: Peripheral blood, tumor tissues and para-carcinoma tissues from 20 rectal cancer patients were collected. Naïve CD4 T cells from the peripheral blood of rectal cancer patients were purified by negative selection using a Naive CD4+ T Cell Isolation Kit II (Miltenyi Biotec). Tumor tissues and para-carcinoma tissues were minced into small pieces and digested in a triple enzyme mixture containing collagenase type IV, hyaluronidase, and deoxyribonuclease for 2 h at room temperature. After digestion, the cells were washed twice in RPMI1640 and cultured in RPMI1640 containing 10% human serum supplemented with L-glutamine and 2-mercaptoethanol and 1000 U/mL of IL-2 for the generation of T cells. Vδ1 T cells and Vδ2 T cells from tumor tissues and para-carcinoma tissues were expanded by anti-TCR γδ antibodies. The inhibitory effects of Vδ1 T cells on naïve CD4 T cells were analyzed using the CFSE method. The cytotoxicity of Vδ2 T cells on rectal cancer lines was determined by the LDH method. RESULTS: The percentage of Vδ1 T cells in rectal tumor tissues from rectal cancer patients was significantly increased, and positively correlated with the T stage. The percentage of Vδ2 T cells in rectal tumor tissues from rectal cancer patients was significantly decreased, and negatively correlated with the T stage. After culture for 14 d with 1 μg/mL anti-TCR γδ antibodies, the percentage of Vδ1 T cells from para-carcinoma tissues was 21.45% ± 4.64%, and the percentage of Vδ2 T cells was 38.64% ± 8.05%. After culture for 14 d, the percentage of Vδ1 T cells from rectal cancer tissues was 67.45% ± 11.75% and the percentage of Vδ2 T cells was 8.94% ± 2.85%. Tumor-infiltrating Vδ1 T cells had strong inhibitory effects, and tumor-infiltrating Vδ2 T cells showed strong cytolytic activity. The inhibitory effects of Vδ1 T cells from para

  14. A measurement of the magnetic dipole moment of the. delta. /sup + +/(1232) from the bremsstrahlung process. pi. p. -->. pi. p. gamma

    SciTech Connect

    Meyer, C.A.

    1987-06-01

    We have measured the cross section from the bremsstrahlung process ..pi../sup +/p ..-->.. ..pi../sup +/p..gamma.. for incident pions of energy 299 MeV. We detected the out going pion in the angular range from 55 to 95/sup 0/ in the lab, and photons were detected near 240/sup 0/ in the lab. We compare this measured cross-section to the MIT theory in order to extract a measurement of the magnetic dipole moment of the ..delta../sup + +/(1232), ..mu../sub ..delta../. In order to compare our results with the MIT theory, we have folded the MIT theory into the acceptance of our apparatus. We find that for pion angles between 55 and 75/sup 0/ the theory gives us a dipole moment of: 2.3..mu../sub p/ < ..mu../sub ..delta../ < 3.3..mu../sup p/ where the quoted error arises from an experimental uncertainty of +-0.25..mu../sub p/ and from theoretical uncertainties of +-0.25 ..mu../sub p/. However, for pion angles between 75 and 95/sup 0/ we find that the MIT theory predicts a cross-section which is larger than our measured cross-section, and makes it difficult to extract a value of ..mu../sub ..delta../. This over prediction is not understood, but consistent with a similar effect when the MIT theory is fit to previous data. 78 figs., 29 tabs.

  15. Regulation of Obesity and Metabolic Complications by Gamma and Delta Tocotrienols.

    PubMed

    Zhao, Lu; Fang, Xiefan; Marshall, Maurice R; Chung, Soonkyu

    2016-01-01

    Tocotrienols (T3s) are a subclass of unsaturated vitamin E that have been extensively studied for their anti-proliferative, anti-oxidative and anti-inflammatory properties in numerous cancer studies. Recently, T3s have received increasing attention due to their previously unrecognized property to attenuate obesity and its associated metabolic complications. In this review, we comprehensively evaluated the recent published scientific literature about the influence of T3s on obesity, with a particular emphasis on the signaling pathways involved. T3s have been demonstrated in animal models or human subjects to reduce fat mass, body weight, plasma concentrations of free fatty acid, triglycerides and cholesterol, as well as to improve glucose and insulin tolerance. Their mechanisms of action in adipose tissue mainly include (1) modulation of fat cell adipogenesis and differentiation; (2) modulation of energy sensing; (3) induction of apoptosis in preadipocytes and (4) modulation of inflammation. Studies have also been conducted to investigate the effects of T3s on other targets, e.g., the immune system, liver, muscle, pancreas and bone. Since δT3 and γT3 are regarded as the most active isomers among T3s, their clinical relevance to reduce obesity should be investigated in human trials. PMID:26978344

  16. Relation of gamma oscillations in scalp recordings to muscular activity.

    PubMed

    Pope, Kenneth J; Fitzgibbon, Sean P; Lewis, Trent W; Whitham, Emma M; Willoughby, John O

    2009-06-01

    We recorded scalp electrical activity before and after full neuro-muscular paralysis in 5 volunteers and determined differences due to elimination of muscular activity on several standard applications of EEG. Due to paralysis, there were reductions in 'noisiness' of the standard scalp recordings which were maximal over the peripheral scalp, not explained by abolition of movement artefact, and best accounted for by sustained EMG activity in resting individuals. There was a corresponding reduction in spectral power in the gamma range. In central leads, the extent of gamma frequency coherence during a non-time-locked mental task (1 s epochs) was reduced by paralysis, likely due to a reduction in gamma-frequency coherence in widely arising EMG signals. In a time-locked mental task (auditory oddball), evoked responses were qualitatively unaffected by paralysis but 3 of 4 induced gamma responses were obscured by EMG. PMID:19229605

  17. delta-Opioid receptors exhibit high efficiency when activating trimeric G proteins in membrane domains.

    PubMed

    Bourova, Lenka; Kostrnova, Alexandra; Hejnova, Lucie; Moravcova, Zuzana; Moon, Hyo-Eun; Novotny, Jiri; Milligan, Graeme; Svoboda, Petr

    2003-04-01

    Low-density membrane fragments (domains) were separated from the bulk of plasma membranes of human embryonic kidney (HEK)293 cells expressing a delta-opioid (DOP) receptor-Gi1alpha fusion protein by drastic homogenization and flotation on equilibrium sucrose density gradients. The functional activity of trimeric G proteins and capacity of the DOP receptor to stimulate both the fusion protein-linked Gi1alpha and endogenous pertussis-toxin sensitive G proteins was measured as d-Ala2, d-Leu5-enkephalin stimulated high-affinity GTPase or guanosine-5'-[gamma-35S]triphosphate ([35S]GTPgammaS) binding. The maximum d-Ala2-d-Leu5 enkephalin (DADLE)-stimulated GTPase was two times higher in low-density membrane fragments than in bulk of plasma membranes; 58 and 27 pmol/mg/min, respectively. The same difference was obtained for [35S]GTPgammaS binding. Contrarily, the low-density domains contained no more than half the DOP receptor binding sites (Bmax = 6.6 pmol/mg versus 13.6 pmol/mg). Thus, when corrected for expression levels of the receptor, low-density domains exhibited four times higher agonist-stimulated GTPase and [35S]GTPgammaS binding than the bulk plasma membranes. The regulator of G protein signaling RGS1, enhanced further the G protein functional activity but did not remove the difference between domain-bound and plasma membrane pools of G protein. The potency of the agonist in functional studies and the affinity of specific [3H]DADLE binding to the receptor were, however, the same in both types of membranes - EC50 = 4.5 +/- 0.1 x 10(-8) and 3.2 +/- 1.4 x 10(-8) m for GTPase; Kd = 1.2 +/- 0.1 and 1.3 +/- 0.1 nm for [3H]DADLE radioligand binding assay. Similar results were obtained when sodium bicarbonate was used for alkaline isolation of membrane domains. By contrast, detergent-insensitive membrane domains isolated following treatment of cells with Triton X100 exhibited no DADLE-stimulated GTPase or GTPgammaS binding. Functional coupling between the DOP receptor

  18. A church-based diet and physical activity intervention for rural, lower Mississippi Delta African American adults: Delta Body and Soul effectiveness study, 2010-2011

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity, diabetes, and hypertension have reached epidemic levels in the largely rural Lower Mississippi Delta (LMD) region. We assessed the effectiveness of a 6-month, church-based, diet and physical activity intervention, conducted during 2010 through 2011, for improving diet quality (measured by ...

  19. Tevatron results on the discovery of sigma^(*)_b, b_s oscillations and the measurement of delta m_s, the lifetime difference delta gamma_s and the cp-violating phase phi

    SciTech Connect

    Heijboer, Aart; /Pennsylvania U.

    2007-10-01

    The author discusses results from the Tevatron experiments on mixing and CP-violation in B{sub s} mesons, including the observation of B{sub s} oscillations and the first precision measurement of the mixing frequency, as well as a measurement of the lifetime difference {Delta}{Lambda}{sub s} and the first measurement of the CP-violating phase {delta}{sub s}. The author also briefly reports on the observation of four new bottom baryons at CDF.

  20. Evaluation of the Association of Menopausal Status with Delta and Beta EEG Activity during Sleep

    PubMed Central

    Campbell, Ian G.; Bromberger, Joyce T.; Buysse, Daniel J.; Hall, Martica H.; Hardin, Kimberly A.; Kravitz, Howard M.; Matthews, Karen A.; Rasor, Marianne O'Neill; Utts, Jessica; Gold, Ellen

    2011-01-01

    Study Objectives: Women report increasing sleep difficulties during menopause, but polysomnographic measures do not detect sleep disturbances. We examined whether two spectral analysis sleep measures, delta and beta power, were related to menopausal status. Design: The Study of Women's Health Across the Nation (SWAN) Sleep Study compared cross-sectionally spectral sleep measures in women in different stages of menopause. Setting: Sleep EEG was recorded in the participants' homes with ambulatory recorders. Participants: A multi-ethnic cohort of premenopausal and early perimenopausal (n = 189), late perimenopausal (n = 73), and postmenopausal (n = 59) women. Measurements: EEG power in the delta and beta frequency bands was calculated for all night NREM and all night REM sleep. Physical, medical, psychological, and socioeconomic data were collected from questionnaires and diaries. Results: Beta EEG power in NREM and REM sleep in late perimenopausal and postmenopausal women exceeded that in pre- and early perimenopausal women. Neither all night delta power nor the trend in delta power across the night differed by menopausal status. In a multivariate model that controlled for the physical, demographic, behavioral, psychological, and health-related changes that accompany menopause, beta power in both NREM and REM sleep EEG was significantly related to menopausal status. The frequency of hot flashes explained part but not all of the relation of beta power to menopausal status. Conclusions: Elevated beta EEG power in late perimenopausal and postmenopausal women provides an objective measure of disturbed sleep quality in these women. Elevated beta EEG activity suggests that arousal level during sleep is higher in these women. Citation: Campbell IG; Bromberger JT; Buysse DJ; Hall MH; Hardin KA; Kravitz HM; Matthews KA; Rasor MO; Utts J; Gold E. Evaluation of the association of menopausal status with delta and beta EEG activity during sleep. SLEEP 2011;34(11):1561-1568. PMID

  1. Quantifying the transition from fluvial- to wave-dominance for river deltas with multiple active channels

    NASA Astrophysics Data System (ADS)

    Nienhuis, J.; Ashton, A. D.; Giosan, L.

    2012-12-01

    The plan-view morphologies of fluvial- and wave-dominated deltas are clearly distinctive, but transitional forms are numerous. A quantitative, process-based description of this transition remains unexplored, particularly for river deltas with multiple active channels. Previous studies focused on general attributes of the fluvial and marine environment, such as the balance between wave energy and river discharge. Here, we propose that the transition between fluvial and wave dominance is directly related to the magnitude of the fluvial bedload flux to the nearshore region versus the alongshore sediment transport capacity of waves removing sediment away from the mouth. In the case of a single-channel delta, this balance can be computed for a given distribution of waves approaching shore. Fluvial dominance occurs when fluvial sediment input exceeds the wave-sustained maximum alongshore sediment transport for all potential shoreline orientations both up- and downdrift of the river mouth. However, deltaic channels have the tendency to bifurcate with increasing fluvial strength. Initial bifurcation splits the fluvial sediment flux among individual channels, while the potential sediment transport by waves remains constant for both river mouths. At higher bifurcation orders, multiple channels interact with each other alongshore, a situation more complicated than the single channel case and one that cannot be simple addressed analytically. We apply a model of plan-view shoreline evolution to simulate the evolution of a deltaic environment with multiple active channels. A highly simplified fluvial domain is represented by deposition of sediment where channels meet the coast. We investigate two scenarios of fluvial delivery. The first scenario deposits fluvial sediment alongshore on a self-similar predefined network of channels. We analyze the effects of different network geometrical parameters, such as bifurcation length, bifurcation angle, and sediment partitioning. In the

  2. {delta}-ALAD activity variations in red blood cells in response to lead accumulation in rock doves (Columba livia)

    SciTech Connect

    Gonzalez, M.; Tejedor, M.C.

    1992-10-01

    The enzyme {delta}-aminolevulinic acid dehydratase ({delta}-ALAD, E.C. 4.2.1.24), catalyses the second step of the haeme biosynthetic pathway and is required to maintain the haemoglobin and cytochrome content in red cells. {delta}-ALAD is not only found in bone marrow cells, the major site of haeme synthesis, but also in circulating erythrocytes and other tissues. An inverse correlation was found between {delta}-ALAD activity in red blood cells and lead concentration in the blood. The degree of {delta}-ALAD inhibition in erythrocytes has been widely accepted as a standard bioassay to detect acute and chronic lead exposure in humans and in avians. The value of this parameter as an indicator for environmental lead has been often reported in doves and Scanlon. In lead-treated rats, an increase in {delta}-ALAD activity in bone marrow cells and in blood samples was shown by radioimmunoassay at 5 and 9 days after the treatment. Similarly, the amount of {delta}-ALAD seems to be more sensitive to lead in avian species than in mammals, the usefulness of blood {delta}-ALAD activity as an index of lead exposure has already been questioned by Hutton in the pigeon and by Jaffe et al. in humans. The present investigation studied the toxic effects of lead on rock dove red blood cell {delta}-ALAD activity in two situations: in doves treated with lead acetate in the laboratory and in doves exposed to the environment of Alcala de Henares. The final lead blood concentrations were lower in the environmental than in the laboratory doves. {delta}-ALAD activity in bone marrow cells and the relationships between lead accumulation and enzyme activity in red cells, are examined. 20 refs., 5 figs., 1 tab.

  3. Active galaxies and the diffuse Gamma-Ray background

    NASA Technical Reports Server (NTRS)

    Kazanas, D.; Protheroe, R. J.

    1983-01-01

    A model for the origin of relativistic particles and gamma rays in active galactic nuclei and quasars, together with recent HEAO-1 observations of the spectra of active galaxies from 2 to 165 keV, provide the basis for a reexamination of the nature of the extragalactic gamma ray background. Active galaxies account for the observed background if their X-ray spectra steepen to E.021 above 100 keV, as observed in Cen-A, together with a further steepening to E.021 as a result of absorption of gamma rays by photon-photon pair production interactions with X-ray photons. The compactness of active galaxies required to give this steepening is consistent with estimates of their typical luminosity and radius.

  4. Gamma-irradiated bacterial preparation having anti-tumor activity

    SciTech Connect

    Vass, A.A.; Tyndall, R.L.; Terzaghi-Howe, P.

    1999-11-16

    This application describes a bacterial preparation from Pseudomonas species isolated {number{underscore}sign}15 ATCC 55638 that has been exposed to gamma radiation exhibits cytotoxicity that is specific for neoplastic carcinoma cells. A method for obtaining a bacterial preparation having antitumor activity consists of suspending a bacterial isolate in media and exposing the suspension to gamma radiation. A bacterial preparation of an aged culture of an amoeba-associated bacteria exhibits anti-reverse transcriptase activity. A method for obtaining a bacterial preparation having anti-reverse transcriptase activity from an amoeba-associated bacterial isolate grown to stationary phase is disclosed.

  5. Taking into account photofission effects in gamma-activation analysis

    SciTech Connect

    Dayvdov, M.G.; Kishel'gof, V.V.; Naumov, A.P.; Trukhov, A.V.

    1986-11-01

    The authors proposed a method for calculating the effect of photofission of U and Th, which is based on the well-known laws of physics of photofission and methods for calculating the activity of fission products. The authors compared the results of numerical calculations of the gamma spectra of photofission products with the measurements performed with a Ge (Li) detector with the spectra from activated model samples of U and Th. The method developed enables calculating the coefficients of interference and is also applicable to the solution of the problems of optimization of gamma activation analysis taking into account U and Th fission.

  6. Gamma-irradiated bacterial preparation having anti-tumor activity

    DOEpatents

    Vass, Arpad A.; Tyndall, Richard L.; Terzaghi-Howe, Peggy

    1999-01-01

    A bacterial preparation from Pseudomonas species isolated #15 ATCC 55638 that has been exposed to gamma radiation exhibits cytotoxicity that is specific for neoplastic carcinoma cells. A method for obtaining a bacterial preparation having antitumor activity consists of suspending a bacterial isolate in media and exposing the suspension to gamma radiation. A bacterial preparation of an aged culture of an amoeba-associated bacteria exhibits anti-reverse transcriptase activity. A method for obtaining a bacterial preparation having anti-reverse transcriptase activity from an amoeba-associated bacterial isolate grown to stationary phase is disclosed.

  7. Sediment infilling and wetland formation dynamics in an active crevasse splay of the Mississippi River delta

    NASA Astrophysics Data System (ADS)

    Cahoon, Donald R.; White, David A.; Lynch, James C.

    2011-08-01

    Crevasse splay environments provide a mesocosm for evaluating wetland formation and maintenance processes on a decadal time scale. Site elevation, water levels, vertical accretion, elevation change, shallow subsidence, and plant biomass were measured at five habitats along an elevation gradient to evaluate wetland formation and development in Brant Pass Splay; an active crevasse splay of the Balize delta of the Mississippi River. The processes of vertical development (vertical accretion, elevation change, and shallow subsidence) were measured with the surface elevation table-marker horizon method. There were three distinct stages to the accrual of elevation capital and wetland formation in the splay: sediment infilling, vegetative colonization, and development of a mature wetland community. Accretion, elevation gain, and shallow subsidence all decreased by an order of magnitude from the open water (lowest elevation) to the forest (highest elevation) habitats. Vegetative colonization occurred within the first growing season following emergence of the mud surface. An explosively high rate of below-ground production quickly stabilized the loosely consolidated sub-aerial sediments. After emergent vegetation colonization, vertical development slowed and maintenance of marsh elevation was driven both by sediment trapping by the vegetation and accumulation of plant organic matter in the soil. Continued vertical development and survival of the marsh then depended on the health and productivity of the plant community. The process of delta wetland formation is both complex and nonlinear. Determining the dynamics of wetland formation will help in understanding the processes driving the past building of the delta and in developing models for restoring degraded wetlands in the Mississippi River delta and other deltas around the world.

  8. Sediment infilling and wetland formation dynamics in an active crevasse splay of the Mississippi River delta

    USGS Publications Warehouse

    Cahoon, Donald R.; White, David A.; Lynch, James C.

    2011-01-01

    Crevasse splay environments provide a mesocosm for evaluating wetland formation and maintenance processes on a decadal time scale. Site elevation, water levels, vertical accretion, elevation change, shallow subsidence, and plant biomass were measured at five habitats along an elevation gradient to evaluate wetland formation and development in Brant Pass Splay; an active crevasse splay of the Balize delta of the Mississippi River. The processes of vertical development (vertical accretion, elevation change, and shallow subsidence) were measured with the surface elevation table–marker horizon method. There were three distinct stages to the accrual of elevation capital and wetland formation in the splay: sediment infilling, vegetative colonization, and development of a mature wetland community. Accretion, elevation gain, and shallow subsidence all decreased by an order of magnitude from the open water (lowest elevation) to the forest (highest elevation) habitats. Vegetative colonization occurred within the first growing season following emergence of the mud surface. An explosively high rate of below-ground production quickly stabilized the loosely consolidated sub-aerial sediments. After emergent vegetation colonization, vertical development slowed and maintenance of marsh elevation was driven both by sediment trapping by the vegetation and accumulation of plant organic matter in the soil. Continued vertical development and survival of the marsh then depended on the health and productivity of the plant community. The process of delta wetland formation is both complex and nonlinear. Determining the dynamics of wetland formation will help in understanding the processes driving the past building of the delta and in developing models for restoring degraded wetlands in the Mississippi River delta and other deltas around the world.

  9. Conical Euler analysis and active roll suppression for unsteady vortical flows about rolling delta wings

    NASA Technical Reports Server (NTRS)

    Lee-Rausch, Elizabeth M.; Batina, John T.

    1993-01-01

    A conical Euler code was developed to study unsteady vortex-dominated flows about rolling, highly swept delta wings undergoing either forced motions or free-to-roll motions that include active roll suppression. The flow solver of the code involves a multistage, Runge-Kutta time-stepping scheme that uses a cell-centered, finite-volume, spatial discretization of the Euler equations on an unstructured grid of triangles. The code allows for the additional analysis of the free to-roll case by simultaneously integrating in time the rigid-body equation of motion with the governing flow equations. Results are presented for a delta wing with a 75 deg swept, sharp leading edge at a free-stream Mach number of 1.2 and at 10 deg, 20 deg, and 30 deg angle of attack alpha. At the lower angles of attack (10 and 20 deg), forced-harmonic analyses indicate that the rolling-moment coefficients provide a positive damping, which is verified by free-to-roll calculations. In contrast, at the higher angle of attack (30 deg), a forced-harmonic analysis indicates that the rolling-moment coefficient provides negative damping at the small roll amplitudes. A free-to-roll calculation for this case produces an initially divergent response, but as the amplitude of motion grows with time, the response transitions to a wing-rock type of limit cycle oscillation, which is characteristic of highly swept delta wings. This limit cycle oscillation may be actively suppressed through the use of a rate-feedback control law and antisymmetrically deflected leading-edge flaps. Descriptions of the conical Euler flow solver and the free-to roll analysis are included in this report. Results are presented that demonstrate how the systematic analysis of the forced response of the delta wing can be used to predict the stable, neutrally stable, and unstable free response of the delta wing. These results also give insight into the flow physics associated with unsteady vortical flows about delta wings undergoing forced

  10. Clonal expansion of lung V delta 1+ T cells in pulmonary sarcoidosis.

    PubMed Central

    Forrester, J M; Newman, L S; Wang, Y; King, T E; Kotzin, B L

    1993-01-01

    Sarcoidosis is a multisystem disease of unknown etiology characterized by the presence of noncaseating granulomas in involved tissues. To investigate a potential role for gamma/delta T cells in the pathogenesis of pulmonary sarcoidosis, we studied lung and blood T cells from patients for preferential expression of particular gamma/delta T cell receptors. An abnormally high percentage of gamma/delta cells was found in the blood of some patients. However, the increased percentage did not reflect an increase in absolute number, and appeared to be secondary to a decrease in T cells expressing alpha/beta receptors. Furthermore, as in normals, the circulating gamma/delta cells in patients predominantly expressed V gamma 9/V delta 2 receptors, a subset that was not enriched at the site of disease. In contrast, in the lung, an increased percentage of gamma/delta cells expressing V delta 1 was found in a subset of patients. Importantly, these cells demonstrated evidence of prior activation by selectively expanding in vitro in the presence of interleukin 2. Furthermore, an analysis of junctional region sequences revealed their clonal nature. These clonal expansions of V delta 1+ cells in pulmonary sarcoidosis provide evidence for a disease process that involves specific recognition of a local antigen by T cells, and contributes new information regarding the nature of the as yet undefined antigenic stimulus. PMID:8423227

  11. Peptide-based, irreversible inhibitors of gamma-secretase activity.

    PubMed

    Piper, Siân C; Amtul, Zareen; Galiñanes-Garcia, Laura; Howard, Victor G; Ziani-Cherif, Chewki; McLendon, Chris; Rochette, Marjorie J; Fauq, Abdul; Golde, Todd E; Murphy, M Paul

    2003-06-01

    The characterization of the enzymes responsible for amyloid beta-peptide (Abeta) production is considered to be a primary goal towards the development of future therapeutics for the treatment of Alzheimer's disease. Inhibitors of gamma-secretase activity were critical in demonstrating that the presenilins (PSs) likely comprised at least part of the active site of the gamma-secretase enzyme complex, with two highly conserved membrane aspartates presumably acting as catalytic residues. However, whether or not these aspartates are actually the catalytic residues of the enzyme complex or are merely essential for normal PS function and/or maturation is still unknown. In this paper, we report the development of reactive inhibitors of gamma-secretase activity that are functionally irreversible. Since such inhibitors have been shown to bind catalytic residues in other aspartyl proteases (e.g., HIV protease), they might be used to determine if the transmembrane aspartates of PSs are involved directly in substrate cleavage. PMID:12763025

  12. Rearrangements of T-cell antigen receptor gamma and delta chain genes are detected in the long-term cultured bone marrow cells of athymic nude mice but not in those of euthymic mice.

    PubMed Central

    Yoshikai, Y; Takeda, Y; Ohga, S; Kishihara, K; Matsuzaki, G; Nomoto, K

    1989-01-01

    We have previously shown that extrathymic rearrangements of T-cell receptor (TcR) gamma and delta chain genes occur in the peripheral lymphoid tissues of athymic nude mice. To further determine where the TcR gene rearrangements occur in nude mice, we investigated the rearrangement and expression of the TcR genes in the long-term cultured bone marrow (LTBM) cells which were homogenous in developments without mature T cells as assessed by FACS analysis. The LTBM derived from euthymic mice contained TcR gamma and delta chain genes in germline configuration, while gene rearrangements of both locus were detected in the LTBM cells from nude mice. These results suggested that gamma and delta gene rearrangements do occur in the bone marrow cells of nude mice and that the T-cell precursors in bone marrow may be increased in frequency in such animals. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2541071

  13. Phase coupling between rhythmic slow activity and gamma characterizes mesiotemporal rapid-eye-movement sleep in humans.

    PubMed

    Clemens, Z; Weiss, B; Szucs, A; Eross, L; Rásonyi, G; Halász, P

    2009-09-29

    In the human sleep literature there is much controversy regarding the existence and the characteristics of hippocampal rhythmic slow activity (RSA). Generally the human RSA is believed to occur in short bursts of theta activity. An earlier study, however, reported mesiotemporal RSA during rapid-eye-movement (REM) sleep that instead of theta fell in the delta frequency band. We conjectured that if this RSA activity is indeed a human analogue of the animal hippocampal theta then characteristics associated with the animal theta should also be reflected in the human recordings. Here our aim was to examine possible phase coupling between mesiotemporal RSA and gamma activity during REM sleep. The study relied on nine epilepsy surgery candidates implanted with foramen ovale electrodes. Positive half-waves of the 1.5-3 Hz RSA were identified by an automatic algorithm during REM sleep. High-frequency activity was assessed for 11 consecutive 20 Hz-wide frequency bands between 20 and 240 Hz. Increase in high frequency activity was phase coupled with RSA in most frequency bands and patients. Such a phase coupling closely resembles that seen between theta and gamma in rodents. We consider this commonality to be an additional reason for regarding delta rather than theta as the human analogue of RSA in animals. PMID:19555738

  14. Coaxial Mono-Energetic Gamma Generator for Active Interrogation

    SciTech Connect

    Ludewigt, Bernhard A.; Antolak, A.J.; Henestroza, E.; Leitner, M.; Leung, K.-N.; Waldron, W.; Wilde, S.; Kwan, J.W.

    2008-08-01

    Compact mono-energetic photon sources are sought for active interrogation systems to detect shielded special nuclear materials in, for example, cargo containers, trucks and other vehicles. A prototype gamma interrogation source has been designed and built that utilizes the 11B(p,gamma)12C reaction to produce 12 MeV gamma-rays which are near the peak of the photofission cross section. In particular, the 11B(p,gamma)12C resonance at 163 kV allows the production of gammas at low proton acceleration voltages, thus keeping the design of a gamma generator comparatively small and simple. A coaxial design has been adopted with a toroidal-shaped plasma chamber surrounding a cylindrical gamma production target. The plasma discharge is driven by a 2 MHz rf-power supply (capable up to 50 kW) using a circular rf-antenna. Permanent magnets embedded in the walls of the plasma chamber generate a multi-cusp field that confines the plasma and allows higher plasma densities and lower gas pressures. About 100 proton beamlets are extracted through a slotted plasma electrode towards the target at the center of the device that is at a negative 180 kV. The target consists of LaB6 tiles that are brazed to a water-cooled cylindrical structure. The generator is designed to operate at 500 Hz with 20 mu s long pulses, and a 1percent duty factor by pulsing the ion source rf-power. A first-generation coaxial gamma source has been built for low duty factor experiments and testing.

  15. Coaxial Mono-Energetic Gamma Generator for Active Interrogation

    SciTech Connect

    Ludewigt, B. A.; Henestroza, E.; Kwan, J. W.; Leitner, M.; Leung, K.-N.; Waldron, W.; Wilde, S.; Antolak, A. J.

    2009-03-10

    Compact mono-energetic photon sources are sought for active interrogation systems to detect shielded special nuclear materials in, for example, cargo containers, trucks and other vehicles. A prototype gamma interrogation source has been designed and built that utilizes the {sup 11}B(p,{gamma}){sup 12}C reaction to produce 12 MeV gamma-rays which are near the peak of the photofission cross section. In particular, the {sup 11}B(p,{gamma}){sup 12}C resonance at 163 kV allows the production of gammas at low proton acceleration voltages, thus keeping the design of a gamma generator comparatively small and simple. A coaxial design has been adopted with a toroidal-shaped plasma chamber surrounding a cylindrical gamma production target. The plasma discharge is driven by a 2 MHz rf-power supply (capable up to 50 kW) using a circular rf-antenna. Permanent magnets embedded in the walls of the plasma chamber generate a multi-cusp field that confines the plasma and allows higher plasma densities and lower gas pressures. About 100 proton beamlets are extracted through a slotted plasma electrode towards the target at the center of the device that is at a negative 180 kV. The target consists of LaB{sub 6} tiles that are brazed to a water-cooled cylindrical structure. The generator is designed to operate at 500 Hz with 20 {mu}s long pulses, and a 1% duty factor by pulsing the ion source rf-power. A first-generation coaxial gamma source has been built for low duty factor experiments and testing.

  16. Hypoxia differentially regulates the mitogen- and stress-activated protein kinases. Role of Ca2+/CaM in the activation of MAPK and p38 gamma.

    PubMed

    Conrad, P W; Millhorn, D E; Beitner-Johnson, D

    2000-01-01

    Hypoxic/ischemic trauma is a primary factor in the pathology of various vascular, pulmonary, and cerebral disease states. Yet, the signaling mechanisms by which cells respond and adapt to changes in oxygen levels are not clearly established. The effects of hypoxia on the stress- and mitogen-activated protein kinase (SAPK and MAPK) signaling pathways were studied in PC12 cells. Exposure to moderate hypoxia (5% O2) was found to progressively stimulate phosphorylation and activation of p38 gamma in particular, and also p38 alpha, two isoforms of the p38 family of stress-activated protein kinases. In contrast, hypoxia had no effect on enzyme activity of p38 beta, p38 beta 2, p38 delta, or on JNK, another stress-activated protein kinase. Prolonged hypoxia also induced phosphorylation and activation of p42/p44 MAPK, although this activation was modest when compared to NGF and UV-induced activation. We further showed that activation of p38 gamma and MAPK during hypoxia requires calcium, as treatment with Ca(2+)-free media or the calmodulin antagonist, W13, blocked the activation of p38 gamma and MAPK, respectively. These studies demonstrate that an extremely typical physiological stress (hypoxia) causes selective activation of specific elements of the SAPKs and MAPKs, and identifies Ca+2/CaM as a critical upstream activator. PMID:10849670

  17. Hippocampal theta, gamma, and theta-gamma coupling: effects of aging, environmental change, and cholinergic activation

    PubMed Central

    Jacobson, Tara K.; Howe, Matthew D.; Schmidt, Brandy; Hinman, James R.; Escabí, Monty A.

    2013-01-01

    Hippocampal theta and gamma oscillations coordinate the timing of multiple inputs to hippocampal neurons and have been linked to information processing and the dynamics of encoding and retrieval. One major influence on hippocampal rhythmicity is from cholinergic afferents. In both humans and rodents, aging is linked to impairments in hippocampus-dependent function along with degradation of cholinergic function. Cholinomimetics can reverse some age-related memory impairments and modulate oscillations in the hippocampus. Therefore, one would expect corresponding changes in these oscillations and possible rescue with the cholinomimetic physostigmine. Hippocampal activity was recorded while animals explored a familiar or a novel maze configuration. Reexposure to a familiar situation resulted in minimal aging effects or changes in theta or gamma oscillations. In contrast, exploration of a novel maze configuration increased theta power; this was greater in adult than old animals, although the deficit was reversed with physostigmine. In contrast to the theta results, the effects of novelty, age, and/or physostigmine on gamma were relatively weak. Unrelated to the behavioral situation were an age-related decrease in the degree of theta-gamma coupling and the fact that physostigmine lowered the frequency of theta in both adult and old animals. The results indicate that age-related changes in gamma and theta modulation of gamma, while reflecting aging changes in hippocampal circuitry, seem less related to aging changes in information processing. In contrast, the data support a role for theta and the cholinergic system in encoding and that hippocampal aging is related to impaired encoding of new information. PMID:23303862

  18. Structural Basis for Iloprost as a Dual Peroxisome Proliferator-activated Receptor [alpha/delta] Agonist

    SciTech Connect

    Jin, Lihua; Lin, Shengchen; Rong, Hui; Zheng, Songyang; Jin, Shikan; Wang, Rui; Li, Yong

    2012-03-15

    Iloprost is a prostacyclin analog that has been used to treat many vascular conditions. Peroxisome proliferator-activated receptors (PPARs) are ligand-regulated transcription factors with various important biological effects such as metabolic and cardiovascular physiology. Here, we report the crystal structures of the PPAR{alpha} ligand-binding domain and PPAR{delta} ligand-binding domain bound to iloprost, thus providing unambiguous evidence for the direct interaction between iloprost and PPARs and a structural basis for the recognition of PPAR{alpha}/{delta} by this prostacyclin analog. In addition to conserved contacts for all PPAR{alpha} ligands, iloprost also initiates several specific interactions with PPARs using its unique structural groups. Structural and functional studies of receptor-ligand interactions reveal strong functional correlations of the iloprost-PPAR{alpha}/{delta} interactions as well as the molecular basis of PPAR subtype selectivity toward iloprost ligand. As such, the structural mechanism may provide a more rational template for designing novel compounds targeting PPARs with more favorable pharmacologic impact based on existing iloprost drugs.

  19. Cowplex usage of the gold gamma - activation analysis information

    SciTech Connect

    Degtyarev, S.I.

    1993-12-31

    A simultaneous gold assay method, evaluation of gold`s grain number and weight, and lithologic type, of ore bearing rock, is described. The basis of this method is gamma activation analysis which permits the assay of 500 grams of gold samples crushed up to 3 mm.

  20. T-cell receptor. gamma. chain-CD3 complex: implication in the cytotoxic activity of a CD3/sup +/ CD4/sup -/ CD8/sup -/ human natural killer clone

    SciTech Connect

    Alarcon, B.; De Vries, J.; Pettey, C.; Boylston, A.; Yssel, H.; Terhorst, C.; Spits, H.

    1987-06-01

    A subset of human T cells has recently been described. These cells express the CD3 complex but they do not carry the classical T-cell receptor (TCR)-..gamma../-..beta.. heterodimer on their surface (WT31/sup -/ CD3/sup +/). Instead, they express a TCR-..gamma.. chain associated with another type of polypeptide termed TCR-delta. The authors report here that a T-cell clone with natural killer (NK)-like activity, WM-14, had a disulfide bridged TCR-..gamma.. homodimer associated with CD3 on its surface. The TCR-..gamma.. chains of WM-14 cells were present in three different glycosylation forms of 43, 40, and 38 kDa, but they appeared to contain the same polypeptide backbone. Since cytotoxicity by WM-14 could be inhibited by anti-CD3 antibodies, they concluded that the TCR-..gamma..-CD3 complex was involved in the NK-like unrestricted killer activity. Although normal CD3-..gamma.., CD3-delta, and CD3-element of chains were present in this clone, the association with the TCR-..gamma.. homodimer may be the cause of a complete processing of the N-linked oligosaccharides attached to the CD3-delta chain.

  1. Active galaxies and the diffuse gamma-ray background

    NASA Technical Reports Server (NTRS)

    Kazanas, D.; Protheroe, R. J.

    1983-01-01

    Active galaxies are shown to account for the observed gamma ray background radiation if a steepening of the spectra above about 100 keV is present. An analytical model is discussed in which protons undergo Fermi acceleration at a shock in a spherical accretion flow onto a massive black hole. Relativistic protons with power law spectra, nuclear interactions producing gamma rays from neutal pion decay and electrons from pion-mu meson-electron decay, with a power law spectrum above several hundred MeV, synchrotron and inverse Compton losses steepening the electron spectrum, a photon spectrum close to the pion gamma spectrum and a high-energy gamma ray spectrum steepened by photon-photon pair production interactions with X rays are covered in the model. Comparisons are made with HEAO 2 data on active galaxies, which have estimated luminosities and radii consistent with the compactness necessary for producing the steepening predicted by the model. The active galaxies spectra would be described by a spherical accretion-shock model.

  2. Gamma power is phase-locked to posterior alpha activity.

    PubMed

    Osipova, Daria; Hermes, Dora; Jensen, Ole

    2008-01-01

    Neuronal oscillations in various frequency bands have been reported in numerous studies in both humans and animals. While it is obvious that these oscillations play an important role in cognitive processing, it remains unclear how oscillations in various frequency bands interact. In this study we have investigated phase to power locking in MEG activity of healthy human subjects at rest with their eyes closed. To examine cross-frequency coupling, we have computed coherence between the time course of the power in a given frequency band and the signal itself within every channel. The time-course of the power was calculated using a sliding tapered time window followed by a Fourier transform. Our findings show that high-frequency gamma power (30-70 Hz) is phase-locked to alpha oscillations (8-13 Hz) in the ongoing MEG signals. The topography of the coupling was similar to the topography of the alpha power and was strongest over occipital areas. Interestingly, gamma activity per se was not evident in the power spectra and only became detectable when studied in relation to the alpha phase. Intracranial data from an epileptic subject confirmed these findings albeit there was slowing in both the alpha and gamma band. A tentative explanation for this phenomenon is that the visual system is inhibited during most of the alpha cycle whereas a burst of gamma activity at a specific alpha phase (e.g. at troughs) reflects a window of excitability. PMID:19098986

  3. Conical Euler simulation and active suppression of delta wing rocking motion

    NASA Technical Reports Server (NTRS)

    Lee, Elizabeth M.; Batina, John T.

    1990-01-01

    A conical Euler code was developed to study unsteady vortex-dominated flows about rolling highly-swept delta wings, undergoing either forced or free-to-roll motions including active roll suppression. The flow solver of the code involves a multistage Runge-Kutta time-stepping scheme which uses a finite volume spatial discretization of the Euler equations on an unstructured grid of triangles. The code allows for the additional analysis of the free-to-roll case, by including the rigid-body equation of motion for its simultaneous time integration with the governing flow equations. Results are presented for a 75 deg swept sharp leading edge delta wing at a freestream Mach number of 1.2 and at alpha equal to 10 and 30 deg angle of attack. A forced harmonic analysis indicates that the rolling moment coefficient provides: (1) a positive damping at the lower angle of attack equal to 10 deg, which is verified in a free-to-roll calculation; (2) a negative damping at the higher angle of attack equal to 30 deg at the small roll amplitudes. A free-to-roll calculation for the latter case produces an initially divergent response, but as the amplitude of motion grows with time, the response transitions to a wing-rock type of limit cycle oscillation. The wing rocking motion may be actively suppressed, however, through the use of a rate-feedback control law and antisymmetrically deflected leading edge flaps. The descriptions of the conical Euler flow solver and the free-to-roll analysis are presented. Results are also presented which give insight into the flow physics associated with unsteady vortical flows about forced and free-to-roll delta wings, including the active roll suppression of this wing-rock phenomenon.

  4. Role of lipid packing in the activity of phospholipase C-delta1 as determined by hydrostatic pressure measurements.

    PubMed Central

    Rebecchi, M; Bonhomme, M; Scarlata, S

    1999-01-01

    Previous studies with phospholipid monolayers revealed a large decrease in the activity of phosphoinositide-specific phospholipase C-delta(1) (PLC-delta(1)) which catalyses the hydrolysis of PtdIns(4, 5)P(2) as lateral pressure is applied to the membrane. If stress on the membrane is the sole inhibitor of PLC-delta(1) activity, the enzyme must penetrate the membrane surface to engage its substrate. To test the effect on PLC-delta(1) activity of lipid packing in the absence of a directional stress, we examined the effects of increasing hydrostatic pressure on enzymic activity. We find that, in contrast with monolayer studies, increasing lipid packing by hydrostatic pressure does not affect membrane binding and increases enzymic activity by 90% in going from atmospheric pressure to 10(8) Pa (approx. 1000 atm). The increase in activity could be accounted for mainly by electrostriction of water around the multiply-charged product. Our results show that when there is no net stress on the monolayer, lipid packing does not alter PLC-delta(1) activity, possibly because penetration of the enzyme into the membrane surface is shallow. We suggest that, in biological membranes, the activity of this and possibly other interfacial proteins is independent of headgroup packing. PMID:10417319

  5. Peroxisome proliferator-activated receptor-gamma ligands inhibit proliferation and induce apoptosis in mantle cell lymphoma.

    PubMed

    Eucker, Jan; Sterz, Jan; Krebbel, Holger; Zavrski, Ivana; Kaiser, Martin; Zang, Chuanbing; Heider, Ulrike; Jakob, Christian; Elstner, Elena; Sezer, Orhan

    2006-08-01

    Peroxisome proliferator-activated receptor-gamma, a nuclear receptor and transcription factor, and its natural and synthetic ligands have become a focus of novel approaches to induction of apoptosis in solid tumors and hematologic malignancies, including malignant B-lineage cells. The effect on mantle cell lymphoma, a subtype with dismal prognosis, has not yet been analyzed. We investigated the effect of 15-deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2), pioglitazone (PGZ) or rosiglitazone (RGZ) on human mantle cell lymphoma cell lines (GRANTA-519, Hbl-2 and JeKo-1). Mantle cell lymphoma cell lines exhibited a high expression of Peroxisome proliferator-activated receptor-gamma protein in Western blot analysis. MTT assays revealed anti-proliferative effects induced by both 15d-PGJ2, the natural activator of Peroxisome proliferator-activated receptor-gamma, and PGZ and RGZ, synthetic Peroxisome proliferator-activated receptor-gamma ligands, in a dose-dependent manner. At a dose of 50 micromol/l, 15d-PGJ2 induced growth inhibition in all cell lines. The anti-proliferative effect of PGZ and RGZ was slightly lower. Induction of apoptosis was indicated by annexin V staining. At a dose of 50 micromol/l, 15d-PGJ2 led to apoptosis in all cell lines (87-99%) after 48 h of incubation. Again, the apoptotic effect with thiazolidinediones was slightly lower at the same dose level. This is the first study evaluating Peroxisome proliferator-activated receptor-gamma expression and its therapeutic implications in human mantle cell lymphoma cells. Thiazolidinediones comprise anti-lymphoma activity in vitro and should be further explored for the treatment of mantle cell lymphoma. PMID:16926626

  6. Antioxidant activity potential of gamma irradiated carrageenan.

    PubMed

    Abad, Lucille V; Relleve, Lorna S; Racadio, Charles Darwin T; Aranilla, Charito T; De la Rosa, Alumanda M

    2013-09-01

    The antioxidant capacity of irradiated κ-, ι-, λ-carrageenans were investigated using the hydroxyl radical scavenging assay, reducing power assay and DPPH radical scavenging capacity assay. The degree of oxidative inhibition increased with increasing concentration and dose. The type of carrageenan had also an influence on its antioxidant activity which followed the order of lambda

  7. Supine posture inhibits cortical activity: Evidence from Delta and Alpha EEG bands.

    PubMed

    Spironelli, Chiara; Busenello, Jessica; Angrilli, Alessandro

    2016-08-01

    Past studies have shown consistent evidence that body position significantly affects brain activity, revealing that both head-down and horizontal bed-rest are associated with cortical inhibition and altered perceptual and cognitive processing. The present study investigates the effects of body position on spontaneous, open-eyes, resting-state EEG cortical activity in 32 young women randomly assigned to one of two conditions, seated position (SP) or horizontal bed rest (BR). A between-group repeated-measure experimental design was used, EEG recordings were made from 38 scalp locations, and low-frequency (delta and alpha) amplitudes of the two groups were compared in four different conditions: when both groups (a) were seated (T0), (b) assumed two different body positions (seated vs. supine conditions, immediate [T1] and 120min later [T2]), and (c) were seated again (T3). Overall, the results showed no a priori between-group differences (T0) before experimental manipulation. As expected, delta amplitude, an index of cortical inhibition in awake resting participants, was significantly increased in group BR, revealing both rapid (T1) and mid-term (T2) inhibitory effects of supine or horizontal positions. Instead, the alpha band was highly sensitive to postural transitions, perhaps due to baroreceptor intervention and, unlike the delta band, underwent habituation and decreased after a 2-h bed rest. These results indicate clear-cut differences at rest between the seated and supine positions, thus supporting the view that the role of body position in the differences found between brain metabolic methods (fMRI and PET) in which participants lie horizontally, and EEG-MEG-TMS techniques with participants in a seated position, has been largely underestimated so far. PMID:27312745

  8. Activation of peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) increases the expression of prostaglandin E2 receptor subtype EP4. The roles of phosphatidylinositol 3-kinase and CCAAT/enhancer-binding protein beta.

    PubMed

    Han, ShouWei; Ritzenthaler, Jeffrey D; Wingerd, Byron; Roman, Jesse

    2005-09-30

    The prostaglandin E2 receptor subtype EP4 has been implicated in the growth and progression of human non-small cell lung carcinoma (NSCLC). However, the factors that control its expression have not been entirely elucidated. Our studies show that NSCLC cells express peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) protein and that treatment with a selective PPARbeta/delta agonist (GW501516) increases EP4 mRNA and protein levels. GW501516 induced NSCLC cell proliferation, and this effect was prevented by PPARbeta/delta antisense or EP4 short interfering RNA (siRNA). GW501516 increased the phosphorylation of Akt and decreased PTEN expression. The selective inhibitor of phosphatidylinositol 3-kinase (PI3-K), wortmannin, and PPARbeta/delta antisense, abrogated the effect of GW501516 on EP4 expression, whereas that of the inhibitor of Erk did not. GW501516 also increased EP4 promoter activity through effects on the region between -1555 and -992 bp in the EP4 promoter, and mutation of the CCAAT/enhancer-binding protein (C/EBP) site in this region abrogated the effect of GW501516. GW501516 increased not only the binding activity of C/EBP to the NF-IL6 site in the EP4 promoter, which was prevented by the inhibitor of PI3-K, but also increased C/EBPbeta protein in a dose- and PPARbeta/delta-dependent manner. The effect of GW501516 on EP4 protein was eliminated in the presence of C/EBPbeta siRNA. Finally, we showed that pretreatment of NSCLC with GW501516 further increased NSCLC cell proliferation in response to exogenous dimethyl-prostaglandin E2 (PGE2) that was diminished in the presence of PPARbeta/delta antisense and EP4 siRNA. Taken together, these findings suggest that activation of PPARbeta/delta induces PGE2 receptor subtype EP4 expression through PI3-K signals and increases human lung carcinoma cell proliferation in response to PGE2. The increase in transcription of the EP4 gene by PPARbeta/delta agonist was associated with increased C

  9. Coaxial Mono-Energetic Gamma Generator for Active Interrogation

    NASA Astrophysics Data System (ADS)

    Ludewigt, B. A.; Antolak, A. J.; Henestroza, E.; Kwan, J. W.; Leitner, M.; Leung, K.-N.; Waldron, W.; Wilde, S.

    2009-03-01

    Compact mono-energetic photon sources are sought for active interrogation systems to detect shielded special nuclear materials in, for example, cargo containers, trucks and other vehicles. A prototype gamma interrogation source has been designed and built that utilizes the 11B(p,γ)12C reaction to produce 12 MeV gamma-rays which are near the peak of the photofission cross section. In particular, the 11B(p,γ)12C resonance at 163 kV allows the production of gammas at low proton acceleration voltages, thus keeping the design of a gamma generator comparatively small and simple. A coaxial design has been adopted with a toroidal-shaped plasma chamber surrounding a cylindrical gamma production target. The plasma discharge is driven by a 2 MHz rf-power supply (capable up to 50 kW) using a circular rf-antenna. Permanent magnets embedded in the walls of the plasma chamber generate a multi-cusp field that confines the plasma and allows higher plasma densities and lower gas pressures. About 100 proton beamlets are extracted through a slotted plasma electrode towards the target at the center of the device that is at a negative 180 kV. The target consists of LaB6 tiles that are brazed to a water-cooled cylindrical structure. The generator is designed to operate at 500 Hz with 20 μs long pulses, and a 1% duty factor by pulsing the ion source rf-power. A first-generation coaxial gamma source has been built for low duty factor experiments and testing.

  10. The optimization of gamma spectra processing in prompt gamma neutron activation analysis (PGNAA)

    NASA Astrophysics Data System (ADS)

    Pinault, Jean-Louis; Solis, Jose

    2009-04-01

    The uncertainty of the elemental analysis is one of the major factors governing the utility of on-line Prompt Gamma Neutron Activation Analysis (PGNAA) in the blending and sorting of bulk materials. In this paper, a general method applicable to Gamma spectra processing is presented and applied to PGNAA in mineral industry. Based on the Fourier transform of spectra and their de-correlation in the Fourier space (the improvement of the conditioning of the correlation matrix), processing of overlapping of characteristic peaks minimizes the propagation of random errors, which optimizes the accuracy and decreases the detection limits of elemental analyses. In comparison with classical methods based on the linear combinations of relevant regions of spectra the improvement may be considerable, especially when several elements are interfering. The method is applied to four case stories covering both borehole logging and on-line analysis on conveyor belt of raw materials.

  11. Characterization of anti-Legionella activity of warnericin RK and delta-lysin I from Staphylococcus warneri.

    PubMed

    Verdon, Julien; Berjeaud, Jean-Marc; Lacombe, Christian; Héchard, Yann

    2008-06-01

    Legionella pneumophila, the causative agent of Legionnaires' disease, is a waterborne bacteria. It can multiply in man-made water systems and infect people who inhale contaminated droplets. We have previously reported a Staphylococcus warneri strain that display an anti-Legionella activity. In this work, we characterized three anti-Legionella peptides that are produced by S. warneri. One peptide, warnericin RK, is original, while the two others are delta-lysin I and delta-lysin II, whose genes were previously described. Due to high sequence similarity of the two delta-lysins, further characterization was performed only on delta-lysin I. Warnericin RK and delta-lysin I displayed the same antibacterial spectrum, which is almost restricted to the Legionella genus. Also, both peptides have a hemolytic activity. These results led to the hypothesis that warnericin RK and delta-lysin I share a similar mode of action, and that Legionella should have a specific feature that may explain the high specificity of these antibacterial peptides. PMID:18339450

  12. Environmental impacts caused by the uncontrolled human activities on water resources availability in the Niger Inland Delta

    NASA Astrophysics Data System (ADS)

    Moussa, Ibrahim; Oyerinde, Ganiyu; Some, Corentin; Abdou, Ali; Mariko, Adama; Wisser, Dominik

    2014-05-01

    The Niger River basin is a significant source of water and food for West Africa. As an agricultural region, the basin is highly dependent on the water availability that is currently under pressure from increased demand with rising populations and climate variability and change. The Niger Inland Delta is one of the largest flood plains (about 40.000skm) in Africa and serves a number of interlinked human activities, such as irrigation, fishing, livestock, and reservoirs. Future changes in the dynamics of river flow may change the inundation dynamics of the delta and impact these activities. At the same time, the population in the basin is likely to double in the next 30 years, putting additional pressure on the Delta's water resources and land use. Most hydrological models do not adequately represent these dynamics of the Inland Delta. Here we present an overview of the hydrological processes that occur over the Niger inland delta. We used digital elevation model and satellite images to analyze the spatio-temporal variations in relation to observed river flow. Based on this analysis, we have developed a representation of these processes fore hydrological models for the basin. The basic analysis of in situ discharges confirms the impact of the inner delta area on the discharge of the main river, characterized by a strong reduction of about 15% to 50% as a result of evaporation and water abstractions for irrigation.

  13. Planetary Geochemistry Using Active Neutron and Gamma Ray Instrumentation

    NASA Technical Reports Server (NTRS)

    Parsons, A.; Bodnarik, J.; Evans, L.; Floyd, S.; Lim, L.; McClanahan, T.; Namkung, M.; Schweitzer, J.; Starr, R.; Trombka, J.

    2010-01-01

    The Pulsed Neutron Generator-Gamma Ray And Neutron Detector (PNG-GRAND) experiment is an innovative application of the active neutron-gamma ray technology so successfully used in oil field well logging and mineral exploration on Earth, The objective of our active neutron-gamma ray technology program at NASA Goddard Space Flight Center (NASA/GSFC) is to bring the PNG-GRAND instrument to the point where it can be flown on a variety of surface lander or rover missions to the Moon, Mars, Venus, asterOIds, comets and the satellites of the outer planets, Gamma-Ray Spectrometers have been incorporated into numerous orbital planetary science missions and, especially in the case of Mars Odyssey, have contributed detailed maps of the elemental composition over the entire surface of Mars, Neutron detectors have also been placed onboard orbital missions such as the Lunar Reconnaissance Orbiter and Lunar Prospector to measure the hydrogen content of the surface of the moon, The DAN in situ experiment on the Mars Science Laboratory not only includes neutron detectors, but also has its own neutron generator, However, no one has ever combined the three into one instrument PNG-GRAND combines a pulsed neutron generator (PNG) with gamma ray and neutron detectors to produce a landed instrument that can determine subsurface elemental composition without drilling. We are testing PNG-GRAND at a unique outdoor neutron instrumentation test facility recently constructed at NASA/GSFC that consists of a 2 m x 2 m x 1 m granite structure in an empty field, We will present data from the operation of PNG-GRAND in various experimental configurations on a known sample in a geometry that is identical to that which can be achieved on a planetary surface. We will also compare the material composition results inferred from our experiments to both an independent laboratory elemental composition analysis and MCNPX computer modeling results,

  14. Analyses of Oxyanion Materials by Prompt Gamma Activation Analysis

    SciTech Connect

    Firestone, Richard B; Perry, D.L.; English, G.A.; Firestone, R.B.; Leung, K.-N.; Garabedian, G.; Molnar, G.L.; Revay, Zs.

    2008-03-24

    Prompt gamma activation analysis (PGAA) has been used to analyze metal ion oxyanion materials that have multiple applications, including medicine, materials, catalysts, and electronics. The significance for the need for accurate, highly sensitive analyses for the materials is discussed in the context of quality control of end products containing the parent element in each material. Applications of the analytical data for input to models and theoretical calculations related to the electronic and other properties of the materials are discussed.

  15. Dependency of {gamma}-secretase complex activity on the structural integrity of the bilayer

    SciTech Connect

    Zhou, Hua; Zhou, Shuxia; Walian, Peter J.; Jap, Bing K.

    2010-11-12

    Research highlights: {yields} Partial solubilization of membranes with CHAPSO can increase {gamma}-secretase activity. {yields} Completely solubilized {gamma}-secretase is inactive. {yields} Purified {gamma}-secretase regains activity after reconstitution into lipid bilayers. {yields} A broad range of detergents can be used to successfully reconstitute {gamma}-secretase. -- Abstract: {gamma}-secretase is a membrane protein complex associated with the production of A{beta} peptides that are pathogenic in Alzheimer's disease. We have characterized the activity of {gamma}-secretase complexes under a variety of detergent solubilization and reconstitution conditions, and the structural state of proteoliposomes by electron microscopy. We found that {gamma}-secretase activity is highly dependent on the physical state or integrity of the membrane bilayer - partial solubilization may increase activity while complete solubilization will abolish it. The activity of well-solubilized {gamma}-secretase can be restored to near native levels when properly reconstituted into a lipid bilayer environment.

  16. Oscillations in sympatho-vagal balance oppose variations in delta-wave activity and the associated renin release.

    PubMed

    Charloux, A; Otzenberger, H; Gronfier, C; Lonsdorfer-Wolf, E; Piquard, F; Brandenberger, G

    1998-05-01

    To determine the potential role of the sympathetic nervous system in the generation of the oscillations in PRA over the 24-h period, we used the autocorrelation coefficient of RR interval (rRR), a new tool to evaluate the sympatho-vagal balance continuously. We determined the influence of the sympathetic nervous system both on the nocturnal PRA oscillations associated to increases in delta-wave activity and on the daytime oscillations that occur randomly in awake subjects. PRA and rRR were determined every 10 min during 24 h in nine healthy subjects under continuous bed rest. Electroencephalographic spectral analysis was used to establish the variations in delta-wave activity during sleep, from 2300-0700 h. The overnight profiles in PRA, rRR and delta-wave activity were analyzed using a modified version of the pulse detection program ULTRA. The temporal link among the profiles of rRR, PRA, and delta-wave activity was quantified using cross-correlation analysis. During sleep, large oscillations in PRA were strongly linked to variations in delta-wave activity. They were preceded by opposite oscillations in rRR, decreases in rRR reflecting predominant vagal activity, and increases in rRR reflecting sympathetic dominance. During the waking periods, the levels of rRR were higher, with smaller variations. The daytime PRA oscillations were not associated with any significant changes in rRR, and conversely, significant oscillations in rRR were not followed by any significant changes in PRA. In conclusion, the sympathetic nervous system is not directly involved in the generation of renin oscillations observed under basal conditions. During sleep, the oscillations in sympatho-vagal balance are inversely related to the variations in delta-wave activity and the associated renin release. The processes that give the intermittent signal for concomitant increases in slow wave activity and renin release from the kidney remain to be identified. PMID:9589649

  17. Implications of gamma band activity in the pedunculopontine nucleus.

    PubMed

    Garcia-Rill, E; Luster, B; D'Onofrio, S; Mahaffey, S; Bisagno, V; Urbano, F J

    2016-07-01

    The fact that the pedunculopontine nucleus (PPN) is part of the reticular activating system places it in a unique position to modulate sensory input and fight-or-flight responses. Arousing stimuli simultaneously activate ascending projections of the PPN to the intralaminar thalamus to trigger cortical high-frequency activity and arousal, as well as descending projections to reticulospinal systems to alter posture and locomotion. As such, the PPN has become a target for deep brain stimulation for the treatment of Parkinson's disease, modulating gait, posture, and higher functions. This article describes the latest discoveries on PPN physiology and the role of the PPN in a number of disorders. It has now been determined that high-frequency activity during waking and REM sleep is controlled by two different intracellular pathways and two calcium channels in PPN cells. Moreover, there are three different PPN cell types that have one or both calcium channels and may be active during waking only, REM sleep only, or both. Based on the new discoveries, novel mechanisms are proposed for insomnia as a waking disorder. In addition, neuronal calcium sensor protein-1 (NCS-1), which is over expressed in schizophrenia and bipolar disorder, may be responsible for the dysregulation in gamma band activity in at least some patients with these diseases. Recent results suggest that NCS-1 modulates PPN gamma band activity and that lithium acts to reduce the effects of over expressed NCS-1, accounting for its effectiveness in bipolar disorder. PMID:26597124

  18. Exercise reduces adipose tissue via cannabinoid receptor type 1 which is regulated by peroxisome proliferator-activated receptor-delta.

    PubMed

    Yan, Zhen Cheng; Liu, Dao Yan; Zhang, Li Li; Shen, Chen Yi; Ma, Qun Li; Cao, Ting Bing; Wang, Li Juan; Nie, Hai; Zidek, Walter; Tepel, Martin; Zhu, Zhi Ming

    2007-03-01

    Obesity is one major cardiovascular risk factor. We tested effects of endurance exercise on cannabinoid receptor type 1 (CB1) and peroxisome proliferator-activated receptor-delta (PPAR-delta)-dependent pathways in adipose tissue. Male Wistar rats were randomly assigned to standard laboratory chow or a high-fat diet without and with regular endurance exercise. Exercise in rats on high-fat diet significantly reduced visceral fat mass, blood pressure, and adipocyte size (each p<0.05). Adipocyte hypertrophy induced by high-fat diet was accompanied by increased CB1 expression in adipose tissue, whereas exercise significantly reduced CB1 expression (each p<0.05). CB1 receptor expression and adipocyte differentiation were directly regulated by PPAR-delta. Adipocyte hypertrophy induced by high-fat diet was accompanied by reduced PPAR-delta. Furthermore, selective silencing of PPAR-delta by RNA interference in 3T3-L1-preadipocyte cells significantly increased CB1 expression from 1.00+/-0.06 (n=3) to 1.91+/-0.06 (n=3; p<0.01) and increased adipocyte differentiation, whereas adenovirus-mediated overexpression of PPAR-delta significantly reduced CB1 expression to 0.39+/-0.03 (n=3; p<0.01) and reduced adipocyte differentiation. In the presence of the CB1 antagonist rimonabant adipocyte differentiation in stimulated 3T3 L1 preadipocyte cells was significantly reduced. The study indicates that high-fat diet-induced hypertrophy of adipocytes is associated with increased CB1 receptor expression which is directly regulated by PPAR-delta. Both CB1 and PPAR-delta are intimately involved in therapeutic interventions against a most important cardiovascular risk factor. PMID:17223076

  19. Exercise reduces adipose tissue via cannabinoid receptor type 1 which is regulated by peroxisome proliferator-activated receptor-{delta}

    SciTech Connect

    Yan Zhencheng; Liu Daoyan; Zhang Lili; Shen Chenyi; Ma Qunli; Cao Tingbing; Wang Lijuan; Nie Hai; Zidek, Walter; Tepel, Martin; Zhu Zhiming . E-mail: zhuzm@yahoo.com

    2007-03-09

    Obesity is one major cardiovascular risk factor. We tested effects of endurance exercise on cannabinoid receptor type 1 (CB1) and peroxisome proliferator-activated receptor-{delta} (PPAR-{delta})-dependent pathways in adipose tissue. Male Wistar rats were randomly assigned to standard laboratory chow or a high-fat diet without and with regular endurance exercise. Exercise in rats on high-fat diet significantly reduced visceral fat mass, blood pressure, and adipocyte size (each p < 0.05). Adipocyte hypertrophy induced by high-fat diet was accompanied by increased CB1 expression in adipose tissue, whereas exercise significantly reduced CB1 expression (each p < 0.05). CB1 receptor expression and adipocyte differentiation were directly regulated by PPAR-{delta}. Adipocyte hypertrophy induced by high-fat diet was accompanied by reduced PPAR-{delta}. Furthermore, selective silencing of PPAR-{delta} by RNA interference in 3T3-L1-preadipocyte cells significantly increased CB1 expression from 1.00 {+-} 0.06 (n = 3) to 1.91 {+-} 0.06 (n = 3; p < 0.01) and increased adipocyte differentiation, whereas adenovirus-mediated overexpression of PPAR-{delta} significantly reduced CB1 expression to 0.39 {+-} 0.03 (n = 3; p < 0.01) and reduced adipocyte differentiation. In the presence of the CB1 antagonist rimonabant adipocyte differentiation in stimulated 3T3 L1 preadipocyte cells was significantly reduced. The study indicates that high-fat diet-induced hypertrophy of adipocytes is associated with increased CB1 receptor expression which is directly regulated by PPAR-{delta}. Both CB1 and PPAR-{delta} are intimately involved in therapeutic interventions against a most important cardiovascular risk factor.

  20. Effect of rottlerin, a PKC-{delta} inhibitor, on TLR-4-dependent activation of murine microglia

    SciTech Connect

    Kim, Dong-Chan; Kim, Sun-Hee; Jeong, Min-Woo; Baek, Nam-in; Kim, Kyong-Tai . E-mail: ktk@postech.ac.kr

    2005-11-11

    In microglia, Toll-like receptors have been shown to recognize pathogen-associated molecular patterns and initiate innate immune responses upon interaction with infectious agents. The effect of rottlerin, a PKC-{delta} specific inhibitor, on TLR-4-mediated signaling was investigated in murine microglia stimulated with lipopolysaccharide and taxol. Pretreatment of microglia cells with rottlerin decreased LPS- and taxol-induced nitric oxide production in a concentration-dependent manner (IC{sub 50} = 99.1 {+-} 1.5 nM). Through MTT and FACS analysis, we found that the inhibition effect of rottlerin was not due to microglial cell death. Rottlerin pretreatment also attenuated LPS-induced phosphorylation of I{kappa}B-{alpha}, nuclear translocation of NF-{kappa}B, and expression of type II nitric oxide synthase. In addition, microglial phagocytosis in response to TLR-4 activation was diminished in which rottlerin was pretreated. Together, these data raise the possibility that certain PKC-{delta} specific inhibitors can modulate TLR-4-derived signaling and inflammatory target gene expression, and can alter susceptibility to microbial infection and chronic inflammatory diseases in central nervous system.

  1. Resting posterior versus frontal delta/theta EEG activity is associated with extraversion and the COMT VAL(158)MET polymorphism.

    PubMed

    Wacker, Jan; Gatt, Justine Megan

    2010-07-01

    Recent studies suggest that resting posterior versus frontal EEG delta/theta activity (delta/theta Pz-Fz) is both sensitive to pharmacological manipulations of neural dopamine and associated with the agency facet of extraversion (i.e., a motivational disposition comprising enthusiasm, energy, assertiveness, achievement striving and social dominance). These observations suggest that posterior versus frontal resting EEG delta/theta activity may represent a useful marker for investigating the molecular genetic basis of extraversion. The present study aimed to test the novel hypothesis of an association between delta/theta Pz-Fz and a functional polymorphism of the enzyme catechol-O-methyltransferase (COMT VAL(158)MET) involved in dopamine catabolism. This was conducted in a large EEG data set from the Brain Resource International Database (BRID; resting EEG from N=1093 healthy individuals, 382 of which also genotyped for COMT VAL(158)MET). In summary, we (1) showed for the first time that the VAL allele is associated with increased delta/theta Pz-Fz; (2) replicated the association between extraversion and delta/theta Pz-Fz in a large, heterogeneous sample including both genders; and (3) documented that the VAL allele of the COMT VAL(158)MET is associated with increased extraversion scores, as previously reported for an overlapping BRID sample. This coherent pattern of findings adds further support to the suggestion that the posterior-anterior distribution of resting EEG slow wave activity in the delta/theta range represents a useful tool for probing the dopaminergic basis of extraversion. PMID:20450956

  2. Long-term exercise increases the DNA binding activity of peroxisome proliferator-activated receptor gamma in rat adipose tissue.

    PubMed

    Petridou, Anatoli; Tsalouhidou, Sofia; Tsalis, George; Schulz, Thorsten; Michna, Horst; Mougios, Vassilis

    2007-08-01

    The aim of the present study was to examine the effect of 8 weeks of voluntary wheel running on the gene expression, at the protein level, of 2 enzymes involved in lipogenesis (fatty acid synthase [FAS] and diacylglycerol acyl transferase 1), 2 proteins involved in lipolysis (hormone-sensitive lipase [HSL] and perilipin), and 3 transcription factors mediating the induction of genes involved in lipid metabolism (the alpha, gamma, and delta members of the peroxisome proliferator-activated receptor, or PPAR, family) in rat liver, gastrocnemius muscle, epididymal fat, and subcutaneous fat. Proteins were measured through Western blot analysis in the tissues of 11 trained and 14 untrained rats. The trained rats had lower FAS in the liver; higher FAS, HSL, and perilipin in epididymal fat; and higher HSL in subcutaneous fat. In addition, the trained rats had higher total protein concentrations in both fat depots. No significant differences in the liver, muscle, or adipose tissue PPAR contents were found between groups. However, the DNA binding activity of PPARgamma, measured through an enzyme immunoassay-based method, was higher in both fat depots of the trained rats. Our findings suggest that long-term wheel running had significant effects on the concentrations of proteins playing key roles in lipogenesis and lipolysis in rat liver and adipose tissue. These effects may be due to PPAR activation rather than induction, rendering the transcriptional regulation of target genes more economical and flexible. The activation of PPARgamma with exercise may mediate its beneficial effect on insulin sensitivity. PMID:17618946

  3. High-energy gamma-ray observations of active galaxies

    NASA Technical Reports Server (NTRS)

    Fichtel, Carl E.

    1994-01-01

    During the period from 1992 May to early 1992 November, the Energetic Gamma-Ray Experiment Telescope (EGRET) on board the Compton Gamma Ray Observatory obtained high-energy gamma-ray data for most of the sky. A total of 18 active galaxies have been seen with high certainty, and it is expected that more will be found in the data when a more thorough analysis is complete. All of those that have been seen are radio-loud quasars or BL Lacertae objects; most have already been identified as blazars. No Seyfert galaxies have been found thus far. If the spectra are represented as a power law in energy, spectral slopes ranging from approximately -1.7 to -2.4 are found. A wide range of z-values exits in the observed sample, eight having values in excess of 1.0. Time variations have been seen, with the timescale for a significant change being as short as days in at least one case. These results imply the existence of very large numbers of relativistic particles, probably close to the central object. Although a large extrapolation is required, their existence also suggests that these active galactic nuclei may be the source of the extragalactic cosmic rays.

  4. The calculation of T{sub {delta}} and V{sub {delta}} in austenitic steel

    SciTech Connect

    Dai Qixun; Yang Ruzeng

    1997-03-01

    The relation between the {gamma}/{gamma} + {delta} boundary temperature, T{sub {delta}}, of austenitic steels and the equivalent weights, [Cr] and [Ni], has been studied, as has the law of variation of the {delta} phase volume, V{sub {delta}}, with temperature. With the aid of a computer, the following regression expressions have been derived from the experimental results: T{sub {delta}} ({degree}C) =- T{sub 4} {minus} 21.2[Cr] + 15.8[Ni] {minus} 223; V{sub {delta}} (%) = 0.715 exp [0.015(T {minus} T{sub {delta}})]. Satisfactory results have been obtained by using these regression expressions.

  5. Prompt gamma activation analysis: An old technique made new

    SciTech Connect

    English, Jerry; Firestone, Richard; Perry, Dale; Leung, Ka-Ngo; Reijonen, Jani; Garabedian, Glenn; Bandong, Bryan; Molnar, Gabor; Revay, Zsolt

    2002-12-01

    The long list of contributors to the prompt gamma activation analysis (PGAA) project is important because it highlights the broad cast of active PGAA researchers from various facilities and backgrounds. PGAA is basically a simple process in principle that was traditionally difficult in application. It is an old technique that has for years been tied to and associated exclusively with nuclear reactor facilities, which has limited its acceptance as a general, analytical tool for identifying and quantifying elements or, more precisely, isotopes, whether radioactive or nonradioactive. Field use was not a viable option.

  6. Activity of cannabis in relation to its delta'-trans-tetrahydro-cannabinol content.

    PubMed Central

    Fairbairn, J. W.; Pickens, J. T.

    1981-01-01

    1 Conditions have been worked out for a reliable estimation of the cataleptic activity of delta'-trans-tetrahydrocannabinol (THC) after oral administration to mice, using the ring test over a period of 6 h. 2 By this method, the activity of cannabis herb and 5 crude fractions were measured against THC; at the same time the THC contents were determined chemically. 3 The B/C ratio (biological activity divided by chemical assay) was calculated for each. With cannabis herb the value was 3.3 and with extracts prepared with ethanol or 70% ethanol the values ranged from 3.2 to 7.1, indicating that in all samples the activity was much higher than would be expected from their THC content. 4. The cannabinoids were completely extracted from a sample of herb using petroleum spirit and the marc examined for a possible synergist. Surprisingly, it contained a powerful inhibitor of the action of THC, which could be restored by intraperitoneal prostaglandin E2 (3 microgram/kg). Some crude fractions had inhibitory activities about 10 times that of aspirin. 5 In contrast, the petroleum spirit extract (referred to in 4) had a surprisingly high B/C ratio of 23, indicating that a powerful synergist of THC activity is present. 6 The net effect of the herb and ethanol extracts is probably due to a balance of synergist and inhibitor. PMID:6266564

  7. Chromospheric activity in Delta Scuti stars - The suspected variable Tau Cygni

    NASA Technical Reports Server (NTRS)

    Fracassini, M.; Pasinetti Fracassini, L. E.; Mariani, A.; Pastori, L.; Teays, T. J.

    1991-01-01

    High-resolution IUE spectra of the suspected variable Tau Cyg were obtained to search for a possible variability of the Mg II h, k double-peaked emission. The observations, spanning an interval of about 6.3 h, have shown flux excursions within or just near 15 percent, a value suggested as the detection limit of actual variations with IUE spectra. A variability, difficult to explain, could be present in the ratios Fk2v/Fk2r. The emission fluxes seem to be higher than those of the Delta Scuti variables Rho Pup and Beta Cas. This comparison could give some insights on the possible role of the convection on the pulsational and chromospheric activities of Tau Cyg. A positive correlation between the total emission fluxes and the rotational velocities of these stars was found.

  8. Bacterial delta-aminolevulinic acid synthase activity is not essential for leghemoglobin formation in the soybean/Bradyrhizobium japonicum symbiosis

    SciTech Connect

    Guerinot, M.L.; Chelm, B.K.

    1986-03-01

    Previous studies of legume nodules have indicated that formation of the heme moiety of leghemoglobin is a function of the bacterial symbiont. The authors now show that a hemA mutant of Bradyrhizobium japonicum that cannot carry out the first step in heme biosynthesis forms fully effective nodules on soybeans. The bacterial mutant strain was constructed by first isolated the wild-type hemA gene encoding delta-aminolevulinic acid synthase (EC 2.3.1.37) from a cosmid library, using a fragment of the Rhizobium meliloti hemA gene as a hybridization probe. A deletion of the hemA gene region, generated in vitro, then was used to construct the analogous chromosomal mutation by gene-directed mutagenesis. The mutant strain had no delta-aminolevulinic acid synthase activity and was unable to grow in minimal medium unless delta-aminolevulinic acid was added. Despite its auxotrophy, the mutant strain incited nodules that appeared normal, contained heme, and were capable of high levels of acetylene reduction. These results rule out bacterial delta-aminolevulinic acid synthase activity as the exclusive source of delta-aminolevulinic acid for heme formation in soybean nodules.

  9. The evaluated gamma-ray activation file (EGAF)

    SciTech Connect

    Firestone, R.B.; Molnar, G.L.; Revay, Zs.; Belgya, T.; McNabb, D.P.; Sleaford, B.W.

    2004-09-22

    The Evaluated Gamma-ray Activation File (EGAF), a new database of prompt and delayed neutron capture g-ray cross sections, has been prepared as part of an International Atomic Energy Agency (IAEA) Coordinated Research Project to develop a ''Database of Prompt Gamma-rays from Slow Neutron Capture for Elemental Analysis.'' Recent elemental g-ray cross-section measurements performed with the guided neutron beam at the Budapest Reactor have been combined with data from the literature to produce the EGAF database. EGAF contains thermal cross sections for {approx} 35,000 prompt and delayed g-rays from 262 isotopes. New precise total thermal radiative cross sections have been derived for many isotopes from the primary and secondary gamma-ray cross sections and additional level scheme data. An IAEA TECDOC describing the EGAF evaluation and tabulating the most prominent g-rays will be published in 2004. The TECDOC will include a CD-ROM containing the EGAF database in both ENSDF and tabular formats with an interactive viewer for searching and displaying the data. The Isotopes Project, Lawrence Berkeley National Laboratory continues to maintain and update the EGAF file. These data are available on the Internet from both the IAEA and Isotopes Project websites.

  10. RADSAT Benchmarks for Prompt Gamma Neutron Activation Analysis Measurements

    SciTech Connect

    Burns, Kimberly A.; Gesh, Christopher J.

    2011-07-01

    The accurate and efficient simulation of coupled neutron-photon problems is necessary for several important radiation detection applications. Examples include the detection of nuclear threats concealed in cargo containers and prompt gamma neutron activation analysis for nondestructive determination of elemental composition of unknown samples. High-resolution gamma-ray spectrometers are used in these applications to measure the spectrum of the emitted photon flux, which consists of both continuum and characteristic gamma rays with discrete energies. Monte Carlo transport is the most commonly used simulation tool for this type of problem, but computational times can be prohibitively long. This work explores the use of multi-group deterministic methods for the simulation of coupled neutron-photon problems. The main purpose of this work is to benchmark several problems modeled with RADSAT and MCNP to experimental data. Additionally, the cross section libraries for RADSAT are updated to include ENDF/B-VII cross sections. Preliminary findings show promising results when compared to MCNP and experimental data, but also areas where additional inquiry and testing are needed. The potential benefits and shortcomings of the multi-group-based approach are discussed in terms of accuracy and computational efficiency.

  11. An experimental search for gamma radiation associated with thunderstorm activity

    SciTech Connect

    Fryberger, D.

    1992-11-01

    This experiment is a repeat of an earlier experiment, but with more sensitive apparatus and in a location with a higher incidence of thunderstorm activity. The earlier experiment was undertaken by Ashby and Whitehead to investigate the theory that ball lightning might be associated with the annihilation of small amounts of antimatter, and it yielded some very interesting but inconclusive results. In the course of about 12 months of data taking, four high rate bursts of gamma radiation were detected. These events lasted a few seconds and had many thousands of counts (16500, 5000, 3700, and [gt] 7700. Unfortunately, the association of these gamma ray bursts with thunderstorms or ball lightning was not clearly established, although one of the bursts did occur during a local thunderstorm in rough coincidence with a lightning bolt striking a flagpole about 100 yards from the gamma ray detection crystals. A pulse height spectrum taken for this burst (no spectrum was taken for the other three) exhibited a significant peak, well above background, the energy of which appeared to be compatible with the 511 keV positron annihilation line. While the peak could not be unambiguously attributed to positron annihilation, this certainly appeared to be the most likely source.

  12. An experimental search for gamma radiation associated with thunderstorm activity

    SciTech Connect

    Fryberger, D.

    1992-11-01

    This experiment is a repeat of an earlier experiment, but with more sensitive apparatus and in a location with a higher incidence of thunderstorm activity. The earlier experiment was undertaken by Ashby and Whitehead to investigate the theory that ball lightning might be associated with the annihilation of small amounts of antimatter, and it yielded some very interesting but inconclusive results. In the course of about 12 months of data taking, four high rate bursts of gamma radiation were detected. These events lasted a few seconds and had many thousands of counts (16500, 5000, 3700, and {gt} 7700. Unfortunately, the association of these gamma ray bursts with thunderstorms or ball lightning was not clearly established, although one of the bursts did occur during a local thunderstorm in rough coincidence with a lightning bolt striking a flagpole about 100 yards from the gamma ray detection crystals. A pulse height spectrum taken for this burst (no spectrum was taken for the other three) exhibited a significant peak, well above background, the energy of which appeared to be compatible with the 511 keV positron annihilation line. While the peak could not be unambiguously attributed to positron annihilation, this certainly appeared to be the most likely source.

  13. The oral activity of delta'-tetrahydrocannabinol and its dependence on prostaglandin E2.

    PubMed Central

    Fairbairn, J. W.; Pickens, J. T.

    1979-01-01

    1 delta'-trans-Tetrahydrocannabinol (THC) is more active orally in mice than previously thought, as cataleptic responses occur at doses from 0.06 mg/kg upwards, with peak activity at 2 to 4 h after dosing. These doses and peaks correspond well with the effects in man. 2 Comparison with chlorpromazine in mice shows that chlorpromazine and THC are equipotent as cataleptics during the first 2 h after dosing; thereafter the THC activity increases to a peak when it is 5.67 times as active as chlorpromazine. 3 The cataleptic effect of THC is abolished by aspirin, indomethacine, diffunisal and phenylbutazone which inhibit the biosynthesis of prostaglandins and is restored by exogenous prostaglandin E2 (PGE2) but not PGE1 and PGF2 alpha. This suggests that the effect of THC depends upon the presence of PGE2. 4 In contrast, the cataleptic effect of chlorpromazine is not affected by pretreatment with aspirin. 5 THC is very much less active intraperitoneally than orally; our results suggest this is not due to poor absorption or extraction into fat depots. 6 Cannabidiol has no cataleptic effect. PMID:574040

  14. Specific components of the SAGA complex are required for Gcn4- and Gcr1-mediated activation of the his4-912delta promoter in Saccharomyces cerevisiae.

    PubMed Central

    Dudley, A M; Gansheroff, L J; Winston, F

    1999-01-01

    Mutations selected as suppressors of Ty or solo delta insertion mutations in Saccharomyces cerevisiae have identified several genes, SPT3, SPT7, SPT8, and SPT20, that encode components of the SAGA complex. However, the mechanism by which SAGA activates transcription of specific RNA polymerase II-dependent genes is unknown. We have conducted a fine-structure mutagenesis of one widely used SAGA-dependent promoter, the delta element of his4-912delta, to identify sequence elements important for its promoter activity. Our analysis has characterized three delta regions necessary for full promoter activity and accurate start site selection: an upstream activating sequence, a TATA region, and an initiator region. In addition, we have shown that factors present at the adjacent UASHIS4 (Gcn4, Bas1, and Pho2) also activate the delta promoter in his4-912delta. Our results suggest a model in which the delta promoter in his4-912delta is primarily activated by two factors: Gcr1 acting at the UASdelta and Gcn4 acting at the UASHIS4. Finally, we tested whether activation by either of these factors is dependent on components of the SAGA complex. Our results demonstrate that Spt3 and Spt20 are required for full delta promoter activity, but that Gcn5, another member of SAGA, is not required. Spt3 appears to be partially required for activation of his4-912delta by both Gcr1 and Gcn4. Thus, our work suggests that SAGA exerts a large effect on delta promoter activity through a combination of smaller effects on multiple factors. PMID:10101163

  15. delta-Aminolevulinic acid dehydratase activity, urinary delta-aminolevulinic acid concentration and zinc protoporphyrin level among people with low level of lead exposure.

    PubMed

    Wang, Qi; Zhao, Huan-hu; Chen, Jian-wei; Hao, Qiao-ling; Gu, Kang-ding; Zhu, Ye-xiang; Zhou, Yi-kai; Ye, Lin-xiang

    2010-01-01

    To evaluate the relationship of delta-aminolevulinic acid dehydratase (ALAD) activity, urinary delta-aminolevulinic acid (ALAU) level and blood zinc protoporphyrin (ZPP) concentration to low blood lead (PbB) levels, these biomarkers were determined for all subjects enrolled from a rural area of southeast China where people had low levels of exposure to lead. The mean values of PbB, ALAD, ALAU and ZPP were 67.11 microg/L (SD: 1.654, range: 10.90-514.04), 339.66 nmol ml(-1)h(-1) (1.419, 78.33-793.13), 20.64 microg/L (1.603, 2.00-326.00), and 0.14 micromol/L (3.437, 0.01-2.26), respectively. ALAD was inversely associated with low levels of PbB. ZPP was inversely related to low levels of PbB but positively related to relatively higher levels of PbB. Alcohol drinking contributed to low ALAD in men. Women had higher ZPP than men. ALAU had no significant association with PbB. In conclusion, ALAD possibly has a non-linear relation with low to moderate levels of PbB. At moderate levels of PbB, ZPP increases with increasing levels of PbB. ALAU is not suitable as an indicator for low levels of lead exposure. PMID:19733117

  16. Minimum Detectable Activity for Tomographic Gamma Scanning System

    SciTech Connect

    Venkataraman, Ram; Smith, Susan; Kirkpatrick, J. M.; Croft, Stephen

    2015-01-01

    For any radiation measurement system, it is useful to explore and establish the detection limits and a minimum detectable activity (MDA) for the radionuclides of interest, even if the system is to be used at far higher values. The MDA serves as an important figure of merit, and often a system is optimized and configured so that it can meet the MDA requirements of a measurement campaign. The non-destructive assay (NDA) systems based on gamma ray analysis are no exception and well established conventions, such the Currie method, exist for estimating the detection limits and the MDA. However, the Tomographic Gamma Scanning (TGS) technique poses some challenges for the estimation of detection limits and MDAs. The TGS combines high resolution gamma ray spectrometry (HRGS) with low spatial resolution image reconstruction techniques. In non-imaging gamma ray based NDA techniques measured counts in a full energy peak can be used to estimate the activity of a radionuclide, independently of other counting trials. However, in the case of the TGS each “view” is a full spectral grab (each a counting trial), and each scan consists of 150 spectral grabs in the transmission and emission scans per vertical layer of the item. The set of views in a complete scan are then used to solve for the radionuclide activities on a voxel by voxel basis, over 16 layers of a 10x10 voxel grid. Thus, the raw count data are not independent trials any more, but rather constitute input to a matrix solution for the emission image values at the various locations inside the item volume used in the reconstruction. So, the validity of the methods used to estimate MDA for an imaging technique such as TGS warrant a close scrutiny, because the pair-counting concept of Currie is not directly applicable. One can also raise questions as to whether the TGS, along with other image reconstruction techniques which heavily intertwine data, is a suitable method if one expects to measure samples whose activities

  17. Differential modulation of high-frequency gamma-electroencephalogram activity and sleep-wake state by noradrenaline and serotonin microinjections into the region of cholinergic basalis neurons.

    PubMed

    Cape, E G; Jones, B E

    1998-04-01

    Several lines of evidence indicate that cholinergic basalis neurons play an important role in cortical activation. The present study was undertaken to determine the effect of noradrenergic and serotonergic modulation of the cholinergic neurons on cortical EEG activity and sleep-wake states. The neurotransmitters were injected into the region of the basalis neurons by remote control in freely moving, naturally sleeping-waking rats during the day when the rats are normally asleep the majority of the time. Effects were observed on behavior and EEG activity, including high-frequency gamma activity (30-60 Hz), which has been demonstrated to reflect behavioral and cortical arousal in the rat. Noradrenaline, which has been shown in previous in vitro studies to depolarize and excite the cholinergic cells, produced a dose-dependent increase in gamma-EEG activity, a decrease in delta activity, and an increase in waking. Serotonin, which has been found in previous in vitro studies to hyperpolarize the cholinergic neurons, produced a dose-dependent decrease in gamma-EEG activity with no significant change in amounts of wake or slow wave sleep. Both chemicals resulted in a dose-dependent decrease in paradoxical sleep. These results demonstrate that noradrenaline and serotonin exert differential modulatory effects on EEG activity through the basal forebrain, the one facilitating gamma activity and eliciting waking and the other diminishing gamma activity and not significantly affecting slow wave sleep. The results also confirm that the cholinergic basalis neurons play an important role in cortical activation and particularly in the high-frequency gamma activity that underlies cortical and behavioral arousal of the wake state. PMID:9502823

  18. Gamma dose from activation of internal shields in IRIS reactor.

    PubMed

    Agosteo, Stefano; Cammi, Antonio; Garlati, Luisella; Lombardi, Carlo; Padovani, Enrico

    2005-01-01

    The International Reactor Innovative and Secure is a modular pressurised water reactor with an integral design. This means that all the primary system components, such as the steam generators, pumps, pressuriser and control rod drive mechanisms, are located inside the reactor vessel, which requires a large diameter. For the sake of better reliability and safety, it is desirable to achieve the reduction of vessel embrittlement as well as the lowering of the dose beyond the vessel. The former can be easily accomplished by the presence of a wide downcomer, filled with water, which surrounds the core region, while the latter needs the presence of additional internal shields. An optimal shielding configuration is under investigation, for reducing the ex-vessel dose due to activated internals and for limiting the amount of the biological shielding. MCNP 4C calculations were performed to evaluate the neutron and the gamma dose during operation and the 60Co activation of various shields configurations. The gamma dose beyond the vessel from activation of its structural components was estimated in a shutdown condition, with the Monte Carlo code FLUKA 2002 and the MicroShield software. The results of the two codes are in agreement and show that the dose is sufficiently low, even without an additional shield. PMID:16381688

  19. Ordered ATP hydrolysis in the gamma complex clamp loader AAA+ machine.

    PubMed

    Johnson, Aaron; O'Donnell, Mike

    2003-04-18

    The gamma complex couples ATP hydrolysis to the loading of beta sliding clamps onto DNA for processive replication. The gamma complex structure shows that the clamp loader subunits are arranged as a circular heteropentamer. The three gamma motor subunits bind ATP, the delta wrench opens the beta ring, and the delta' stator modulates the delta-beta interaction. Neither delta nor delta' bind ATP. This report demonstrates that the delta' stator contributes a catalytic arginine for hydrolysis of ATP bound to the adjacent gamma(1) subunit. Thus, the delta' stator contributes to the motor function of the gamma trimer. Mutation of arginine 169 of gamma, which removes the catalytic arginines from only the gamma(2) and gamma(3) ATP sites, abolishes ATPase activity even though ATP site 1 is intact and all three sites are filled. This result implies that hydrolysis of the three ATP molecules occurs in a particular order, the reverse of ATP binding, where ATP in site 1 is not hydrolyzed until ATP in sites 2 and/or 3 is hydrolyzed. Implications of these results to clamp loaders of other systems are discussed. PMID:12582167

  20. The role of peroxisome proliferator-activated receptor-{beta}/{delta} in epidermal growth factor-induced HaCaT cell proliferation

    SciTech Connect

    Liang Pengfei; Jiang Bimei; Yang Xinghua; Xiao Xianzhong Huang Xu; Long Jianhong; Zhang Pihong; Zhang Minghua; Xiao Muzhang; Xie Tinghong; Huang Xiaoyuan

    2008-10-15

    Epidermal growth factor (EGF) has been shown to be a potent mitogen for epidermal cells both in vitro and in vivo, thus contributing to the development of an organism. It has recently become clear that peroxisome proliferator-activated receptor-{beta}/{delta} (PPAR{beta}/{delta}) expression and activation is involved in the cell proliferation. However, little is known about the role of PPAR{beta}/{delta} in EGF-induced proliferation of HaCaT keratinocytes. In this study, HaCaT cells were cultured in the presence and absence of EGF and we identified that EGF induced an increase of PPAR{beta}/{delta} mRNA and protein level expression in time-dependent and dose-dependent manner, and AG1487, an EGF receptor (EGFR) special inhibitor, caused attenuation of PPAR{beta}/{delta} protein expression. Electrophoretic mobility shift assay (EMSA) revealed that EGF significantly increased PPAR{beta}/{delta} binding activity in HaCaT keratinocytes. Antisense phosphorothioate oligonucleotides (asODNs) against PPAR{beta}/{delta} caused selectively inhibition of PPAR{beta}/{delta} protein content induced by EGF and significantly attenuated EGF-mediated cell proliferation. Treatment of the cells with L165041, a specific synthetic ligand for PPAR{beta}/{delta}, significantly enhanced EGF-mediated cell proliferation. Finally, c-Jun ablation inhibited PPAR{beta}/{delta} up-regulation induced by EGF, and chromatin immunoprecipitation (ChIP) showed that c-Jun bound to the PPAR{beta}/{delta} promoter and the binding increased in EGF-stimulated cells. These results demonstrate that EGF induces PPAR{beta}/{delta} expression in a c-Jun-dependent manner and PPAR{beta}/{delta} plays a vital role in EGF-stimulated proliferation of HaCaT cells.

  1. The sediment-starved Yellow River Delta as remotely controlled by human activities in the river basin

    NASA Astrophysics Data System (ADS)

    Wang, H.; Bi, N.

    2015-12-01

    Human presented significant disturbances on the natural processes of land-ocean interactions in context of global change. Here we illustrate how the signals of human activities in the river basin have been transferred to the coastal ocean along the hydrological pathway and remotely controlled the Yellow River Delta. Dam-orientated water and sediment regulation scheme (WSRS) has resulted in effective erosion of the lower channel and mitigation of siltation within the reservoirs. However, significant impacts have been identified on the delta morphology and coastal ecosystem ten years after the WSRS, which was unexpected at the beginning of engineering efforts. The coarser sediment derived from the channel erosion during the first phase of WSRS was directly contributed to the rapid accretion of present river mouth, whereas the delta was starved and declined due to insufficient sediment supply and regime shift of sediment transport. The fine-grained sediment exported from the Xiaolangdi Reservoir during the second phase of WSRS seemed to be a critical carrier for the nutrients and pollutants. The human-altered hydrological cycle, enhanced delivery of nutrient and pollutants and the changing estuarine environment present unpredictable impacts on both terrestrial and aquatic ecosystem in the delta region. These confirm that humans are modifying the river-coast system in ways that go well beyond climate change, and an integrated management of the river-coast continuum is crucially important for the sustainability of the river-delta system.

  2. Translation of moderate-to-vigorous physical activity recommendations into pedometer-based stepping targets in the Lower Mississippi Delta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Lower Mississippi Delta (LMD) region of the United States is characterized by high levels of poverty, physical inactivity, obesity, and related chronic diseases. There is a pressing need to identify new strategies that will increase adherence to physical activity guidelines. Walking is an import...

  3. Steps Ahead: Adaptation of physical activity and dietary guidelines for reducing unhealthy weight gain in the Lower Misissippi Delta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of our study was to test the effectiveness of adapting the Dietary Guidelines for Americans (2010) (DG), with and without a physical activity (PA) component, in reducing weight gain in the Lower Mississippi Delta region (LMD) of the United States. A sample of 121 White and African-Americ...

  4. Comparison of activation effects in {gamma}-ray detector materials

    SciTech Connect

    Truscott, P.R.; Evans, H.E.; Dyer, C.S.; Peerless, C.L.; Flatman, J.C.; Cosby, M.; Knight, P.; Moss, C.E.

    1996-06-01

    Activation induced by cosmic and trapped radiation in {gamma}-ray detector materials represents a significant source of background for space-based detector systems. Selection of detector materials should therefore include consideration of this background source. Results are presented from measurements of induced radioactivity in different scintillators activated either as a result of irradiation by mono-energetic protons at accelerator facilities, or flight on board the Space Shuttle. Radiation transport computer codes are used to help compare the effects observed from the scintillators, by identifying and quantifying the influence on the background spectra from more than one hundred of the radionuclides produced by spallation. For the space experiment data, the simulation results also permit determination of the contributions to detector activation from the different sources of radiation in the Shuttle cabin.

  5. Calibration of the delayed-gamma neutron activation facility

    SciTech Connect

    Ma, R.; Zhao, X.; Rarback, H.M.; Yasumura, S.; Dilmanian, F.A.; Moore, R.I.; Lo Monte, A.F.; Vodopia, K.A.; Liu, H.B.; Economos, C.D.; Nelson, M.E.; Aloia, J.F.; Vaswani, A.N.; Weber, D.A.; Pierson, R.N. Jr.; Joel, D.D.

    1996-02-01

    The delayed-gamma neutron activation facility at Brookhaven National Laboratory was originally calibrated using an anthropomorphic hollow phantom filled with solutions containing predetermined amounts of Ca. However, 99{percent} of the total Ca in the human body is not homogeneously distributed but contained within the skeleton. Recently, an artificial skeleton was designed, constructed, and placed in a bottle phantom to better represent the Ca distribution in the human body. Neutron activation measurements of an anthropomorphic and a bottle (with no skeleton) phantom demonstrate that the difference in size and shape between the two phantoms changes the total body calcium results by less than 1{percent}. To test the artificial skeleton, two small polyethylene jerry-can phantoms were made, one with a femur from a cadaver and one with an artificial bone in exactly the same geometry. The femur was ashed following the neutron activation measurements for chemical analysis of Ca. Results indicate that the artificial bone closely simulates the real bone in neutron activation analysis and provides accurate calibration for Ca measurements. Therefore, the calibration of the delayed-gamma neutron activation system is now based on the new bottle phantom containing an artificial skeleton. This change has improved the accuracy of measurement for total body calcium. Also, the simple geometry of this phantom and the artificial skeleton allows us to simulate the neutron activation process using a Monte Carlo code, which enables us to calibrate the system for human subjects larger and smaller than the phantoms used as standards. {copyright} {ital 1996 American Association of Physicists in Medicine.}

  6. Phosphoinositide-specific phospholipase C-delta 1: effect of monolayer surface pressure and electrostatic surface potentials on activity.

    PubMed

    Rebecchi, M; Boguslavsky, V; Boguslavsky, L; McLaughlin, S

    1992-12-29

    We added phospholipase C-delta 1 (PLC-delta) to the aqueous subphase beneath monolayers formed from mixtures of phosphatidylinositol 4,5-bisphosphate (2% PIP2), phosphatidylserine (33% PS), and phosphatidylcholine (65% PC) and then measured the initial rate of hydrolysis of PIP2 after addition of 10 microM free calcium. Increasing the surface pressure of the monolayer, pi, from 20 to 40 mN/m decreased the rate of hydrolysis 200-fold. The rate of hydrolysis depends exponentially on the surface pressure: rate alpha exp(-pi Ap/kT) where k is the Boltzmann constant, T is the temperature, and Ap congruent to 1 nm2. Similar results were obtained with different (1 and 100 microM) free [Ca2+] and with different mole fractions of PIP2. The results are consistent with a model in which PLC-delta binds to PIP2 with high affinity (Ka = 10(6) M-1) in the absence of calcium ions [Rebecchi, M.J., Peterson, A., & McLaughlin, S. (1993) Biochemistry (preceding paper in this issue)], and a portion of PLC-delta of area Ap inserts into the monolayer doing work = pi Ap prior to hydrolysis of PIP2. Removing the monovalent acidic lipid PS from the monolayer decreases the activity of PLC-delta 4-fold, this effect of PS on activity is similar to the effect of monovalent acidic lipids on the binding of PLC-delta to PIP2 in bilayer vesicles. PMID:1334430

  7. Activation of macrophage peroxisome proliferator-activated receptor-gamma by diclofenac results in the induction of cyclooxygenase-2 protein and the synthesis of anti-inflammatory cytokines.

    PubMed

    Ayoub, Samir S; Botting, Regina M; Joshi, Amrish N; Seed, Michael P; Colville-Nash, Paul R

    2009-07-01

    Cyclooxygenase-2 (COX-2) is an inducible isoform of the COX family of enzymes central to the synthesis of pro-inflammatory prostaglandins. Induction of COX-2 is mediated by many endogenous and exogenous molecules that include pro-inflammatory cytokines and bacterial lipopolysaccharide (LPS). It has been demonstrated that COX-2 can also be induced by diclofenac in cultured J774.2 macrophages. This induction was delayed compared to COX-2 induced by LPS and paracetamol selectively inhibited activity of this protein. The aim of the present study was to determine the transcription factor involved in the production of COX-2 after treatment of J774.2 cells with 500 microM diclofenac. Pre-treatment of cells with the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) antagonists GW9662 (0.1-1 microM) or biphenol A Diglycidyl Ether (100-200 microM) resulted in reduction of the induction of COX-2 by diclofenac, but not by LPS. Induction of COX-2 by the PPAR-gamma agonist 15deoxyDelta(12,14)prostaglandin J(2) was also reduced when the cells were pre-treated with the PPAR-gamma antagonists BADGE or GW9662. On the other hand, pre-treatment of cells with the nuclear factor-kappa-B (NF-kappaB) Super-repressor IkappaBalpha (150-600 nM) reduced the induction of COX-2 by LPS, but not by diclofenac. We, therefore, have identified that PPAR-gamma activation is a requirement for COX-2 induction after diclofenac stimulation of J774.2 cells. These results along with the finding that treatment of J774.2 macrophages with diclofenac resulted in the release of the anti-inflammatory cytokines, interleukin-10 and transforming growth factor-beta suggest that the diclofenac-induced COX-2 protein may possess anti-inflammatory actions. PMID:19219624

  8. Effect of carbonitride dissolution on T{sub {delta}} and V{sub {delta}} of austenitic steels

    SciTech Connect

    Yang Ruzeng; Dai Qixun

    1997-03-01

    The authors deal with the effect of carbide dissolution on the {gamma}/{gamma}+{delta} boundary temperature, T{sub {delta}}, and the {delta} phase volume, V{sub {delta}}, as well as the equilibrium relation between the alloying elements at the {gamma}/{gamma}+{delta} boundary of austenitic steels at high temperature, and study the variation of the ferrite volume with temperature in {alpha}+{gamma} dual phase steel. The relevant expressions are derived from many experimental results, which may provide a basis for quantitative calculation, the design of compositions, the determination of working processes and prediction of the mechanical properties and microstructure of the austenitic steels.

  9. Sedative activity of cannabis in relation to its delta'-trans-tetrahydrocannabinol and cannabidiol content.

    PubMed Central

    Pickens, J. T.

    1981-01-01

    1. The oral sedative potencies of cannabis herb, crude ethanolic and petroleum-ether fractions, were assayed against delta'-trans-tetrahydrocannabinol (THC) administered orally to mice, by measuring spontaneous motor activity over 30 min periods, at selected times, up to 6 h. 2. The THC contents of the extracts were determined chemically by gas-liquid chromatography analysis and the B/C ratio (biological activity divided by chemical activity) calculated for each. The B/C values for cannabis herb, which contained THC but no CBD, was 4.47 and for ethanolic and petroleum-ether extracts, 5.26 and 4.39, respectively. 3. The sedative potency expressed as SDA50, the dose required to give 50% effect over 6 h, was 1.06 (0.98 to 1.15) mg/kg for THC; 4.72 (4.22 to 5.27) mg/kg for cannabidiol and 1.26 (1.22 to 1.80) mg/kg for chlorpromazine. 4. An infusion of cannabis herb made with boiling water was shown to have sedative activity of very low potency. 5. When the cannabinoids were completely extracted from a sample of herb with petroleum-ether the aqueous and ethanolic extracts of the marc had some sedative activity; but the 70% ethanolic fraction had none. 6. The sedative activity of THC, cannabis herb and a water soluble fraction is blocked by aspirin, a cyclo-oxygenase inhibitor, and restored by prostaglandin E2 (PGE2). 7. The sedative effect of chlorpromazine is not blocked by aspirin. PMID:6269680

  10. Ligands for the Nuclear Peroxisome Proliferator-Activated Receptor Gamma.

    PubMed

    Sauer, Sascha

    2015-10-01

    Nuclear receptors are ligand-activated transcription factors, which represent a primary class of drug targets. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is a key player in various biological processes. PPARγ is widely known as the target protein of the thiazolidinediones for treating type 2 diabetes. Moreover, PPARγ ligands can induce anti-inflammatory and potentially additional beneficial effects. Recent mechanistic insights of PPARγ modulation give hope the next generation of efficient PPARγ-based drugs with fewer side effects can be developed. Furthermore, chemical approaches that make use of synergistic action of combinatorial ligands are promising alternatives for providing tailored medicine. Lessons learned from fine-tuning the action of PPARγ can provide avenues for efficient molecular intervention via many other nuclear receptors to combat common diseases. PMID:26435213

  11. Effects of chlorpyrifos ethyl on acetylcholinesterase activity in climbing perch cultured in rice fields in the Mekong Delta, Vietnam.

    PubMed

    Nguyen, Tam Thanh; Berg, Håkan; Nguyen, Hang Thi Thuy; Nguyen, Cong Van

    2015-07-01

    Climbing perch is commonly harvested in rice fields and associated wetlands in the Mekong Delta. Despite its importance in providing food and income to local households, there is little information how this fish species is affected by the high use of pesticides in rice farming. Organophosphate insecticides, such as chlorpyrifos ethyl, which are highly toxic to aquatic organisms, are commonly used in the Mekong Delta. This study shows that the brain acetylcholinesterase (AChE) activity in climbing perch fingerlings cultured in rice fields, was significantly inhibited by a single application of chlorpyrifos ethyl, at doses commonly applied by rice farmers (0.32-0.64 kg/ha). The water concentration of chlorpyrifos ethyl decreased below the detection level within 3 days, but the inhibition of brain AChE activity remained for more than 12 days. In addition, the chlorpyrifos ethyl treatments had a significant impact on the survival and growth rates of climbing perch fingerlings, which were proportional to the exposure levels. The results indicate that the high use of pesticides among rice farmers in the Mekong Delta could have a negative impact on aquatic organisms and fish yields, with implications for the aquatic biodiversity, local people's livelihoods and the aquaculture industry in the Mekong Delta. PMID:25828891

  12. Examination of the mechanism by which heparin antagonizes activation of a model endothelium by interferon-gamma (IFN-gamma).

    PubMed

    Douglas, M S; Rix, D A; Dark, J H; Talbot, D; Kirby, J A

    1997-03-01

    IFN-gamma increases the potential immunogenicity of vascular endothelial cells by up-regulation of intercellular adhesion molecule-1 (ICAM-1) and class I MHC antigen expression and by induction of class II MHC antigens and certain chemokines. In this study the mechanism by which the glycosaminoglycan (GAG) heparin antagonizes the activation of a model endothelium by IFN-gamma was investigated. Radioligand binding assays demonstrated that total binding of 125I-IFN-gamma to the EAhy.926 endothelial hybridoma cell line was reduced in the presence of heparin or heparan sulphate (HS); the structurally dissimilar GAG chondroitin sulphate had no effect. Treatment of the cells with chlorate, a metabolic inhibitor of GAG sulphation, was found to reduce both the subsequent binding of IFN-gamma and its ability to induce expression of class II MHC antigens. Treatment with heparinase II dramatically reduced the binding of IFN-gamma, while chondroitin ABC lyase had no effect. A cationic peptide from the C-terminal region of IFN-gamma was also found to reduce binding of intact IFN-gamma to the cells. These results appear to demonstrate that IFN-gamma is sequestered at the surface of endothelial cells by electrostatic interaction between specific basic amino acid residues and sulphated domains on HS, the most abundant endothelial GAG. This interaction is competitively inhibited by heparin, which is structurally related to HS. These observations are consistent with the model that IFN-gamma is bound by membrane-associated HS before engagement with the high-affinity receptor and signal transduction. Inhibition of the interaction between proinflammatory cytokines and membrane-associated GAG molecules may provide a mechanism for inducing clinically useful immunosuppression. PMID:9067536

  13. Minimum Detectable Activity in gamma spectrometry and its use in low level activity measurements.

    PubMed

    Done, L; Ioan, M-R

    2016-08-01

    In this paper there are described three different algorithms of Minimum Detectable Activity (MDA) calculus, and its use in high resolution gamma spectrometry. In the first part, few introductive theoretical aspects related to the MDA are presented. Further, the theory was applied to real gamma rays spectrometry measurements and the results were compared with the activities reference values. Two different gamma spectrometry systems, both of them using High Purity Germanium (HPGe) detectors, but having different efficiencies, were used. Samples having different geometries and radionuclides content were measured. The measured samples were made by dissolving of some acids containing anthropogenic radionuclides in water, obtaining a density of 1g/cm(3). Choosing this type of matrix was done because of its high homogeneity. PMID:27172893

  14. Gamma band unit activity and population responses in the pedunculopontine nucleus.

    PubMed

    Simon, Christen; Kezunovic, Nebojsa; Ye, Meijun; Hyde, James; Hayar, A; Williams, D K; Garcia-Rill, E

    2010-07-01

    The pedunculopontine nucleus (PPN) is involved in the activated states of waking and paradoxical sleep, forming part of the reticular activating system (RAS). The studies described tested the hypothesis that single unit and/or population responses of PPN neurons are capable of generating gamma band frequency activity. Whole cell patch clamp recordings (immersion chamber) and population responses (interface chamber) were conducted on 9- to 20-day-old rat brain stem slices. Regardless of cell type (I, II, or III) or type of response to the nonselective cholinergic receptor agonist carbachol (excitation, inhibition, biphasic), almost all PPN neurons fired at gamma band frequency, but no higher, when subjected to depolarizing steps (50 +/- 2 Hz, mean +/- SE). Nonaccommodating neurons fired at 18-100 Hz throughout depolarizing steps, while most accommodating neurons exhibited gamma band frequency of action potentials followed by gamma band membrane oscillations. These oscillations were blocked by the sodium channel blocker tetrodotoxin (TTX), suggesting that at least some are mediated by sodium currents. Population responses in the PPN showed that carbachol induced peaks of activation in the theta and gamma range, while glutamatergic receptor agonists induced overall increases in activity at theta and gamma frequencies, although in differing patterns. Gamma band activity appears to be a part of the intrinsic membrane properties of PPN neurons, and the population as a whole generates different patterns of gamma band activity under the influence of specific transmitters. Given sufficient excitation, the PPN may impart gamma band activation on its targets. PMID:20463196

  15. Gamma Band Unit Activity and Population Responses in the Pedunculopontine Nucleus

    PubMed Central

    Simon, Christen; Kezunovic, Nebojsa; Ye, Meijun; Hyde, James; Hayar, A.; Williams, D. K.

    2010-01-01

    The pedunculopontine nucleus (PPN) is involved in the activated states of waking and paradoxical sleep, forming part of the reticular activating system (RAS). The studies described tested the hypothesis that single unit and/or population responses of PPN neurons are capable of generating gamma band frequency activity. Whole cell patch clamp recordings (immersion chamber) and population responses (interface chamber) were conducted on 9- to 20-day-old rat brain stem slices. Regardless of cell type (I, II, or III) or type of response to the nonselective cholinergic receptor agonist carbachol (excitation, inhibition, biphasic), almost all PPN neurons fired at gamma band frequency, but no higher, when subjected to depolarizing steps (50 ± 2 Hz, mean ± SE). Nonaccommodating neurons fired at 18–100 Hz throughout depolarizing steps, while most accommodating neurons exhibited gamma band frequency of action potentials followed by gamma band membrane oscillations. These oscillations were blocked by the sodium channel blocker tetrodotoxin (TTX), suggesting that at least some are mediated by sodium currents. Population responses in the PPN showed that carbachol induced peaks of activation in the theta and gamma range, while glutamatergic receptor agonists induced overall increases in activity at theta and gamma frequencies, although in differing patterns. Gamma band activity appears to be a part of the intrinsic membrane properties of PPN neurons, and the population as a whole generates different patterns of gamma band activity under the influence of specific transmitters. Given sufficient excitation, the PPN may impart gamma band activation on its targets. PMID:20463196

  16. Ethanol Disinhibits Dorsolateral Striatal Medium Spiny Neurons Through Activation of A Presynaptic Delta Opioid Receptor.

    PubMed

    Patton, Mary H; Roberts, Bradley M; Lovinger, David M; Mathur, Brian N

    2016-06-01

    The dorsolateral striatum mediates habit formation, which is expedited by exposure to alcohol. Across species, alcohol exposure disinhibits the DLS by dampening GABAergic transmission onto this structure's principal medium spiny projection neurons (MSNs), providing a potential mechanistic basis for habitual alcohol drinking. However, the molecular and circuit components underlying this disinhibition remain unknown. To examine this, we used a combination of whole-cell patch-clamp recordings and optogenetics to demonstrate that ethanol potently depresses both MSN- and fast-spiking interneuron (FSI)-MSN GABAergic synaptic transmission in the DLS. Concentrating on the powerfully inhibitory FSI-MSN synapse, we further show that acute exposure of ethanol (50 mM) to striatal slices activates delta opioid receptors that reside on FSI axon terminals and negatively couple to adenylyl cyclase to induce a long-term depression of GABA release onto both direct and indirect pathway MSNs. These findings elucidate a mechanism through which ethanol may globally disinhibit the DLS. PMID:26758662

  17. Germa-gamma-lactones as novel inhibitors of bacterial urease activity.

    PubMed

    Amtul, Zareen; Follmer, Cristian; Mahboob, Sumera; Atta-Ur-Rahman; Mazhar, Muhammad; Khan, Khalid M; Siddiqui, Rafat A; Muhammad, Sajjad; Kazmi, Syed A; Choudhary, Mohammad Iqbal

    2007-05-01

    Organogermanium compounds have been used as pharmacological agents. However, very few reports are available on the synthesis and antibacterial activities of lactones containing organogermaniums. The purpose of the present investigation was to determine the effects of different lactone-substituted organogermaniums on bacterial growth and their urease activity. We report synthesis of 12 germa-gamma-lactones (GeL) and their antimicrobial activities against several bacterial pathogens. Antibacterial action of all GeL was highly selective against Gram-negative bacilli, particularly Proteus mirabilis, an important pathogen infecting the urinary tract. Furthermore, our data indicate that 8-quinoline derivatives were more potent against P. mirabilis than 2-methyl-8-quinoline. For example, the beta-(o-methylphenyl)-gamma,gamma-bis(8-quinolinoxy)germa-gamma-lactone and beta-(o-methoxyphenyl)-gamma,gamma-bis(8-quinolinoxy)germa-gamma-lactone were maximally active with MIC(90) of 61 and 94 microM, respectively. In vitro studies demonstrated a linear correlation between antibacterial activity and inhibition of P. mirabilis urease enzyme. Further kinetic analyses revealed that inhibition occurred in a noncompetitive and concentration-dependent manner with the minimum IC(50) of 31 microM for beta-(o-methoxyphenyl)-gamma,gamma-bis(8-quinolinoxy)germa-gamma-lactone. In conclusion, these findings suggest that GeL have potential to be developed as antimicrobial agents against P. mirabilis infection. PMID:17367756

  18. Basal Forebrain Cholinergic Neurons Primarily Contribute to Inhibition of Electroencephalogram Delta Activity, Rather Than Inducing Behavioral Wakefulness in Mice.

    PubMed

    Chen, Li; Yin, Dou; Wang, Tian-Xiao; Guo, Wei; Dong, Hui; Xu, Qi; Luo, Yan-Jia; Cherasse, Yoan; Lazarus, Michael; Qiu, Zi-Long; Lu, Jun; Qu, Wei-Min; Huang, Zhi-Li

    2016-07-01

    The basal forebrain (BF) cholinergic neurons have long been thought to be involved in behavioral wakefulness and cortical activation. However, owing to the heterogeneity of BF neurons and poor selectivity of traditional methods, the precise role of BF cholinergic neurons in regulating the sleep-wake cycle remains unclear. We investigated the effects of cell-selective manipulation of BF cholinergic neurons on the sleep-wake behavior and electroencephalogram (EEG) power spectrum using the pharmacogenetic technique, the 'designer receptors exclusively activated by designer drugs (DREADD)' approach, and ChAT-IRES-Cre mice. Our results showed that activation of BF cholinergic neurons expressing hM3Dq receptors significantly and lastingly decreased the EEG delta power spectrum, produced low-delta non-rapid eye movement sleep, and slightly increased wakefulness in both light and dark phases, whereas inhibition of BF cholinergic neurons expressing hM4Di receptors significantly increased EEG delta power spectrum and slightly decreased wakefulness. Next, the projections of BF cholinergic neurons were traced by humanized Renilla green fluorescent protein (hrGFP). Abundant and highly dense hrGFP-positive fibers were observed in the secondary motor cortex and cingulate cortex, and sparse hrGFP-positive fibers were observed in the ventrolateral preoptic nucleus, a known sleep-related structure. Finally, we found that activation of BF cholinergic neurons significantly increased c-Fos expression in the secondary motor cortex and cingulate cortex, but decreased c-Fos expression in the ventrolateral preoptic nucleus. Taken together, these findings reveal that the primary function of BF cholinergic neurons is to inhibit EEG delta activity through the activation of cerebral cortex, rather than to induce behavioral wakefulness. PMID:26797244

  19. A Church-Based Diet and Physical Activity Intervention for Rural, Lower Mississippi Delta African American Adults: Delta Body and Soul Effectiveness Study, 2010–2011

    PubMed Central

    Thomson, Jessica L.; Mayo, Tanyatta; Edmond, Emanuel

    2013-01-01

    Introduction Obesity, diabetes, and hypertension have reached epidemic levels in the largely rural Lower Mississippi Delta (LMD) region. We assessed the effectiveness of a 6-month, church-based diet and physical activity intervention, conducted during 2010 through 2011, for improving diet quality (measured by the Healthy Eating Index-2005) and increasing physical activity of African American adults in the LMD region. Methods We used a quasi-experimental design in which 8 self-selected eligible churches were assigned to intervention or control. Assessments included dietary, physical activity, anthropometric, and clinical measures. Statistical tests for group comparisons included χ2, Fisher’s exact, and McNemar’s tests for categorical variables, and mixed-model regression analysis for continuous variables and modeling intervention effects. Results Retention rates were 85% (176 of 208) for control and 84% (163 of 195) for intervention churches. Diet quality components, including total fruit, total vegetables, and total quality improved significantly in both control (mean [standard deviation], 0.3 [1.8], 0.2 [1.1], and 3.4 [9.6], respectively) and intervention (0.6 [1.7], 0.3 [1.2], and 3.2 [9.7], respectively) groups, while significant increases in aerobic (22%) and strength/flexibility (24%) physical activity indicators were apparent in the intervention group only. Regression analysis indicated that intervention participation level and vehicle ownership were significant positive predictors of change for several diet quality components. Conclusion This church-based diet and physical activity intervention may be effective in improving diet quality and increasing physical activity of LMD African American adults. Components key to the success of such programs are participant engagement in educational sessions and vehicle access. PMID:23742940

  20. Peroxisome proliferator-activated receptor gamma overexpression suppresses proliferation of human colon cancer cells

    SciTech Connect

    Tsukahara, Tamotsu; Haniu, Hisao

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer We examined the correlation between PPAR{gamma} expression and cell proliferation. Black-Right-Pointing-Pointer PPAR{gamma} overexpression reduces cell viability. Black-Right-Pointing-Pointer We show the synergistic effect of cell growth inhibition by a PPAR{gamma} agonist. -- Abstract: Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) plays an important role in the differentiation of intestinal cells and tissues. Our previous reports indicate that PPAR{gamma} is expressed at considerable levels in human colon cancer cells. This suggests that PPAR{gamma} expression may be an important factor for cell growth regulation in colon cancer. In this study, we investigated PPAR{gamma} expression in 4 human colon cancer cell lines, HT-29, LOVO, DLD-1, and Caco-2. Real-time polymerase chain reaction (PCR) and Western blot analysis revealed that the relative levels of PPAR{gamma} mRNA and protein in these cells were in the order HT-29 > LOVO > Caco-2 > DLD-1. We also found that PPAR{gamma} overexpression promoted cell growth inhibition in PPAR{gamma} lower-expressing cell lines (Caco-2 and DLD-1), but not in higher-expressing cells (HT-29 and LOVO). We observed a correlation between the level of PPAR{gamma} expression and the cells' sensitivity for proliferation.

  1. Analytical Methodologies for Detection of Gamma-Valerolactone, Delta-Valerolactone, Acephate and Azinphos Methyl and Their Associated Metabolites in Complex Biological Matrices

    SciTech Connect

    Zink, E.; Clark, R.; Grant, K.; Campbell, J.; Hoppe, E.

    2005-01-01

    Non-invasive biomonitoring for chemicals of interest in law enforcement and similar monitoring of pesticides, together with their metabolites, can not only save money but can lead to faster medical attention for individuals exposed to these chemicals. This study describes methods developed for the analysis of gamma-valerolactone (GVL), delta-valerolactone (DVL), acephate, and azinphos methyl in saliva and serum. Liquid chromatography/mass spectrometry (LC/MS) operated in the negative and positive ion mode and gas chromatography/mass spectrometry (GC/MS) were used to analyze GVL and DVL. Although both analytical techniques worked well, lower detection limits were obtained with GC/MS. The lactones and their corresponding sodium salts were spiked into both saliva and serum. The lactones were isolated from saliva or serum using newly developed extraction techniques and then subsequently analyzed using GC/MS. The sodium salts of the lactones are nonvolatile and require derivatization prior to analysis by this method. N-methyl-N-(t-butyldimethylsilyl)-trifluoroacetamide (MTBSTFA) was ultimately selected as the reagent for derivatization because the acidic conditions required for reactions with diazomethane caused the salts to undergo intramolecular cyclization to the corresponding lactones. In vitro studies were conducted using rat liver microsomes to determine other metabolites associated with these compounds. Azinphos methyl and acephate are classified as organophosphate pesticides, and are known to be cholinesterase inhibitors in humans and insects, causing neurotoxicity. For this reason they have both exposure and environmental impact implications. These compounds were spiked into serum and saliva and prepared for analysis by GC/MS. Continuation of this research would include analysis by GC/MS under positive ion mode to determine the parent ions of the unknown metabolites. Further research is planned through an in vivo analysis of the lactones and pesticides. These

  2. Analytical Methodologies for Detection of Gamma-valerolactone, Delta-valerolactone, Acephate, and Azinphos Methyl and their Associated Metabolites in Complex Biological Matrices

    SciTech Connect

    Zink, Erika M.; Clark, Ryan J.; Grant, Karen E.; Campbell, James A.; Hoppe, Eric W.

    2005-01-01

    Non-invasive biomonitoring for chemicals of interest in law enforcement and similar monitoring of pesticides together with their metabolites can not only save money but can lead to faster medical attention for individuals exposed to these chemicals. This study describes methods developed for the analysis of gamma-valerolactone (GVL), delta-valerolactone (DVL), acephate, and azinphos methyl in saliva and serum. Liquid chromatography/mass spectrometry (LC/MS) operated in the negative ion mode and in the positive ion mode and gas chromatography/mass spectrometry (GC/MS) were used to analyze GVL and DVL. Although both analytical techniques worked well, lower detection limits were obtained with GC/MS. The lactones and their corresponding sodium salts were spiked into both saliva and serum. The lactones were isolated from saliva or serum using newly developed extraction techniques and then subsequently analyzed using GC/MS. The sodium salts of the lactones are nonvolatile and require derivatization prior to analysis by this method. N-methyl-N-(t-butyldimethylsilyl)-trifluoroacetamide (MTBSTFA) was ultimately selected as the reagent for derivatization because the acidic conditions required for reactions with diazomethane caused the salts to undergo intramolecular cyclization to the corresponding lactones. In vitro studies were conducted using rat liver microsomes to determine other metabolites associated with these compounds. Azinphos methyl and acephate are classified as organophosphate pesticides, and are known to be cholinesterase inhibitors in humans and insects, causing neurotoxicity. For this reason they have both exposure and environmental impact implications. These compounds were spiked into serum and saliva and prepared for analysis by GC/MS. Continuation of this research would include analysis by GC/MS under positive ion mode to determine the parent ions of the unknown metabolites. Further research is planned through an in vivo analysis of the lactones and

  3. Extensive expansion of primary human gamma delta T cells generates cytotoxic effector memory cells that can be labeled with Feraheme for cellular MRI.

    PubMed

    Siegers, Gabrielle M; Ribot, Emeline J; Keating, Armand; Foster, Paula J

    2013-03-01

    Gamma delta T cells (GDTc) comprise a small subset of cytolytic T cells shown to kill malignant cells in vitro and in vivo. We have developed a novel protocol to expand GDTc from human blood whereby GDTc were initially expanded in the presence of alpha beta T cells (ABTc) that were then depleted prior to use. We achieved clinically relevant expansions of up to 18,485-fold total GDTc, with 18,849-fold expansion of the Vδ1 GDTc subset over 21 days. ABTc depletion yielded 88.1 ± 4.2 % GDTc purity, and GDTc continued to expand after separation. Immunophenotyping revealed that expanded GDTc were mostly CD27-CD45RA- and CD27-CD45RA+ effector memory cells. GDTc cytotoxicity against PC-3M prostate cancer, U87 glioblastoma and EM-2 leukemia cells was confirmed. Both expanded Vδ1 and Vδ2 GDTc were cytotoxic to PC-3M in a T cell antigen receptor- and CD18-dependent manner. We are the first to label GDTc with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles for cellular MRI. Using protamine sulfate and magnetofection, we achieved up to 40 % labeling with clinically approved Feraheme (Ferumoxytol), as determined by enumeration of Perls' Prussian blue-stained cytospins. Electron microscopy at 2,800× magnification verified the presence of internalized clusters of iron oxide; however, high iron uptake correlated negatively with cell viability. We found improved USPIO uptake later in culture. MRI of GDTc in agarose phantoms was performed at 3 Tesla. The signal-to-noise ratios for unlabeled and labeled cells were 56 and 21, respectively. Thus, Feraheme-labeled GDTc could be readily detected in vitro via MRI. PMID:23100099

  4. Cell death is induced by ciglitazone, a peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) agonist, independently of PPAR{gamma} in human glioma cells

    SciTech Connect

    Lee, Myoung Woo; Kim, Dae Seong; Kim, Hye Ryung; Kim, Hye Jin; Yang, Jin Mo; Ryu, Somi; Noh, Yoo Hun; Lee, Soo Hyun; Son, Meong Hi; Jung, Hye Lim; Yoo, Keon Hee; Koo, Hong Hoe; Sung, Ki Woong

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Greater than 30 {mu}M ciglitazone induces cell death in glioma cells. Black-Right-Pointing-Pointer Cell death by ciglitazone is independent of PPAR{gamma} in glioma cells. Black-Right-Pointing-Pointer CGZ induces cell death by the loss of MMP via decreased Akt. -- Abstract: Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) regulates multiple signaling pathways, and its agonists induce apoptosis in various cancer cells. However, their role in cell death is unclear. In this study, the relationship between ciglitazone (CGZ) and PPAR{gamma} in CGZ-induced cell death was examined. At concentrations of greater than 30 {mu}M, CGZ, a synthetic PPAR{gamma} agonist, activated caspase-3 and induced apoptosis in T98G cells. Treatment of T98G cells with less than 30 {mu}M CGZ effectively induced cell death after pretreatment with 30 {mu}M of the PPAR{gamma} antagonist GW9662, although GW9662 alone did not induce cell death. This cell death was also observed when cells were co-treated with CGZ and GW9662, but was not observed when cells were treated with CGZ prior to GW9662. In cells in which PPAR{gamma} was down-regulated cells by siRNA, lower concentrations of CGZ (<30 {mu}M) were sufficient to induce cell death, although higher concentrations of CGZ ( Greater-Than-Or-Slanted-Equal-To 30 {mu}M) were required to induce cell death in control T98G cells, indicating that CGZ effectively induces cell death in T98G cells independently of PPAR{gamma}. Treatment with GW9662 followed by CGZ resulted in a down-regulation of Akt activity and the loss of mitochondrial membrane potential (MMP), which was accompanied by a decrease in Bcl-2 expression and an increase in Bid cleavage. These data suggest that CGZ is capable of inducing apoptotic cell death independently of PPAR{gamma} in glioma cells, by down-regulating Akt activity and inducing MMP collapse.

  5. Visual Cortical Gamma-Band Activity During Free Viewing of Natural Images

    PubMed Central

    Brunet, Nicolas; Bosman, Conrado A.; Roberts, Mark; Oostenveld, Robert; Womelsdorf, Thilo; De Weerd, Peter; Fries, Pascal

    2015-01-01

    Gamma-band activity in visual cortex has been implicated in several cognitive operations, like perceptual grouping and attentional selection. So far, it has been studied primarily under well-controlled visual fixation conditions and using well-controlled stimuli, like isolated bars or patches of grating. If gamma-band activity is to subserve its purported functions outside of the laboratory, it should be present during natural viewing conditions. We recorded neuronal activity with a 252-channel electrocorticographic (ECoG) grid covering large parts of the left hemisphere of 2 macaque monkeys, while they freely viewed natural images. We found that natural viewing led to pronounced gamma-band activity in the visual cortex. In area V1, gamma-band activity during natural viewing showed a clear spectral peak indicative of oscillatory activity between 50 and 80 Hz and was highly significant for each of 65 natural images. Across the ECoG grid, gamma-band activity during natural viewing was present over most of the recorded visual cortex and absent over most remaining cortex. After saccades, the gamma peak frequency slid down to 30–40 Hz at around 80 ms postsaccade, after which the sustained 50- to 80-Hz gamma-band activity resumed. We propose that gamma-band activity plays an important role during natural viewing. PMID:24108806

  6. Nile Delta

    Atmospheric Science Data Center

    2013-04-15

    article title:  The Nile River Delta     View Larger Image ... of eastern Africa. At the apex of the fertile Nile River Delta is the Egyptian capital city of Cairo. To the west are the Great Pyramids ...

  7. Peroxisome proliferator-activated receptor-delta agonist ameliorated inflammasome activation in nonalcoholic fatty liver disease

    PubMed Central

    Lee, Hyun Jung; Yeon, Jong Eun; Ko, Eun Jung; Yoon, Eileen L; Suh, Sang Jun; Kang, Keunhee; Kim, Hae Rim; Kang, Seoung Hee; Yoo, Yang Jae; Je, Jihye; Lee, Beom Jae; Kim, Ji Hoon; Seo, Yeon Seok; Yim, Hyung Joon; Byun, Kwan Soo

    2015-01-01

    AIM: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors (PPAR)-δ agonist treatment in nonalcoholic fatty liver disease (NAFLD) models. METHODS: Male C57BL/6J mice were classified according to control or high fat diet (HFD) with or without PPAR-δ agonist (GW) over period of 12 wk [control, HFD, HFD + lipopolysaccharide (LPS), HFD + LPS + GW group]. HepG2 cells were exposed to palmitic acid (PA) and/or LPS in the absence or presence of GW. RESULTS: HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin (IL)-1β in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In HepG2 cells, PA and LPS treatment markedly increased mRNA of several nucleotide-binding and oligomerization domain-like receptor family members (NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1β. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-α. CONCLUSION: PPAR-δ agonist reduces fatty acid-induced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD. PMID:26668503

  8. {delta}-Opioid receptor-stimulated Akt signaling in neuroblastoma x glioma (NG108-15) hybrid cells involves receptor tyrosine kinase-mediated PI3K activation

    SciTech Connect

    Heiss, Anika; Ammer, Hermann; Eisinger, Daniela A.

    2009-07-15

    {delta}-Opioid receptor (DOR) agonists possess cytoprotective properties, an effect associated with activation of the 'pro-survival' kinase Akt. Here we delineate the signal transduction pathway by which opioids induce Akt activation in neuroblastoma x glioma (NG108-15) hybrid cells. Exposure of the cells to both [D-Pen{sup 2,5}]enkephalin and etorphine resulted in a time- and dose-dependent increase in Akt activity, as measured by means of an activation-specific antibody recognizing phosphoserine-473. DOR-mediated Akt signaling is blocked by the opioid antagonist naloxone and involves inhibitory G{sub i/o} proteins, because pre-treatment with pertussis toxin, but not over-expression of the G{sub q/11} scavengers EBP50 and GRK2-K220R, prevented this effect. Further studies with Wortmannin and LY294002 revealed that phophoinositol-3-kinase (PI3K) plays a central role in opioid-induced Akt activation. Opioids stimulate Akt activity through transactivation of receptor tyrosine kinases (RTK), because pre-treatment of the cells with inhibitors for neurotrophin receptor tyrosine kinases (AG879) and the insulin-like growth factor receptor IGF-1 (AG1024), but not over-expression of the G{beta}{gamma} scavenger phosducin, abolished this effect. Activated Akt translocates to the nuclear membrane, where it promotes GSK3 phosphorylation and prevents caspase-3 cleavage, two key events mediating inhibition of cell apoptosis and enhancement of cell survival. Taken together, these results demonstrate that in NG108-15 hybrid cells DOR agonists possess cytoprotective properties mediated by activation of the RTK/PI3K/Akt signaling pathway.

  9. Activity profiles of dalargin and its analogues in mu-, delta- and kappa-opioid receptor selective bioassays.

    PubMed

    Pencheva, N; Pospisek, J; Hauzerova, L; Barth, T; Milanov, P

    1999-10-01

    1. To elucidate the structural features ensuring action of [D-Ala2, Leu5]-enkephalyl-Arg (dalargin), a series of dalargin analogues were tested for their effectiveness in depressing electrically-evoked contractions of the guinea-pig myenteric plexus-longitudinal muscle preparations (mu- and kappa-opioid receptors) and the vasa deferentia of the hamster (delta-opioid receptors), mouse (mu-, delta- and kappa-opioid receptors), rat (similar to mu-opioid receptors) and rabbit (kappa-opioid receptors). The naloxone KB values in the myenteric plexus were also obtained. 2. [L-Ala2]-dalargin was 19 times less potent than dalargin, and its pharmacological activity was peptidase-sensitive. The ratio of delta-activity to mu-activity for [L-Ala2]-dalargin was 6.78, and KB was 7.9 nM. This emphasizes the role that D-configuration of Ala2 plays in determining the active folding of dalargin molecule as well as in conferring resistance to peptidases. 3. [Met5]-dalargin was equipotent to dalargin in the myenteric plexus, but was more potent in the vasa deferentia of hamster and mouse (KB=5.5 nM). Leu5 and the interdependence of Leu5 and D-Ala2 are of importance for the selectivity of dalargin for mu-opioid receptors. 4. Dalarginamide was more potent and selective for mu-opioid receptors than dalargin, whilst dalarginethylamide, though equipotent to dalarginamide in the myenteric plexus, was more potent at delta-opioid receptors (KB=5.0 nM). [D-Phe4]-dalarginamide and N-Me-[D-Phe4]-dalarginamide were inactive indicating the contribution of L-configuration of Phe4 to the pharmacological potency of dalargin. 5. N-Me-[L-Phe4]-dalarginamide possessed the highest potency and selectivity for mu-opioid receptors (the ratio of delta-activity to mu-activity was 0.00053; KB=2.6 nM). The CONH2 terminus combined with the N-methylation of L-Phe4 increased the potency and selectivity of dalargin for mu-opioid receptors. PMID:10516634

  10. Mosquitoes and the Environment in Nile Delta Villages with Previous Rift Valley Fever Activity.

    PubMed

    Zayed, Abdelbaset B; Britch, Seth C; Soliman, Mohamed I; Linthicum, Kenneth J

    2015-06-01

    Egypt is affected by serious human and animal mosquito-borne diseases such as Rift Valley fever (RVF). We investigated how potential RVF virus mosquito vector populations are affected by environmental conditions in the Nile Delta region of Egypt by collecting mosquitoes and environmental data from 3 key governorates before and after 2012 seasonal flooding. We found that environmental effects varied among species, life stages, pre- and postflood groupings, and geographic populations of the same species, and that mosquito community composition could change after flooding. Our study provides preliminary data for modeling mosquitoes and mosquito-borne diseases in the Nile Delta region. PMID:26181689

  11. The WISE Gamma-Ray Strip Parametrization: The Nature of the Gamma-Ray Active Galactic Nuclei of Uncertain Type

    SciTech Connect

    Massaro, F.; D'Abrusco, R.; Tosti, G.; Ajello, M.; Gasparrini, D.; Grindlay, J.E.; Smith, Howard A.; /Harvard-Smithsonian Ctr. Astrophys.

    2012-04-02

    Despite the large number of discoveries made recently by Fermi, the origins of the so called unidentified {gamma}-ray sources remain unknown. The large number of these sources suggests that among them there could be a population that significantly contributes to the isotropic gamma-ray background and is therefore crucial to understand their nature. The first step toward a complete comprehension of the unidentified {gamma}-ray source population is to identify those that can be associated with blazars, the most numerous class of extragalactic sources in the {gamma}-ray sky. Recently, we discovered that blazars can be recognized and separated from other extragalactic sources using the infrared (IR) WISE satellite colors. The blazar population delineates a remarkable and distinctive region of the IR color-color space, the WISE blazar strip. In particular, the subregion delineated by the {gamma}-ray emitting blazars is even narrower and we named it as the WISE Gamma-ray Strip (WGS). In this paper we parametrize the WGS on the basis of a single parameter s that we then use to determine if {gamma}-ray Active Galactic Nuclei of the uncertain type (AGUs) detected by Fermi are consistent with the WGS and so can be considered blazar candidates. We find that 54 AGUs out of a set 60 analyzed have IR colors consistent with the WGS; only 6 AGUs are outliers. This result implies that a very high percentage (i.e., in this sample about 90%) of the AGUs detected by Fermi are indeed blazar candidates.

  12. Effect of cold rolling on the precipitation behavior of {delta} phase in INCONEL 718

    SciTech Connect

    Liu, W.C.; Yao, M.; Chen, Z.L.

    1999-01-01

    Systematic research has been undertaken on the effect of cold rolling on the precipitation kinetics of {delta} phase in INCONEL 718. Above 910 C, cold rolling promotes the precipitation of {delta} phase. Below 910 C, the precipitation of {delta} phase is still preceded by the {gamma}{double_prime} precipitation in cold-rolled INCONEL 718. Cold rolling promotes not only the precipitation of {gamma}{double_prime} phase but also the {gamma}{double_prime} {r_arrow} {delta} transformation. The relationship between the weight percentage of {delta} phase and aging time follows the Avrami equation. Below 910 C, as cold rolling reduction and temperature increase, the time exponent (n) decreases, whereas the rate of {delta} precipitation increases. The apparent activation energy of {delta} precipitation varies in the range of 1113 to 577 kJ/mol for 25 to 65% cold-rolled INCONEL 718 and decreases as cold rolling reduction increases. Precipitation-time-temperature (PTT) diagrams have been determined for the four cold-rolled INCONEL 718. The noses of the PTT curves are located at about 910 C. These curves are shifted significantly to longer times as cold rolling reductions decrease.

  13. Delta Opioid activation of the Mitogen-activated protein kinase cascade does not require transphosphorylation of Receptor Tyrosine Kinases

    PubMed Central

    Kramer, H Kenneth; Onoprishvili, Irma; Andria, Matthew L; Hanna, Kayane; Sheinkman, Karina; Haddad, Lisa B; Simon, Eric J

    2002-01-01

    Background In this study, we investigated the mechanism(s) by which delta opioids induce their potent activation of extracellular signal-regulated protein kinases (ERKs) in different cell lines expressing the cloned δ-opioid receptor (δ-OR). While it has been known for some time that OR stimulation leads to the phosphorylation of both ERK isoforms, the exact progression of events has remained elusive. Results Our results indicate that the transphosphorylation of an endogenous epidermal growth factor receptor (EGFR) in the human embryonic kidney (HEK-293) cell line does not occur when co-expressed δ-ORs are stimulated by the δ-opioid agonist, D-Ser-Leu-enkephalin-Thr (DSLET). Moreover, neither pre-incubation of cultures with the selective EGFR antagonist, AG1478, nor down-regulation of the EGFR to a point where EGF could no longer activate ERKs had an inhibitory effect on ERK activation by DSLET. These results appear to rule out any structural or catalytic role for the EGFR in the δ-opioid-mediated MAPK cascade. To confirm these results, we used C6 glioma cells, a cell line devoid of the EGFR. In δ-OR-expressing C6 glioma cells, opioids produce a robust phosphorylation of ERK 1 and 2, whereas EGF has no stimulatory effect. Furthermore, antagonists to the RTKs that are endogenously expressed in C6 glioma cells (insulin receptor (IR) and platelet-derived growth factor receptor (PDGFR)) were unable to reduce opioid-mediated ERK activation. Conclusion Taken together, these data suggest that the transactivation of resident RTKs does not appear to be required for OR-mediated ERK phosphorylation and that the tyrosine-phosphorylated δ-OR, itself, is likely to act as its own signalling scaffold. PMID:11897012

  14. Reduction in cortical gamma synchrony during depolarized state of slow wave activity in mice

    PubMed Central

    Hwang, Eunjin; McNally, James M.; Choi, Jee Hyun

    2013-01-01

    EEG gamma band oscillations have been proposed to account for the neural synchronization crucial for perceptual integration. While increased gamma power and synchronization is generally observed during cognitive tasks performed during wake, several studies have additionally reported increased gamma power during sleep or anesthesia, raising questions about the characteristics of gamma oscillation during impaired consciousness and its role in conscious processing. Phase-amplitude modulation has been observed between slow wave activity (SWA, 0.5–4 Hz) and gamma oscillations during ketamine/xylazine anesthesia or sleep, showing increased gamma activity corresponding to the depolarized (ON) state of SWA. Here we divided gamma activity into its ON and OFF (hyperpolarized) state components based on the phase of SWA induced by ketamine/xylazine anesthesia and compared their power and synchrony with wake state levels in mice. We further investigated the state-dependent changes in both gamma power and synchrony across primary motor and primary somatosensory cortical regions and their interconnected thalamic regions throughout anesthesia and recovery. As observed previously, gamma power was as high as during wake specifically during the ON state of SWA. However, the synchrony of this gamma activity between somatosensory-motor cortical regions was significantly reduced compared to the baseline wake state. In addition, the somatosensory-motor cortical synchrony of gamma oscillations was reduced and restored in an anesthetic state-dependent manner, reflecting the changing depth of anesthesia. Our results provide evidence that during anesthesia changes in long-range information integration between cortical regions might be more critical for changes in consciousness than changes in local gamma oscillatory power. PMID:24379760

  15. 3D modeling, ligand binding and activation studies of the cloned mouse delta, mu; and kappa opioid receptors.

    PubMed

    Filizola, M; Laakkonen, L; Loew, G H

    1999-11-01

    Refined 3D models of the transmembrane domains of the cloned delta, mu and kappa opioid receptors belonging to the superfamily of G-protein coupled receptors (GPCRs) were constructed from a multiple sequence alignment using the alpha carbon template of rhodopsin recently reported. Other key steps in the procedure were relaxation of the 3D helix bundle by unconstrained energy optimization and assessment of the stability of the structure by performing unconstrained molecular dynamics simulations of the energy optimized structure. The results were stable ligand-free models of the TM domains of the three opioid receptors. The ligand-free delta receptor was then used to develop a systematic and reliable procedure to identify and assess putative binding sites that would be suitable for similar investigation of the other two receptors and GPCRs in general. To this end, a non-selective, 'universal' antagonist, naltrexone, and agonist, etorphine, were used as probes. These ligands were first docked in all sites of the model delta opioid receptor which were sterically accessible and to which the protonated amine of the ligands could be anchored to a complementary proton-accepting residue. Using these criteria, nine ligand-receptor complexes with different binding pockets were identified and refined by energy minimization. The properties of all these possible ligand-substrate complexes were then examined for consistency with known experimental results of mutations in both opioid and other GPCRs. Using this procedure, the lowest energy agonist-receptor and antagonist-receptor complexes consistent with these experimental results were identified. These complexes were then used to probe the mechanism of receptor activation by identifying differences in receptor conformation between the agonist and the antagonist complex during unconstrained dynamics simulation. The results lent support to a possible activation mechanism of the mouse delta opioid receptor similar to that recently

  16. Mosquitoes and the environment in Nile Delta villages with previous rift valley fever activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Egypt is affected by serious human and animal mosquito-borne diseases such as Rift Valley fever (RVF). We investigated how potential RVF virus mosquito vector populations are affected by environmental conditions in the Nile Delta region of Egypt by collecting mosquitoes and environmental data from t...

  17. Synthetic method and biological activities of cis-fused alpha-methylene gamma-lactones.

    PubMed

    Higuchi, Yohsuke; Shimoma, Fumito; Ando, Masayoshi

    2003-06-01

    A reliable method was developed for the synthesis of cis-fused alpha-methylene gamma-lactones via alpha-methyl gamma-lactones. Bromination of alpha-methyl gamma-lactones with LDA/CBr(4) or TMSOTf/PTAB and successive dehydrobromination with DBU or TBAF of the resulting alpha-bromo-alpha-methyl gamma-lactones gave the desired alpha-methylene gamma-lactones in high yield. This method was successfully applied to the synthesis of biologically active compounds. alpha-Methylene gamma-lactone derivatives 1c, 2c, 4c, and 17 showed cell growth inhibitory activity to P388 lymphocytic leukemia. They also showed significant activities to crop diseases. Thus, alpha-methylene gamma-lactone 1c showed preventive activity in controlling scab of apple caused by Venturia inaequalis. alpha-Methylene gamma-lactones 2c, 4c, 17, and 18 also showed significant preventive activities in controlling damping off of cucumber caused by Pythium aphanidermatum. PMID:12828467

  18. Coincidence Prompt Gamma-Ray Neutron Activation Analysis

    SciTech Connect

    R.P. gandner; C.W. Mayo; W.A. Metwally; W. Zhang; W. Guo; A. Shehata

    2002-11-10

    The normal prompt gamma-ray neutron activation analysis for either bulk or small beam samples inherently has a small signal-to-noise (S/N) ratio due primarily to the neutron source being present while the sample signal is being obtained. Coincidence counting offers the possibility of greatly reducing or eliminating the noise generated by the neutron source. The present report presents our results to date on implementing the coincidence counting PGNAA approach. We conclude that coincidence PGNAA yields: (1) a larger signal-to-noise (S/N) ratio, (2) more information (and therefore better accuracy) from essentially the same experiment when sophisticated coincidence electronics are used that can yield singles and coincidences simultaneously, and (3) a reduced (one or two orders of magnitude) signal from essentially the same experiment. In future work we will concentrate on: (1) modifying the existing CEARPGS Monte Carlo code to incorporate coincidence counting, (2) obtaining coincidence schemes for 18 or 20 of the common elements in coal and cement, and (3) optimizing the design of a PGNAA coincidence system for the bulk analysis of coal.

  19. O-GlcNAc modification of PPAR{gamma} reduces its transcriptional activity

    SciTech Connect

    Ji, Suena; Park, Sang Yoon; Roth, Juergen; Kim, Hoe Suk; Cho, Jin Won

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer We found that PPAR{gamma} is modified by O-GlcNAc in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer The Thr54 of PPAR{gamma}1 is the major O-GlcNAc site. Black-Right-Pointing-Pointer Transcriptional activity of PPAR{gamma}1 was decreased on treatment with the OGA inhibitor. -- Abstract: The peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), a member of the nuclear receptor superfamily, is a key regulator of adipogenesis and is important for the homeostasis of the adipose tissue. The {beta}-O-linked N-acetylglucosamine (O-GlcNAc) modification, a posttranslational modification on various nuclear and cytoplasmic proteins, is involved in the regulation of protein function. Here, we report that PPAR{gamma} is modified by O-GlcNAc in 3T3-L1 adipocytes. Mass spectrometric analysis and mutant studies revealed that the threonine 54 of the N-terminal AF-1 domain of PPAR{gamma} is the major O-GlcNAc site. Transcriptional activity of wild type PPAR{gamma} was decreased 30% by treatment with the specific O-GlcNAcase (OGA) inhibitor, but the T54A mutant of PPAR{gamma} did not respond to inhibitor treatment. In 3T3-L1 cells, an increase in O-GlcNAc modification by OGA inhibitor reduced PPAR{gamma} transcriptional activity and terminal adipocyte differentiation. Our results suggest that the O-GlcNAc state of PPAR{gamma} influences its transcriptional activity and is involved in adipocyte differentiation.

  20. Controlling nuclear JAKs and STATs for specific gene activation by IFN{gamma}

    SciTech Connect

    Noon-Song, Ezra N.; Ahmed, Chulbul M.; Dabelic, Rea; Canton, Johnathan; Johnson, Howard M.

    2011-07-08

    Highlights: {yields} Gamma interferon (IFN{gamma}) and its receptor subunit, IFNGR1, interact with the promoter region of IFN{gamma}-associated genes along with transcription factor STAT1{alpha}. {yields} We show that activated Janus kinases pJAK2 and pJAK1 also associate with IFNGR1 in the nucleus. {yields} The activated Janus kinases are responsible for phosphorylation of tyrosine 41 on histone H3, an important epigenetic event for specific gene activation. -- Abstract: We previously showed that gamma interferon (IFN{gamma}) and its receptor subunit, IFNGR1, interacted with the promoter region of IFN{gamma}-activated genes along with transcription factor STAT1{alpha}. Recent studies have suggested that activated Janus kinases pJAK2 and pJAK1 also played a role in gene activation by phosphorylation of histone H3 on tyrosine 41. This study addresses the question of the role of activated JAKs in specific gene activation by IFN{gamma}. We carried out chromatin immunoprecipitation (ChIP) followed by PCR in IFN{gamma} treated WISH cells and showed association of pJAK1, pJAK2, IFNGR1, and STAT1 on the same DNA sequence of the IRF-1 gene promoter. The {beta}-actin gene, which is not activated by IFN{gamma}, did not show this association. The movement of activated JAK to the nucleus and the IRF-1 promoter was confirmed by the combination of nuclear fractionation, confocal microscopy and DNA precipitation analysis using the biotinylated GAS promoter. Activated JAKs in the nucleus was associated with phosphorylated tyrosine 41 on histone H3 in the region of the GAS promoter. Unphosphorylated JAK2 was found to be constitutively present in the nucleus and was capable of undergoing activation in IFN{gamma} treated cells, most likely via nuclear IFNGR1. Association of pJAK2 and IFNGR1 with histone H3 in IFN{gamma} treated cells was demonstrated by histone H3 immunoprecipitation. Unphosphorylated STAT1 protein was associated with histone H3 of untreated cells. IFN{gamma

  1. Effects of Muslims praying (Salat) on EEG gamma activity.

    PubMed

    Doufesh, Hazem; Ibrahim, Fatimah; Safari, Mohammad

    2016-08-01

    This study investigates the difference of mean gamma EEG power between actual and mimic Salat practices in twenty healthy Muslim subjects. In the actual Salat practice, the participants were asked to recite and performing the physical steps in all four stages of Salat; whereas in the mimic Salat practice, they were instructed to perform only the physical steps without recitation. The gamma power during actual Salat was statistically higher than during mimic Salat in the frontal and parietal regions in all stages. In the actual Salat practice, the left hemisphere exhibited significantly higher mean gamma power in all cerebral regions and all stages, except the central-parietal region in the sitting position, and the frontal area in the bowing position. Increased gamma power during Salat, possibly related to an increase in cognitive and attentional processing, supports the concept of Salat as a focus attention meditation. PMID:27502795

  2. Selective activation of p38alpha and p38gamma by hypoxia. Role in regulation of cyclin D1 by hypoxia in PC12 cells.

    PubMed

    Conrad, P W; Rust, R T; Han, J; Millhorn, D E; Beitner-Johnson, D

    1999-08-13

    Hypoxic/ischemic trauma is a primary factor in the pathology of a multitude of disease states. The effects of hypoxia on the stress- and mitogen-activated protein kinase signaling pathways were studied in PC12 cells. Exposure to moderate hypoxia (5% O(2)) progressively stimulated phosphorylation and activation of p38gamma in particular, and also p38alpha, two stress-activated protein kinases. In contrast, hypoxia had no effect on enzyme activity of p38beta, p38beta(2), p38delta, or on c-Jun N-terminal kinase, another stress-activated protein kinase. Prolonged hypoxia also induced phosphorylation and activation of p42/p44 mitogen-activated protein kinase, although this activation was modest compared with nerve growth factor- and ultraviolet light-induced activation. Hypoxia also dramatically down-regulated immunoreactivity of cyclin D1, a gene that is known to be regulated negatively by p38 at the level of gene expression (Lavoie, J. N., L'Allemain, G., Brunet, A., Muller, R., and Pouyssegur, J. (1996) J. Biol. Chem. 271, 20608-20616). This effect was partially blocked by SB203580, an inhibitor of p38alpha but not p38gamma. Overexpression of a kinase-inactive form of p38gamma was also able to reverse in part the effect of hypoxia on cyclin D1 levels, suggesting that p38alpha and p38gamma converge to regulate cyclin D1 during hypoxia. These studies demonstrate that an extremely typical physiological stress (hypoxia) causes selective activation of specific p38 signaling elements; and they also identify a downstream target of these pathways. PMID:10438538

  3. Activation of AMPK alpha and gamma-isoform complexes in the intact ischemic rat heart

    Technology Transfer Automated Retrieval System (TEKTRAN)

    AMP-activated protein kinase (AMPK) plays a key role in modulating cellular metabolic processes. AMPK, a serine-threonine kinase, is a heterotrimeric complex of catalytic alpha-subunits and regulatory beta- and gamma-subunits with multiple isoforms. Mutations in the cardiac gamma(2)-isoform have bee...

  4. IL-7 splicing variant IL-7{delta}5 induces human breast cancer cell proliferation via activation of PI3K/Akt pathway

    SciTech Connect

    Pan, Deshun; Liu, Bing; Jin, Xiaobao; Zhu, Jiayong

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer This study confirms the role of IL-7{delta}5 in breast cancer cell proliferation. Black-Right-Pointing-Pointer IL-7{delta}5 promotes breast cancer cell proliferation and cell cycle progression. Black-Right-Pointing-Pointer IL-7{delta}5 promotes cell proliferation via activation of PI3K/Akt pathway. -- Abstract: Various tumor cells express interleukin 7 (IL-7) and IL-7 variants. IL-7 has been confirmed to stimulate solid tumor cell proliferation. However, the effect of IL-7 variants on tumor cell proliferation remains unclear. In this study, we evaluated the role of IL-7{delta}5 (an IL-7 variant lacking exon 5) on proliferation and cell cycle progression of human MDA-MB-231 and MCF-7 breast cancer cells. The results showed that IL-7{delta}5 promoted cell proliferation and cell cycle progression from G1 phase to G2/M phase, associated with upregulation of cyclin D1 expression and the downregulation of p27{sup kip1} expression. Mechanistically, we found that IL-7{delta}5 induced the activation of Akt. Inhibition of PI3K/Akt pathway by LY294002 reversed the proliferation and cell cycle progression of MDA-MB-231 and MCF-7 cells induced by IL-7{delta}5. In conclusion, our findings demonstrate that IL-7{delta}5 variant induces human breast cancer cell proliferation and cell cycle progression via activation of PI3K/Akt pathway. Thus, IL-7{delta}5 may be a potential target for human breast cancer therapeutics intervention.

  5. Gamma-ray bursts, QSOs and active galaxies.

    PubMed

    Burbidge, Geoffrey

    2007-05-15

    The similarity of the absorption spectra of gamma-ray burst (GRB) sources or afterglows with the absorption spectra of quasars (QSOs) suggests that QSOs and GRB sources are very closely related. Since most people believe that the redshifts of QSOs are of cosmological origin, it is natural to assume that GRBs or their afterglows also have cosmological redshifts. For some years a few of us have argued that there is much optical evidence suggesting a very different model for QSOs, in which their redshifts have a non-cosmological origin, and are ejected from low-redshift active galaxies. In this paper I extend these ideas to GRBs. In 2003, Burbidge (Burbidge 2003 Astrophys. J. 183, 112-120) showed that the redshift periodicity in the spectra of QSOs appears in the redshift of GRBs. This in turn means that both the QSOs and the GRB sources are similar objects ejected from comparatively low-redshift active galaxies. It is now clear that many of the GRBs of low redshift do appear in, or very near, active galaxies.A new and powerful result supporting this hypothesis has been produced by Prochter et al. (Prochter et al. 2006 Astrophys. J. Lett. 648, L93-L96). They show that in a survey for strong MgII absorption systems along the sightlines to long-duration GRBs, nearly every sightline shows at least one absorber. If the absorbers are intervening clouds or galaxies, only a small fraction should show absorption of this kind. The number found by Prochter et al. is four times higher than that normally found for the MgII absorption spectra of QSOs. They believe that this result is inconsistent with the intervening hypothesis and would require a statistical fluctuation greater than 99.1% probability. This is what we expect if the absorption is intrinsic to the GRBs and the redshifts are not associated with their distances. In this case, the absorption must be associated with gas ejected from the QSO. This in turn implies that the GRBs actually originate in comparatively low

  6. Dopaminergic neurotoxicant 6-OHDA induces oxidative damage through proteolytic activation of PKC{delta} in cell culture and animal models of Parkinson's disease

    SciTech Connect

    Latchoumycandane, Calivarathan; Anantharam, Vellareddy; Jin, Huajun; Kanthasamy, Anumantha; Kanthasamy, Arthi

    2011-11-15

    The neurotoxicant 6-hydroxydopamine (6-OHDA) is used to investigate the cellular and molecular mechanisms underlying selective degeneration of dopaminergic neurons in Parkinson's disease (PD). Oxidative stress and caspase activation contribute to the 6-OHDA-induced apoptotic cell death of dopaminergic neurons. In the present study, we sought to systematically characterize the key downstream signaling molecule involved in 6-OHDA-induced dopaminergic degeneration in cell culture and animal models of PD. Treatment of mesencephalic dopaminergic neuronal N27 cells with 6-OHDA (100 {mu}M) for 24 h significantly reduced mitochondrial activity and increased cytosolic cytochrome c, followed by sequential activation of caspase-9 and caspase-3. Co-treatment with the free radical scavenger MnTBAP (10 {mu}M) significantly attenuated 6-OHDA-induced caspase activities. Interestingly, 6-OHDA induced proteolytic cleavage and activation of protein kinase C delta (PKC{delta}) was completely suppressed by treatment with a caspase-3-specific inhibitor, Z-DEVD-FMK (50 {mu}M). Furthermore, expression of caspase-3 cleavage site-resistant mutant PKC{delta}{sup D327A} and kinase dead PKC{delta}{sup K376R} or siRNA-mediated knockdown of PKC{delta} protected against 6-OHDA-induced neuronal cell death, suggesting that caspase-3-dependent PKC{delta} promotes oxidative stress-induced dopaminergic degeneration. Suppression of PKC{delta} expression by siRNA also effectively protected N27 cells from 6-OHDA-induced apoptotic cell death. PKC{delta} cleavage was also observed in the substantia nigra of 6-OHDA-injected C57 black mice but not in control animals. Viral-mediated delivery of PKC{delta}{sup D327A} protein protected against 6-OHDA-induced PKC{delta} activation in mouse substantia nigra. Collectively, these results strongly suggest that proteolytic activation of PKC{delta} is a key downstream event in dopaminergic degeneration, and these results may have important translational value for

  7. Activation of PPAR{gamma} is not involved in butyrate-induced epithelial cell differentiation

    SciTech Connect

    Ulrich, S.; Waechtershaeuser, A.; Loitsch, S.; Knethen, A. von; Bruene, B.; Stein, J. . E-mail: j.stein@em.uni-frankfurt.de

    2005-10-15

    Histone deacetylase-inhibitors affect growth and differentiation of intestinal epithelial cells by inducing expression of several transcription factors, e.g. Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) or vitamin D receptor (VDR). While activation of VDR by butyrate mainly seems to be responsible for cellular differentiation, the activation of PPAR{gamma} in intestinal cells remains to be elucidated. The aim of this study was to determine the role of PPAR{gamma} in butyrate-induced cell growth inhibition and differentiation induction in Caco-2 cells. Treatment with PPAR{gamma} ligands ciglitazone and BADGE (bisphenol A diglycidyl) enhanced butyrate-induced cell growth inhibition in a dose- and time-dependent manner, whereas cell differentiation was unaffected after treatment with PPAR{gamma} ligands rosiglitazone and MCC-555. Experiments were further performed in dominant-negative PPAR{gamma} mutant cells leading to an increase in cell growth whereas butyrate-induced cell differentiation was again unaffected. The present study clearly demonstrated that PPAR{gamma} is involved in butyrate-induced inhibition of cell growth, but seems not to play an essential role in butyrate-induced cell differentiation.

  8. Activities of gamma-glutamyl transpeptidase and erythrocyte glutathione dependent enzymes in nasopharyngeal carcinoma patients and normal controls.

    PubMed

    Ngah, W Z; Shamaan, N A; Said, M H; Azhar, M T

    1993-01-01

    Plasma gamma-glutamyltranspeptidase (gamma-GT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities were determined in normal and nasopharyngeal carcinoma (NPC) patients. No difference in enzyme activities was observed in the three major races of the Malaysian population, i.e. Malay, Chinese and Indian patients. However, plasma gamma-GT, erythrocyte glutathione S-transferase (GST) and GPx activities were significantly increased in all NPC patients, while GR activity remained unchanged. Patients with elevated plasma gamma-GT activities also had increased GST and GPx activities. Plasma gamma-GT and GPx activities were then found to be affected by treatment. Patients with plasma gamma-GT activity greater than 70 IU/l had very poor prognoses but patients with decreased gamma-GT activities were found to be in remission. PMID:8105826

  9. Activation of PPAR{delta} up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic {beta}-cells

    SciTech Connect

    Wan, Jun; Jiang, Li; Lue, Qingguo; Ke, Linqiu; Li, Xiaoyu; Tong, Nanwei

    2010-01-15

    Recent evidence indicates that decreased oxidative capacity, lipotoxicity, and mitochondrial aberrations contribute to the development of insulin resistance and type 2 diabetes. The goal of this study was to investigate the effects of peroxisome proliferator-activated receptor {delta} (PPAR{delta}) activation on lipid oxidation, mitochondrial function, and insulin secretion in pancreatic {beta}-cells. After HIT-T15 cells (a {beta}-cell line) were exposed to high concentrations of palmitate and GW501516 (GW; a selective agonist of PPAR{delta}), we found that administration of GW increased the expression of PPAR{delta} mRNA. GW-induced activation of PPAR{delta} up-regulated carnitine palmitoyltransferase 1 (CPT1), long-chain acyl-CoA dehydrogenase (LCAD), pyruvate dehydrogenase kinase 4 (PDK4), and uncoupling protein 2 (UCP2); alleviated mitochondrial swelling; attenuated apoptosis; and reduced basal insulin secretion induced by increased palmitate in HIT cells. These results suggest that activation of PPAR{delta} plays an important role in protecting pancreatic {beta}-cells against aberrations caused by lipotoxicity in metabolic syndrome and diabetes.

  10. Evidence for susceptibility of intrathymic T-cell precursors and their progeny carrying T-cell antigen receptor phenotypes TCR alpha beta + and TCR gamma delta + to human immunodeficiency virus infection: a mechanism for CD4+ (T4) lymphocyte depletion.

    PubMed Central

    Schnittman, S M; Denning, S M; Greenhouse, J J; Justement, J S; Baseler, M; Kurtzberg, J; Haynes, B F; Fauci, A S

    1990-01-01

    Individuals infected by the human immunodeficiency virus type 1 (HIV-1) demonstrate progressive depletion and qualitative dysfunction of the helper T4 (CD4+) cell population. Mechanisms proposed for attrition of CD4+ T cells include direct cytopathicity of these mature cells following infection as well as infection of early T-lymphocyte progenitors. The latter mechanism could lead to failure to regenerate mature functioning CD4+ T cells. The present study determines the susceptibility of thymocytes at various stages of maturity to infection with HIV-1. Various normal thymocyte populations were inoculated with HIV-1, including unfractionated (UF), CD3- CD4- CD8- ["triple negative" (TN)], CD4+ CD8+ ["double positive" (DP)] thymocytes, and thymocyte populations obtained by limited dilution cloning. Cultures were studied for the presence of HIV-1 DNA by polymerase chain reaction in addition to examination for reverse transcriptase activity. We determined that transformed T-cell and thymocyte cell lines completely lacking CD4 were not susceptible to infection by HIV-1, whereas all of the following lines were: UF thymocytes (70-90% CD4hi+); DP thymocytes (99% CD4hi+); TN thymocytes (0% CD4hi+); and TCR alpha beta +, TCR gamma delta +, or CD16+ CD3- (natural killer) thymocyte clones expressing variable levels of CD4 and representing the progeny of TN thymocytes. [TCR alpha beta + and TCR gamma delta + refer to the chains of the T-cell antigen receptor (TCR), and CD4hi refers to a strong rightward shift (greater than 30 linear channels) of the CD4 curve on flow cytometric analysis compared with control.] Monoclonal antibodies (mAbs) to CD4 (T4a epitope) but not to CD3 (T3) were capable of blocking infection of mature and immature CD4hi+ thymocytes. Moreover, anti-CD4(T4a) mAbs also inhibited infection of CD4hi- TN thymocytes, indicating that these T-cell precursors--despite their apparent "triple negativity" (CD3- CD4hi- CD8-)--expressed sufficient CD4 molecules to become

  11. Correlation between annual activity patterns of venomous snakes and rural people in the Niger Delta, southern Nigeria

    PubMed Central

    2013-01-01

    Background Venomous snakes are among the most serious health hazards for rural people in tropical regions of the world. Herein we compare the monthly activity patterns of eight venomous snake species (Elapidae and Viperidae) with those of rural people in the Niger Delta area of southern Nigeria, in order to identify the periods of highest potential risk for persons, and the human group actually at greater risk of snakebite. Results We documented that above-ground activity of all venomous snakes peaked in the wet season, and that high snake activity and high human activity were most highly correlated between April and August. In addition, we documented that women and teenagers were at relatively higher risk of encountering a venomous snake than adult males, despite they are less often in the field than men. Conclusions Our results suggest that future programs devoted to mitigate the social and health effects of snakebites in the Niger Delta region should involve especially women and teenagers, with ad-hoc education projects if appropriate. We urge that international organizations working on social and health problems in the developing world, such as IRD, DFID, UNDP, should provide advice through specific programs targeted at especially these categories which have been highlighted in comparatively potential higher threat from snakebites than adult men. PMID:23849681

  12. Mitogen-activated protein kinase p38b interaction with delta class glutathione transferases from the fruit fly, Drosophila melanogaster.

    PubMed

    Wongtrakul, Jeerang; Sukittikul, Suchada; Saisawang, Chonticha; Ketterman, Albert J

    2012-01-01

    Glutathione transferases (GSTs) are a family of multifunctional enzymes involved in xenobiotic biotransformation, drug metabolism, and protection against oxidative damage. The p38b mitogen-activated protein kinase is involved in cellular stress response. This study screened interactions between Drosophila melanogaster Meigen (Diptera: Drosophilidae) Delta class glutathione transferases (DmGSTs) and the D. melanogaster p38b MAPK. Therefore, 12 DmGSTs and p38b kinase were obtained as recombinant proteins. The study showed that DmGSTD8 and DmGSTD11b significantly increased p38b activity toward ATF2 and jun, which are transcription factor substrates. DmGSTD3 and DmGSTD5 moderately increased p38b activity for jun. In addition, GST activity in the presence of p38b was also measured. It was found that p38b affected substrate specificity toward CDNB (1-chloro-2,4-dinitrobenzene) and DCNB (1,2-dichloro-4-nitrobenzene) of several GST isoforms, i.e., DmGSTD2, DmGSTD5, DmGSTD8, and DmGSTD11b. The interaction of a GST and p38b can affect the substrate specificity of either enzyme, which suggests induced conformational changes affecting catalysis. Similar interactions do not occur for all the Delta enzymes and p38b, which suggests that these interactions could be specific. PMID:23438069

  13. Delta inulin: a novel, immunologically active, stable packing structure comprising β-D-[2 -> 1] poly(fructo-furanosyl) α-D-glucose polymers.

    PubMed

    Cooper, Peter D; Petrovsky, Nikolai

    2011-05-01

    We report a novel isoform of β-D-[2 → 1] poly(fructo-furanosyl) α-D-glucose termed delta inulin (DI), comparing it with previously described alpha (AI), beta (BI) and gamma (GI) isoforms. In vitro, DI is the most immunologically active weight/weight in human complement activation and in binding to monocytes and regulating their chemokine production and cell surface protein expression. In vivo, this translates into potent immune adjuvant activity, enhancing humoral and cellular responses against co-administered antigens. As a biocompatible polysaccharide particle, DI is safe and well tolerated by subcutaneous or intramuscular injection. Physico-chemically, DI forms as an insoluble precipitate from an aqueous solution of suitable AI, BI or GI held at 37-48°C, whereas the precipitate from the same solution at lower temperatures has the properties of AI or GI. DI can also be produced by heat conversion of GI suspensions at 56°C, whereas GI is converted from AI at 45°C. DI is distinguished from GI by its higher temperature of solution in dilute aqueous suspension and by its lower solubility in dimethyl sulfoxide, both consistent with greater hydrogen bonding in DI's polymer packing structure. DI suspensions can be dissolved by heat, re-precipitated by cooling as AI and finally re-converted back to DI by repeated heat treatment. Thus, DI, like the previously described inulin isoforms, reflects the formation of a distinct polymer aggregate packing structure via reversible noncovalent bonding. DI forms the basis for a potent new human vaccine adjuvant and further swells the growing family of carbohydrate structures with immunological activity. PMID:21147758

  14. The delta EEG (sleep)-inducing peptide (DSIP). XI. Amino-acid analysis, sequence, synthesis and activity of the nonapeptide.

    PubMed

    Schoenenberger, G A; Maier, P F; Tobler, H J; Wilson, K; Monnier, M

    1978-09-01

    A peptide which induces slow-wave EEG (sleep) after intraventricular infusion into the brain has been isolated from the extracorporeal dialysate of cerebral venous blood in rabbits submitted to hypnogenic electrical stimulation of the intralaminar thalamic area. It was shown by amino-acid analysis and sequence determination to be Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu and named "Delta Sleep-Inducing Peptide" (DSIP). This compound was synthesized as well as 5 possible metabolic products (1--8, 2--9, 2--8, 1--4 and 5--9), 2 nonapeptide analogues (with one and two amino-acids exchanged) and a related tripeptide (Trp-Ser-Glu). All 9 synthetic peptides were infused intraventricularly in rabbits (6 nmol/kg in 0.05 ml of CSF-like solution over 3.5 min) and tested under double-blind conditions. A total of 61 rabbits including controls were used. The EEG from the frontal neocortex and the limbic archicortex were subjected to direct fast-Fourier transformation and analyzed by an 1108 computer system. A highly specific delta and spindle EEG-enhancing effect of the synthetic DSIP could be demonstrated. The mean increase of EEG delta activity reached 35% in the neocortex and limbic cortex as compared to control animals receiving CSF-like solution or any of the other 8 peptides. The final chemical characterization of the synthetic DSIP revealed that only the pure alpha-aspartyl peptide is highly active in contrast to its beta-Asp isomer. A neurohumoral modulating and programming activity was suggested. PMID:568769

  15. Prompt Gamma-Ray Neutron Activation Analysis (PGNAA) for Elemental Analysis

    SciTech Connect

    Robin P. Gardner

    2006-04-11

    This research project was to improve the prompt gamma-ray neutron activation analysis (PGNAA) measurement approach for bulk analysis, oil well logging, and small sample thermal enutron bean applications.

  16. Mortality salience modulates cortical responses to painful somatosensory stimulation: Evidence from slow wave and delta band activity.

    PubMed

    Valentini, Elia; Koch, Katharina; Nicolardi, Valentina; Aglioti, Salvatore Maria

    2015-10-15

    Social psychology studies show that awareness of one's eventual death profoundly influences human cognition and behaviour by inducing defensive reactions against end-of-life-related anxiety. Much less is known about the impact of reminders of mortality on brain activity. Here we tested whether reminders of mortality can induce a modulation of the slow electroencephalographic activity triggered by somatosensory nociceptive or auditory threatening stimulation and if this modulation is related to mood and anxiety as well as personality traits. We found a specific slow wave (SW) modulation only for nociceptive stimulation and only following mortality salience induction (compared to reminders of an important failed exam). The enhancement of SW negativity at the scalp vertex was associated with increased state anxiety and negative mood, whereas higher self-esteem was associated with reduced SW amplitude. In addition, mortality salience was linked to an increased amplitude of frontal delta band, which was correlated also with increased positive mood and higher self-esteem. The results indicate that SW and delta spectral activity may represent both proximal and distal defences associated with reminders of death and that neurophysiological correlates of somatosensory representation of painful and threatening stimuli may be useful for existential neuroscience studies. PMID:26188186

  17. Enhanced Stimulus-Induced Gamma Activity in Humans during Propofol-Induced Sedation

    PubMed Central

    Diukova, Ana; Singh, Krish; Hall, Judith; Wise, Richard

    2013-01-01

    Stimulus-induced gamma oscillations in the 30–80 Hz range have been implicated in a wide number of functions including visual processing, memory and attention. While occipital gamma-band oscillations can be pharmacologically modified in animal preparations, pharmacological modulation of stimulus-induced visual gamma oscillations has yet to be demonstrated in non-invasive human recordings. Here, in fifteen healthy humans volunteers, we probed the effects of the GABAA agonist and sedative propofol on stimulus-related gamma activity recorded with magnetoencephalography, using a simple visual grating stimulus designed to elicit gamma oscillations in the primary visual cortex. During propofol sedation as compared to the normal awake state, a significant 60% increase in stimulus-induced gamma amplitude was seen together with a 94% enhancement of stimulus-induced alpha suppression and a simultaneous reduction in the amplitude of the pattern-onset evoked response. These data demonstrate, that propofol-induced sedation is accompanied by increased stimulus-induced gamma activity providing a potential window into mechanisms of gamma-oscillation generation in humans. PMID:23483920

  18. Failure of cAMP agonists to activate rescued deltaF508 CFTR in CFBE41o- airway epithelial monolayers.

    PubMed

    Bebok, Zsuzsa; Collawn, James F; Wakefield, John; Parker, William; Li, Yao; Varga, Karoly; Sorscher, Eric J; Clancy, J P

    2005-12-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-regulated chloride channel. Mutations in the CFTR gene result in cystic fibrosis (CF). The most common mutation, deltaF508, results in endoplasmic reticulum-associated degradation (ERAD) of CFTR. DeltaF508 CFTR has been described as a temperature-sensitive mutation that can be rescued following growth at 27 degrees C. In order to study the processing and function of wild-type and rescued deltaF508 CFTR at the cell surface under non-polarized and polarized conditions, we developed stable cell lines expressing deltaF508 or wild-type CFTR. CFBE41o- is a human airway epithelial cell line capable of forming high resistance, polarized monolayers when cultured on permeable supports, while HeLa cells are normally grown under non-polarizing conditions. Immunoprecipitation, cell surface biotinylation, immunofluorescence, and functional assays confirmed the presence of deltaF508 CFTR at the cell surface in both cell lines after incubating the cells for 48 h at 27 degrees C. However, stimulators of wild-type CFTR such as forskolin, beta2-adrenergic or A2B-adenosine receptor agonists failed to activate rescued deltaF508 CFTR in CFBE41o- monolayers. Rescued deltaF508 CFTR could be stimulated with genistein independent of pretreatment with cAMP signalling agonists. Interestingly, rescued deltaF508 CFTR in HeLa cells could be efficiently stimulated with either forskolin or genistein to promote Cl- transport. These results indicate that deltaF508 CFTR, when rescued in CFBE41o- human airway epithelial cells, is poorly responsive to signalling pathways known to regulate wild-type CFTR. Furthermore, the differences in rescue and activation of deltaF508 CFTR in the two cell lines suggest that cell-type specific differences in deltaF508 CFTR processing are likely to complicate efforts to identify potentiators and/or correctors of the deltaF508 defect. PMID:16210354

  19. Tiber delta CO2-CH4 degassing: A possible hybrid, tectonically active Sediment-Hosted Geothermal System near Rome

    NASA Astrophysics Data System (ADS)

    Ciotoli, G.; Etiope, G.; Marra, F.; Florindo, F.; Giraudi, C.; Ruggiero, L.

    2016-01-01

    Fiumicino town in the Tiber River delta, near Rome International Airport (Italy), is historically affected by large amounts of carbon dioxide (CO2) in the ground and gas eruptions triggered by shallow drilling. While it is known that CO2 originates from carbonate thermometamorphism and/or mantle degassing, the origin of methane (CH4) associated with CO2 is uncertain and the outgassing spatial distribution is unknown. Combining isotope gas geochemistry, soil gas, and structural-stratigraphic analyses, we provide evidence for a hybrid fluid source system, classifiable as Sediment-Hosted Geothermal System (SHGS), where biotic CH4 from sedimentary rocks is carried by deep geothermic CO2 through active segments of a half-graben. Molecular and isotopic composition of CH4 and concentration of heavier alkanes (ethane and propane), obtained from gas vents and soil gas throughout the delta area, reveal that thermogenic CH4 (up to 3.7 vol% in soil gas; δ13CCH4: -37 to -40‰ VPDB-Vienna Peedee Belemnite, and δ2HCH4: -162 to -203‰ VSMOW - Vienna Standard Mean Ocean Water in gas vents) prevails over possible microbial and abiotic components. The hydrocarbons likely result from known Meso-Cenozoic petroleum systems of the Latium Tyrrhenian coast. Overmaturation of source rocks or molecular fractionation induced by gas migration are likely responsible for increased C1/C2+ ratios. CO2 and CH4 soil gas anomalies are scattered along NW-SE and W-E alignments, which, based on borehole, geomorphologic, and structural-stratigraphic analyses, coincide with active faults of a half-graben that seems to have controlled the recent evolution of the Tiber delta. This SHGS can be a source of considerable greenhouse gas emissions to the atmosphere and hazards for humans and buildings.

  20. Specification of High Activity Gamma-Ray Sources.

    ERIC Educational Resources Information Center

    International Commission on Radiation Units and Measurements, Washington, DC.

    The report is concerned with making recommendations for the specifications of gamma ray sources, which relate to the quantity of radioactive material and the radiation emitted. Primary consideration is given to sources in teletherapy and to a lesser extent those used in industrial radiography and in irradiation units used in industry and research.…

  1. Feature integration in visual working memory: parietal gamma activity is related to cognitive coordination.

    PubMed

    Morgan, Helen M; Muthukumaraswamy, Suresh D; Hibbs, Carina S; Shapiro, Kimron L; Bracewell, R Martyn; Singh, Krish D; Linden, David E J

    2011-12-01

    The mechanism by which distinct subprocesses in the brain are coordinated is a central conundrum of systems neuroscience. The parietal lobe is thought to play a key role in visual feature integration, and oscillatory activity in the gamma frequency range has been associated with perception of coherent objects and other tasks requiring neural coordination. Here, we examined the neural correlates of integrating mental representations in working memory and hypothesized that parietal gamma activity would be related to the success of cognitive coordination. Working memory is a classic example of a cognitive operation that requires the coordinated processing of different types of information and the contribution of multiple cognitive domains. Using magnetoencephalography (MEG), we report parietal activity in the high gamma (80-100 Hz) range during manipulation of visual and spatial information (colors and angles) in working memory. This parietal gamma activity was significantly higher during manipulation of visual-spatial conjunctions compared with single features. Furthermore, gamma activity correlated with successful performance during the conjunction task but not during the component tasks. Cortical gamma activity in parietal cortex may therefore play a role in cognitive coordination. PMID:21940605

  2. Membrane Potential Dynamics of Spontaneous and Visually Evoked Gamma Activity in V1 of Awake Mice

    PubMed Central

    Perrenoud, Quentin; Pennartz, Cyriel M. A.; Gentet, Luc J.

    2016-01-01

    Cortical gamma activity (30–80 Hz) is believed to play important functions in neural computation and arises from the interplay of parvalbumin-expressing interneurons (PV) and pyramidal cells (PYRs). However, the subthreshold dynamics underlying its emergence in the cortex of awake animals remain unclear. Here, we characterized the intracellular dynamics of PVs and PYRs during spontaneous and visually evoked gamma activity in layers 2/3 of V1 of awake mice using targeted patch-clamp recordings and synchronous local field potentials (LFPs). Strong gamma activity patterned in short bouts (one to three cycles), occurred when PVs and PYRs were depolarizing and entrained their membrane potential dynamics regardless of the presence of visual stimulation. PV firing phase locked unconditionally to gamma activity. However, PYRs only phase locked to visually evoked gamma bouts. Taken together, our results indicate that gamma activity corresponds to short pulses of correlated background synaptic activity synchronizing the output of cortical neurons depending on external sensory drive. PMID:26890123

  3. Transcriptional activation of peroxisome proliferator-activated receptor-{gamma} requires activation of both protein kinase A and Akt during adipocyte differentiation

    SciTech Connect

    Kim, Sang-pil; Ha, Jung Min; Yun, Sung Ji; Kim, Eun Kyoung; Chung, Sung Woon; Hong, Ki Whan; Kim, Chi Dae; Bae, Sun Sik

    2010-08-13

    Research highlights: {yields} Elevated cAMP activates both PKA and Epac. {yields} PKA activates CREB transcriptional factor and Epac activates PI3K/Akt pathway via Rap1. {yields} Akt modulates PPAR-{gamma} transcriptional activity in concert with CREB. -- Abstract: Peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}) is required for the conversion of pre-adipocytes. However, the mechanism underlying activation of PPAR-{gamma} is unclear. Here we showed that cAMP-induced activation of protein kinase A (PKA) and Akt is essential for the transcriptional activation of PPAR-{gamma}. Hormonal induction of adipogenesis was blocked by a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), by a protein kinase A (PKA) inhibitor (H89), and by a Rap1 inhibitor (GGTI-298). Transcriptional activity of PPAR-{gamma} was markedly enhanced by 3-isobutyl-1-methylxanthine (IBMX), but not insulin and dexamethasone. In addition, IBMX-induced PPAR-{gamma} transcriptional activity was blocked by PI3K/Akt, PKA, or Rap1 inhibitors. 8-(4-Chlorophenylthio)-2'-O-methyl-cAMP (8-pCPT-2'-O-Me-cAMP) which is a specific agonist for exchanger protein directly activated by cAMP (Epac) significantly induced the activation of Akt. Furthermore, knock-down of Akt1 markedly attenuated PPAR-{gamma} transcriptional activity. These results indicate that both PKA and Akt signaling pathways are required for transcriptional activation of PPAR-{gamma}, suggesting post-translational activation of PPAR-{gamma} might be critical step for adipogenic gene expression.

  4. Effect of delta opioid receptor activation on spatial cognition and neurogenesis in cerebral ischemic rats.

    PubMed

    Wang, Shu-Yan; Duan, Ya-Le; Zhao, Bing; Wang, Xiang-Rui; Zhao, Zheng; Zhang, Guang-Ming

    2016-05-01

    This study aimed to investigate whether a selective delta opioid receptor agonist, [D-Ala2, D-Leu5]-Enkephalin (DADLE), regulates neurogenesis in the hippocampus of ischemic rats. Using an intracerebral cannula, rats were subjected to cerebral ischemia using the standard four-vessel occlusion. DADLE (2.5nmol), DADLE (2.5nmol) with naltrindole (NAL) (2.5nmol), or vehicle was administered at the onset of reperfusion. Bromodeoxyuridine (BrdU, 100mg/kg, intraperitoneal) was used to label newly formed cells from days 1 to 7 after ischemia. Immunohistochemistry was used to evaluate cell proliferation and apoptosis and differentiation 7days 28 days, respectively, after ischemia. Morris water maze test was conducted to test spatial learning and memory 23-27 days after ischemia. We found that DADLE treatment improved performance in the Morris water maze test, promoted proliferation and differentiation of newly formed neurons, and inhibited differentiation into astrocytes in a rat model of cerebral ischemia. Furthermore, the protective effects of DADLE were significantly reversed by co-administration of NAL (P<0.05), a highly potent and selective delta opioid receptor antagonist. Our findings suggest that DADLE promotes spatial cognitive function recovery and regulates neurogenesis after ischemia, which may provide a promising therapeutic strategy for cerebral ischemia. PMID:27016387

  5. Ion activity products of iron sulfides in groundwaters: Implications from the Choshui fan-delta, Western Taiwan

    NASA Astrophysics Data System (ADS)

    Chen, Wen-Fu; Liu, Tsung-Kwei

    2005-07-01

    Precipitation of iron sulfides is an important process in groundwater geochemistry because it reduces iron mobility in anaerobic aquifers. Iron sulfides occur in various allotropic forms such as amorphous FeS and pyrite, and their solubility products differ up to 13 orders of magnitude. However, few data for ion activity products (IAP) of iron sulfides defined by the equation: H + + FeS (S) = Fe 2+ + HS - in groundwater have been reported in the literature. We computed IAP values of iron sulfides for 46 groundwater samples from the Choshui fan-delta of Taiwan and 65 samples from other areas of the world. The mean of -log(IAP) values obtained for the 46 samples is 3.07 ± 0.34 (1σ), which is consistent with the solubility constant 3.00 ± 0.12 ( Davison et al., 1999) of amorphous FeS, implying that the anaerobic aquifers in the Choshui fan-delta are still undergoing active sulfate-reduction processes and keeping the groundwater saturated with amorphous FeS. We suggest that the -logKsp value 3.91 of amorphous FeS adopted in the databases for WATEQF and PHREEQC computer programs ought to be revised to 3.00. Otherwise, the saturation indices (SI) calculated by the two computer programs will be an order of magnitude too high.

  6. Biological activities of conjugated fatty acids: conjugated eicosadienoic (conj. 20:2delta(c11,t13/t12,c14)), eicosatrienoic (conj. 20:3delta(c8,t12,c14)), and heneicosadienoic (conj. 21:2delta(c12,t14/c13,t15)) acids and other metabolites of conjugated linoleic acid.

    PubMed

    Park, Yeonhwa; Storkson, Jayne M; Albright, Karen J; Liu, Wei; Pariza, Michael W

    2005-02-21

    The elongated form of conjugated linoleic acid (CLA), conjugated eicosadienoic acid (CEA, conj. 20:2delta(c11,t13/t12,c14)), was generated from CLA by liver microsomal fractions. Subsequent testing showed that dietary CEA significantly reduced body fat, and increased lean mass similar to CLA when compared to controls. CEA also decreased lipoprotein lipase activity and triacylglyceride, and increased glycerol release in 3T3-L1 adipocytes, correlated with the trans-12,cis-14 isomer, but CEA required a longer incubation period than cells treated with CLA. Based on the fact that CEA fed animals had CLA in tissue, we suggest that the effect of CEA is due to the CLA converted from CEA in the system. The delta-6 desaturated and elongated form of trans-10,cis-12 CLA (conjugated eicosatrienoic acid, CETA, conj. 20:3delta(c8,t12,c14)) inhibited LPL activity and increased glycerol release but was less active than trans-10,cis-12 CLA or CEA. The 21-carbon conjugated fatty acid, conjugated heneicosadienoic acid (CHDA, conj. 21:2delta(c12,t14/c13,t15)), was not active on LPL inhibition, triacylglyceride, or glycerol release in 3T3-L1 adipocytes. We also provide evidence that CLA was metabolized to conjugated dodecadienoic acid (conj. 12:2delta(c3,t5/t4,c6)). In addition, there were indications of the presence of conjugated tetradecadienoic acid (conj. 14:2delta(c5,t7/t6,c8)), suggesting that CLA can be metabolized through fatty acid beta-oxidation. This is the first work to report the presence of conjugated 12 and 14 carbon fatty acids, originated from CLA, and the biological activities of CEA, CETA and CHDA. PMID:15708360

  7. Gamma irradiation improves the antioxidant activity of Aloe vera (Aloe barbadensis miller) extracts

    NASA Astrophysics Data System (ADS)

    Mi Lee, Eun; Bai, Hyoung-Woo; Sik Lee, Seung; Hyun Hong, Sung; Cho, Jae-Young; Yeoup Chung, Byung

    2012-08-01

    Aloe has been widely used in food products, pharmaceuticals, and cosmetics because of its aromatic and therapeutic properties. In the present study, the ethanolic extracts of aloe gel were gamma-irradiated from 10 to 100 kGy. After gamma irradiation, the color of the ethanolic extracts of aloe gel changed to red; this color persisted up to 40 kGy but disappeared above 50 kGy. Liquid chromatography/mass spectrometry analysis demonstrated the production of a new, unknown compound (m/z=132) after gamma irradiation of the ethanolic extracts of aloe gel. The amount of this unknown compound increased with increasing irradiation up to 80 kGy, and it was degraded at 100 kGy. Interestingly, it was found that gamma irradiation significantly increased the antioxidant activity, as measured by the 1,1-diphenyl-2-picrylhydrazyl-radical scavenging capacity. The antioxidant activity of aloe extract was dramatically increased from 53.9% in the non-irradiated sample to 92.8% in the sample irradiated at 40 kGy. This strong antioxidant activity was retained even at 100 kGy. These results indicate that gamma irradiation of aloe extract can enhance its antioxidant activity through the formation of a new compound. Based on these results, increased antioxidant activity of aloe extracts by gamma rays can be applied to various industries, especially cosmetics, foodstuffs, and pharmaceuticals.

  8. Interferon-gamma induces the synthesis and activation of cytosolic phospholipase A2.

    PubMed Central

    Wu, T; Levine, S J; Lawrence, M G; Logun, C; Angus, C W; Shelhamer, J H

    1994-01-01

    Both IFN-alpha/beta and IFN-gamma have recently been demonstrated to induce a rapid but transient activation of phospholipase A2 (PLA2) in BALB/c 3T3 fibroblasts and a human neuroblastoma cell line. We report that IFN-gamma induces the synthesis and prolonged activation of cytosolic phospholipase A2 (cPLA2) in a human bronchial epithelial cell line (BEAS 2B). Treatment of the cells with IFN-gamma (300 U/ml) increased the release of [3H]arachidonic acid (AA) from prelabeled cells with a maximal effect at 12 h after stimulation. The increased [3H]AA release was inhibited by the PLA2 inhibitor p-bromophenacyl bromide (10(-5) M). Calcium ionophore A23187 (10(-5) M) further increased the [3H]AA release from the IFN-gamma-treated cells. Subcellular enzyme activity assay revealed that IFN-gamma increased PLA2 activity in both the cytosol and membrane fractions with a translocation of the cPLA2 to cell membranes in a Ca(2+)-free cell lysing buffer. Treatment with IFN-gamma also induced the release of 15-HETE, an arachidonic acid metabolite. Immunoblot showed that IFN-gamma induced the synthesis of cPLA2 protein. Nuclear run-on assay demonstrated that IFN-gamma initiated cPLA2 gene transcription within 15 min, and this effect was sustained at 4 h and returned to near control level at 12 h. The cPLA2 mRNA level was assayed by reverse transcription and PCR. IFN-gamma was found to increase the cPLA2 mRNA after 2-24 h treatment. Furthermore, the IFN-gamma induced cPLA2 mRNA increase was blocked by inhibitors of protein kinase C and calcium/calmodulin-dependent protein kinases, suggesting the involvement of these protein kinases in IFN-gamma-induced gene expression of cPLA2. This study shows that IFN-gamma induces the synthesis and prolonged activation of cPLA2. Images PMID:8113394

  9. Structural recognition and functional activation of Fc[gamma]R by innate pentraxins

    SciTech Connect

    Lu, Jinghua; Marnell, Lorraine L.; Marjon, Kristopher D.; Mold, Carolyn; Du Clos, Terry W.; Sun, Peter D.

    2009-10-05

    Pentraxins are a family of ancient innate immune mediators conserved throughout evolution. The classical pentraxins include serum amyloid P component (SAP) and C-reactive protein, which are two of the acute-phase proteins synthesized in response to infection. Both recognize microbial pathogens and activate the classical complement pathway through C1q. More recently, members of the pentraxin family were found to interact with cell-surface Fc{gamma} receptors (Fc{gamma}R) and activate leukocyte-mediated phagocytosis. Here we describe the structural mechanism for pentraxin's binding to Fc{gamma}R and its functional activation of Fc{gamma}R-mediated phagocytosis and cytokine secretion. The complex structure between human SAP and Fc{gamma}RIIa reveals a diagonally bound receptor on each SAP pentamer with both D1 and D2 domains of the receptor contacting the ridge helices from two SAP subunits. The 1:1 stoichiometry between SAP and Fc{gamma}RIIa infers the requirement for multivalent pathogen binding for receptor aggregation. Mutational and binding studies show that pentraxins are diverse in their binding specificity for Fc{gamma}R isoforms but conserved in their recognition structure. The shared binding site for SAP and IgG results in competition for Fc{gamma}R binding and the inhibition of immune-complex-mediated phagocytosis by soluble pentraxins. These results establish antibody-like functions for pentraxins in the Fc{gamma}R pathway, suggest an evolutionary overlap between the innate and adaptive immune systems, and have new therapeutic implications for autoimmune diseases.

  10. Peroxisome proliferator-activated receptor-{gamma} as a regulator of lung inflammation and repair.

    PubMed

    Standiford, Theodore J; Keshamouni, Venkateshwar G; Reddy, Raju C

    2005-01-01

    Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily that regulate the expression of genes involved in a variety of biological processes, including lipid metabolism and insulin sensitivity. Members of the PPAR family-in particular, PPAR-gamma-have more recently been shown to broadly regulate inflammatory and reparative responses. PPAR-gamma is expressed in both alveolar macrophages and neutrophils, and the ligand-dependent activation of this receptor results in suppression of leukocyte effector responses, including cytokine production, the elaboration of reactive oxygen and nitrogen species, and migratory responses. In addition to antiinflammatory effects, PPAR-gamma regulates diverse processes in lung stromal/parenchymal cells, including cell growth, differentiation, and apoptosis. Studies examining in vivo effects of PPAR-gamma have produced complex and at times conflicting results. However, evidence to date generally suggests that PPAR-gamma functions to dampen inflammation and injury in various animal models of acute lung injury. PPAR-gamma may also play an important role in other inflammatory/immune lung diseases, including ischemia-reperfusion injury, allergic airway inflammation, and cancer. The role of PPAR-gamma in human lung diseases, including acute lung injury, requires further study. PMID:16222042

  11. Fermi-LAT detection of ongoing gamma-ray activity from the new gamma-ray source Fermi J1654-1055 (PMN J1632-1052)

    NASA Astrophysics Data System (ADS)

    Kocevski, D.; Ajello, M.; Buson, S.; Buehler, R.; Giomi, M.

    2016-02-01

    During the week between February 8 and 15, 2016, the Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, observed gamma-ray activity from a new transient source, Fermi J1654-1055.

  12. DELTAS: A new Global Delta Sustainability Initiative (Invited)

    NASA Astrophysics Data System (ADS)

    Foufoula-Georgiou, E.

    2013-12-01

    Deltas are economic and environmental hotspots, food baskets for many nations, home to a large part of the world population, and hosts of exceptional biodiversity and rich ecosystems. Deltas, being at the land-water interface, are international, regional, and local transport hubs, thus providing the basis for intense economic activities. Yet, deltas are deteriorating at an alarming rate as 'victims' of human actions (e.g. water and sediment reduction due to upstream basin development), climatic impacts (e.g. sea level rise and flooding from rivers and intense tropical storms), and local exploration (e.g. sand or aggregates, groundwater and hydrocarbon extraction). Although many efforts exist on individual deltas around the world, a comprehensive global delta sustainability initiative that promotes awareness, science integration, data and knowledge sharing, and development of decision support tools for an effective dialogue between scientists, managers and policy makers is lacking. Recently, the international scientific community proposed to establish the International Year of Deltas (IYD) to serve as the beginning of such a Global Delta Sustainability Initiative. The IYD was proposed as a year to: (1) increase awareness and attention to the value and vulnerability of deltas worldwide; (2) promote and enhance international and regional cooperation at the scientific, policy, and stakeholder level; and (3) serve as a launching pad for a 10-year committed effort to understand deltas as complex socio-ecological systems and ensure preparedness in protecting and restoring them in a rapidly changing environment. In this talk, the vision for such an international coordinated effort on delta sustainability will be presented as developed by a large number of international experts and recently funded through the Belmont Forum International Opportunities Fund. Participating countries include: U.S., France, Germany, U.K., India, Japan, Netherlands, Norway, Brazil, Bangladesh

  13. Geochemistry of sediments and surface soils from the Nile Delta and lower Nile valley studied by epithermal neutron activation analysis

    NASA Astrophysics Data System (ADS)

    Arafa, Wafaa M.; Badawy, Wael M.; Fahmi, Naglaa M.; Ali, Khaled; Gad, Mohamed S.; Duliu, Octavian G.; Frontasyeva, Marina V.; Steinnes, Eiliv

    2015-07-01

    The distributions of 36 major and trace elements in 40 surface soil and sediment samples collected from the Egyptian section of the river Nile were determined by epithermal neutron activation analysis and compared with corresponding data for the Upper Continental Crust and North American Shale Composite. Their relative distributions indicate the presence of detrital material of igneous origin, most probably resulting from weathering on Ethiopian highlands and transported by the Blue Nile, the Nile main tributary. The distributions of the nickel, zinc, and arsenic contents suggest that the lower part of the Nile and its surroundings including the Nile Delta is not seriously polluted with metals from local human activity. The geographical distributions of Na, Cl, and I as well as results of principal component analysis suggest atmospheric supply of these elements from the ocean. In general the present data may contribute to a better understanding of the geochemistry of the Nile sediments.

  14. Frontal predominance of a relative increase in sleep delta and theta EEG activity after sleep loss in humans

    NASA Technical Reports Server (NTRS)

    Cajochen, C.; Foy, R.; Dijk, D. J.; Czeisler, C. A. (Principal Investigator)

    1999-01-01

    The effect of sleep deprivation (40 h) on topographic and temporal aspects of electroencephalographic (EEG) activity during sleep was investigated by all night spectral analysis in six young volunteers. The sleep-deprivation-induced increase of EEG power density in the delta and theta frequencies (1-7 Hz) during nonREM sleep, assessed along the antero-posterior axis (midline: Fz, Cz, Pz, Oz), was significantly larger in the more frontal derivations (Fz, Cz) than in the more parietal derivations (Pz, Oz). This frequency-specific frontal predominance was already present in the first 30 min of recovery sleep, and dissipated in the course of the 8-h sleep episode. The data demonstrate that the enhancement of slow wave EEG activity during sleep following extended wakefulness is most pronounced in frontal cortical areas.

  15. Implementation of gamma-ray instrumentation for solid solar system bodies using neutron activation method

    NASA Astrophysics Data System (ADS)

    Litvak, M. L.; Golovin, D. V.; Jun, I.; Kozyrev, A. S.; Mitrofanov, I. G.; Sanin, A. B.; Shvetsov, V. N.; Timoshenko, G. N.; Zontikov, A.

    2016-06-01

    In this paper we present the results of ground tests performed with a flight model and with industry prototypes of passive and active gamma ray spectrometers with the objective of understanding their capability to distinguish the elemental composition of planetary bodies in the solar system. The gamma instrumentation, which was developed for future space missions was used in the measurements at a special ground test facility where a simulant of planetary material was fabricated with a martian-like composition. In this study, a special attention was paid to the gamma lines from activation reaction products generated by a pulsed neutron generator. The instrumentation was able to detect and identify gamma lines attributed to O, Na, Mg, Al, Si, K, Ca and Fe.

  16. Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA around the gamma-delta-beta-globin gene complex.

    PubMed Central

    Charache, S; Dover, G; Smith, K; Talbot, C C; Moyer, M; Boyer, S

    1983-01-01

    Increased production of fetal hemoglobin (HbF) was observed in a patient with sickle cell anemia treated with 5-azacytidine. Each of four courses of therapy resulted in a rapid and prolonged increase in the percentage of HbF containing reticulocytes (F reticulocytes) and HbF containing erythrocytes (F cells). The percentage of HbF in peripheral blood rose from 1.8 to 8.9%. The rise in HbF production was accompanied by an increase in peripheral blood hemoglobin concentration from 8 to 12 g/dl and an increase in mean erythrocyte volume. Treatment with 5-azacytidine resulted in hypomethylation of total genomic and a Y-chromosome-specific DNA fragment isolated from both peripheral blood and bone marrow. Of 15 restriction enzyme sites around the gamma-delta-beta-globin gene complex, only 2 became hypomethylated: one 107 bases 5' to the gamma G and the other 107 bases 5' to the gamma A globin genes. Images PMID:6192443

  17. REGULATION OF RAT HEPATIC DELTA-AMINOLEVULINIC ACID SYNTHETASE AND HEME OXYGENASE ACTIVITIES: EVIDENCE FOR CONTROL BY HEME AND AGAINST MEDIATION BY PROSTHETIC IRON

    EPA Science Inventory

    The effects of in vivo administration of 6 compounds on the activity of delta-aminolevulinic acid (ALA) synthetase and heme oxygenase were determined. The order of decreasing potency in reducing ALA synthetase activity was heme, bilirubin, protoporphyrin IX, bilirubin dimethyl es...

  18. PPAR-gamma activation fails to provide myocardial protection in ischemia and reperfusion in pigs.

    PubMed

    Xu, Ya; Gen, Michael; Lu, Li; Fox, Jennifer; Weiss, Sara O; Brown, R Dale; Perlov, Daniel; Ahmad, Hasan; Zhu, Peili; Greyson, Clifford; Long, Carlin S; Schwartz, Gregory G

    2005-03-01

    Peroxisome proliferator-activated receptor (PPAR)-gamma modulates substrate metabolism and inflammatory responses. In experimental rats subjected to myocardial ischemia-reperfusion (I/R), thiazolidinedione PPAR-gamma activators reduce infarct size and preserve left ventricular function. Troglitazone is the only PPAR-gamma activator that has been shown to be protective in I/R in large animals. However, because troglitazone contains both alpha-tocopherol and thiazolidinedione moieties, whether PPAR-gamma activation per se is protective in myocardial I/R in large animals remains uncertain. To address this question, 56 pigs were treated orally for 8 wk with troglitazone (75 mg x kg(-1) x day(-1)), rosiglitazone (3 mg x kg(-1) x day(-1)), or alpha-tocopherol (73 mg x kg(-1) x day(-1), equimolar to troglitazone dose) or received no treatment. Pigs were then anesthetized and subjected to 90 min of low-flow regional myocardial ischemia and 90 min of reperfusion. Myocardial expression of PPAR-gamma, determined by ribonuclease protection assay, increased with troglitazone and rosiglitazone compared with no treatment. Rosiglitazone had no significant effect on myocardial contractile function (Frank-Starling relations), substrate uptake, or expression of proinflammatory cytokines during I/R compared with untreated pigs. In contrast, preservation of myocardial contractile function and lactate uptake were greater and cytokine expression was attenuated in pigs treated with troglitazone or alpha-tocopherol compared with untreated pigs. Multivariate analysis indicated that presence of an alpha-tocopherol, but not a thiazolidinedione, moiety in the test compound was significantly related to greater contractile function and lactate uptake and lower cytokine expression during I/R. We conclude that PPAR-gamma activation is not protective in a porcine model of myocardial I/R. Protective effects of troglitazone are attributable to its alpha-tocopherol moiety. These findings, in

  19. Intracellular mechanisms modulating gamma band activity in the pedunculopontine nucleus (PPN).

    PubMed

    Luster, Brennon R; Urbano, Francisco J; Garcia-Rill, Edgar

    2016-06-01

    The pedunculopontine nucleus is a part of the reticular activating system, and is active during waking and REM sleep. Previous results showed that all PPN cells tested fired maximally at gamma frequencies when depolarized. This intrinsic membrane property was shown to be mediated by high-threshold N- and P/Q-type Ca(2+) channels. Recent studies show that the PPN contains three independent populations of neurons which can generate gamma band oscillations through only N-type channels, only P/Q-type channels, or both N- and P/Q-type channels. This study investigated the intracellular mechanisms modulating gamma band activity in each population of neurons. We performed in vitro patch-clamp recordings of PPN neurons from Sprague-Dawley rat pups, and applied 1-sec ramps to induce intrinsic membrane oscillations. Our results show that there are two pathways modulating gamma band activity in PPN neurons. We describe populations of neurons mediating gamma band activity through only N-type channels and the cAMP/PKA pathway (presumed "REM-on" neurons), through only P/Q-type channels and the CaMKII pathway (presumed "Wake-on" neurons), and a third population which can mediate gamma activity through both N-type channels and cAMP/PK and P/Q-type channels and CaMKII (presumed "Wake/REM-on" neurons). These novel results suggest that PPN gamma oscillations are modulated by two independent pathways related to different Ca(2+) channel types. PMID:27354537

  20. Protein tyrosine kinase activity is essential for Fc gamma receptor-mediated intracellular killing of Staphylococcus aureus by human monocytes.

    PubMed Central

    Zheng, L; Nibbering, P H; Zomerdijk, T P; van Furth, R

    1994-01-01

    Our previous study revealed that the intracellular killing of Staphylococcus aureus by human monocytes after cross-linking Fc gamma receptor I (Fc gamma RI) or Fc gamma RII is a phospholipase C (PLC)-dependent process. The aim of the present study was to investigate whether protein tyrosine kinase (PTK) activity plays a role in the Fc gamma R-mediated intracellular killing of bacteria and activation of PLC in these cells. The results showed that phagocytosis of bacteria by monocytes was not affected by the PTK inhibitors genistein and tyrphostin-47. The intracellular killing of S. aureus by monocytes after cross-linking Fc gamma RII or Fc gamma RII with anti-Fc gamma R monoclonal antibody and a bridging antibody or with human immunoglobulin G (IgG) was inhibited by these compounds in a dose-dependent fashion. The production of O2- by monocytes after stimulation with IgG or IgG-opsonized S. aureus was almost completely blocked by the PTK inhibitor. These results indicate that inhibition of PTK impairs the oxygen-dependent bactericidal mechanisms of monocytes. Genistein and tyrphostin-47, which do not affect the enzymatic activity of purified PLC, prevented activation of PLC after cross-linking Fc gamma RI or Fc gamma RII, measured as an increase in the intracellular inositol 1,4,5-trisphosphate concentration. Cross-linking Fc gamma RI or Fc gamma RII induced rapid tyrosine phosphorylation of several proteins in monocytes, one of which was identified as PLC-gamma 1, and the phosphorylation could be completely blocked by PTK inhibitors, leading to the conclusion that activation of PLC after cross-linking Fc gamma R in monocytes is regulated by PTK activity. Together, these results demonstrate that PTK activity is essential for the activation of PLC which is involved in the Fc gamma R-mediated intracellular killing of S. aureus by human monocytes. Images PMID:7927687

  1. Inducible Conditional Vascular-Specific Overexpression of Peroxisome Proliferator-Activated Receptor Beta/Delta Leads to Rapid Cardiac Hypertrophy

    PubMed Central

    Wagner, Kay-Dietrich; Vukolic, Ana; Baudouy, Delphine; Michiels, Jean-François

    2016-01-01

    Peroxisome proliferator-activated receptors are nuclear receptors which function as ligand-activated transcription factors. Among them, peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) is highly expressed in the heart and thought to have cardioprotective functions due to its beneficial effects in metabolic syndrome. As we already showed that PPARβ/δ activation resulted in an enhanced cardiac angiogenesis and growth without impairment of heart function, we were interested to determine the effects of a specific activation of PPARβ/δ in the vasculature on cardiac performance under normal and in chronic ischemic heart disease conditions. We analyzed the effects of a specific PPARβ/δ overexpression in endothelial cells on the heart using an inducible conditional vascular-specific mouse model. We demonstrate that vessel-specific overexpression of PPARβ/δ induces rapid cardiac angiogenesis and growth with an increase in cardiomyocyte size. Upon myocardial infarction, vascular overexpression of PPARβ/δ, despite the enhanced cardiac vessel formation, does not protect against chronic ischemic injury. Our results suggest that the proper balance of PPARβ/δ activation in the different cardiac cell types is required to obtain beneficial effects on the outcome in chronic ischemic heart disease. PMID:27057154

  2. Two Active States of the Narrow-Line Gamma-Ray-Loud AGN GB 1310 + 487

    NASA Technical Reports Server (NTRS)

    Sokolovsky, K. V.; Schinzel, F. K.; Tanaka, Y. T.; Abolmasov, P. K.; Angelakis, E.; Bulgarelli, A.; Carrasco, L.; Cenko, S. B.; Cheung, C. C.; Clubb, K. I.; D'Ammando, F.; Escande, L.; Fegan, S. J.; Filippenko, A. V.; Finke, J. D.; Fuhrmann, L.; Fukazawa, Y.; Hays, E.; Healey, S. E.; Ikejiri, Y.; Itoh, R.; Kawabata, K. S.; Komatsu, T.; Kovalev, Yu. A.; Kovalev, Y. Y.; Krichbaum, T. P.

    2014-01-01

    Context. Previously unremarkable, the extragalactic radio source GB1310 487 showed gamma-ray flare on 2009 November 18, reaching a daily flux of approximately 10(exp -6) photons cm(exp -2) s(exp -1) at energies E greater than 100MeV and became one of the brightest GeV sources for about two weeks. Its optical spectrum shows strong forbidden-line emission while lacking broad permitted lines, which is not typical for a blazar. Instead, the spectrum resembles those of narrow emission-line galaxies. Aims. We investigate changes in the object's radio-to-GeV spectral energy distribution (SED) during and after the prominent gamma-ray flare with the aim of determining the nature of the object and of constraining the origin of the variable high-energy emission. Methods. The data collected by the Fermi and AGILE satellites at gamma-ray energies; Swift at X-ray and ultraviolet (UV); the Kanata, NOT, and Keck telescopes at optical; OAGH and WISE at infrared (IR); and IRAM30m, OVRO 40m, Effelsberg 100m, RATAN-600, and VLBA at radio are analyzed together to trace the SED evolution on timescales of months. Results. The gamma-ray radio-loud narrow-line active galactic nucleus (AGN) is located at redshift z = 0.638. It shines through an unrelated foreground galaxy at z = 0.500. The AGN light is probably amplified by gravitational lensing. The AGN SED shows a two-humped structure typical of blazars and gamma-ray-loud narrow-line Seyfert 1 galaxies, with the high-energy (inverse-Compton) emission dominating by more than an order of magnitude over the low-energy (synchrotron) emission during gamma-ray flares. The difference between the two SED humps is smaller during the low-activity state. Fermi observations reveal a strong correlation between the gamma-ray flux and spectral index, with the hardest spectrum observed during the brightest gamma-ray state. The gamma-ray flares occurred before and during a slow rising trend in the radio, but no direct association between gamma-ray and

  3. Optogenetically induced spatiotemporal gamma oscillations and neuronal spiking activity in primate motor cortex

    PubMed Central

    Lu, Yao; Truccolo, Wilson; Wagner, Fabien B.; Vargas-Irwin, Carlos E.; Ozden, Ilker; Zimmermann, Jonas B.; May, Travis; Agha, Naubahar S.; Wang, Jing

    2015-01-01

    Transient gamma-band (40–80 Hz) spatiotemporal patterns are hypothesized to play important roles in cortical function. Here we report the direct observation of gamma oscillations as spatiotemporal waves induced by targeted optogenetic stimulation, recorded by intracortical multichannel extracellular techniques in macaque monkeys during their awake resting states. Microelectrode arrays integrating an optical fiber at their center were chronically implanted in primary motor (M1) and ventral premotor (PMv) cortices of two subjects. Targeted brain tissue was transduced with the red-shifted opsin C1V1(T/T). Constant (1-s square pulses) and ramp stimulation induced narrowband gamma oscillations during awake resting states. Recordings across 95 microelectrodes (4 × 4-mm array) enabled us to track the transient gamma spatiotemporal patterns manifested, e.g., as concentric expanding and spiral waves. Gamma oscillations were induced well beyond the light stimulation volume, via network interactions at distal electrode sites, depending on optical power. Despite stimulation-related modulation in spiking rates, neuronal spiking remained highly asynchronous during induced gamma oscillations. In one subject we examined stimulation effects during preparation and execution of a motor task and observed that movement execution largely attenuated optically induced gamma oscillations. Our findings demonstrate that, beyond previously reported induced gamma activity under periodic drive, a prolonged constant stimulus above a certain threshold may carry primate motor cortex network dynamics into gamma oscillations, likely via a Hopf bifurcation. More broadly, the experimental capability in combining microelectrode array recordings and optogenetic stimulation provides an important approach for probing spatiotemporal dynamics in primate cortical networks during various physiological and behavioral conditions. PMID:25761956

  4. Optogenetically induced spatiotemporal gamma oscillations and neuronal spiking activity in primate motor cortex.

    PubMed

    Lu, Yao; Truccolo, Wilson; Wagner, Fabien B; Vargas-Irwin, Carlos E; Ozden, Ilker; Zimmermann, Jonas B; May, Travis; Agha, Naubahar S; Wang, Jing; Nurmikko, Arto V

    2015-06-01

    Transient gamma-band (40-80 Hz) spatiotemporal patterns are hypothesized to play important roles in cortical function. Here we report the direct observation of gamma oscillations as spatiotemporal waves induced by targeted optogenetic stimulation, recorded by intracortical multichannel extracellular techniques in macaque monkeys during their awake resting states. Microelectrode arrays integrating an optical fiber at their center were chronically implanted in primary motor (M1) and ventral premotor (PMv) cortices of two subjects. Targeted brain tissue was transduced with the red-shifted opsin C1V1(T/T). Constant (1-s square pulses) and ramp stimulation induced narrowband gamma oscillations during awake resting states. Recordings across 95 microelectrodes (4 × 4-mm array) enabled us to track the transient gamma spatiotemporal patterns manifested, e.g., as concentric expanding and spiral waves. Gamma oscillations were induced well beyond the light stimulation volume, via network interactions at distal electrode sites, depending on optical power. Despite stimulation-related modulation in spiking rates, neuronal spiking remained highly asynchronous during induced gamma oscillations. In one subject we examined stimulation effects during preparation and execution of a motor task and observed that movement execution largely attenuated optically induced gamma oscillations. Our findings demonstrate that, beyond previously reported induced gamma activity under periodic drive, a prolonged constant stimulus above a certain threshold may carry primate motor cortex network dynamics into gamma oscillations, likely via a Hopf bifurcation. More broadly, the experimental capability in combining microelectrode array recordings and optogenetic stimulation provides an important approach for probing spatiotemporal dynamics in primate cortical networks during various physiological and behavioral conditions. PMID:25761956

  5. Reduction in delta activity predicted improved negative affect in Major Depressive Disorder.

    PubMed

    Cheng, Philip; Goldschmied, Jennifer; Casement, Melynda; Kim, Hyang Sook; Hoffmann, Robert; Armitage, Roseanne; Deldin, Patricia

    2015-08-30

    While prior research has demonstrated a paradoxical antidepressant effect of slow-wave disruption (SWD), the specific dimensions of depression affected is still unclear. The current study aimed to extend this research by utilizing a dimensional approach in examining the antidepressant effects of SWD. Of particular interest is the affective dimension, as negative affect in depression is arguably the most salient characteristic of depression. This sample included 16 individuals with depression (10 female) recruited from the community. Participants slept in the lab for three nights (adaptation, baseline night, and SWD) with polysomnography, and completed measures of negative affect and depression severity the following morning. Results show that reduction in delta power was linearly associated with improved negative affect. Comparison of individual change scores revealed that half of the individuals showed improved negative affect, which is comparable to the reported 40-60% antidepressant response rate to sleep deprivation. Results suggest that vulnerability in the sleep homeostatic system may be a contributing individual differences factor in response to slow-wave disruption in depression. PMID:26123231

  6. Synthesis and structure-activity relationship of substitutions at the C-1 position of Delta9-tetrahydrocannabinol.

    PubMed

    Burdick, David; DeOrazio, Russell; Guzzo, Peter; Habershaw, Alicia; Helle, Mark; Paul, Bernard; Wolf, Mark

    2010-02-15

    A novel series of Delta9-tetrahydrocannabinol (Delta9-THC) analogues were synthesized to determine their potential as cannabinoid receptor modulators. Chemistry focused on conversion of the phenol of Delta9-THC to other functionality through palladium catalyzed reactions with an intermediate triflate 2. Two analogues with sub 100 nM affinity for the CB1 and CB2 receptors were identified. PMID:20079638

  7. Spontaneous fast gamma activity in the septal hippocampal region correlates with spatial learning in humans.

    PubMed

    Cornwell, B R; Overstreet, C; Grillon, C

    2014-03-15

    Hippocampal neuronal populations exhibit multiple kinds of activity patterns, from the dominant theta rhythm during active exploration to high-frequency ripple-like activity during periods of relative inactivity. In animals, evidence is rapidly accruing that these high-frequency ripple activity patterns subserve retention of spatial learning performance. In a translational effort to address the possible function of offline hippocampal processes in humans, we measured spontaneous gamma activity during an awake rest period within a virtual spatial learning context. Whole-head magnetoencephalographic (MEG) recordings were taken while healthy participants (N=24) quietly rested (eyes open) between encoding and retrieval phases of a hippocampal-dependent virtual Morris water maze task. Results are that fast gamma activity (80-140 Hz) in the septal or posterior region of the hippocampus (bilaterally) was positively correlated across participants with subsequent within-session spatial learning rate. Fast gamma did not predict initial retrieval performance following rest, failing to provide evidence of a direct link between spontaneous high-frequency activity patterns during awake rest and consolidation of previous spatial memories. The findings nevertheless are consistent with a prospective role for offline human hippocampal processes in spatial learning and indicate that higher spontaneous gamma activity in the septal hippocampal region is related to faster updating of spatial knowledge in familiar virtual surroundings. PMID:24388977

  8. Renewed gamma-ray activity of the Blazar 3C 454.3 detected by AGILE

    NASA Astrophysics Data System (ADS)

    Bulgarelli, A.; Parmiggiani, N.; Fioretti, V.; Zoli, A.; Lucarelli, F.; Verrecchia, F.; Pittori, C.; Vercellone, S.; Piano, G.; Munar-Adrover, P.; Tavani, M.; Donnarumma, I.; Striani, E.; Cardillo, M.; Gianotti, F.; Trifoglio, M.; Giuliani, A.; Mereghetti, S.; Caraveo, P.; Perotti, F.; Chen, A.; Argan, A.; Costa, E.; Del Monte, E.; Evangelista, Y.; Feroci, M.; Lazzarotto, F.; Lapshov, I.; Pacciani, L.; Soffitta, P.; Sabatini, S.; Vittorini, V.; Pucella, G.; Rapisarda, M.; Di Cocco, G.; Fuschino, F.; Galli, M.; Labanti, C.; Marisaldi, M.; Pellizzoni, A.; Pilia, M.; Trois, A.; Barbiellini, G.; Vallazza, E.; Longo, F.; Morselli, A.; Picozza, P.; Prest, M.; Lipari, P.; Zanello, D.; Cattaneo, P. W.; Rappoldi, A.; Colafrancesco, S.; Ferrari, A.; Antonelli, A.; Giommi, P.; Salotti, L.; Valentini, G.; D'Amico, F.

    2016-06-01

    The AGILE satellite is detecting a significant enhancement in gamma-ray activity from the FSRQ 3C 454.3 (known as 1AGLR J2254+1609) since the recent AGILE ATel #9157, and the optical activity reported in ATel #9150.

  9. Peroxisome proliferator-activated receptor gamma ligands induce growth inhibition and apoptosis of human B lymphocytic leukemia.

    PubMed

    Zang, Chuanbing; Liu, Hongyu; Posch, Maximilian G; Waechter, Maries; Facklam, Margit; Fenner, Martin H; Ruthardt, Martin; Possinger, Kurt; Phillip Koeffler, H; Elstner, Elena

    2004-04-01

    This study examined the expression and structural intactness of peroxisome proliferator-activated receptor gamma (PPARgamma) in human acute lymphocytic leukemia (ALL) cells and determined the effect of PPARgamma ligands on growth and apoptosis of these cells. We noted that all lymphocytic leukemia cell lines expressed PPARgamma and no PPARgamma mutations were found in these cell lines as indicated by SSCP analysis. Effect of the PPARgamma ligands on the proliferation, differentiation and apoptosis of B type ALL cells was further examined. Treatment of these cells with the PPARgamma ligands Pioglitazone (PGZ) and 15-deoxy-delta (12,14)-prostaglandin J2 (15d-PGJ2) resulted in growth inhibition in a dose-dependent manner which was associated with a G1 to S cell cycle arrest. However, this effect appeared to be PPARgamma-independent since several PPARgamma antagonists could not reverse this effect. No differentiation was induced by this treatment. Four out of five cell lines underwent apoptosis after culture with the PPARgamma ligands. This effect was partially caspase-dependent because a pan-caspase inhibitor partially reversed this effect. In conclusion, our results suggest that PPARgamma ligands may offer a new therapeutic approach to aid in the treatment of ALL. PMID:15109539

  10. Sex-dimorphic psychomotor activation after perinatal exposure to (-)-delta 9-tetrahydrocannabinol. An ontogenic study in Wistar rats.

    PubMed

    Navarro, M; Rubio, P; Rodríguez de Fonseca, F

    1994-12-01

    The ontogeny and the adult expression of motor behaviors were studied in male and female rats born from mothers exposed to delta 9-tetrahydrocannabinol (THC, 5 mg/kg) during gestation and lactation. Perinatal exposure to THC increased both rearing and locomotor activities in males and females at immature preweanling ages (P-15 and P-20). These effects disappeared after ceasing THC exposure (postweaning ages), but they were observed again in adult (P-70) females. The effects appeared as persistently high motor activity in familiar environments, disappearing the characteristic habituation profile in locomotor and exploratory behaviors. In novel environment condition tests, adult (P-70) THC-exposed females, but not males, exhibited lower locomotor activity in the socio-sexual approach test, and an increase in the emergence latency in the dark-light emergence test. Additionally, animals of both sexes exposed to THC showed a increase in the time spent grooming measured in novelty conditions. These findings suggest that perinatal exposure to THC affects both the development and the adult expression of motor behaviors and it resulted in a sex-dimorphic psychomotor activation very similar to that observed after perinatal exposure to other drugs of abuse. A possible role of THC-induced pituitary-adrenal (PA) axis activation was also evaluated by measuring plasma corticosterone levels in adult animals perinatally exposed: THC-exposed females exhibit a clear increase of this adrenal hormone, whereas THC-exposed males displayed lower levels of this hormone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7701042

  11. Induction of indoleamine 2,3-dioxygenase: a mechanism of the antitumor activity of interferon. gamma

    SciTech Connect

    Ozaki, Y.; Edelstein, M.P.; Duch, D.S.

    1988-02-01

    The antiproliferative effects of interferon ..cap alpha.. (IFN-..cap alpha..) and interferon ..gamma.. (IFN-..gamma..) were found to be cell-dependent. Among the human cell lines examined, IFN-..gamma.. had a greater antiproliferative effect against cell lines that exhibited induction of indoleamine 2,3-dioxygenase, such as the KB oral carcinoma or WiDr colon adenocarcinoma, than against those that lacked the enzyme activity, such as the SW480 colon adenocarcinoma of NCI-H128 small-cell lung carcinoma. Induction of this dioxygenase showed a clear temporal relationship with increased metabolism of L-tryptophan and the depletion of this amino acid in the culture medium. While 70-80% of L-tryptophan remained in the medium of IFN-..cap alpha..- or vehicle-treated cells, virtually all of this amino acid was depleted in the medium of the IFN-..gamma..-treated group following 2-3 days of culture. Supplementing the growth medium with additional L-tryptophan reversed the antiproliferative effect of IFN-..gamma.. against KB cells in a dose- and time-dependent manner. The antiproliferative effects of IFN-..cap alpha.. and IFN-..gamma.. on SW480 and NCI-H128 cells, which are independent of the dioxygenase activity, and the inability of added L-tryptophan to reverse the effects of IFN-..gamma.. in WiDr cells suggest multiple mechanisms of action of the IFNs. The data show that the antiproliferative effect of IFN-..gamma.. through induction of indoleamine 2,3-dioxygenase, with a consequent L-tryptophan deprivation, is an effective means of regulating cell growth.

  12. Stereospecificity of human DNA polymerases alpha, beta, gamma, delta and epsilon, HIV-reverse transcriptase, HSV-1 DNA polymerase, calf thymus terminal transferase and Escherichia coli DNA polymerase I in recognizing D- and L-thymidine 5'-triphosphate as substrate.

    PubMed Central

    Focher, F; Maga, G; Bendiscioli, A; Capobianco, M; Colonna, F; Garbesi, A; Spadari, S

    1995-01-01

    L-beta-Deoxythymidine (L-dT), the optical enantiomer of D-beta-deoxythymidine (D-dT), and L-enantiomers of nucleoside analogs, such as 5-iodo-2'-deoxy-L-uridine (L-IdU) and E-5-(2-bromovinyl)-2'-deoxy-L-uridine (L-BVdU), are not recognized in vitro by human cytosolic thymidine kinase (TK), but are phosphorylated by herpes simplex virus type 1 (HSV-1) TK and inhibit HSV-1 proliferation in infected cells. Here we report that: (i) L-dT is selectively phosphorylated in vivo to L-dTMP by HSV-1 TK and L-dTMP is further phosphorylated to the di- and triphosphate forms by non-stereospecific cellular kinases; (ii) L-dTTP not only inhibits HSV-1 DNA polymerase in vitro, but also human DNA polymerase alpha, gamma, delta and epsilon, human immunodeficiency virus reverse transcriptase (HIV-1 RT), Escherichia coli DNA polymerase 1 and calf thymus terminal transferase, although DNA polymerase beta was resistant; (iii) whereas DNA polymerase beta, gamma, delta and epsilon are unable to utilize L-dTTP as a substrate, the other DNA polymerases clearly incorporate at least one L-dTMP residue, with DNA polymerase alpha and HIV-1 RT able to further elongate the DNA chain by catalyzing the formation of the phosphodiester bond between the incorporated L-dTMP and an incoming L-dTTP; (iv) incorporated L-nucleotides at the 3'-OH terminus make DNA more resistant to 3'-->5' exonucleases. In conclusion, our results suggest a possible mechanism for the inhibition of viral proliferation by L-nucleosides. Images PMID:7544886

  13. Stereospecificity of human DNA polymerases alpha, beta, gamma, delta and epsilon, HIV-reverse transcriptase, HSV-1 DNA polymerase, calf thymus terminal transferase and Escherichia coli DNA polymerase I in recognizing D- and L-thymidine 5'-triphosphate as substrate.

    PubMed

    Focher, F; Maga, G; Bendiscioli, A; Capobianco, M; Colonna, F; Garbesi, A; Spadari, S

    1995-08-11

    L-beta-Deoxythymidine (L-dT), the optical enantiomer of D-beta-deoxythymidine (D-dT), and L-enantiomers of nucleoside analogs, such as 5-iodo-2'-deoxy-L-uridine (L-IdU) and E-5-(2-bromovinyl)-2'-deoxy-L-uridine (L-BVdU), are not recognized in vitro by human cytosolic thymidine kinase (TK), but are phosphorylated by herpes simplex virus type 1 (HSV-1) TK and inhibit HSV-1 proliferation in infected cells. Here we report that: (i) L-dT is selectively phosphorylated in vivo to L-dTMP by HSV-1 TK and L-dTMP is further phosphorylated to the di- and triphosphate forms by non-stereospecific cellular kinases; (ii) L-dTTP not only inhibits HSV-1 DNA polymerase in vitro, but also human DNA polymerase alpha, gamma, delta and epsilon, human immunodeficiency virus reverse transcriptase (HIV-1 RT), Escherichia coli DNA polymerase 1 and calf thymus terminal transferase, although DNA polymerase beta was resistant; (iii) whereas DNA polymerase beta, gamma, delta and epsilon are unable to utilize L-dTTP as a substrate, the other DNA polymerases clearly incorporate at least one L-dTMP residue, with DNA polymerase alpha and HIV-1 RT able to further elongate the DNA chain by catalyzing the formation of the phosphodiester bond between the incorporated L-dTMP and an incoming L-dTTP; (iv) incorporated L-nucleotides at the 3'-OH terminus make DNA more resistant to 3'-->5' exonucleases. In conclusion, our results suggest a possible mechanism for the inhibition of viral proliferation by L-nucleosides. PMID:7544886

  14. HCV core protein induces hepatic lipid accumulation by activating SREBP1 and PPAR{gamma}

    SciTech Connect

    Kim, Kook Hwan; Hong, Sung Pyo; Kim, KyeongJin; Park, Min Jung; Kim, Kwang Jin; Cheong, JaeHun . E-mail: molecule85@pusan.ac.kr

    2007-04-20

    Hepatic steatosis is a common feature in patients with chronic hepatitis C virus (HCV) infection. HCV core protein plays an important role in the development of hepatic steatosis in HCV infection. Because SREBP1 (sterol regulatory element binding protein 1) and PPAR{gamma} (peroxisome proliferators-activated receptor {gamma}) are involved in the regulation of lipid metabolism of hepatocyte, we sought to determine whether HCV core protein may impair the expression and activity of SREBP1 and PPAR{gamma}. In this study, it was demonstrated that HCV core protein increases the gene expression of SREBP1 not only in Chang liver, Huh7, and HepG2 cells transiently transfected with HCV core protein expression plasmid, but also in Chang liver-core stable cells. Furthermore, HCV core protein enhanced the transcriptional activity of SREBP1. In addition, HCV core protein elevated PPAR{gamma} transcriptional activity. However, HCV core protein had no effect on PPAR{gamma} gene expression. Finally, we showed that HCV core protein stimulates the genes expression of lipogenic enzyme and fatty acid uptake associated protein. Therefore, our finding provides a new insight into the mechanism of hepatic steatosis by HCV infection.

  15. A peroxisome proliferator-activated receptor-gamma agonist and other constituents from Chromolaena odorata.

    PubMed

    Dat, Nguyen Tien; Lee, Kyeong; Hong, Young-Soo; Kim, Young Ho; Minh, Chau Van; Lee, Jung Joon

    2009-06-01

    Peroxisome proliferator-activated receptors (PPARs) are key regulators of lipid and glucose metabolism and have become important therapeutic targets for various diseases. The phytochemical investigation of the chloroform-soluble extract of Chromolaena odorata led to the isolation of a PPAR-gamma agonist, (9 S,13 R)-12-oxo-phytodienoic acid (1), together with 12 other compounds. The structures of chromomoric acid G (2), a new dehydrogenated derivative of 1, and chromolanone (3) were elucidated based on spectroscopic methods. Compound 1 showed a significant effect on PPAR-gamma activation in comparison with rosiglitazone. However, compound 2 was inactive, suggesting that the dehydrogenation of the prostaglandin-like structure in 1 abrogates its PPAR-gamma agonistic activity. PMID:19242902

  16. Gamma radiation effects on phenolics, antioxidants activity and in vitro digestion of pistachio ( Pistachia vera) hull

    NASA Astrophysics Data System (ADS)

    Behgar, M.; Ghasemi, S.; Naserian, A.; Borzoie, A.; Fatollahi, H.

    2011-09-01

    The effect of gamma radiation (10, 20, 30, 40, 50 and 60 kGy) on tannin, total phenolics, antioxidants activity and in vitro digestion of pistachio hulls has been investigated in this study. The possibility of using the radial diffusion method based on software measurement of the rings area has also been investigated in this study. The software based method in radial diffusion method showed a higher r2 (0.995) value when compared to the traditional method. Irradiation reduced the tannin content ( P<0.01) and activity of antioxidants ( P<0.05) of pistachio hull extracts but increased the total phenolic content ( P<0.05). There was no effect of gamma irradiation on the in vitro digestion of the pistachio hull. Irradiation decreased the digestion rate of the pistachio hull at the dose of 40 kGy when compared to the control. This study showed that gamma irradiation decreased tannin and antioxidants activity of pistachio hull.

  17. Testing of regolith of celestial bolides with active neutron gamma-ray spectrometry

    NASA Astrophysics Data System (ADS)

    Vostrukhin, Andrey; Mitrofanov, Igor; Golovin, Dmitry; Litvak, Maxim; Sanin, Anton

    2015-04-01

    Current space instruments for studying planet's surface include gamma ray spectrometers that detect natural radioactive isotopes as well as gamma-rays induced in subsurface by galactic cosmic rays. When measuring from celestial body's surface, statistics and amount of detected elements can be dramatically increased with active methods, where soil exposed to artificial flux of particles. One good example is the Russian Dynamic Albedo of Neutron (DAN) instrument onboard Martian Science Laboratory mission (Curiosity rover) developed in 2005-2011. It is the first active neutron spectrometer flown to another planet as part of a landed mission to investigate subsurface water distribution and which has now successfully operated for more than two years on the Martian surface. Presentation describes a number of space instruments for different landers and rovers being developed in Russian Space Research Institute for studying Moon and Mars, as well as method of active neutron and gamma spectrometry overview.

  18. Results of mobile gamma scanning activities in St. Louis, Missouri

    SciTech Connect

    Rodriguez, R E; Witt, D A; Cottrell, W D; Carrier, R F

    1991-06-01

    From 1942 through approximately 1966, the Mallinckrodt Chemical Works operated four plants in St. Louis, Missouri, for the Manhattan Engineer District and the Atomic Energy Commission. A variety of production processes using uranium- and radium-bearing ore materials were performed at the plants. It is the policy of the DOE to verify that radiological conditions at such sites or facilities comply with current DOE guidelines. Guidelines for release and use of such sites have become more stringent as research has provided more information since previous cleanups. The Formerly Utilized Sites Remedial Action Program (FUSRAP) was established as part of that effort to confirm the closeout status of facilities under contract to agencies preceding DOE during early nuclear energy development. Under the FUSRAP program, the Mallinckrodt properties have been previously investigated to determine the extent of on-site radiological contamination. At the request of DOE, Oak Ridge National Laboratory (ORNL) conducted a survey in May 1990, of public roadways and suspected haul routes between the Mallinckrodt plant and storage sites in St. Louis to ensure that no residual radioactive materials were conveyed off-site. A mobile gamma scanning van with an on-board computer system was used to identify possible anomalies. Suspect areas are those displaying measurements deviating from gamma exposure rates identified as typical for radiologically unenhanced areas in the vicinity of the areas of interest. The instrumentation highlighted three anomaly locations each of which measured less than 1m{sup 2} in size. None of the slightly elevated radiation levels originated from material associated with former AEC-related processing operations in the area. The anomalies resulted from elevated concentrations of radionuclides present in phosphate fertilizers, increased thorium in road-base gravel, and emanations from the radioactive storage site near the Latty Avenue airport. 9 refs., 3 figs.

  19. The alpha-5 segment of Bacillus thuringiensis delta-endotoxin: in vitro activity, ion channel formation and molecular modelling.

    PubMed Central

    Gazit, E; Bach, D; Kerr, I D; Sansom, M S; Chejanovsky, N; Shai, Y

    1994-01-01

    A peptide with a sequence corresponding to the highly conserved alpha-5 segment of the Cry delta-endotoxin family (amino acids 193-215 of Bacillus thuringiensis CryIIIA [Gazit and Shai (1993) Biochemistry 32, 3429-3436]), was investigated with respect to its interaction with insect membranes, cytotoxicity in vitro towards Spodoptera frugiperda (Sf-9) cells, and its propensity to form ion channels in planar lipid membranes (PLMs). Selectively labelled analogues of alpha-5 at either the N-terminal amino acid or the epsilon-amine of its lysine, were used to monitor the interaction of the peptides with insect membranes. The fluorescent emission spectra of the 7-nitrobenz-2-oxa-1,3-diazole-4-yl (NBD)-labelled alpha-5 peptides displayed a blue shift upon binding to insect (Spodoptera littoralis) mid-gut membranes, reflecting the relocation of the fluorescent probes to an environment of increased apolarity, i.e. within the lipidic constituent of the membrane. Moreover, midgut membrane-bound NBD-labelled alpha-5 peptides were protected from enzymic proteolysis. Functional characterization of alpha-5 has revealed that it is cytotoxic to Sf-9 insect cells, and that it forms ion channels in PLMs with conductances ranging from 30 to 1000 pS. A proline-substituted analogue of alpha-5 is less cytolytic and slightly more exposed to enzymic digestion. Molecular modelling utilizing simulated annealing via molecular dynamics suggests that a transbilayer pore may be formed by alpha-5 monomers that assemble to form a left-handed coiled coil of approximately parallel helices. These findings further support a role for alpha-5 in the toxic mechanism of delta-endotoxins, and assign alpha-5 as one of the transmembrane helices which form the toxic pore. The suggested role is consistent with the recent finding that cleavage of CryIVB delta-endotoxin in a loop between alpha-5 and alpha-6 is highly important for its larvicidal activity [Angsuthanasombat, Crickmore and Ellar (1993) FEMS

  20. The Differential Interactions of Peroxisome Proliferator-Activated Receptor [gamma] Ligands with Tyr473 Is a Physical Basis for Their Unique Biological Activities

    SciTech Connect

    Einstein, Monica; Akiyama, Taro E.; Castriota, Gino A.; Wang, Chuanlin F.; McKeever, Brian; Mosley, Ralph T.; Becker, Joseph W.; Moller, David E.; Meinke, Peter T.; Wood, Harold B.; Berger, Joel P.

    2008-08-01

    Despite their proven antidiabetic efficacy, widespread use of peroxisome proliferator-activated receptor (PPAR){gamma} agonists has been limited by adverse cardiovascular effects. To overcome this shortcoming, selective PPAR{gamma} modulators (SPPAR{gamma}Ms) have been identified that have antidiabetic efficacy comparable with full agonists with improved tolerability in preclinical species. The results of structural studies support the proposition that SPPAR{gamma}Ms interact with PPAR{gamma} differently from full agonists, thereby providing a physical basis for their novel activities. Herein, we describe a novel PPAR{gamma} ligand, SPPAR{gamma}M2. This compound was a partial agonist in a cell-based transcriptional activity assay, with diminished adipogenic activity and an attenuated gene signature in cultured human adipocytes. X-ray cocrystallography studies demonstrated that, unlike rosiglitazone, SPPAR{gamma}M2 did not interact with the Tyr473 residue located within helix 12 of the ligand binding domain (LBD). Instead, SPPAR{gamma}M2 was found to bind to and activate human PPAR{gamma} in which the Tyr473 residue had been mutated to alanine (hPPAR{gamma}Y473A), with potencies similar to those observed with the wild-type receptor (hPPAR{gamma}WT). In additional studies, we found that the intrinsic binding and functional potencies of structurally distinct SPPAR{gamma}Ms were not diminished by the Y473A mutation, whereas those of various thiazolidinedione (TZD) and non-TZD PPAR{gamma} full agonists were reduced in a correlative manner. These results directly demonstrate the important role of Tyr473 in mediating the interaction of full agonists but not SPPAR{gamma}Ms with the PPAR{gamma} LBD, thereby providing a precise molecular determinant for their differing pharmacologies.

  1. Electromagnetic excitation of the Delta(1232) resonance

    SciTech Connect

    V. Pascalutsa; M. Vanderhaeghen; Shin Nan Yang

    2006-09-05

    We review the description of the lowest-energy nucleon excitation--the Delta(1232)-resonance. Much of the recent effort has been focused on the precision measurements of the nucleon to Delta transition by means of electromagnetic probes. We review the results of those measurements and confront them with the state-of-the-art calculations based on chiral effective-field theories (EFT), lattice QCD, and QCD-inspired models. Some of the theoretical approaches are reviewed in detail. In particular, we describe the chiral EFT of QCD in the energy domain of the Delta-resonance, and its applications to the electromagnetic nucleon-to-Delta transition (gamma N Delta). We also describe the recent dynamical and unitary-isobar models of pion electroproduction which are extensively used in the extraction of the gamma* N Delta form factors from experiment. Furthermore, we discuss the link of the gamma* N Delta form factors to generalized parton distributions (GPDs), as well as the predictions of perturbative QCD for these transition form factors. The present status of understanding the Delta-resonance properties and the nature of its excitation is summarized.

  2. Analysis of historical delta values for IAEA/LANL NDA training courses

    SciTech Connect

    Geist, William; Santi, Peter; Swinhoe, Martyn; Bonner, Elisa

    2009-01-01

    The Los Alamos National Laboratory (LANL) supports the International Atomic Energy Agency (IAEA) by providing training for IAEA inspectors in neutron and gamma-ray Nondestructive Assay (NDA) of nuclear material. Since 1980, all new IAEA inspectors attend this two week course at LANL gaining hands-on experience in the application of NDA techniques, procedures and analysis to measure plutonium and uranium nuclear material standards with well known pedigrees. As part of the course the inspectors conduct an inventory verification exercise. This exercise provides inspectors the opportunity to test their abilities in performing verification measurements using the various NDA techniques. For an inspector, the verification of an item is nominally based on whether the measured assay value agrees with the declared value to within three times the historical delta value. The historical delta value represents the average difference between measured and declared values from previous measurements taken on similar material with the same measurement technology. If the measurement falls outside a limit of three times the historical delta value, the declaration is not verified. This paper uses measurement data from five years of IAEA courses to calculate a historical delta for five non-destructive assay methods: Gamma-ray Enrichment, Gamma-ray Plutonium Isotopics, Passive Neutron Coincidence Counting, Active Neutron Coincidence Counting and the Neutron Coincidence Collar. These historical deltas provide information as to the precision and accuracy of these measurement techniques under realistic conditions.

  3. Gamma-glutamyltransferase activity in mammary gland of pregnant rats and its regulation by ovarian hormones, prolactin and placental lactogen.

    PubMed Central

    Bussmann, L E; Deis, R P

    1984-01-01

    Ovariectomy and ovariectomy plus hysterectomy on day 18 of pregnancy increased gamma-glutamyltransferase activity in the mammary gland. The withdrawal of progesterone and the subsequent release of prolactin are responsible for the rise in enzyme activity. Rat placental lactogen in the absence of prolactin and progesterone is able to induce gamma-glutamyltransferase activity. PMID:6149746

  4. Aromatic Residues {epsilon}Trp-55 and {delta}Trp-57 and the Activation of Acetylcholine Receptor Channels.

    PubMed

    Bafna, Pallavi A; Jha, Archana; Auerbach, Anthony

    2009-03-27

    The two transmitter binding sites of the neuromuscular acetylcholine (ACh) receptor channel contain several aromatic residues, including a tryptophan located on the complementary, negative face of each binding pocket. These two residues, Trp-55 in the epsilon subunit and Trp-57 in the delta subunit, were mutated (AEFHILRVY), and for most constructs the rate constants for acetylcholine binding and channel gating were estimated by using single channel kinetic analyses. The rate constants for unliganded channel opening and closing were also estimated for some mutants. From these measurements we calculated all of the equilibrium constants of the "allosteric" cycle as follows: diliganded gating, unliganded gating, dissociation from the C(losed) conformation, and dissociation from the O(pen) conformation. The results indicate the following. (i) These aromatic side chains play a relatively minor role in ACh receptor channel activation. (ii) The main consequence of mutations is to reduce the affinity of the O conformation of the binding site for ACh, with the effect being greater at the epsilon subunit. (iii) In epsilon (but not delta) the aromatic nature of the side chain is important in determining affinity, to a slightly greater degree in the O conformation. Phi value analyses (of both tryptophan residues) show Phi approximately 1 for both the ACh binding and diliganded gating reactions. (iv) This suggests that the structural boundaries of the dynamic elements of the gating conformational change may not be subunit-delimited, and (v) the mutated tryptophan residues experience energy changes that occur relatively early in both the ligand-binding and channel-gating reactions. PMID:19171937

  5. Relationship between Body Mass Index, C-Peptide, and Delta-5-Desaturase Enzyme Activity Estimates in Adult Males

    PubMed Central

    Pickens, C. Austin; Matsuo, Karen H.; Fenton, Jenifer I.

    2016-01-01

    Obesity, in particular abdominal obesity, alters the composition of plasma and tissue fatty acids (FAs), which contributes to inflammation and insulin resistance. FA metabolism is modulated by desaturases and may affect adipokine and insulin secretion. Therefore, we examined relationships between adipokines, a marker of insulin production, and plasma FA desaturase enzyme activity estimates (EAEs) in obesity. Plasma phospholipid (PPL) FAs were isolated from 126 males (ages 48 to 65 years), derivatized, and analyzed using gas chromatography. Delta-6 desaturase (D6D) and delta-5 desaturase (D5D) EAEs were calculated as the ratio of PPL 20:3/18:2 and 20:4/20:3, respectively. In body mass index (BMI) and waist circumference (WC) adjusted polytomous logistic regression analyses, PPL FAs and FA desaturase EAEs were associated with C-peptide and adiponectin. Individuals with elevated D6D EAEs were less likely (OR 0.33) to have serum adiponectin concentrations > 5.37 μg/mL, compared with adiponectin concentrations ≤ 3.62 μg/mL. Individuals with increased D5D EAEs were less likely (OR 0.8) to have C-peptide concentrations ≥ 3.32 ng/mL, and > 1.80 and ≤ 3.29 ng/mL, compared with those with C-peptide ≤ 1.76 ng/mL. The proinflammatory cytokine tumor necrosis factor-α (TNF- α) was positively associated with C-peptide, but TNF- α was not associated with the D5D EAE. C-peptide and adiponectin concentrations are associated with specific PPL FAs and FA desaturase EAEs. The relationship between C-peptide concentrations and D5D EAEs remained significant after adjusting for BMI, WC, and TNF-α. Thus, future research should investigate whether D5D inhibition may occur through a C-peptide mediated pathway. PMID:27023786

  6. Synthesis of Sr{sub 0.9}K{sub 0.1}FeO{sub 3-{delta}} electrocatalysts by mechanical activation

    SciTech Connect

    Monteiro, J.F.; Waerenborgh, J.C.

    2013-02-15

    Potassium-substituted SrFeO{sub 3-{delta}} for possible application as oxygen evolution electrode in alkaline or molten salt media was prepared by mechanical activation and characterized by X-ray diffraction, dilatometric and thermogravimetric analysis, Moessbauer spectroscopy, and electrical conductivity measurements. Room temperature mechanical activation of a mixture of oxide precursors with subsequent thermal treatments at 700-900 Degree-Sign C results in the formation of Sr{sub 0.9}K{sub 0.1}FeO{sub 3-{delta}} with tetragonal perovskite-like structure. Such allows to decrease the synthesis temperature, if compared to the conventional solid-state route, and to prevent possible volatilization of potassium. The results of Moessbauer spectroscopy studies indicate that the oxygen nonstoichiometry in the samples annealed in air at 900-1100 Degree-Sign C with subsequent rapid cooling vary in the range {delta}=0.30-0.32. The electrical conductivity in air exhibits a metal-like behaviour at temperatures above 400 Degree-Sign C and semiconductor behaviour in the low-temperature range, reaching 13-30 S/cm under prospective operation conditions for alkaline electrolyzers ({<=}90 Degree-Sign C). - graphical abstract: XRD patterns of Sr{sub 0.9}K{sub 0.1}FeO{sub 3-{delta}} powders, as-prepared and after annealing at different temperatures. Log({sigma}{center_dot}T) vs. 1000/T plot of the electrical conductivity of Sr{sub 0.9}K{sub 0.1}FeO{sub 3-{delta}}. The inset shows the thermal variation of {sigma}. Ceramics used were prepared by mechanical activation followed by a two-step sintering process at 900 Degree-Sign C for 1 h and 1000 Degree-Sign C for 5 h (82% densification). Highlights: Black-Right-Pointing-Pointer Sr{sub 0.9}K{sub 0.1}FeO{sub 3-{delta}} was successfully obtained by mechanical activation of oxide precursors. Black-Right-Pointing-Pointer Synthesis temperature is significantly lower when compared to a conventional solid-state route. Black

  7. Utilization of recycled neutron source to teach prompt gamma analysis activation-PGNA

    NASA Astrophysics Data System (ADS)

    Delgado-Correal, Camilo; Munera, Hector

    2008-03-01

    Neutron activation analysis based on prompt gamma ray emission has significantly developed during the past twenty years. The technique is particularly suited for the identification of low atomic number elements, as nitrogen that is a main component of drugs and explosives. Identification of these substances is important in the context of humanitarian demining, and in the control of illicit traffic of drugs and explosives. As a good example of recycling of radioactive sources, a ^241Am-Be neutron source emitting 10^7neutron/s, that was not longer in use for other purposes at Ingeominas, was used to build a neutron irradiator that can be used to teach prompt gamma ray analysis, and other nuclear techniques. We irradiated individual samples, each about 4 gram, of three different elements: nitrogen in urea, silicon in milled rock, and cadmium in cadmium oxide. The prompt gamma rays emitted in the nuclear reactions ^112Cd (neutron,gamma) ^113Cd, ^28Si (neutron,gamma) ^29Si and ^14N (neutron,gamma) ^15N were identified using a well-type NaI (Tl) detector, connected to a multi-channel analyzer.

  8. The effects of acute-phase inducers and dimethyl sulphoxide on delta-aminolaevulinate synthase activity in human HepG2 hepatoma cells.

    PubMed Central

    Iwasa, F; Sassa, S; Kappas, A

    1989-01-01

    The effects of acute-phase inducers and dimethyl sulphoxide (Me2SO) on delta-aminolaevulinate (ALA) synthase in HepG2 cells were examined. Treatment of cells with Me2SO resulted in a significant increase in ALA synthase activity. Interleukin-6 increased ALA synthase activity only slightly, but it substantially potentiated the induction of ALA synthase by Me2SO. These data suggest that ALA synthase activity in liver is altered during acute-phase reactions. PMID:2541694

  9. The effects of lead on delta-aminolevulinic acid dehydratase activity, growth, hemoglobin content, and reproduction in Daphnia magna.

    PubMed

    Berglind, R; Dave, G; Sjöbeck, M L

    1985-04-01

    The effects of continuous exposure to lead for various periods and recovery in clean water on delta-aminolevulinic acid dehydratase (ALA-D) activity, hemoglobin content, growth, and reproduction were studied in Daphnia magna. Steady-state inhibition of ALA-D activity was reached within 2 days in 16, 64, and 256 micrograms Pb liter-1, but restoration in clean water was prolonged in relation to previous exposure. In spite of the inhibition of ALA-D activity hemoglobin content increased after 2 days in 16 and 24 micrograms Pb liter-1. Furthermore, hemoglobin content in previously exposed animals increased during recovery in clean water. Maximum hemoglobin content (2.9 times control value) was found after 2 days recovery of animals exposed to 64 micrograms Pb liter-1. These findings suggest that some enzyme(s) other than ALA-D in the biosynthetic pathway of hemoglobin formation is (are) more sensitive to lead. Growth, in contrast to reproduction, was stimulated by low concentrations of lead (less than 64 micrograms Pb liter-1), although in 256 micrograms Pb liter-1 growth was also significantly impaired. After 19 days the 16 and 50% reproductive impairment concentrations were less than or equal to 1 and 10 micrograms Pb liter-1, respectively. PMID:3987601

  10. Effects of lead on delta-aminolevulinic acid dehydratase activity, growth, hemoglobin content, and reproduction in Daphnia magna

    SciTech Connect

    Berglind, R.; Dave, G.; Sjoebeck, M.L.

    1985-04-01

    The effects of continuous exposure to lead for various periods and recovery in clean water on delta-aminolevulinic acid dehydratase (ALA-D) activity, hemoglobin content, growth, and reproduction were studied in Daphnia magna. Steady-state inhibition of ALA-D activity was reached within 2 days in 16, 64, and 256 micrograms Pb liter-1, but restoration in clean water was prolonged in relation to previous exposure. In spite of the inhibition of ALA-D activity hemoglobin content increased after 2 days in 16 and 24 micrograms Pb liter-1. Furthermore, hemoglobin content in previously exposed animals increased during recovery in clean water. Maximum hemoglobin content (2.9 times control value) was found after 2 days recovery of animals exposed to 64 micrograms Pb liter-1. These findings suggest that some enzyme(s) other than ALA-D in the biosynthetic pathway of hemoglobin formation is (are) more sensitive to lead. Growth, in contrast to reproduction, was stimulated by low concentrations of lead (less than 64 micrograms Pb liter-1), although in 256 micrograms Pb liter-1 growth was also significantly impaired. After 19 days the 16 and 50% reproductive impairment concentrations were less than or equal to 1 and 10 micrograms Pb liter-1, respectively.

  11. Carbonic anhydrase III regulates peroxisome proliferator-activated receptor-{gamma}2

    SciTech Connect

    Mitterberger, Maria C.; Kim, Geumsoo; Rostek, Ursula; Levine, Rodney L.; Zwerschke, Werner

    2012-05-01

    Carbonic anhydrase III (CAIII) is an isoenzyme of the CA family. Because of its low specific anhydrase activity, physiological functions in addition to hydrating CO{sub 2} have been proposed. CAIII expression is highly induced in adipogenesis and CAIII is the most abundant protein in adipose tissues. The function of CAIII in both preadipocytes and adipocytes is however unknown. In the present study we demonstrate that adipogenesis is greatly increased in mouse embryonic fibroblasts (MEFs) from CAIII knockout (KO) mice, as demonstrated by a greater than 10-fold increase in the induction of fatty acid-binding protein-4 (FABP4) and increased triglyceride formation in CAIII{sup -/-} MEFs compared with CAIII{sup +/+} cells. To address the underlying mechanism, we investigated the expression of the two adipogenic key regulators, peroxisome proliferator-activated receptor-{gamma}2 (PPAR{gamma}2) and CCAAT/enhancer binding protein-{alpha}. We found a considerable (approximately 1000-fold) increase in the PPAR{gamma}2 expression in the CAIII{sup -/-} MEFs. Furthermore, RNAi-mediated knockdown of endogenous CAIII in NIH 3T3-L1 preadipocytes resulted in a significant increase in the induction of PPAR{gamma}2 and FABP4. When both CAIII and PPAR{gamma}2 were knocked down, FABP4 was not induced. We conclude that down-regulation of CAIII in preadipocytes enhances adipogenesis and that CAIII is a regulator of adipogenic differentiation which acts at the level of PPAR{gamma}2 gene expression. -- Highlights: Black-Right-Pointing-Pointer We discover a novel function of Carbonic anhydrase III (CAIII). Black-Right-Pointing-Pointer We show that CAIII is a regulator of adipogenesis. Black-Right-Pointing-Pointer We demonstrate that CAIII acts at the level of PPAR{gamma}2 gene expression. Black-Right-Pointing-Pointer Our data contribute to a better understanding of the role of CAIII in fat tissue.

  12. Natural processes in delta restoration: application to the Mississippi Delta.

    PubMed

    Paola, Chris; Twilley, Robert R; Edmonds, Douglas A; Kim, Wonsuck; Mohrig, David; Parker, Gary; Viparelli, Enrica; Voller, Vaughan R

    2011-01-01

    Restoration of river deltas involves diverting sediment and water from major channels into adjoining drowned areas, where the sediment can build new land and provide a platform for regenerating wetland ecosystems. Except for local engineered structures at the points of diversion, restoration mainly relies on natural delta-building processes. Present understanding of such processes is sufficient to provide a basis for determining the feasibility of restoration projects through quantitative estimates of land-building rates and sustainable wetland area under different scenarios of sediment supply, subsidence, and sea-level rise. We are not yet to the point of being able to predict the evolution of a restored delta in detail. Predictions of delta evolution are based on field studies of active deltas, deltas in mine-tailings ponds, experimental deltas, and countless natural experiments contained in the stratigraphic record. These studies provide input for a variety of mechanistic delta models, ranging from radially averaged formulations to more detailed models that can resolve channels, topography, and ecosystem processes. Especially exciting areas for future research include understanding the mechanisms by which deltaic channel networks self-organize, grow, and distribute sediment and nutrients over the delta surface and coupling these to ecosystem processes, especially the interplay of topography, network geometry, and ecosystem dynamics. PMID:21329199

  13. Gamma irradiation effect on the chemical composition and the antioxidant activity of Ipomoea batatas L

    SciTech Connect

    Tahir, D. Halide, H. Kurniawan, D.; Wahab, A. W.

    2014-09-25

    The chemical composition and antioxidant activity of Ipomoea batatas L. (sweet potato) were studied by x-ray fluorescence (XRF) spectroscopy, Fourier transform infrared spectroscopy, and by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity. The irradiation treatment was performed by using Cs-137 as a gamma sources in experimental equipment. Treatment by irradiation emerges as a possible conservation technique that has been tested successfully in several food products. The amount of chemical composition was changed and resulting new chemical for absorbed dose 40 mSv. Interestingly, it was found that gamma irradiation significantly increased the antioxidant activity, as measured by DPPH radical scavenging capacity. The antioxidant activity of Ipomoea batatas L. extract was dramatically increased in the non-irradiated sample to the sample irradiated at 40 mSv. These results indicate that gamma irradiation of Ipomoea batatas L. extract can enhance its antioxidant activity through the formation of a new chemical compound. Based on these results, increased antioxidant activity of Ipomoea batatas L. extracts by gamma rays can be applied to various industries, especially cosmetics, foodstuffs, and pharmaceuticals.

  14. Gamma irradiation effect on the chemical composition and the antioxidant activity of Ipomoea batatas L.

    NASA Astrophysics Data System (ADS)

    Tahir, D.; Halide, H.; Wahab, A. W.; Kurniawan, D.

    2014-09-01

    The chemical composition and antioxidant activity of Ipomoea batatas L. (sweet potato) were studied by x-ray fluorescence (XRF) spectroscopy, Fourier transform infrared spectroscopy, and by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity. The irradiation treatment was performed by using Cs-137 as a gamma sources in experimental equipment. Treatment by irradiation emerges as a possible conservation technique that has been tested successfully in several food products. The amount of chemical composition was changed and resulting new chemical for absorbed dose 40 mSv. Interestingly, it was found that gamma irradiation significantly increased the antioxidant activity, as measured by DPPH radical scavenging capacity. The antioxidant activity of Ipomoea batatas L. extract was dramatically increased in the non-irradiated sample to the sample irradiated at 40 mSv. These results indicate that gamma irradiation of Ipomoea batatas L. extract can enhance its antioxidant activity through the formation of a new chemical compound. Based on these results, increased antioxidant activity of Ipomoea batatas L. extracts by gamma rays can be applied to various industries, especially cosmetics, foodstuffs, and pharmaceuticals.

  15. Two cis-DNA elements involved in myeloid-cell-specific expression and gamma interferon (IFN-gamma) activation of the human high-affinity Fc gamma receptor gene: a novel IFN regulatory mechanism.

    PubMed Central

    Perez, C; Wietzerbin, J; Benech, P D

    1993-01-01

    The human high-affinity receptor for the constant region of immunoglobulin G (human Fc gamma R1) is encoded by two mRNAs induced selectively by gamma interferon (IFN-gamma) and expressed in cells of myeloid lineage. The cis-DNA element (GRR) previously found to confer IFN-gamma responsiveness to this gene acts as an inducible enhancer and is the target of an IFN-gamma-activated factor(s) (GIRE-BP) in cells of different origins. Although the GRR motif is not related to the DNA elements involved in the regulation of other IFN-stimulated genes, GIRE-BP binding depends on the IFN-gamma-dependent activation of the 91-kDa protein known to be one of the factors of a transcriptional complex activated by IFN-alpha. Deletions of the Fc gamma R1 promoter allowed us to identify a 25-bp element, downstream from the GRR motif, conferring cell-type-specific expression. This element, called MATE (myeloid activating transcription element), is the DNA target for constitutive factors forming two complexes, MATE-BP1 and MATE-BP2. In accordance with the functional analysis, MATE-BP binding activities were detected in extracts prepared from myeloid cell lines such as THP-1, HL-60, and U-937 but not in HeLa cell extracts. The MATE motif is present not only in the promoter of other Fc receptor genes but also in several promoters of genes whose expression is restricted to monocytic cells. Our results suggest that human Fc gamma R1 gene expression in myeloid cells is initiated by the interaction of IFN-gamma-activated factors with cell-type-specific factors through their binding to the GRR and MATE motifs. Images PMID:8455606

  16. Effect of gamma irradiation on the physiological activity of Korean soybean fermented foods, Chungkookjang and Doenjang

    NASA Astrophysics Data System (ADS)

    Byun, Myung-Woo; Son, Jun-Ho; Yook, Hong-Sun; Jo, Cheorun; Kim, Dong-Ho

    2002-06-01

    Effects of gamma irradiation on the physiological activity of Korean soybean fermented foods were investigated. Chungkookjang, the whole cooked soybean product and Doenjang, soybean paste were purchased and irradiated at 5, 10 and 20 kGy of absorbed doses. The physiological activity was evaluated by angiotensin converting enzyme inhibition, xanthine oxidase inhibition, tyrosinase inhibition and radical scavenging ability and results indicated that at 10 kGy or below did not show any significant change on physiological activities by irradiation.

  17. Activation of peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) induces cell death through MAPK-dependent mechanism in osteoblastic cells

    SciTech Connect

    Kim, Sung Hun; Yoo, Chong Il; Kim, Hui Taek; Park, Ji Yeon; Kwon, Chae Hwa; Keun Kim, Yong . E-mail: kim430@pusan.ac.kr

    2006-09-01

    The present study was undertaken to determine the role of the mitogen-activated protein kinase (MAPK) subfamilies in cell death induced by PPAR{gamma} agonists in osteoblastic cells. Ciglitazone and troglitazone, PPAR{gamma} agonists, resulted in a concentration- and time-dependent cell death, which was largely attributed to apoptosis. But a PPAR{alpha} agonist ciprofibrate did not affect the cell death. Ciglitazone caused reactive oxygen species (ROS) generation and ciglitazone-induced cell death was prevented by antioxidants, suggesting an important role of ROS generation in the ciglitazone-induced cell death. ROS generation and cell death induced by ciglitazone were inhibited by the PPAR{gamma} antagonist GW9662. Ciglitazone treatment caused activation of extracellular signal-regulated kinase (ERK) and p38. Activation of ERK was dependent on epidermal growth factor receptor (EGFR) and that of p38 was independent. Ciglitazone-induced cell death was significantly prevented by PD98059, an inhibitor of ERK upstream kinase MEK1/2, and SB203580, a p38 inhibitor. Ciglitazone treatment increased Bax expression and caused a loss of mitochondrial membrane potential, and its effect was prevented by N-acetylcysteine, PD98059, and SB203580. Ciglitazone induced caspase activation, which was prevented by PD98059 and SB203580. The general caspase inhibitor z-DEVD-FMK and the specific inhibitor of caspases-3 DEVD-CHO exerted the protective effect against the ciglitazone-induced cell death. The EGFR inhibitors AG1478 and suramin protected against the ciglitazone-induced cell death. Taken together, these findings suggest that the MAPK signaling pathways play an active role in mediating the ciglitazone-induced cell death of osteoblasts and function upstream of a mitochondria-dependent mechanism. These data may provide a novel insight into potential therapeutic strategies for treatment of osteoporosis.

  18. Results of mobile gamma scanning activities in Tonawanda, New York

    SciTech Connect

    Cottrell, W.D.; Witt, D.A.; Rodriguez, R.E.; Carrier, R.F.

    1990-12-01

    During the 1940s, the Linde Air Products Division of Union Carbide operated a plant in Tonawanda, New York, for the Manhattan Engineer District (MED) and the Atomic Energy Commission (AEC). Uranium production and some nickel processing were conducted at the site. It is the policy of the US Department of Energy (DOE) to verify that radiological conditions at such sites or facilities comply with current DOE guidelines. Guidelines for release and use of such sites have become more stringent as research has provided more information since previous cleanups. The Formerly Utilized Sites Remedial Action Program (FUSRAP) was established as part of that effort to confirm the closeout status of facilities under contract to agencies preceding DOE during early nuclear energy development. Under the FUSRAP program, the Linde site itself has been previously investigated to determine the extent of on-site radiological contamination. As a precaution to insure that no residual radioactive materials were transported off-site, the Department of Energy requested that ORNL survey the area in the vicinity of the Linde Plant, the waste water treatment facility on Tower Road, the Sheridan Park Fire Station (District 4), and the Tonawanda Landfill to assess whether any residual radioactive material could be detected. The survey was conducted the week of April 3, 1990. Results of analysis of soil samples from the Tonawanda Landfill revealed slightly elevated concentrations of {sup 238}U and {sup 226}Ra suggestive of residuals from former Linde Plant operations. Therefore, it is recommended that additional surveying of the landfill property and of Sheridan Creek from south of the Linde property to its confluence with the Niagara River be conducted. The survey should include the measurement of gamma radiation levels and radionuclide analysis of silt samples. 6 refs., 4 figs., 1 tab.

  19. Synthesis of theanine from glutamic acid gamma-methyl ester and ethylamine catalyzed by Escherichia coli having gamma-glutamyltranspeptidase activity.

    PubMed

    Zhang, Fei; Zheng, Qing-Zhong; Jiao, Qing-Cai; Liu, Jun-Zhong; Zhao, Gen-Hai

    2010-08-01

    Glutamic acid gamma-methyl ester (GAME) was used as substrate for theanine synthesis catalyzed by Escherichia coli cells possessing gamma-glutamyltranspeptidase activity. The yield was about 1.2-fold higher than with glutamine as substrate. The reaction was optimal at pH 10 and 45 degrees C, and the optimal substrate ratio of GAME to ethylamine was 1:10 (mol/mol). With GAME at 100 mmol, 95 mmol theanine was obtained after 8 h. PMID:20383735

  20. Pedunculopontine Nucleus Gamma Band Activity-Preconscious Awareness, Waking, and REM Sleep.

    PubMed

    Urbano, Francisco J; D'Onofrio, Stasia M; Luster, Brennon R; Beck, Paige B; Hyde, James Robert; Bisagno, Veronica; Garcia-Rill, Edgar

    2014-01-01

    The pedunculopontine nucleus (PPN) is a major component of the reticular activating system (RAS) that regulates waking and REM sleep, states of high-frequency EEG activity. Recently, we described the presence of high threshold, voltage-dependent N- and P/Q-type calcium channels in RAS nuclei that subserve gamma band oscillations in the mesopontine PPN, intralaminar parafascicular nucleus (Pf), and pontine subcoeruleus nucleus dorsalis (SubCD). Cortical gamma band activity participates in sensory perception, problem solving, and memory. Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions. That is, the RAS may play an early permissive role in volition. Our latest results suggest that (1) the manifestation of gamma band activity during waking may employ a separate intracellular pathway compared to that during REM sleep, (2) neuronal calcium sensor (NCS-1) protein, which is over expressed in schizophrenia and bipolar disorder, modulates gamma band oscillations in the PPN in a concentration-dependent manner, (3) leptin, which undergoes resistance in obesity resulting in sleep dysregulation, decreases sodium currents in PPN neurons, accounting for its normal attenuation of waking, and (4) following our discovery of electrical coupling in the RAS, we hypothesize that there are cell clusters within the PPN that may act in concert. These results provide novel information on the mechanisms controlling high-frequency activity related to waking and REM sleep by elements of the RAS. PMID:25368599

  1. Pedunculopontine Nucleus Gamma Band Activity-Preconscious Awareness, Waking, and REM Sleep

    PubMed Central

    Urbano, Francisco J.; D’Onofrio, Stasia M.; Luster, Brennon R.; Beck, Paige B.; Hyde, James Robert; Bisagno, Veronica; Garcia-Rill, Edgar

    2014-01-01

    The pedunculopontine nucleus (PPN) is a major component of the reticular activating system (RAS) that regulates waking and REM sleep, states of high-frequency EEG activity. Recently, we described the presence of high threshold, voltage-dependent N- and P/Q-type calcium channels in RAS nuclei that subserve gamma band oscillations in the mesopontine PPN, intralaminar parafascicular nucleus (Pf), and pontine subcoeruleus nucleus dorsalis (SubCD). Cortical gamma band activity participates in sensory perception, problem solving, and memory. Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions. That is, the RAS may play an early permissive role in volition. Our latest results suggest that (1) the manifestation of gamma band activity during waking may employ a separate intracellular pathway compared to that during REM sleep, (2) neuronal calcium sensor (NCS-1) protein, which is over expressed in schizophrenia and bipolar disorder, modulates gamma band oscillations in the PPN in a concentration-dependent manner, (3) leptin, which undergoes resistance in obesity resulting in sleep dysregulation, decreases sodium currents in PPN neurons, accounting for its normal attenuation of waking, and (4) following our discovery of electrical coupling in the RAS, we hypothesize that there are cell clusters within the PPN that may act in concert. These results provide novel information on the mechanisms controlling high-frequency activity related to waking and REM sleep by elements of the RAS. PMID:25368599

  2. Chemical synthesis of nucleoside-gamma-[32P]triphosphates of high specific activity.

    PubMed

    Janecka, A; Panusz, H; Pankowski, J; Koziołkiewicz, W

    1980-01-01

    A simple chemical procedure for the preparation of four common ribonucleoside 5-gamma-[32P]triphosphates of high specific activity (up to 10 Ci/mmole) based on the condensation of orthophosphoric acid with the corresponding nucleoside 5-diphosphate in the presence of ethyl chloroformate as well as the methods of purification and identification of the products are described. PMID:7375446

  3. Measuring the activity of a 51Cr neutrino source based on the gamma-radiation spectrum

    NASA Astrophysics Data System (ADS)

    Gorbachev, V. V.; Gavrin, V. N.; Ibragimova, T. V.; Kalikhov, A. V.; Malyshkin, Yu. M.; Shikhin, A. A.

    2015-12-01

    A technique for the measurement of activities of intense β sources by measuring the continuous gamma-radiation (internal bremsstrahlung) spectra is developed. A method for reconstructing the spectrum recorded by a germanium semiconductor detector is described. A method for the absolute measurement of the internal bremsstrahlung spectrum of 51Cr is presented.

  4. AGILE confirmation of enhanced gamma-ray activity from the Blazar 1ES 1959+650

    NASA Astrophysics Data System (ADS)

    Lucarelli, F.; Pittori, C.; Verrecchia, F.; Bulgarelli, A.; Fioretti, V.; Zoli, A.; Piano, G.; Munar-Adrover, P.; Tavani, M.; Donnarumma, I.; Vercellone, S.; Striani, E.; Cardillo, M.; Gianotti, F.; Trifoglio, M.; Giuliani, A.; Mereghetti, S.; Caraveo, P.; Perotti, F.; Chen, A.; Argan, A.; Costa, E.; Del Monte, E.; Evangelista, Y.; Feroci, M.; Lazzarotto, F.; Lapshov, I.; Pacciani, L.; Soffitta, P.; Sabatini, S.; Vittorini, V.; Pucella, G.; Rapisarda, M.; Di Cocco, G.; Fuschino, F.; Galli, M.; Labanti, C.; Marisaldi, M.; Pellizzoni, A.; Pilia, M.; Trois, A.; Barbiellini, G.; Vallazza, E.; Longo, F.; Morselli, A.; Picozza, P.; Prest, M.; Lipari, P.; Zanello, D.; Cattaneo, P. W.; Rappoldi, A.; Colafrancesco, S.; Parmiggiani, N.; Ferrari, A.; Antonelli, A.; Giommi, P.; Salotti, L.; Valentini, G.; D'Amico, F.

    2016-06-01

    Following ATel #9148, reporting multi-wavelength activity from the BL Lac type blazar 1ES 1959+650, AGILE also detects increased gamma-ray emission above 100 MeV from a position compatible with this BL Lac source.

  5. Chemical composition and lipoxygenase activity in soybeans (Glycine max L. Merr.) submitted to gamma irradiation

    NASA Astrophysics Data System (ADS)

    Barros, Érica Amanda de; Broetto, Fernando; Bressan, Dayanne F.; Sartori, Maria M. P.; Costa, Vladimir E.

    2014-05-01

    Soybeans are an important food due to their functional and nutritional characteristics. However, consumption by western populations is limited by the astringent taste of soybeans and their derivatives which results from the action of lipoxygenase, an enzyme activated during product processing. The aim of this study was to evaluate the effect of gamma irradiation on the chemical composition and specific activity of lipoxygenase in different soybean cultivars. Soybeans were stored in plastic bags and irradiated with doses of 2.5, 5 and 10 kGy. The chemical composition (moisture, protein, lipids, ashes, crude fiber, and carbohydrates) and lipoxygenase specific activity were determined for each sample. Gamma irradiation induced a small increase of protein and lipid content in some soybean cultivars, which did not exceed the highest content of 5% and 26%, respectively, when compared to control. Lipoxygenase specific activity decreased in the three cultivars with increasing gamma irradiation dose. In conclusion, the gamma irradiation doses used are suitable to inactivate part of lipoxygenase while not causing expressive changes in the chemical composition of the cultivars studied.

  6. Stability evaluation and correction of a pulsed neutron generator prompt gamma activation analysis system

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Source output stability is important for accurate measurement in prompt gamma neutron activation. This is especially true when measuring low-concentration elements such as in vivo nitrogen (~2.5% of body weight). We evaluated the stability of the compact DT neutron generator within an in vivo nitrog...

  7. Delta II Mars Pathfinder

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Final preparations for lift off of the DELTA II Mars Pathfinder Rocket are shown. Activities include loading the liquid oxygen, completing the construction of the Rover, and placing the Rover into the Lander. After the countdown, important visual events include the launch of the Delta Rocket, burnout and separation of the three Solid Rocket Boosters, and the main engine cutoff. The cutoff of the main engine marks the beginning of the second stage engine. After the completion of the second stage, the third stage engine ignites and then cuts off. Once the third stage engine cuts off spacecraft separation occurs.

  8. Transcriptional cofactors exhibit differential preference toward peroxisome proliferator-activated receptors alpha and delta in uterine cells.

    PubMed

    Lim, Hyunjung J; Moon, Irene; Han, Kyuyong

    2004-06-01

    We previously showed that peroxisome proliferator-activated receptor delta (PPARdelta) is crucial for embryo implantation as a receptor for cyclooxygenase-2-derived prostacyclin in mice. PPARs belong to the nuclear receptor superfamily. They form heterodimer with a retinoid X receptor, recruit transcriptional cofactors, and bind to a specific recognition element for regulation of target genes. Although cofactors are generally shared by various nuclear receptors, some are involved in cell-specific events. The objective of this investigation was to examine interactions of transcriptional cofactors with PPARdelta in uterine cells for its effectiveness in regulating gene expression. We chose two uterine cellular systems: periimplantation mouse uterus and AN(3)CA human uterine cell line. As examined by in situ hybridization, steroid receptor coactivator (SRC)-2, SRC-3, PPAR-interacting protein, receptor-interacting protein 140 (RIP140), nuclear receptor corepressor (N-CoR), and silencing mediator for retinoid and thyroid hormone receptor (SMRT) exhibit overlapping expression with that of PPARdelta in the periimplantation mouse uterus. Glutathione-S-transferase (GST) pull-down assays show that PPARdelta physically interacts with SRC 1-3, RIP140, PPAR-binding protein, N-CoR, and SMRT in the absence of ligands, suggesting their potent interactions with PPARdelta. Transient transfection assays in AN(3)CA cells show that among members of the SRC family, only SRC-2 serves as a true coactivator for PPARdelta, whereas all SRC members could enhance PPARalpha-induced transcriptional activation. Interestingly, N-CoR and SMRT potently repress PPARdelta-induced transcriptional activation but fail to repress PPARalpha activity. RIP140 is effective in repressing basal and PPAR-induced transcriptional activation. Collectively, the results suggest that gene regulation by PPARdelta in the uterine cells uniquely responds to SRC-2, N-CoR, SMRT, or RIP140, and these interactions may be

  9. Comparison of [Dmt1]DALDA and DAMGO in binding and G protein activation at mu, delta, and kappa opioid receptors.

    PubMed

    Zhao, Guo-Min; Qian, Xuanxuan; Schiller, Peter W; Szeto, Hazel H

    2003-12-01

    [Dmt1]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt = 2',6'-dimethyltyrosine) binds with high affinity and selectivity to the mu opioid receptor and is a surprisingly potent and long-acting analgesic, especially after intrathecal administration. In an attempt to better understand the unique pharmacological profile of [Dmt1]DALDA, we have prepared [3H][Dmt1]DALDA and compared its binding properties with that of [3H]DAMGO ([d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin). Kinetic studies revealed rapid association of [3H][Dmt1]DALDA when incubated with mouse brain membranes (K+1 = 0.155 nM(-1) min(-1)). Dissociation of [3H][Dmt1]DALDA was also rapid (K(-1) = 0.032 min(-1)) and indicated binding to a single site. [3H][Dmt1]DALDA binds with very high affinity to human mu opioid receptor (hMOR) (Kd = 0.199 nM), and Kd and Bmax were reduced by sodium but not Gpp(NH)p [guanosine 5'-(beta,gamma-imido)triphosphate]. Similar Kd values were obtained in brain and spinal cord tissues and SH-SY5Y cells. The hMOR:hDOR (human delta opioid receptor) selectivity of [Dmt1]DALDA ( approximately 10,000) is 8-fold higher than DAMGO. However, [Dmt1]DALDA is less selective than DAMGO against hKOR (human kappa opioid receptor) (26-versus 180-fold). The Ki values for a number of opioid ligands were generally higher when determined by competitive displacement binding against [3H][Dmt1]DALDA compared with [3H]DAMGO, with the exception of Dmt1-substituted peptide analogs. All Dmt1 analogs showed much higher affinity for the mu receptor than corresponding Tyr1 analogs. [35S]GTPgammaS (guanosine 5'-O -(3-[35S]thio)triphosphate) binding showed that [Dmt1]DALDA and DAMGO are full agonists at hMOR and hDOR but are only partial agonists at hKOR. The very high affinity and selectivity of [3H][Dmt1]DALDA for the mu receptor, together with its very low nonspecific binding (10-15%) and metabolic stability, make [3H][Dmt1]DALDA an ideal radioligand for labeling mu receptors. PMID:14534366

  10. Vitamin E, glutathione S-transferase and gamma-glutamyl transpeptidase activities in cultured hepatocytes of rats treated with carcinogens.

    PubMed

    Ong, F B; Wan Ngah, W Z; Top, A G; Khalid, B A; Shamaan, N A

    1994-03-01

    1. The effects of alpha-tocopherol and gamma-tocotrienol on glutathione S-transferase (GST) and gamma-glutamyl transpeptidase (gamma-GT) activities in cultured hepatocytes prepared from rats treated with diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) were investigated. 2. Both the alpha-tocopherol and gamma-tocotrienol treated hepatocytes showed significantly higher (P < 0.05) GST activities than untreated hepatocytes prepared from the carcinogen treated rats in the first 3 days of culture. Treatment with alpha-tocopherol and gamma-tocotrienol generally resulted in a tendency to increase the GST activities above that in the untreated hepatocytes. 3. Treatment with high doses (125-250 microM) of alpha-tocopherol and low doses (12.5-25 microM) of gamma-tocotrienol generally resulted in a significant reduction in gamma-GT activities at 1-3 days. gamma-GT activities are reduced as the dose of alpha-tocopherol and gamma-tocotrienol are increased. PMID:7910569

  11. 1,25 dihydroxyvitamin D3 stimulates phospholipase C-gamma in rat colonocytes: role of c-Src in PLC-gamma activation.

    PubMed Central

    Khare, S; Bolt, M J; Wali, R K; Skarosi, S F; Roy, H K; Niedziela, S; Scaglione-Sewell, B; Aquino, B; Abraham, C; Sitrin, M D; Brasitus, T A; Bissonnette, M

    1997-01-01

    Our laboratory has previously demonstrated that 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) rapidly stimulated polyphosphoinositide (PI) hydrolysis, raised intracellular Ca2+, and activated two Ca2+-dependent protein kinase C (PKC) isoforms, PKC-alpha and -betaII in the rat large intestine. We also showed that the direct addition of 1,25(OH)2D3 to isolated colonic membranes failed to stimulate PI hydrolysis, but required secosteroid treatment of intact colonocytes, suggesting the involvement of a soluble factor. Furthermore, this PI hydrolysis was restricted to the basal lateral plasma membrane of these cells. In the present studies, therefore, we examined whether polyphosphoinositide-phospholipase C-gamma (PI-PLC-gamma), a predominantly cytosolic isoform of PI-PLC, was involved in the hydrolysis of colonic membrane PI by 1,25(OH)2D3. This isoform has been shown to be activated and membrane-associated by tyrosine phosphorylation. We found that 1,25(OH)2D3 caused a significant increase in the biochemical activity, particulate association, and the tyrosine phosphorylation of PLC-gamma, specifically in the basal lateral membranes. This secosteroid also induced a twofold increase in the activity of Src, a proximate activator of PLC-gamma in other cells, with peaks at 1 and 9 min in association with Src tyrosine dephosphorylation. 1,25(OH)2D3 also increased the physical association of activated c-Src with PLC-gamma. In addition, Src isolated from colonocytes treated with 1,25(OH)2D3, demonstrated an increased ability to phosphorylate exogenous PLC-gamma in vitro. Inhibition of 1,25(OH)2D3-induced Src activation by PP1, a specific Src family protein tyrosine kinase inhibitor, blocked the ability of this secosteroid to stimulate the translocation and tyrosine phosphorylation of PLC-gamma in the basolateral membrane (BLM). Src activation was lost in D deficiency, and was reversibly restored with the in vivo repletion of 1,25(OH)2D3. These studies demonstrate for the first time

  12. Comparison of morphology of active cyclic steps created by turbidity currents on Squamish Delta, British Columbia, Canada with flume experiments

    NASA Astrophysics Data System (ADS)

    Yokokawa, Miwa; Yamamoto, Shinya; Higuchi, Hiroyuki; Hughes Clarke, John E.; Izumi, Norihiro

    2015-04-01

    Upper-flow-regime bedforms, such as cyclic steps and antidunes, have been reported to be formed by turbidity currents. Their formative conditions are, however, not fully understood because of the difficulty of field surveys in the deep sea. Field observations of turbidity currents and seabed topography on the Squamish delta in Howe Sound, British Columbia, Canada have been undertaken which found bedwaves actively migrating in the upstream direction in channels formed on the prodelta slope. Their topography and behavior suggest that they are cyclic steps formed by turbidity currents. Because Squamish delta is as shallow as around 150 m, and easy to access compared with general submarine canyons, it is thought to be one of the best places for studying characteristics of cyclic steps formed by turbidity currents through field observations. In this study, we have analyzed configurations of cyclic steps with the use of data obtained in the field observation of 2011, and compare them with the data from the flume experiments. On the prodelta slope, three major active channels are clearly developed. In addition to the sonar survey, a 600 kHz ADCP was installed in 150m of water just seaward of the termination of the North Channel. In addition, 1200kHz ADCP and 500kHz M3s are suspended from the research vessel in 60 m of water and 300 m distance from the delta edge. We selected images showing large daily differences. The steps move vigorously at the upper 600m parts of the prodelta slope, so that we measured the steps in this area. From the profiles perpendicular to the bedwave crest lines through the center of channels, wavelength and wave height for each step, mean slope were measured on the software for quantitative image analyses manually. Wave steepness for each step was calculated using the wavelength and wave height measured as above. The mean slope ranges from 6.8° ~ 2.7° (more proximal, steeper), mean wavelength and wave heights of steps range from 24.5 to 87.6m

  13. The WISE Gamma-Ray Strip Parameterization: The Nature of the Gamma-Ray Active Galactic Nuclei of Uncertain Type

    NASA Astrophysics Data System (ADS)

    Massaro, F.; D'Abrusco, R.; Tosti, G.; Ajello, M.; Gasparrini, D.; Grindlay, J. E.; Smith, Howard A.

    2012-05-01

    Despite the large number of discoveries made recently by Fermi, the origins of the so-called unidentified γ-ray sources remain unknown. The large number of these sources suggests that there could be a population among them that significantly contributes to the isotropic gamma-ray background and it is therefore crucial to understand their nature. The first step toward a complete comprehension of the unidentified γ-ray source population is to identify those that can be associated with blazars, the most numerous class of extragalactic sources in the γ-ray sky. Recently, we discovered that blazars can be recognized and separated from other extragalactic sources using the infrared (IR) WISE satellite colors. The blazar population delineates a remarkable and distinctive region of the IR color-color space, the WISE blazar strip. In particular, the subregion delineated by the γ-ray emitting blazars is even narrower and we named it the WISE Gamma-ray Strip (WGS). In this paper, we parameterize the WGS on the basis of a single parameter s that we then use to determine if γ-ray active galactic nuclei of the uncertain type (AGUs) detected by Fermi are consistent with the WGS and can be considered blazar candidates. We find that 54 AGUs out of a set of 60 analyzed have IR colors consistent with the WGS; only 6 AGUs are outliers. This result implies that a very high percentage (i.e., in this sample about 90%) of the AGUs detected by Fermi are indeed blazar candidates.

  14. Spatial and temporal relationships of electrocorticographic alpha and gamma activity during auditory processing.

    PubMed

    Potes, Cristhian; Brunner, Peter; Gunduz, Aysegul; Knight, Robert T; Schalk, Gerwin

    2014-08-15

    Neuroimaging approaches have implicated multiple brain sites in musical perception, including the posterior part of the superior temporal gyrus and adjacent perisylvian areas. However, the detailed spatial and temporal relationship of neural signals that support auditory processing is largely unknown. In this study, we applied a novel inter-subject analysis approach to electrophysiological signals recorded from the surface of the brain (electrocorticography (ECoG)) in ten human subjects. This approach allowed us to reliably identify those ECoG features that were related to the processing of a complex auditory stimulus (i.e., continuous piece of music) and to investigate their spatial, temporal, and causal relationships. Our results identified stimulus-related modulations in the alpha (8-12 Hz) and high gamma (70-110 Hz) bands at neuroanatomical locations implicated in auditory processing. Specifically, we identified stimulus-related ECoG modulations in the alpha band in areas adjacent to primary auditory cortex, which are known to receive afferent auditory projections from the thalamus (80 of a total of 15,107 tested sites). In contrast, we identified stimulus-related ECoG modulations in the high gamma band not only in areas close to primary auditory cortex but also in other perisylvian areas known to be involved in higher-order auditory processing, and in superior premotor cortex (412/15,107 sites). Across all implicated areas, modulations in the high gamma band preceded those in the alpha band by 280 ms, and activity in the high gamma band causally predicted alpha activity, but not vice versa (Granger causality, p<1e(-8)). Additionally, detailed analyses using Granger causality identified causal relationships of high gamma activity between distinct locations in early auditory pathways within superior temporal gyrus (STG) and posterior STG, between posterior STG and inferior frontal cortex, and between STG and premotor cortex. Evidence suggests that these

  15. Active Neutron and Gamma-Ray Instrumentation for In Situ Planetary Science Applications

    NASA Technical Reports Server (NTRS)

    Parsons, A.; Bodnarik, J.; Evans, L.; Floyd, A.; Lim, L.; McClanahan, T.; Namkung, M.; Nowicki, S.; Schweitzer, J.; Starr, R.; Trombka, J.

    2011-01-01

    We describe the development of an instrument capable of detailed in situ bulk geochemical analysis of the surface of planets, moons, asteroids, and comets. This instrument technology uses a pulsed neutron generator to excite the solid materials of a planet and measures the resulting neutron and gamma-ray emission with its detector system. These time-resolved neutron and gamma-ray data provide detailed information about the bulk elemental composition, chemical context, and density distribution of the soil within 50 cm of the surface. While active neutron scattering and neutron-induced gamma-ray techniques have been used extensively for terrestrial nuclear well logging applications, our goal is to apply these techniques to surface instruments for use on any solid solar system body. As described, experiments at NASA Goddard Space Flight Center use a prototype neutron-induced gamma-ray instrument and the resulting data presented show the promise of this technique for becoming a versatile, robust, workhorse technology for planetary science, and exploration of any of the solid bodies in the solar system. The detection of neutrons at the surface also provides useful information about the material. This paper focuses on the data provided by the gamma-ray detector.

  16. THE REMARKABLE {gamma}-RAY ACTIVITY IN THE GRAVITATIONALLY LENSED BLAZAR PKS 1830-211

    SciTech Connect

    Donnarumma, I.; De Rosa, A.; Vittorini, V.; Tavani, M.; Striani, E.; Pacciani, L.; Popovic, L. C.; Simic, S.; Kuulkers, E.; Vercellone, S.; Verrecchia, F.; Pittori, C.; Giommi, P.; Barbiellini, G.; Bulgarelli, A.

    2011-08-01

    We report the extraordinary {gamma}-ray activity (E > 100 MeV) of the gravitationally lensed blazar PKS 1830-211 (z = 2.507) detected by AGILE between 2010 October and November. On October 14, the source experienced a factor of {approx}12 flux increase with respect to its average value and remained brightest at this flux level ({approx}500 x 10{sup -8} photons cm{sup -2} s{sup -1}) for about four days. The one-month {gamma}-ray light curve across the flare showed a mean flux F(E > 100 MeV) = 200 x 10{sup -8} photons cm{sup -2} s{sup -1}, which resulted in a factor of four enhancement with respect to the average value. Following the {gamma}-ray flare, the source was observed in near-IR (NIR)-optical energy bands at the Cerro Tololo Inter-American Observatory and in X-Rays by Swift/X-Ray Telescope and INTEGRAL/IBIS. The main result of these multifrequency observations is that the large variability observed in {gamma}-rays does not have a significant counterpart at lower frequencies: no variation greater than a factor of {approx}1.5 appeared in the NIR and X-Ray energy bands. PKS 1830-211 is then a good '{gamma}-ray only flaring' blazar showing substantial variability only above 10-100 MeV. We discuss the theoretical implications of our findings.

  17. Stimulus-induced and state-dependent sustained gamma activity is tightly coupled to the hemodynamic response in humans.

    PubMed

    Koch, Stefan P; Werner, Peter; Steinbrink, Jens; Fries, Pascal; Obrig, Hellmuth

    2009-11-01

    A prompt behavioral response to a stimulus depends both on the salience of the stimulus as well as the subject's preparedness. Thus, both stimulus properties and cognitive factors, such as attention, may determine the strength of neuronal synchronization in the gamma range. For a comprehensive investigation of stimulus-response processing through noninvasive imaging, it is, however, a crucial issue whether both kinds of gamma modulation elicit a hemodynamic response. Here, we show that, in the human visual cortex, stimulus strength and internal state modulate sustained gamma activity and hemodynamic response in close correspondence. When participants reported velocity changes of gratings varying in contrast, gamma activity (35-70 Hz) increased systematically with contrast. For stimuli of constant contrast, the amplitude of gamma activity before the behaviorally relevant velocity change was inversely correlated to the behavioral response latency. This indicates that gamma activity also reflects an overall attentive state. For both sources of variance, gamma activity was tightly coupled to the hemodynamic response measured through optical topography. Because of the close relationship between high-frequency neuronal activity and the hemodynamic signal, we conclude that both stimulus-induced and state-dependent gamma activity trigger a metabolic demand and are amenable to vascular-based imaging. PMID:19890006

  18. Antioxidant activities of fucoidan degraded by gamma irradiation and acidic hydrolysis

    NASA Astrophysics Data System (ADS)

    Lim, Sangyong; Choi, Jong-il; Park, Hyun

    2015-04-01

    Low molecular weight fucoidan, prepared by radical degradation using gamma ray was investigated for its antioxidant activities with different assay methods. As the molecular weight of fucoidan decreased with a higher absorbed dose, ferric-reducing antioxidant power values increased, but β-carotene bleaching inhibition did not change significantly. The antioxidant activity of acid-degraded fucoidan was also examined to investigate the effect of different degradation methods. At the same molecular weight, fucoidan degraded by gamma irradiation showed higher 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity than that observed with the acidic method. This result reveals that in addition to molecular weight, the degradation method affects the antioxidant activity of fucoidan.

  19. Beta and gamma oscillatory activities associated with olfactory memory tasks: different rhythms for different functional networks?

    PubMed Central

    Martin, Claire; Ravel, Nadine

    2014-01-01

    Olfactory processing in behaving animals, even at early stages, is inextricable from top down influences associated with odor perception. The anatomy of the olfactory network (olfactory bulb, piriform, and entorhinal cortices) and its unique direct access to the limbic system makes it particularly attractive to study how sensory processing could be modulated by learning and memory. Moreover, olfactory structures have been early reported to exhibit oscillatory population activities easy to capture through local field potential recordings. An attractive hypothesis is that neuronal oscillations would serve to “bind” distant structures to reach a unified and coherent perception. In relation to this hypothesis, we will assess the functional relevance of different types of oscillatory activity observed in the olfactory system of behaving animals. This review will focus primarily on two types of oscillatory activities: beta (15–40 Hz) and gamma (60–100 Hz). While gamma oscillations are dominant in the olfactory system in the absence of odorant, both beta and gamma rhythms have been reported to be modulated depending on the nature of the olfactory task. Studies from the authors of the present review and other groups brought evidence for a link between these oscillations and behavioral changes induced by olfactory learning. However, differences in studies led to divergent interpretations concerning the respective role of these oscillations in olfactory processing. Based on a critical reexamination of those data, we propose hypotheses on the functional involvement of beta and gamma oscillations for odor perception and memory. PMID:25002840

  20. To Perceive or Not Perceive: The Role of Gamma-band Activity in Signaling Object Percepts

    PubMed Central

    Castelhano, João; Rebola, José; Leitão, Bruno; Rodriguez, Eugenio; Castelo-Branco, Miguel

    2013-01-01

    The relation of gamma-band synchrony to holistic perception in which concerns the effects of sensory processing, high level perceptual gestalt formation, motor planning and response is still controversial. To provide a more direct link to emergent perceptual states we have used holistic EEG/ERP paradigms where the moment of perceptual “discovery” of a global pattern was variable. Using a rapid visual presentation of short-lived Mooney objects we found an increase of gamma-band activity locked to perceptual events. Additional experiments using dynamic Mooney stimuli showed that gamma activity increases well before the report of an emergent holistic percept. To confirm these findings in a data driven manner we have further used a support vector machine classification approach to distinguish between perceptual vs. non perceptual states, based on time-frequency features. Sensitivity, specificity and accuracy were all above 95%. Modulations in the 30–75 Hz range were larger for perception states. Interestingly, phase synchrony was larger for perception states for high frequency bands. By focusing on global gestalt mechanisms instead of local processing we conclude that gamma-band activity and synchrony provide a signature of holistic perceptual states of variable onset, which are separable from sensory and motor processing. PMID:23785494

  1. Gamma band activity and the P3 reflect post-perceptual processes, not visual awareness

    PubMed Central

    Pitts, Michael A.; Padwal, Jennifer; Fennelly, Daniel; Martínez, Antígona; Hillyard, Steven A.

    2014-01-01

    A primary goal in cognitive neuroscience is to identify neural correlates of conscious perception (NCC). By contrasting conditions in which subjects are aware versus unaware of identical visual stimuli, a number of candidate NCCs have emerged, among them induced gamma band activity in the EEG and the P3 event-related potential. In most previous studies, however, the critical stimuli were always directly relevant to the subjects’ task, such that aware versus unaware contrasts may well have included differences in post-perceptual processing in addition to differences in conscious perception per se. Here, in a series of EEG experiments, visual awareness and task relevance were manipulated independently. Induced gamma activity and the P3 were absent for task-irrelevant stimuli regardless of whether subjects were aware of such stimuli. For task-relevant stimuli, gamma and the P3 were robust and dissociable, indicating that each reflects distinct post-perceptual processes necessary for carrying-out the task but not for consciously perceiving the stimuli. Overall, this pattern of results challenges a number of previous proposals linking gamma band activity and the P3 to conscious perception. PMID:25063731

  2. Gamma Activity Coupled to Alpha Phase as a Mechanism for Top-Down Controlled Gating

    PubMed Central

    Bonnefond, Mathilde; Jensen, Ole

    2015-01-01

    Coupling between neural oscillations in different frequency bands has been proposed to coordinate neural processing. In particular, gamma power coupled to alpha phase is proposed to reflect gating of information in the visual system but the existence of such a mechanism remains untested. Here, we recorded ongoing brain activity using magnetoencephalography in subjects who performed a modified Sternberg working memory task in which distractors were presented in the retention interval. During the anticipatory pre-distractor period, we show that the phase of alpha oscillations was coupled with the power of high (80-120Hz) gamma band activity, i.e. gamma power consistently was lower at the trough than at the peak of the alpha cycle (9-12Hz). We further show that high alpha power was associated with weaker gamma power at the trough of the alpha cycle. This result is in line with alpha activity in sensory region implementing a mechanism of pulsed inhibition silencing neuronal firing every ~100 ms. PMID:26039691

  3. A short-term physical activity randomized trial in the Lower Mississippi Delta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to determine if a short-term pedometer-based intervention results in immediate increases in time spent in moderate-to-vigorous physical activity (MVPA) compared to a minimal educational intervention. A sample of 43 overweight adults 35 to 64 years of age participated in...

  4. Microsomal enzyme activities in beluga whales from the Mackenzie River Delta, Northwest Territories, Canada

    SciTech Connect

    Lockhart, L.; Metner, D.; Muir, D.; Delorme, P.; Dahlke, L.

    1995-12-31

    On two occasions the authors have obtained samples of liver from freshly killed beluga whales harvested by Inuit hunters. The first samples were obtained from whales trapped in the Husky Lakes; with the onset of winter, ice restricted these whales to small breathing holes where they were taken by hunters. They were found to be starving, with body weights about 200 kg less than those expected for whales of their length. Liver mixed-function oxygenase activities, ethoxyresorufin-O-deethylase and aryl hydrocarbon hydroxylase, correlated closely with blubber residues of polychlorinated biphenyls. A second group of whales was taken in the summer hunt in Kugmallit Bay and showed no sign of starvation. The enzyme activities in these whales had weaker statistical relationships to PCB residues. These observations suggested that mobilization of blubber by the starving whales may have released PCBs to act pharmacologically. The authors could not test this hypothesis directly on whales, but an experiment was carried out on laboratory fish to try to examine it. Arctic char were given low dosages of PCB congener 126 and then maintained on diets of full normal ration, half-ration and quarter-ration over a period of 48 weeks, with sub-sampling at intervals. Fish receiving less than maintenance rations responded with decreases in body fat and increases in EROD activities. These laboratory results suggest that correlations between enzymatic activities and PCBs in the starving whales may indeed have been the result of the loss of blubber and concomitant release of PCBs.

  5. DOES IRON OR HEME CONTROL RAT HEPATIC DELTA-AMINOLEVULINIC ACID SYNTHETASE ACTIVITY

    EPA Science Inventory

    Disodium ethylenediamine tetraacetic acid and/or allylisopropylacetamide administration to rat pups did not evoke a premature induction of hepatic d-aminolevulinic acid synthetase. Administration of iron to adult rats did not alter d-aminolevulinic acid synthetase activity and ha...

  6. The activation mechanism of alpha1beta2gamma2S and alpha3beta3gamma2S GABAA receptors.

    PubMed

    Keramidas, Angelo; Harrison, Neil L

    2010-01-01

    The alpha1beta2gamma2 and alpha3beta3gamma2 are two isoforms of gamma-aminobutyric acid type A (GABAA) receptor that are widely distributed in the brain. Both are found at synapses, for example in the thalamus, where they mediate distinctly different inhibitory postsynaptic current profiles, particularly with respect to decay time. The two isoforms were expressed in HEK293 cells, and single-channel activity was recorded from outside-out patches. The kinetic characteristics of both isoforms were investigated by analyzing single-channel currents over a wide range of GABA concentrations. Alpha1beta2gamma2 channels exhibited briefer active periods than alpha3beta3gamma2 channels over the entire range of agonist concentrations and had lower intraburst open probabilities at subsaturating concentrations. Activation mechanisms were constructed by fitting postulated schemes to data recorded at saturating and subsaturating GABA concentrations simultaneously. Reaction mechanisms were ranked according to log-likelihood values and how accurately they simulated ensemble currents. The highest ranked mechanism for both channels consisted of two sequential binding steps, followed by three conducting and three nonconducting configurations. The equilibrium dissociation constant for GABA at alpha3beta3gamma2 channels was approximately 2.6 microM compared with approximately 19 microM for alpha1beta2gamma2 channels, suggesting that GABA binds to the alpha3beta3gamma2 channels with higher affinity. A notable feature of the mechanism was that two consecutive doubly liganded shut states preceded all three open configurations. The lifetime of the third shut state was briefer for the alpha3beta3gamma2 channels. The longer active periods, higher affinity, and preference for conducting states are consistent with the slower decay of inhibitory currents at synapses that contain alpha3beta3gamma2 channels. The reaction mechanism we describe here may also be appropriate for the analysis of other

  7. Time course of lipolytic activity and lipid peroxidation after whole-body gamma irradiation of rats

    SciTech Connect

    Rejholcova, M.; Wilhelm, J.

    1989-01-01

    The content of fluorescing products of lipid peroxidation (LFP) and hormone-stimulated lipolytic activity were determined in rat epididymal adipose tissue during a 29-day interval after whole-body gamma irradiation. An increase in LFP was accompanied by a decrease in lipolytic activity. It is suggested that these effects are interrelated and that the decrease in lipolysis in irradiated, semi fasting rats is an additional deteriorating factor leading to death in some animals.

  8. Anti-diabetic action of Punica granatum flower extract: activation of PPAR-gamma and identification of an active component.

    PubMed

    Huang, Tom H W; Peng, Gang; Kota, Bhavani P; Li, George Q; Yamahara, Johji; Roufogalis, Basil D; Li, Yuhao

    2005-09-01

    Peroxisome proliferator-activated receptor (PPAR)-gamma activators are widely used in the treatment of type 2 diabetes because they improve the sensitivity of insulin receptors. Punica granatum flower (PGF) has been used as an anti-diabetic medicine in Unani medicinal literature. The mechanism of actions is, however, unknown. In the current study, we demonstrated that 6-week oral administration of methanol extract from PGF (500 mg/kg, daily) inhibited glucose loading-induced increase of plasma glucose levels in Zucker diabetic fatty rats (ZDF), a genetic animal model for type 2 diabetes, whereas it did not inhibit the increase in Zucker lean rats (ZL). The treatment did not lower the plasma glucose levels in fasted ZDF and ZL rats. Furthermore, RT-PCR results demonstrated that the PGF extract treatment in ZDF rats enhanced cardiac PPAR-gamma mRNA expression and restored the down-regulated cardiac glucose transporter (GLUT)-4 (the insulin-dependent isoform of GLUTs) mRNA. These results suggest that the anti-diabetic activity of PGF extract may result from improved sensitivity of the insulin receptor. From the in vitro studies, we demonstrated that the PGF extract enhanced PPAR-gamma mRNA and protein expression and increased PPAR-gamma-dependent mRNA expression and activity of lipoprotein lipase in human THP-1-differentiated macrophage cells. Phytochemical investigation demonstrated that gallic acid in PGF extract is mostly responsible for this activity. Thus, our findings indicate that PPAR-gamma is a molecular target for PGF extract and its prominent component gallic acid, and provide a better understanding of the potential mechanism of the anti-diabetic action of PGF. PMID:16102567

  9. Anti-diabetic action of Punica granatum flower extract: Activation of PPAR-{gamma} and identification of an active component

    SciTech Connect

    Huang, Tom H.W.; Peng Gang; Kota, Bhavani P.; Li, George Q.; Yamahara, Johji; Roufogalis, Basil D.; Li Yuhao . E-mail: yuhao@pharm.usyd.edu.au

    2005-09-01

    Peroxisome proliferator-activated receptor (PPAR)-{gamma} activators are widely used in the treatment of type 2 diabetes because they improve the sensitivity of insulin receptors. Punica granatum flower (PGF) has been used as an anti-diabetic medicine in Unani medicinal literature. The mechanism of actions is, however, unknown. In the current study, we demonstrated that 6-week oral administration of methanol extract from PGF (500 mg/kg, daily) inhibited glucose loading-induced increase of plasma glucose levels in Zucker diabetic fatty rats (ZDF), a genetic animal model for type 2 diabetes, whereas it did not inhibit the increase in Zucker lean rats (ZL). The treatment did not lower the plasma glucose levels in fasted ZDF and ZL rats. Furthermore, RT-PCR results demonstrated that the PGF extract treatment in ZDF rats enhanced cardiac PPAR-{gamma} mRNA expression and restored the down-regulated cardiac glucose transporter (GLUT)-4 (the insulin-dependent isoform of GLUTs) mRNA. These results suggest that the anti-diabetic activity of PGF extract may result from improved sensitivity of the insulin receptor. From the in vitro studies, we demonstrated that the PGF extract enhanced PPAR-{gamma} mRNA and protein expression and increased PPAR-{gamma}-dependent mRNA expression and activity of lipoprotein lipase in human THP-1-differentiated macrophage cells. Phytochemical investigation demonstrated that gallic acid in PGF extract is mostly responsible for this activity. Thus, our findings indicate that PPAR-{gamma} is a molecular target for PGF extract and its prominent component gallic acid, and provide a better understanding of the potential mechanism of the anti-diabetic action of PGF.

  10. Altered polymorphonuclear leukocyte Fc gamma R expression contributes to decreased candicidal activity during intraabdominal sepsis

    SciTech Connect

    Simms, H.H.; D'Amico, R.; Monfils, P.; Burchard, K.W. )

    1991-03-01

    We investigated the effects of untreated intraabdominal sepsis on polymorphonuclear leukocyte (PMN) candicidal activity. Two groups of swine were studied. Group I (n=6) underwent sham laparotomy, group II (n=7) underwent cecal ligation and incision. Untreated intraabdominal sepsis resulted in a progressive decrease in PMN candicidal activity. Concomitant rosetting and phagocytosis assays demonstrated a decrease in both the attachment and phagocytosis of Candida albicans opsonized with both normal and septic swine serum by PMNs in group II. Iodine 125-labeled swine immunoglobulin G (IgG) and fluorescein isothioalanate (FITC)-labeled swine IgG were used to investigate Fc gamma receptor ligand interactions. Scatchard analyses demonstrated a progressive decline in both the binding affinity constant and number of IgG molecules bound per PMN. Stimulation of the oxidative burst markedly reduced 125I-labeled IgG binding in both group I and group II, with a greater decrement being seen in animals with intraabdominal sepsis. Further, in group II, PMN recycling of the Fc gamma receptor to the cell surface after generation of the oxidative burst was reduced by postoperative day 4. Binding of monoclonal antibodies to Fc gamma receptor II, but not Fc gamma receptor I/III markedly reduced intracellular candicidal activity. Immunofluorescence studies revealed a homogeneous pattern of FITC-IgG uptake by nearly all group I PMNs, whereas by postoperative day 8 a substantial number of PMNs from group II failed to internalize the FITC-IgG. These studies suggest that untreated intraabdominal sepsis reduces PMN candicidal activity and that this is due, in part, to altered PMN Fc gamma receptor ligand interactions.

  11. Prompt gamma activation analysis (PGAA) and short-lived neutron activation analysis (NAA) applied to the characterization of legacy materials

    SciTech Connect

    Firestone, Richard B; English, G.A.; Firestone, R.B.; Perry, D.L.; Reijonen, J.P.; Leung, Ka-Ngo; Garabedian, G.F.; Molnar, G.L.; Revay, Zs.

    2008-02-13

    Without quality historical records that provide the composition of legacy materials, the elemental and/or chemical characterization of such materials requires a manual analytical strategy that may expose the analyst to unknown toxicological hazards. In addition, much of the existing legacy inventory also incorporates radioactivity, and, although radiological composition may be determined by various nuclear-analytical methods, most importantly, gamma-spectroscopy, current methods of chemical characterization still require direct sample manipulation, thereby presenting special problems with broad implications for both the analyst and the environment. Alternately, prompt gamma activation analysis (PGAA) provides a'single-shot' in-situ, non-destructive method that provides a complete assay of all major entrained elemental constituents.1-3. Additionally, neutron activation analysis (NAA) using short-lived activation products complements PGAA and is especially useful when NAA activation surpasses the PGAA in elemental sensitivity.

  12. Molecular Characterization and Expression Analysis of the Peroxisome Proliferator Activated Receptor Delta (PPARδ) Gene before and after Exercise in Horse

    PubMed Central

    Cho, Hyun-Woo; Shin, Sangsu; Park, Jeong-Woong; Choi, Jae-Young; Kim, Nam-Young; Lee, Woon-Kyu; Lee, Hak-Kyo; Song, Ki-Duk; Cho, Byung-Wook

    2015-01-01

    While athletic abilities such as speed, endurance and recovery are important in the horse, genes related to these abilities have not been extensively investigated. Here, we characterized the horse peroxisome proliferator-activated receptor delta (PPARδ) gene and analyzed the expression of PPARδ during exercise. PPARδ is a known regulator of β-oxidation, muscle fiber transformation, and running endurance. Through evolutionary analysis using the synonymous and non-synonymous mutation ratio, it was revealed that positive selection occurred in the horse PPARδ gene. Two important domains related to nuclear hormone receptors, C4 zinc finger and ligand binding domain, were also found to be conserved well in horse PPARδ. Horse PPARδ was expressed ubiquitously in many tissues, but the expression level was various depending on the tissues. In the skeletal muscle, PPARδ increased about 2.5 folds after 30 min of exercise. Unlike in muscle, the increase of PPARδ expression was observed at 60 min but not 30 min of exercise in leukocytes. This finding might be useful for testing the endurance of horse using blood samples. Conclusively, the horse PPARδ gene is evolutionarily conserved well and can be used as a biomarker of endurance in horse. PMID:25924962

  13. Identification of estrogenic activity change in sewage, industrial and livestock effluents by gamma-irradiation

    NASA Astrophysics Data System (ADS)

    Ahn, Byeong-Yong; Kang, Sung-Wook; Yoo, Jisu; Kim, Woong-Ki; Bae, Paek-Hyun; Jung, Jinho

    2012-11-01

    In this study, reduction of estrogenic activity in three different types of effluents from sewage, industrial and livestock wastewater treatment plants by gamma-irradiation was investigated using the yeast two-hybrid assay. After gamma-ray treatment at a dose of 10 kGy, estrogenic activities of sewage, industrial and livestock effluents decreased from 4.4 to 3.0, 1.5 to 1.0 and 16 to 9.9 ng-EEQ L-1, respectively. The substantial reduction of estrogenic activity in livestock effluent was attributable to the degradation of 17β-estradiol (E2), estrone (E1) and 17α-ethynylestradiol (EE2). Although bisphenol A (BPA) was found at the highest concentration in all effluents, its contribution to the estrogenic activity was not significant due to its low relative estrogenic potency. Meanwhile, the calculated estrogenic activity based on concentrations of E2, E1, EE2 and BPA in the effluents significantly differed from the measured ones. Overestimation may have resulted by dissolved organic matters in effluents inhibiting the estrogenic activity of E2, E1, EE2 and BPA, whereas underestimation was likely due to estrogenic by-products generated by gamma-irradiation.

  14. The use of an active coded aperture for improved directional measurements in high energy gamma-ray astronomy

    NASA Technical Reports Server (NTRS)

    Johansson, A.; Beron, B. L.; Campbell, L.; Eichler, R.; Hofstadter, R.; Hughes, E. B.; Wilson, S.; Gorodetsky, P.

    1980-01-01

    The coded aperture, a refinement of the scatter-hole camera, offers a method for the improved measurement of gamma-ray direction in gamma-ray astronomy. Two prototype coded apertures have been built and tested. The more recent of these has 128 active elements of the heavy scintillator BGO. Results of tests for gamma-rays in the range 50-500 MeV are reported and future application in space discussed.

  15. The Crystal Structure of the Ivy delta4-16:0-ACP Desaturase Reveals Structural Details of the Oxidized Active Site and Potential Determinants of Regioselectivity

    SciTech Connect

    Guy,J.; Whittle, E.; Kumaran, D.; Lindqvist, Y.; Shanklin, J.

    2007-01-01

    The multifunctional acyl-acyl carrier protein (ACP) desaturase from Hedera helix (English ivy) catalyzes the {Delta}{sup 4} desaturation of 16:0-ACP and the{Delta}{sup 9} desaturation of 18:0-ACP and further desaturates{Delta}{sup 9}-16:1 or {Delta}{sup 9}-18:1 to the corresponding {Delta}{sup 4,9} dienes. The crystal structure of the enzyme has been solved to 1.95{angstrom} resolution, and both the iron-iron distance of 3.2{angstrom} and the presence of a {mu}-oxo bridge reveal this to be the only reported structure of a desaturase in the oxidized FeIII-FeIII form. Significant differences are seen between the oxidized active site and the reduced active site of the Ricinus communis (castor) desaturase; His{sup 227} coordination to Fe2 is lost, and the side chain of Glu{sup 224}, which bridges the two iron ions in the reduced structure, does not interact with either iron. Although carboxylate shifts have been observed on oxidation of other diiron proteins, this is the first example of the residue moving beyond the coordination range of both iron ions. Comparison of the ivy and castor structures reveal surface amino acids close to the annulus of the substrate-binding cavity and others lining the lower portion of the cavity that are potential determinants of their distinct substrate specificities. We propose a hypothesis that differences in side chain packing explains the apparent paradox that several residues lining the lower portion of the cavity in the ivy desaturase are bulkier than their equivalents in the castor enzyme despite the necessity for the ivy enzyme to accommodate three more carbons beyond the diiron site.

  16. Allyl alcohol activation of protein kinase C delta leads to cytotoxicity of rat hepatocytes.

    PubMed

    Maddox, Jane F; Roth, Robert A; Ganey, Patricia E

    2003-05-01

    Hepatotoxicity of allyl alcohol involves its bioactivation to acrolein and subsequent protein sulfhydryl loss and lipid peroxidation. However, the links between these events and hepatocellular death are not known. The purpose of these studies was to examine whether specific signal transduction pathways are associated with allyl alcohol toxicity in hepatocytes. Inhibition or augmentation of cyclic AMP and/or protein kinase A (PKA) by Rp-Ado-3N,5N-cyclic monophosphorothioate triethylamine salt or 3-isobutyl-1-methylxanthine had no effect on allyl alcohol-induced cell death. H-7, an inhibitor of PKA, PKC, and PKG, partially inhibited cell killing by allyl alcohol, whereas chelerythrine chloride, a nonselective PKC inhibitor, almost completely abolished allyl alcohol cytotoxicity. Neither 2,2N,3,3N,4,4N-hexahydroxy-1,1N,-biphenyl-6,6N-dimethanol-dimethyl ether, a selective PKC alpha and beta inhibitor, nor bisindolylmaleimide I, an inhibitor of PKC alpha, beta, and epsilon, had any effect on allyl alcohol cytotoxicity. In contrast, rottlerin, a selective PKCdelta inhibitor, blocked hepatocellular killing by allyl alcohol. Cytoprotection by chelerythrine chloride and rottlerin was not the result of inhibition of bioactivation of allyl alcohol because each inhibitor also prevented cell death from acrolein. Western blotting and immunohistochemical techniques revealed that allyl alcohol stimulated phosphorylation and translocation of PKCdelta to hepatocyte membranes (i.e., activation), and this activity was inhibited by rottlerin. Cell death appeared to occur via oncotic necrosis rather than apoptosis based on single-stranded DNA ELISA and propidium iodide staining. Together, these results indicate that activation of PKCdelta is a critical, early event in initiating hepatocyte injury and death from allyl alcohol. PMID:12755590

  17. Metals control activity and expression of the heme biosynthesis enzyme delta-aminolevulinic acid dehydratase in Bradyrhizobium japonicum.

    PubMed Central

    Chauhan, S; Titus, D E; O'Brian, M R

    1997-01-01

    The heme biosynthesis enzyme delta-aminolevulinic acid dehydratase (ALAD) requires magnesium or zinc for activity, depending on the organism, and the heme moiety contains iron. Thus, metals are important for heme formation in at least two different ways. Bradyrhizobium japonicum ALAD* is an engineered derivative of wild-type ALAD that requires Zn2+ for activity rather than Mg2+ (S. Chauhan and M. R. O'Brian, J. Biol. Chem. 270:19823-19827, 1995). The pH optimum for ALAD* activity was over 3.5 units lower than for that of the wild-type enzyme, and ALAD* activity was inhibited by lead and cadmium, as reported for the zinc-containing dehydratases of animals. In addition, ALAD* was significantly more thermostable than ALAD; the temperature optima are 50 and 37 degrees C, respectively. These observations strongly suggest that the metal contributes to both catalysis and structure, and this conclusion may be extrapolated to ALADs in general. Although iron did not affect the activity of the preformed protein, enzyme assays and immunoblot analysis demonstrated that the iron concentration in which the cells were grown had a strong positive effect on ALAD activity and the protein level. RNase protection analysis showed that the transcript quantity of hemB, the gene encoding ALAD, was iron dependent; thus, iron regulates hemB at the mRNA level. Induction of hemB mRNA in response to iron was rapid, suggesting that the factor(s) needed to mediate iron control was present in iron-limited cells and did not need to be synthesized de novo. ALAD protein levels and enzyme activities were similar in cells of the wild type and a heme-defective strain, indicating that control by iron is not an indirect effect of the cellular heme status. We conclude that the heme biosynthetic pathway is coordinated with cellular iron levels and that this control may prevent the accumulation of toxic porphyrin intermediates. PMID:9287008

  18. Genomic organization of the mouse peroxisome proliferator-activated receptor beta/delta gene: alternative promoter usage and splicing yield transcripts exhibiting differential translational efficiency.

    PubMed Central

    Larsen, Leif K; Amri, Ez-Zoubir; Mandrup, Susanne; Pacot, Corinne; Kristiansen, Karsten

    2002-01-01

    Peroxisome proliferator-activated receptor (PPAR) beta/delta is ubiquitously expressed, but the level of expression differs markedly between different cell types. In order to determine the molecular mechanisms governing PPARbeta/delta gene expression, we have isolated and characterized the mouse gene encoding PPARbeta/delta. The gene spans approx. 41 kb and comprises 11 exons of which the six exons located in the 3'-end of the gene are included in all transcripts. Primer-extension and 5'-rapid amplification of cDNA ends experiments revealed the presence of multiple transcription start points and splice variants, originating from the use of at least four different promoters. One of these transcription start points was found to be used predominantly in all tissues examined. Initiation from this major transcription start point gives rise to a transcript with a 548 nt 5'-untranslated leader containing eight upstream AUG codons. We show that the presence of the 548 nt leader resulted in a low translational efficiency of the corresponding PPARbeta/delta mRNA and propose, based on structural features of the 5'-untranslated region, that translational initiation may be mediated via an internal ribosome entry site-dependent mechanism. PMID:12059785

  19. Regulation of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase expression and activity in the hypophysectomized rat ovary: Interactions between the stimulatory effect of human chorionic gonadotropin and the luteolytic effect of prolactin

    SciTech Connect

    Martel, C.; Labrie, C.; Dupont, E.; Couet, J.; Trudel, C.; Rheaume, E.; Simard, J.; Luu-The, V.; Pelletier, G.; Labrie, F. )

    1990-12-01

    The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) catalyzes an obligatory step in the conversion of pregnenolone and other 5-ene-3 beta-hydroxysteroids into progesterone as well as precursors of all androgens and estrogens in the ovary. Since 3 beta-HSD is likely to be an important target for regulation by pituitary hormones, we have studied the effect of chronic treatment with LH (hCG), FSH, and PRL on ovarian 3 beta-HSD expression and activity in hypophysectomized adult female rats. Human CG (hCG) (10 IU, twice a day (bid)), ovine FSH (0.5 microgram, bid), and ovine PRL (1 mg, bid) were administered, singly or in combination, for a period of 10 days starting 15 days after hypophysectomy. In hypophysectomized rats, PRL exerted a potent inhibitory effect on all the parameters studied. In fact, PRL caused a 81% decrease in ovarian 3 beta-HSD mRNA content accompanied by a similar decrease in 3 beta-HSD activity and protein levels. In addition, ovarian weight decreased by 40% whereas serum progesterone fell dramatically from 1.92 nmol/liter to undetectable levels after treatment with PRL. Whereas hCG alone had only slight stimulatory effects on 3 beta-HSD mRNA, protein content and activity levels, treatment with the gonadotropin partially or completely reversed the potent inhibitory effects of oPRL on all the parameters measured. FSH, on the other hand, had no significant effect on 3 beta-HSD expression and activity. In situ hybridization experiments using the 35S-labeled rat ovary 3 beta-HSD cDNA probe show that the inhibitory effect of PRL is exerted primarily on luteal cell 3 beta-HSD expression and activity. On the other hand, it can be seen that hCG stimulates 3 beta-HSD mRNA accumulation in interstitial cells.

  20. FADS2 genotype regulates delta-6 desaturase activity and inflammation in human adipose tissue.

    PubMed

    Vaittinen, Maija; Walle, Paula; Kuosmanen, Emmi; Männistö, Ville; Käkelä, Pirjo; Ågren, Jyrki; Schwab, Ursula; Pihlajamäki, Jussi

    2016-01-01

    Obesity is associated with disturbed lipid metabolism and low-grade inflammation in tissues. The aim of this study was to investigate the association between FA metabolism and adipose tissue (AT) inflammation in the Kuopio Obesity Surgery study. We investigated the association of surgery-induced weight loss and FA desaturase (FADS)1/2 genotypes with serum and AT FA profile and with AT inflammation, measured as interleukin (IL)-1β and NFκB pathway gene expression, in order to find potential gene-environment interactions. We demonstrated an association between serum levels of saturated and polyunsaturated n-6 FAs, and estimated enzyme activities of FADS1/2 genes with IL-1β expression in AT both at baseline and at follow-up. Variation in the FADS1/2 genes associated with IL-1β and NFκB pathway gene expression in SAT after weight reduction, but not at baseline. In addition, the FA composition in subcutaneous and visceral fat correlated with serum FAs, and the associations between serum PUFAs and estimated D6D enzyme activity with AT inflammation were also replicated with corresponding AT FAs and AT inflammation. We conclude that the polymorphism in FADS1/2 genes associates with FA metabolism and AT inflammation, leading to an interaction between weight loss and FADS1/2 genes in the regulation of AT inflammation. PMID:26609056

  1. Recombinative events of the T cell antigen receptor delta gene in peripheral T cell lymphomas.

    PubMed Central

    Kanavaros, P; Farcet, J P; Gaulard, P; Haioun, C; Divine, M; Le Couedic, J P; Lefranc, M P; Reyes, F

    1991-01-01

    Recombinative events of the T cell antigen receptor (TCR) delta-chain gene were studied in 37 cases of peripheral T cell lymphoma (PTCL) and related to their clinical presentation and the expression of the alpha beta or gamma delta heterodimers as determined by immunostaining of frozen tissue samples. There were 22 cases of alpha beta, 5 cases of gamma delta, and 10 cases of silent TCR expressing neither the alpha beta nor gamma delta TCR. 5 different probes were used to examine the delta locus. The 22 cases of alpha beta PTCL displayed biallelic and monoallelic deletions; a monoallelic V delta 1 J delta 1 rearrangement was observed in 1 case and a monoallelic germ line configuration in 7 cases. The 5 cases of gamma delta PTCL displayed biallelic rearrangements: the productive rearrangements could be ascribed to V delta 1J delta 1 joining in 3 cases and VJ delta 1 joining in 2 cases according to the combined pattern of DNA hybridization with the appropriate probes and of cell reactivity with the TCR delta-1, delta TCS-1, and anti-V delta 2 monoclonal antibodies. In the VJ delta 1 joining, the rearranged V segments were located between V delta 1 and V delta 2. Interestingly, in the third group of 10 cases of silent PTCL, 5 cases were found to have a TCR gene configuration identical to that in the TCR alpha beta PTCL, as demonstrated by biallelic delta gene deletion. These 5 cases were CD3 positive. The 5 remaining cases showed a monoallelic delta gene rearrangement with a monoallelic germ line configuration in 4 and a monoallelic deletion in 1. Four of these cases were CD3 negative, which was consistent with an immature genotype the TCR commitent of which could not be ascertained. Finally, TCR gamma delta PTCL consisted of a distinct clinical morphological and molecular entity whereas TCR alpha beta and silent PTCL had a similar presentation. Images PMID:1991851

  2. Interferon gamma regulates accumulation of the proteasome activator PA28 and immunoproteasomes at nuclear PML bodies.

    PubMed

    Fabunmi, R P; Wigley, W C; Thomas, P J; DeMartino, G N

    2001-01-01

    PA28 is an interferon (gamma) (IFN(gamma)) inducible proteasome activator required for presentation of certain major histocompatibility (MHC) class I antigens. Under basal conditions in HeLa and Hep2 cells, a portion of nuclear PA28 is concentrated at promyelocytic leukemia oncoprotein (PML)-containing bodies also commonly known as PODs or ND10. IFN(gamma) treatment greatly increased the number and size of the PA28- and PML-containing bodies, and the effect was further enhanced in serum-deprived cells. PML bodies are disrupted in response to certain viral infections and in diseases such as acute promyelocytic leukemia (APL). Like PML, PA28 was delocalized from PML bodies by expression of the cytomegalovirus protein, IE1, and in NB4 cells, an APL model line. Moreover, retinoic acid treatment, which causes remission of APL in patients and reformation of PML-containing bodies in NB4 cells, relocalized PA28 to this site. In contrast, the proteasome, the functional target of PA28, was not detected at PML bodies under basal conditions in HeLa and Hep2 cells, but IFN(gamma) promoted accumulation of 'immunoproteasomes' at this site. These results establish PA28 as a novel component of nuclear PML bodies, and suggest that PA28 may assemble or activate immunoproteasomes at this site as part of its role in proteasome-dependent MHC class I antigen presentation. PMID:11112687

  3. Telmisartan prevented cognitive decline partly due to PPAR-{gamma} activation

    SciTech Connect

    Mogi, Masaki; Li Jianmei; Tsukuda, Kana; Iwanami, Jun; Min, Li-Juan; Sakata, Akiko; Fujita, Teppei; Iwai, Masaru; Horiuchi, Masatsugu

    2008-10-24

    Telmisartan is a unique angiotensin receptor blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor (PPAR)-{gamma}. Here, we investigated the preventive effect of telmisartan on cognitive decline in Alzheimer disease. In ddY mice, intracerebroventricular injection of A{beta} 1-40 significantly attenuated their cognitive function evaluated by shuttle avoidance test. Pretreatment with a non-hypotensive dose of telmisartan significantly inhibited such cognitive decline. Interestingly, co-treatment with GW9662, a PPAR-{gamma} antagonist, partially inhibited this improvement of cognitive decline. Another ARB, losartan, which has less PPAR-{gamma} agonistic effect, also inhibited A{beta}-injection-induced cognitive decline; however the effect was smaller than that of telmisartan and was not affected by GW9662. Immunohistochemical staining for A{beta} showed the reduced A{beta} deposition in telmisartan-treated mice. However, this reduction was not observed in mice co-administered GW9662. These findings suggest that ARB has a preventive effect on cognitive impairment in Alzheimer disease, and telmisartan, with PPAR-{gamma} activation, could exert a stronger effect.

  4. Degradation of Biochemical Activity in Soil Sterilized by Dry Heat and Gamma Radiation

    NASA Technical Reports Server (NTRS)

    Shih, K. L.; Souza, K. A.

    1978-01-01

    The effect of soil sterilization by dry heat (0.08% relative humidity), gamma radiation, or both on soil phosphatase, urease, and decarboxylase activity was studied. Soil sterilized by a long exposure to dry heat at relatively low temperatures (eight weeks at 100.5 C) retained higher activities than did soil exposed to a higher temperature (two weeks at 124.5 C), while all activity was destroyed by four days at 148.5 C. Sterilization with 7.5 Mrads destroyed less activity than did heat sterilization. The effect of several individually nonsterizing doses of heat radiation is described.

  5. Ceramide stimulates ABCA12 expression via peroxisome proliferator-activated receptor {delta} in human keratinocytes.

    PubMed

    Jiang, Yan J; Uchida, Yoshikazu; Lu, Biao; Kim, Peggy; Mao, Cungui; Akiyama, Masashi; Elias, Peter M; Holleran, Walter M; Grunfeld, Carl; Feingold, Kenneth R

    2009-07-10

    ABCA12 (ATP binding cassette transporter, family 12) is a cellular membrane transporter that facilitates the delivery of glucosylceramides to epidermal lamellar bodies in keratinocytes, a process that is critical for permeability barrier formation. Following secretion of lamellar bodies into the stratum corneum, glucosylceramides are metabolized to ceramides, which comprise approximately 50% of the lipid in stratum corneum. Gene mutations of ABCA12 underlie harlequin ichthyosis, a devastating skin disorder characterized by abnormal lamellar bodies and a severe barrier abnormality. Recently we reported that peroxisome proliferator-activated receptor (PPAR) and liver X receptor activators increase ABCA12 expression in human keratinocytes. Here we demonstrate that ceramide (C(2)-Cer and C(6)-Cer), but not C(8)-glucosylceramides, sphingosine, or ceramide 1-phosphate, increases ABCA12 mRNA expression in a dose- and time-dependent manner. Inhibitors of glucosylceramide synthase, sphingomyelin synthase, and ceramidase and small interfering RNA knockdown of human alkaline ceramidase, which all increase endogenous ceramide levels, also increased ABCA12 mRNA levels. Moreover, simultaneous treatment with C(6)-Cer and each of these same inhibitors additively increased ABCA12 expression, indicating that ceramide is an important inducer of ABCA12 expression and that the conversion of ceramide to other sphingolipids or metabolites is not required. Finally, both exogenous and endogenous ceramides preferentially stimulate PPARdelta expression (but not other PPARs or liver X receptors), whereas PPARdelta knockdown by siRNA transfection specifically diminished the ceramide-induced increase in ABCA12 mRNA levels, indicating that PPARdelta is a mediator of the ceramide effect. Together, these results show that ceramide, an important lipid component of epidermis, up-regulates ABCA12 expression via the PPARdelta-mediated signaling pathway, providing a substrate-driven, feed

  6. Functional properties of the CaV1.2 calcium channel activated by calmodulin in the absence of alpha2delta subunits.

    PubMed

    Ravindran, Arippa; Kobrinsky, Evgeny; Lao, Qi Zong; Soldatov, Nikolai M

    2009-01-01

    Voltage-activated CaV1.2 calcium channels require association of the pore-forming alpha1C subunit with accessory CaVbeta and alpha2delta subunits. Binding of a single calmodulin (CaM) to alpha1C supports Ca2+-dependent inactivation (CDI). The human CaV1.2 channel is silent in the absence of CaVbeta and/or alpha2delta. Recently, we found that coexpression of exogenous CaM (CaMex) supports plasma membrane targeting, gating facilitation and CDI of the channel in the absence of CaVbeta. Here we discovered that CaMex and its Ca2+-insensitive mutant (CaM1234) rendered active alpha1C/CaVbeta channel in the absence of alpha2delta. Coexpression of CaMex with alpha1C and beta2d in calcium-channel-free COS-1 cells recovered gating of the channel and supported CDI. Voltage-dependence of activation was shifted by approximately +40 mV to depolarization potentials. The calcium current reached maximum at +40 mV (20 mM Ca2+) and exhibited approximately 3 times slower activation and 5 times slower inactivation kinetics compared to the wild-type channel. Furthermore, both CaMex and CaM1234 accelerated recovery from inactivation and induced facilitation of the calcium current by strong depolarization prepulse, the properties absent from the human vascular/neuronal CaV1.2 channel. The data suggest a previously unknown action of CaM that in the presence of CaVbeta; translates into activation of the alpha2delta-deficient calcium channel and alteration of its properties. PMID:19106618

  7. Activation of delta-type opioid receptors modulates the responses of cat terminal ileum to field electrical stimulation.

    PubMed

    Venkova, K; Pencheva, N; Radomirov, R

    1990-01-01

    1. The effects of (D-Ala2, D-Leu5) enkephalin amide (DADLE) on the responses of the cat terminal ileum to field electrical stimulation (pulse duration of 0.5 msec, train duration of 10 sec, 30 V) were evaluated by the changes in the contractile or the relaxatory responses of longitudinal and circular strips to electrical stimuli with a frequency of 2, 10 or 30 Hz. 2. Stimulation with a frequency of 2, 10 or 30 Hz elicited contractile responses from the longitudinal strips while in the circular strips 2 Hz stimulation induced contractions and 10 or 30 Hz stimulation caused relaxation. Tetrodotoxin (TTX) (0.1 mumol/l) abolished the electrically-induced responses in both longitudinal and circular strips. 3. DADLE (1 nmol/l) significantly inhibited the cholinergic contractile responses of the longitudinal strips to 2, 10 or 30 Hz stimulation and the contractile responses of the circular strips to 2 Hz stimulation. The relaxatory responses of the circular strips to 10 or 30 Hz stimulation were insignificantly increased by DADLE. 4. On the background of guanetidine (10 mumol/l) and atropine (3 mumol/l) DADLE significantly decreased the nonadrenergic, noncholinergic relaxatory responses of the circular strips to 2, 10 or 30 Hz stimulation. 5. DADLE did not change the maximum effects and the EC50 values of acetylcholine and noradrenaline in both longitudinal and circular strips. 6. It is suggested that in the cat terminal ileum activation of delta-type opioid receptors modulates the mechanical activity suppressing the cholinergic responses in the longitudinal and circular layers as well as the adrenergic and nonadrenergic, noncholinergic responses in the circular layer. PMID:2153605

  8. Production of 5,8,11-Eicosatrienoic Acid (Mead Acid) by a (Delta)6 Desaturation Activity-Enhanced Mutant Derived from a (Delta)12 Desaturase-Defective Mutant of an Arachidonic Acid-Producing Fungus, Mortierella alpina 1S-4

    PubMed Central

    Kawashima, H.; Nishihara, M.; Hirano, Y.; Kamada, N.; Akimoto, K.; Konishi, K.; Shimizu, S.

    1997-01-01

    Enhanced production of 5,8,11-eicosatrienoic acid (Mead acid, 20:3(omega)9) was attained by a mutant fungus, Mortierella alpina M209-7, derived from (Delta)12 desaturase-defective M. alpina Mut48. The 20:3(omega)9 production by M209-7 was 1.3 times greater than that by its parent strain, Mut48. This is thought to be due to its enhanced (Delta)6 desaturation activity, which was 1.4 times higher than that of Mut48. In both strains, 87 to 88% of the total lipids comprised triacylglycerol (TG) and 85% of 20:3(omega)9 was contained in TG. On optimization of the culture conditions for M209-7, earlier glucose feeding and shifting of the growth temperature from 28 to 19(deg)C on the second day were shown to be effective. Under the optimal conditions with a 10-liter jar fermentor, 20:3(omega)9 production reached 1.65 g/liter of culture medium (corresponding to 118 mg/g of dry mycelia and 28.9% of total fatty acids), which is about twice that reported previously (0.8 g/liter). PMID:16535598

  9. Production of 5,8,11-Eicosatrienoic Acid (Mead Acid) by a (Delta)6 Desaturation Activity-Enhanced Mutant Derived from a (Delta)12 Desaturase-Defective Mutant of an Arachidonic Acid-Producing Fungus, Mortierella alpina 1S-4.

    PubMed

    Kawashima, H; Nishihara, M; Hirano, Y; Kamada, N; Akimoto, K; Konishi, K; Shimizu, S

    1997-05-01

    Enhanced production of 5,8,11-eicosatrienoic acid (Mead acid, 20:3(omega)9) was attained by a mutant fungus, Mortierella alpina M209-7, derived from (Delta)12 desaturase-defective M. alpina Mut48. The 20:3(omega)9 production by M209-7 was 1.3 times greater than that by its parent strain, Mut48. This is thought to be due to its enhanced (Delta)6 desaturation activity, which was 1.4 times higher than that of Mut48. In both strains, 87 to 88% of the total lipids comprised triacylglycerol (TG) and 85% of 20:3(omega)9 was contained in TG. On optimization of the culture conditions for M209-7, earlier glucose feeding and shifting of the growth temperature from 28 to 19(deg)C on the second day were shown to be effective. Under the optimal conditions with a 10-liter jar fermentor, 20:3(omega)9 production reached 1.65 g/liter of culture medium (corresponding to 118 mg/g of dry mycelia and 28.9% of total fatty acids), which is about twice that reported previously (0.8 g/liter). PMID:16535598

  10. Radioactivity of Potassium Solutions: A Comparison of Calculated Activity to Measured Activity from Gross Beta Counting and Gamma Spectroscopy

    SciTech Connect

    Gaylord, R F

    2005-07-26

    In order to determine if the measured beta activity for a solution containing potassium was exactly as predicted, particularly since the CES gas counter is not calibrated specifically with K-40, an experiment was conducted to compare measured activities from two radioanalytical methods (gamma spectroscopy and gas proportional counting) to calculated activities across a range of potassium concentrations. Potassium, being ubiquitous and naturally radioactive, is a well-known and common interference in gross beta counting methods. By measuring the observed beta activity due to K-40 in potassium-containing solutions across a wide range of concentrations, it was found that the observed beta activity agrees well with the beta activity calculated from the potassium concentration measured by standard inorganic analytical techniques, such as ICP-OES, and that using the measured potassium concentration to calculate the expected beta activity, and comparing this to the observed beta activity to determine if potassium can account for all the observed activity in a sample, is a valid technique. It was also observed that gamma spectroscopy is not an effective means of measuring K-40 activity below approximately 700 pCi/L, which corresponds to a solution with approximately 833 mg/L total potassium. Gas proportional counting for gross beta activity has a much lower detection limit, typically 20-50 picoCi/L for a liquid low in total dissolved solids, which corresponds to a potassium concentration of approximately 30-70 ppm K.

  11. Characterization of the human activator protein-2gamma (AP-2gamma) gene: control of expression by Sp1/Sp3 in breast tumour cells.

    PubMed Central

    Hasleton, Mark D; Ibbitt, J Claire; Hurst, Helen C

    2003-01-01

    The activator protein-2 (AP-2) family of DNA-binding transcription factors are developmentally regulated and also play a role in human neoplasia. In particular, the AP-2gamma protein has been shown to be overexpressed in a high percentage of breast tumours. In the present study, we report the complete sequence determination of the human TFAP2C gene encoding the AP-2gamma transcription factor plus the mapping of the transcription start site used in breast tumour-derived cells. The 5'-end of the gene lies within a CpG island and transcription is initiated at a single site within a classical initiator motif. We have gone on to investigate why some breast tumour-derived cell lines readily express AP-2gamma, whereas others do not, and show that the proximal promoter (+191 to -312) is differentially active in the two cell phenotypes. DNase footprinting led to the identification of three Sp1/Sp3-binding sites within this region, two of which are absolutely required both for promoter function and cell-type-specific activity. By Western blotting a panel of expressing and non-expressing breast tumour lines we show that the latter have higher levels of Sp3. Furthermore, increasing Sp3 levels in AP-2gamma-expressing cells led to the repression of AP-2gamma promoter activity, particularly when Sp3 inhibitory function was maximized through sumoylation. We propose that differences in the level and activity of Sp3 between breast tumour lines can determine the expression level of their AP-2gamma gene. PMID:12733991

  12. Active galactic nuclei at gamma-ray energies

    NASA Astrophysics Data System (ADS)

    Dermer, Charles Dennison; Giebels, Berrie

    2016-06-01

    Active Galactic Nuclei can be copious extragalactic emitters of MeV-GeV-TeV γ rays, a phenomenon linked to the presence of relativistic jets powered by a super-massive black hole in the center of the host galaxy. Most of γ-ray emitting active galactic nuclei, with more than 1500 known at GeV energies, and more than 60 at TeV energies, are called "blazars". The standard blazar paradigm features a jet of relativistic magnetized plasma ejected from the neighborhood of a spinning and accreting super-massive black hole, close to the observer direction. Two classes of blazars are distinguished from observations: the flat-spectrum radio-quasar class (FSRQ) is characterized by strong external radiation fields, emission of broad optical lines, and dust tori. The BL Lac class (from the name of one of its members, BL Lacertae) corresponds to weaker advection-dominated flows with γ-ray spectra dominated by the inverse Compton effect on synchrotron photons. This paradigm has been very successful for modeling the broadband spectral energy distributions of blazars. However, many fundamental issues remain, including the role of hadronic processes and the rapid variability of a few FSRQs and several BL Lac objects whose synchrotron spectrum peaks at UV or X-ray frequencies. A class of γ-ray-emitting radio galaxies, which are thought to be the misaligned counterparts of blazars, has emerged from the results of the Fermi-Large Area Telescope and of ground-based Cherenkov telescopes. Soft γ-ray emission has been detected from a few nearby Seyfert galaxies, though it is not clear whether those γ rays originate from the nucleus. Blazars and their misaligned counterparts make up most of the ≳100 MeV extragalactic γ-ray background (EGB), and are suspected of being the sources of ultra-high energy cosmic rays. The future "Cherenkov Telescope Array", in synergy with the Fermi-Large Area Telescope and a wide range of telescopes in space and on the ground, will write the next chapter

  13. Interaction of ultraviolet and X-ray radiation with gamma rays produced by a jet in active galactic nuclei

    NASA Technical Reports Server (NTRS)

    Zbyszewska, Magda

    1994-01-01

    Recent observations by the Compton Gamma-Ray Observatory give evidence for the existence of a type of blazar with strong gamma-ray emission. Data obtained by EGRET for the quasar 3C 279 show a spectrum between 100 MeV and 10 GeV. Photons of such energies should interact with the X-rays and produce positron/electron pairs. If the optical depth against pair production for the gamma rays is large (tau(gamma gamma) greater than 1), the gamma-ray spectrum should be affected. The importance of this process has been pointed out by, e.g., Maraschi, Ghisellini, & Celotti (1992). Several works (e.g., Dermer 1993; Zbyszewska 1993; Sikora, Begelman, & Rees 1993) concerning gamma-ray radiation from quasar 3C 279 have proposed a model in which the gamma rays are produced via interaction between a moving cloud of relativistic electrons and external soft photons. The presence of gamma rays in active galactic nuclei spectra gives constraints on the localization and the luminosity of the medium which produces ultraviolet/X-ray photons. We investigate what conditions should be fulfilled in the above model to avoid the absorption of the gamma rays due to pair production.

  14. Telmisartan protects against diabetic vascular complications in a mouse model of obesity and type 2 diabetes, partially through peroxisome proliferator activated receptor-{gamma}-dependent activity

    SciTech Connect

    Toyama, Kensuke; Nakamura, Taishi; Kataoka, Keiichiro; Yasuda, Osamu; Fukuda, Masaya; Tokutomi, Yoshiko; Dong, Yi-Fei; Ogawa, Hisao; Kim-Mitsuyama, Shokei

    2011-07-08

    Highlights: {yields} Telmisartan, an angiotensin receptor blocker, acts as a partial PPAR{gamma} agonist. {yields} The protective effects of telmisartan against diabetic vascular injury were associated with attenuation of vascular NF{kappa}B activation and TNF {alpha}. {yields} PPAR{gamma} activity of telmisartan was involved in the normalization of vascular PPAR{gamma} downregulation in diabetic mice. {yields} We provided the first evidence indicating that PPAR{gamma} activity of telmisartan contributed to the protective effects of telmisartan against diabetic vascular complication. -- Abstract: Experimental and clinical data support the notion that peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) activation is associated with anti-atherosclerosis as well as anti-diabetic effect. Telmisartan, an angiotensin receptor blocker (ARB), acts as a partial PPAR{gamma} agonist. We hypothesized that telmisartan protects against diabetic vascular complications, through PPAR{gamma} activation. We compared the effects of telmisartan, telmisartan combined with GW9662 (a PPAR{gamma} antagonist), and losartan with no PPAR{gamma} activity on vascular injury in obese type 2 diabetic db/db mice. Compared to losartan, telmisartan significantly ameliorated vascular endothelial dysfunction, downregulation of phospho-eNOS, and coronary arterial remodeling in db/db mice. More vascular protective effects of telmisartan than losartan were associated with greater anti-inflammatory effects of telmisartan, as shown by attenuation of vascular nuclear factor kappa B (NF{kappa}B) activation and tumor necrosis factor {alpha}. Coadministration of GW9662 with telmisartan abolished the above mentioned greater protective effects of telmisartan against vascular injury than losartan in db/db mice. Thus, PPAR{gamma} activity appears to be involved in the vascular protective effects of telmisartan in db/db mice. Moreover, telmisartan, but not losartan, prevented the downregulation of

  15. Mississippi Delta

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The streamers of clouds draped over the Gulf of Mexico in this true-color MODIS image from February 27, 2002, suggest that a cold, dry wind was blowing southward over the United States and began to pick up moisture over the Gulf, causing these strips of clouds. That the clouds didn't pick up until some distance from the coastline allowed MODIS to get a perfect view of the dynamic Gulf Coast environment spanning (left to right) Texas, Louisiana, Mississippi, Alabama, and Florida's Western Panhandle. The Mississippi River runs roughly down the center of the image, and is joined in Louisiana by the Red River coming in from the northwest. Over the past 7000 years, the actual delta, where the main river channel empties into the Gulf, has wandered around what we now think of as the Louisiana coast. Considering all the sediment visible in this image, it's not hard to imagine that the river carries about 2.4 billion kilograms of sediment into the Gulf each year. Deposition of some of this sediment has been building up the current delta, called the Birdfoot Delta, for obvious reasons, for about 700 years. The coastal waters are alive with microscopic organisms called phytoplankton, which contain colorful pigments, including chlorophyll, for harvesting sunlight. Beyond the sediment plume off Louisiana, the waters are very dark, which could indicate that a large amount of chlorophyll is present, absorbing lots of sunlight and causing the water to appear dark. Farther south, the waters appear bright blue, which could be a signature of coccolithophores, which use highly reflective calcium carbonate to build scaly coverings for themselves. The brighter offshore waters could also be caused by a blue-green algae called Trichodesmium, an organism that can not only harness carbon dioxide for photosynthesis, but can also take nitrogen from the air and turn it into a form that can be used by living organisms. Credit: Jacques Descloitres, MODIS Land Rapid Response Team, NASA/GSFC

  16. Intercomparison of activity size distributions of thoron progeny by alpha- and gamma-counting methods.

    PubMed

    Cheng, Y S; Yu, C C; Tu, K W

    1994-01-01

    It is difficult to calibrate sampling devices using radon or thoron progeny or particles measuring 1-4 nm; therefore, an interlaboratory comparison is important to verify the performance of graded diffusion batteries for the activity size distributions of the "unattached" progeny. This paper describes the results of an interlaboratory comparison of 220Rn progeny size distributions using graded diffusion batteries by alpha- and gamma-counting methods with different data inversion schemes. Graded diffusion batteries designed at the Inhalation Toxicology Research Institute and at the Environmental Measurement Laboratory were used in the study. Screens and backup filters from the Environmental Measurement Laboratory-graded diffusion batteries were counted simultaneously in alpha counters for total alpha activities, and those of the Inhalation Toxicology Research Institute-graded diffusion batteries were counted in a gamma detector for gamma activities from 212Pb. Because of the different counting methods and data analysis procedures used, this interlaboratory study of 220Rn progeny allows a more rigorous way of testing instrument performance. 212Pb particles generated in well-controlled environments of oxygen, nitrogen, or oxygen with 1 ppm of nitrogen oxide were measured. In general, good agreement in activity size distributions was obtained from these two methods. Some differences observed in individual size spectra were attributable to the data inversion programs used in each laboratory. When the data were analyzed by the same computer program, most differences disappeared. PMID:8253581

  17. Activity determination, kinetic analyses and isoenzyme identification of gamma glutamyltransferase in human neutrophils.

    PubMed

    Sener, Azize; Yardimci, Turay

    2005-05-31

    Gamma-glutamyltransferase (GGT, EC 2.3.2.2) which hydrolyzes glutathione (GSH), is required for the maintenance of normal intracellular GSH concentration. GGT is a membrane enzyme present in leukocytes and platelets. Its activity has also been observed in human neutrophils. In this study, GGT was purified from Triton X-100 solubilized neutrophils and its kinetic parameters were determined. For kinetic analyses of transpeptidation reaction, gamma-glutamyl p-nitroanilide was used as the substrate and glycylglycine as the acceptor. Apparent K(m) values were determined as 1.8 mM for gamma-glutamyl p-nitroanilide and 16.9 mM for glycylglycine. The optimum pH of GGT activity was 8.2 and the optimum temperature was 37 degrees C. It had thermal stability with 58 % relative activity at 56 degrees C for 30 min incubation. L-serine, in the presence of borate, was detected as the competitive inhibitor. Bromcresol green inhibited neutrophil GGT activity as a noncompetitive inhibitor. The neutrophils seem to contain only the isoenzyme that is present in platelets. We characterized the kinetic properties and compared the type of the isoenzyme of neutrophil GGT with platelet GGT via polyacrylamide gel electrophoresis (PAGE) under a standard set of conditions. PMID:15943911

  18. Nucleus accumbens NMDA receptor activation regulates amphetamine cross-sensitization and deltaFosB expression following sexual experience in male rats.

    PubMed

    Beloate, Lauren N; Weems, Peyton W; Casey, Graham R; Webb, Ian C; Coolen, Lique M

    2016-02-01

    Sexual experience in male rats followed by a period of abstinence causes sensitization to d-Amphetamine (Amph) reward, evidenced by an increased conditioned place preference (CPP) for low doses of Amph. Moreover, sexual experience induces neural plasticity within the nucleus accumbens (NAc), including induction of deltaFosB, which plays a key role in Amph reward cross-sensitization. The NMDA receptor subunit NR1 is also upregulated by mating, but the functional relevance of NMDA receptors in sex experience-induced effects is unknown. Here, we examined the influence of intra-NAc MK 801 infusions on sex experience-induced NAc deltaFosB and cFos expression, as well as mating- and Amph-induced CPP in adult male rats. In experiment 1, males received MK 801 or saline into the NAc during each of 4 consecutive days of mating or handling and were tested for Amph CPP and experience-induced deltaFosB 10 days later. Intra-NAc MK 801 during sexual behavior prevented experience-induced increases in Amph CPP and NAc deltaFosB expression without affecting sexual behavior. In experiment 2, the effects of intra-NAc MK 801 on mating-induced CPP were examined by intra-NAc infusion of MK 801 or saline prior to mating on conditioning days. Intra-NAc MK 801 did not affect mating-induced CPP. Next, effects of intra-NAc MK 801 on mating-induced cFos immunoreactivity were examined. MK 801 prevented mating-induced cFos expression in NAc shell and core. Together, these results provide evidence that NAc NMDA receptor activation during sexual behavior plays a key role in mating-induced cFos and deltaFosB expression and subsequent experience-induced cross-sensitization to Amph reward. PMID:26391065

  19. The Notch ligands Jagged2, Delta1, and Delta4 induce differentiation and expansion of functional human NK cells from CD34+ cord blood hematopoietic progenitor cells.

    PubMed

    Beck, Rose C; Padival, Mallika; Yeh, David; Ralston, Justine; Cooke, Kenneth R; Lowe, John B

    2009-09-01

    Notch receptor signaling is required for T cell development, but its role in natural killer (NK) cell development is poorly understood. We compared the ability of the 5 mammalian Notch ligands (Jagged1, Jagged2, Delta1, Delta3, or Delta4) to induce NK cell development from human hematopoietic progenitor cells (HPCs). CD34(+) HPCs were cultured with OP9 stromal cell lines transduced with 1 of the Notch ligands or with OP9 stromal cells alone, in the presence of IL-7, Flt3L, and IL-15. Differentiation and expansion of CD56(+)CD3(-) cells were greatly accelerated in the presence of Jagged2, Delta-1, or Delta-4, versus culture in the absence of ligand or in the presence of Jagged1 or Delta3. At 4 weeks, cultures containing Jagged2, Delta1, or Delta4 contained 80% to 90% NK cells, with the remaining cells being CD33(+) myelogenous cells. Notch-induced NK (N-NK) cells resembled CD56(bright) NK cells in that they were CD16(-), CD94(-), CD117(+), and killer immunoglobulin-like receptors (KIR(-)). They also expressed NKp30, NKp44, NKp46, 2B4, and DNAM-1, with partial expression of NKG2D. The N-NK cells displayed cytotoxic activity against the K562 and RPMI-8226 cell lines, at levels similar to activated peripheral blood (PB) NK cells, although killing of Daudi cells was not present. N-NK cells were also capable of interferon (IFN)-gamma secretion. Thus, Notch ligands have differential ability to induce and expand immature, but functional, NK cells from CD34(+) HPCs. The use of Notch ligands to generate functional NK cells in vitro may be significant for cellular therapy purposes. PMID:19660715

  20. Cellular and circuit models of increased resting-state network gamma activity in schizophrenia.

    PubMed

    White, R S; Siegel, S J

    2016-05-01

    Schizophrenia (SCZ) is a disorder characterized by positive symptoms (hallucinations, delusions), negative symptoms (blunted affect, alogia, reduced sociability, and anhedonia), as well as persistent cognitive deficits (memory, concentration, and learning). While the biology underlying subjective experiences is difficult to study, abnormalities in electroencephalographic (EEG) measures offer a means to dissect potential circuit and cellular changes in brain function. EEG is indispensable for studying cerebral information processing due to the introduction of techniques for the decomposition of event-related activity into its frequency components. Specifically, brain activity in the gamma frequency range (30-80Hz) is thought to underlie cognitive function and may be used as an endophenotype to aid in diagnosis and treatment of SCZ. In this review we address evidence indicating that there is increased resting-state gamma power in SCZ. We address how modeling this aspect of the illness in animals may help treatment development as well as providing insights into the etiology of SCZ. PMID:26577758

  1. Active Neutron and Gamma Ray Instrumentation for In Situ Planetary Science Applications

    NASA Technical Reports Server (NTRS)

    Parsons, A.; Bodnarik, J.; Evans, L.; Floyd, S.; Lim, L.; McClanahan, T.; Namkung, M.; Schweitzer, J.; Starr, R.; Trombka, J.

    2010-01-01

    The Pulsed Neutron Generator-Gamma Ray And Neutron Detectors (PNG-GRAND) experiment is an innovative application of the active neutron-gamma ray technology so successfully used in oil field well logging and mineral exploration on Earth. The objective of our active neutron-gamma ray technology program at NASA Goddard Space Flight Center (NASA-GSFC) is to bring the PNG-GRAND instrument to the point where it can be flown on a variety of surface lander or rover missions to the Moon, Mars, Menus, asteroids, comets and the satellites of the outer planets. Gamma-Ray Spectrometers (GRS) have been incorporated into numerous orbital planetary science missions and, especially its the case of the Mars Odyssey GRS, have contributed detailed maps of the elemental composition over the entire surface of Mars. However, orbital gamma ray measurements have low spatial sensitivity (100's of km) due to their low surface emission rates from cosmic rays and subsequent need to be averaged over large surface areas. PNG-GRAND overcomes this impediment by incorporating a powerful neutron excitation source that permits high sensitivity surface and subsurface measurements of bulk elemental compositions. PNG-GRAND combines a pulsed neutron generator (PNG) with gamma ray and neutron detectors to produce a landed instrument to determine subsurface elemental composition without needing to drill into a planet's surface a great advantage in mission design. We are currently testing PNG-GRAND prototypes at a unique outdoor neutron instrumentation test facility recently constructed at NASA/GSFC that consists of a 2 m x 2 in x 1 m granite structure placed outdoors in an empty field. Because an independent trace elemental analysis has been performed on the material, this granite sample is a known standard with which to compare both Monte Carlo simulations and our experimentally measured elemental composition data. We will present data from operating PNG-GRAND in various experimental configurations on a

  2. Phenotypic and functional characteristics of active suppressor cells against IFN-gamma production in PHA-stimulated cord blood lymphocytes

    SciTech Connect

    Seki, H.; Taga, K.; Matsuda, A.; Uwadana, N.; Hasui, M.; Miyawaki, T.; Taniguchi, N.

    1986-11-15

    Cord blood mononuclear cells (MNC) were defective in their ability to produce interferon-gamma (IFN-gamma) on stimulation with phytohemagglutinin (PHA) or recombinant interleukin 2, whereas cord MNC could induce comparable amounts of IFN-gamma with adult controls on stimulation with a streptococcal preparation, OK-432. Moreover, irradiation of cord MNC with 1500 rad before PHA stimulation could restore the IFN-gamma production. Kinetic studies indicated that such augmentation of IFN-gamma production by irradiation was evident when cord MNC were irradiated before or by 12 hr of PHA-stimulated culture. But irradiation after 18 hr or more of PHA stimulation did not exert any significant augmentation on IFN-gamma production by cord MNC. It seemed most likely that the ability of IFN-gamma production is already mature at birth, but radiosensitive suppressor effectors on IFN-gamma production are activated within cord MNC at an early stage of PHA stimulation, resulting in poor IFN-gamma production by cord MNC. PHA-induced IFN-gamma production by OKT3+, OKT4+, and OKT8- cord cells were markedly enhanced by irradiation with 1,500 rad before the culture. Coculture experiments disclosed that cord OKT4+ cells, but not OKT4- cells, when prestimulated with PHA for 24 hr, exerted active suppression on PHA-induced IFN-gamma production by adult MNC in a dose-dependent manner. These results suggested that radiosensitive suppressor effectors on IFN-gamma production were induced within the OKT4+ T cell subset of cord MNC on PHA stimulation.

  3. DEXAMETHASONE DEPLETES GAMMA-DELTA T CELLS AND ALTERS THE ACTIVATION STATE AND RESPONSIVENESS OF BOVINE PERIPHERAL BLOOD LYMPHOCYTE SUBPOPULATIONS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Administration of dexamethasone (DEX) to cattle is commonly used in models of stress-induced effects on host defense, including models investigating interactions of microorganisms with their host. Much less is known about the effects of DEX on the adaptive immune response in cattle than in other sp...

  4. DEXAMETHASONE DEPLETES GAMMA DELTA T CELLS AND ALTERS THE ACTIVATION STATE AND RESPONSIVENESS OF BOVINE PERIPHERAL BLOOD LYMPHOCYTE SUBPOPULATIONS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Administration of dexamethasone (DEX) to cattle is commonly used in models of stress-induced effects on the host defense, including those employed to investigate interactions of microorganisms with their host. Much less is known about the effects of DEX on the adaptive immune response in cattle tha...

  5. Gamma-ray active galactic nucleus type through machine-learning algorithms

    NASA Astrophysics Data System (ADS)

    Hassan, T.; Mirabal, N.; Contreras, J. L.; Oya, I.

    2013-01-01

    The Fermi Gamma-ray Space Telescope (Fermi) is producing the most detailed inventory of the gamma-ray sky to date. Despite tremendous achievements approximately 25 per cent of all Fermi extragalactic sources in the Second Fermi Large Area Telescope Catalogue (2FGL) are listed as active galactic nuclei (AGN) of uncertain type. Typically, these are suspected blazar candidates without a conclusive optical spectrum or lacking spectroscopic observations. Here, we explore the use of machine-learning algorithms - random forests and support vector machines - to predict specific AGN subclass based on observed gamma-ray spectral properties. After training and testing on identified/associated AGN from the 2FGL we find that 235 out of 269 AGN of uncertain type have properties compatible with gamma-ray BL Lacertae and flat-spectrum radio quasars with accuracy rates of 85 per cent. Additionally, direct comparison of our results with class predictions made after following the infrared colour-colour space of Massaro et al. shows that the agreement rate is over four-fifths for 54 overlapping sources, providing independent cross-validation. These results can help tailor follow-up spectroscopic programmes and inform future pointed surveys with ground-based Cherenkov telescopes.

  6. Imaging of heterogeneous materials by prompt gamma-ray neutron activation analysis

    SciTech Connect

    Staples, P.; Prettyman, T.; Lestone, J.

    1998-12-01

    The authors have used a tomographic gamma scanner (TGS) to produce tomographic prompt gamma-ray neutron activation analysis imaging (PGNAA) of heterogeneous matrices. The TGS was modified by the addition of graphite reflectors that contain isotopic neutron sources for sample interrogation. The authors are in the process of developing the analysis methodology necessary for a quantitative assay of large containers of heterogeneous material. This nondestructive analysis (NDA) technique can be used for material characterization and the determination of neutron assay correction factors. The most difficult question to be answered is the determination of the source-to-sample coupling term. To assist in the determination of the coupling term, the authors have obtained images for a range of sample that are very well characterized, such as, homogenous pseudo one-dimensional samples to three-dimensional heterogeneous samples. They then compare the measurements to MCNP calculations. For an accurate quantitative measurement, it is also necessary to determine the sample gamma-ray self attenuation at higher gamma-ray energies, namely pair production should be incorporated into the analysis codes.

  7. Transitions, cross sections and neutron binding energy in 186Re by Prompt Gamma Activation Analysis

    NASA Astrophysics Data System (ADS)

    Lerch, A. G.; Hurst, A. M.; Firestone, R. B.; Revay, Zs.; Szentmiklosi, L.; McHale, S. R.; McClory, J. W.; Detwiler, B.; Carroll, J. J.

    2014-03-01

    The nuclide 186Re possesses an isomer with 200,000 year half-life while its ground state has a half-life of 3.718 days. It is also odd-odd and well-deformed nucleus, so should exhibit a variety of other interesting nuclear-structure phenomena. However, the available nuclear data is rather sparse; for example, the energy of the isomer is only known to within + 7 keV and, with the exception of the J?=1- ground state, every proposed level is tentative in the ENSDF. Previously, Prompt Gamma Activation Analysis (PGAA) was utilized to study natRe with 186,188Re being produced via thermal neutron capture. Recently, an enriched 185Re target was irradiated by thermal neutrons at the Budapest Research Reactor to build on those results. Prompt (primary and secondary) and delayed gamma-ray transitions were measured with a large-volume, Compton-suppressed HPGe detector. Absolute cross sections for each gamma transition were deduced and corrected for self attenuation within the sample. Fifty-two primary gamma-ray transitions were newly identified and used to determine a revised value of the neutron binding energy. DICEBOX was used to simulate the decay scheme and the total radiative thermal neutron capture cross section was found to be 97+/-3 b Supported by DTRA (Detwiler) through HDTRA1-08-1-0014.

  8. IL-21R signaling suppresses IL-17+ gamma delta T cell responses and production of IL-17 related cytokines in the lung at steady state and after Influenza A virus infection.

    PubMed

    Moser, Emily K; Sun, Jie; Kim, Taeg S; Braciale, Thomas J

    2015-01-01

    Influenza A virus (IAV) infection of the respiratory tract elicits a robust immune response, which is required for efficient virus clearance but at the same time can contribute to lung damage and enhanced morbidity. IL-21 is a member of the type I cytokine family and has many different immune-modulatory functions during acute and chronic virus infections, although its role in IAV infection has not been fully evaluated. In this report we evaluated the contributions of IL-21/IL-21 receptor (IL-21R) signaling to host defense in a mouse model of primary IAV infection using IL-21R knock out (KO) mice. We found that lack of IL-21R signaling had no significant impact on virus clearance, adaptive T cell responses, or myeloid cell accumulations in the respiratory tract. However, a subset of inflammatory cytokines were elevated in the bronchoalveolar lavage fluid of IL-21R KO mice, including IL-17. Although there was only a small increase in Th17 cells in the lungs of IL-21R KO mice, we observed a dramatic increase in gamma delta (γδ) T cells capable of producing IL-17 both after IAV infection and at steady state in the respiratory tract. Finally, we found that IL-21R signaling suppressed the accumulation of IL-17+ γδ T cells in the respiratory tract intrinsically. Thus, our study reveals a previously unrecognized role of IL-21R signaling in regulating IL-17 production by γδ T cells. PMID:25849970

  9. Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone attenuates postincisional pain by regulating macrophage polarization

    SciTech Connect

    Hasegawa-Moriyama, Maiko; Ohnou, Tetsuya; Godai, Kohei; Kurimoto, Tae; Nakama, Mayo; Kanmura, Yuichi

    2012-09-14

    Highlights: Black-Right-Pointing-Pointer Rosiglitazone attenuated postincisional pain. Black-Right-Pointing-Pointer Rosiglitazone alters macrophage polarization to F4/80{sup +}CD206{sup +} M2 macrophages at the incisional sites. Black-Right-Pointing-Pointer Transplantation of rosiglitazone-treated macrophages produced analgesic effects. -- Abstract: Acute inflammation triggered by macrophage infiltration to injured tissue promotes wound repair and may induce pain hypersensitivity. Peroxisome proliferator-activated receptor {gamma} (PPAR){gamma} signaling is known to regulate heterogeneity of macrophages, which are often referred to as classically activated (M1) and alternatively activated (M2) macrophages. M1 macrophages have considerable antimicrobial activity and produce a wide variety of proinflammatory cytokines. In contrast, M2 macrophages are involved in anti-inflammatory and homeostatic functions linked to wound healing and tissue repair. Although it has been suggested that PPAR{gamma} agonists attenuate pain hypersensitivity, the molecular mechanism of macrophage-mediated effects of PPAR{gamma} signaling on pain development has not been explored. In this study, we investigated the link between the phenotype switching of macrophage polarization induced by PPAR{gamma} signaling and the development of acute pain hypersensitivity. Local administration of rosiglitazone significantly ameliorated hypersensitivity to heat and mechanical stimuli, and paw swelling. Consistent with the down-regulation of nuclear factor {kappa}B (NF{kappa}B) phosphorylation by rosiglitazone at the incisional sites, the number of F4/80{sup +}iNOS{sup +} M1 macrophages was decreased whereas numbers of F4/80{sup +}CD206{sup +} M2 macrophages were increased in rosiglitazone-treated incisional sites 24 h after the procedure. In addition, gene induction of anti-inflammatory M2-macrophage-associated markers such as arginase1, FIZZ1 and interleukin (IL)-10 were significantly increased, whereas

  10. Interferon-gamma-dependent cytotoxic activation of human astrocytes and astrocytoma cells.

    PubMed

    Hashioka, Sadayuki; Klegeris, Andis; Schwab, Claudia; McGeer, Patrick L

    2009-12-01

    Astrocytes and microglia become activated in a broad spectrum of inflammatory neurodegenerative diseases. Activated microglia are widely believed to be the principal source of inflammation-induced neuronal degeneration in these disorders. To investigate the neurotoxic potential of human astrocytes, we exposed them and human astrocytic U-373 MG cells to a variety of inflammatory stimulants. We then assessed the effects of their supernatants on human SH-SY5 cells. When astrocytes and U-373 MG cells were stimulated with interferon (IFN)-gamma (150U/ml), their supernatants significantly reduced SH-SY5Y cell viability. Other powerful inflammatory stimulants such as lipopolysaccharide (0.5mug/ml), tumor necrosis factor-alpha (10ng/ml) and interleukin-1beta (10ng/ml), alone or in combination, were without effect. These combinations were also unable to enhance the IFN-gamma effect. The induced cytotoxicities were reversed by JAK inhibitor I, a potent and specific inhibitor of JAKs. This result indicates that the neurotoxic effect was proceeding through the IFN-gamma receptor (IFNGR)-JAK-STAT intracellular pathway. To establish that the IFNGR is expressed on both cultured astrocytes and U-373 MG cells, we performed RT-PCR on total RNA extracts to identify a specific IFNGR product. We showed the protein product on these cultured cells by immunocytochemistry using an antibody to IFNGR. Finally, using human postmortem material, we showed sharp upregulation of the IFNGR on activated astrocytes in affected areas in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. These findings suggest that activated astrocytes may become neurotoxic when stimulated by IFN-gamma and may therefore exacerbate the pathology in a spectrum of neurodegenerative diseases. PMID:18375019

  11. Beta- and gamma-band activity reflect predictive coding in the processing of causal events.

    PubMed

    van Pelt, Stan; Heil, Lieke; Kwisthout, Johan; Ondobaka, Sasha; van Rooij, Iris; Bekkering, Harold

    2016-06-01

    In daily life, complex events are perceived in a causal manner, suggesting that the brain relies on predictive processes to model them. Within predictive coding theory, oscillatory beta-band activity has been linked to top-down predictive signals and gamma-band activity to bottom-up prediction errors. However, neurocognitive evidence for predictive coding outside lower-level sensory areas is scarce. We used magnetoencephalography to investigate neural activity during probability-dependent action perception in three areas pivotal for causal inference, superior temporal sulcus, temporoparietal junction and medial prefrontal cortex, using bowling action animations. Within this network, Granger-causal connectivity in the beta-band was found to be strongest for backward top-down connections and gamma for feed-forward bottom-up connections. Moreover, beta-band power in TPJ increased parametrically with the predictability of the action kinematics-outcome sequences. Conversely, gamma-band power in TPJ and MPFC increased with prediction error. These findings suggest that the brain utilizes predictive-coding-like computations for higher-order cognition such as perception of causal events. PMID:26873806

  12. Music training leads to the development of timbre-specific gamma band activity.

    PubMed

    Shahin, Antoine J; Roberts, Larry E; Chau, Wilkin; Trainor, Laurel J; Miller, Lee M

    2008-05-15

    Oscillatory gamma band activity (GBA, 30-100 Hz) has been shown to correlate with perceptual and cognitive phenomena including feature binding, template matching, and learning and memory formation. We hypothesized that if GBA reflects highly learned perceptual template matching, we should observe its development in musicians specific to the timbre of their instrument of practice. EEG was recorded in adult professional violinists and amateur pianists as well as in 4- and 5-year-old children studying piano in the Suzuki method before they commenced music lessons and 1 year later. The adult musicians showed robust enhancement of induced (non-time-locked) GBA, specifically to their instrument of practice, with the strongest effect in professional violinists. Consistent with this result, the children receiving piano lessons exhibited increased power of induced GBA for piano tones with 1 year of training, while children not taking lessons showed no effect. In comparison to induced GBA, evoked (time-locked) gamma band activity (30-90 Hz, approximately 80 ms latency) was present only in adult groups. Evoked GBA was more pronounced in musicians than non-musicians, with synchronization equally exhibited for violin and piano tones but enhanced for these tones compared to pure tones. Evoked gamma activity may index the physical properties of a sound and is modulated by acoustical training, while induced GBA may reflect higher perceptual learning and is shaped by specific auditory experiences. PMID:18375147

  13. Radiography apparatus using gamma rays emitted by water activated by fusion neutrons

    DOEpatents

    Smith, Donald L.; Ikeda, Yujiro; Uno, Yoshitomo

    1996-01-01

    Radiography apparatus includes an arrangement for circulating pure water continuously between a location adjacent a source of energetic neutrons, such as a tritium target irradiated by a deuteron beam, and a remote location where radiographic analysis is conducted. Oxygen in the pure water is activated via the .sup.16 O(n,p).sup.16 N reaction using .sup.14 -MeV neutrons produced at the neutron source via the .sup.3 H(d,n).sup.4 He reaction. Essentially monoenergetic gamma rays at 6.129 (predominantly) and 7.115 MeV are produced by the 7.13-second .sup.16 N decay for use in radiographic analysis. The gamma rays have substantial penetrating power and are useful in determining the thickness of materials and elemental compositions, particularly for metals and high-atomic number materials. The characteristic decay half life of 7.13 seconds of the activated oxygen is sufficient to permit gamma ray generation at a remote location where the activated water is transported, while not presenting a chemical or radioactivity hazard because the radioactivity falls to negligible levels after 1-2 minutes.

  14. Radiography apparatus using gamma rays emitted by water activated by fusion neutrons

    DOEpatents

    Smith, D.L.; Ikeda, Yujiro; Uno, Yoshitomo

    1996-11-05

    Radiography apparatus includes an arrangement for circulating pure water continuously between a location adjacent a source of energetic neutrons, such as a tritium target irradiated by a deuteron beam, and a remote location where radiographic analysis is conducted. Oxygen in the pure water is activated via the {sup 16}O(n,p){sup 16}N reaction using {sup 14}N-MeV neutrons produced at the neutron source via the {sup 3}H(d,n){sup 4}He reaction. Essentially monoenergetic gamma rays at 6.129 (predominantly) and 7.115 MeV are produced by the 7.13-second {sup 16}N decay for use in radiographic analysis. The gamma rays have substantial penetrating power and are useful in determining the thickness of materials and elemental compositions, particularly for metals and high-atomic number materials. The characteristic decay half life of 7.13 seconds of the activated oxygen is sufficient to permit gamma ray generation at a remote location where the activated water is transported, while not presenting a chemical or radioactivity hazard because the radioactivity falls to negligible levels after 1--2 minutes. 15 figs.

  15. Music training leads to the development of timbre-specific gamma band activity

    PubMed Central

    Shahin, Antoine J.; Roberts, Larry E.; Chau, Wilkin; Trainor, Laurel J.; Miller, Lee M.

    2015-01-01

    Oscillatory gamma band activity (GBA, 30–100Hz) has been shown to correlate with perceptual and cognitive phenomena including feature binding, template matching, and learning and memory formation. We hypothesized that if GBA reflects highly learned perceptual template matching, we should observe its development in musicians specific to the timbre of their instrument of practice. EEG was recorded in adult professional violinists and amateur pianists as well as in four- and five-year-old children studying piano in the Suzuki method before they commenced music lessons and one year later. The adult musicians showed robust enhancement of induced (non-time-locked) GBA, specifically to their instrument of practice, with the strongest effect in professional violinists. Consistent with this result, the children receiving piano lessons exhibited increased power of induced GBA for piano tones with one year of training, while children not taking lessons showed no effect. In comparison to induced GBA, evoked (time-locked) gamma band activity (30–90 Hz, ~80 ms latency) was present only in adult groups. Evoked GBA was more pronounced in musicians than non-musicians, with synchronization equally exhibited for violin and piano tones but enhanced for these tones compared to pure tones. Evoked gamma activity may index the physical properties of a sound and is modulated by acoustical training, while induced GBA may reflect higher perceptual learning and is shaped by specific auditory experiences. PMID:18375147

  16. The 124Sb activity standardization by gamma spectrometry for medical applications

    NASA Astrophysics Data System (ADS)

    de Almeida, M. C. M.; Iwahara, A.; Delgado, J. U.; Poledna, R.; da Silva, R. L.

    2010-07-01

    This work describes a metrological activity determination of 124Sb, which can be used as radiotracer, applying gamma spectrometry methods with hyper pure germanium detector and efficiency curves. This isotope with good activity and high radionuclidic purity is employed in the form of meglumine antimoniate (Glucantime) or sodium stibogluconate (Pentostam) to treat leishmaniasis. 124Sb is also applied in animal organ distribution studies to solve some questions in pharmacology. 124Sb decays by β-emission and it produces several photons (X and gamma rays) with energy varying from 27 to 2700 keV. Efficiency curves to measure point 124Sb solid sources were obtained from a 166mHo standard that is a multi-gamma reference source. These curves depend on radiation energy, sample geometry, photon attenuation, dead time and sample-detector position. Results for activity determination of 124Sb samples using efficiency curves and a high purity coaxial germanium detector were consistent in different counting geometries. Also uncertainties of about 2% ( k=2) were obtained.

  17. Delta spots and great flares

    NASA Technical Reports Server (NTRS)

    Zirin, Harold; Liggett, Margaret A.

    1987-01-01

    The development of delta spots and the great flares they produce are reviewed based on 18 years of observations. Delta groups are found to develop in three ways: (1) by the eruption of a single complex active region formed below the surface; (2) by the eruption of large satellite spots near a large older spot; and (3) by the collision of spots of opposite polarity from different dipoles. It is shown that the present sample of 21 delta spots never separate once they lock together, and that the driving force for the shear is spot motion. Indicators for the prediction of the occurrence of great flares are identified.

  18. Gamma irradiation: a method to produce an abiotic control for biological activated carbon.

    PubMed

    Stoquart, C; Vázquez-Rodríguez, G A; Servais, P; Barbeau, B

    2013-01-01

    The aim of this paper was to investigate the feasibility of using gamma irradiation to inhibit the microbial activity of biological powder activated carbon (PAC) without impacting its adsorptive properties. First of all, the range of dose of gamma rays required to produce abiotic PAC was selected on the basis of heterotrophic plate counts (HPC) inactivation and methylene blue (MB) adsorption kinetics. Doses inferior to 10 kGy were not sufficient to inhibit the culture of heterotrophic bacteria. On the other hand, doses superior to 15 kGy were demonstrated to affect the adsorption rate of MB. Consequently, a dose comprised between 10 and 15 kGy was selected for further investigation. In order to validate the adequacy of the range of dose (i.e. 10-15 kGy), adsorption characteristics were tested by monitoring the removal kinetics of refractory dissolved organic carbon (RDOC). No significant differences were observed between irradiated and non-irradiated biological PAC for the adsorption of RDOC. Irradiated, non-irradiated and virgin PAC were also evaluated in terms of abundance of viable (using the LIVE/DEAD BacLight method) bacteria and in terms of heterotrophic biomass activity. The results of the BacLight method demonstrated that attachment of the biofilm on the PAC was not impacted by the irradiation and heterotrophic activity measurements demonstrated that the latter could be radically reduced in the range of dose selected. In conclusion, when using a proper dose, the gamma irradiation of colonized activated carbon drastically reduced the heterotrophic activity on activated carbon without significantly impacting its adsorptive behaviour. PMID:24617066

  19. Peroxisome proliferator-activated receptor gamma agonists protect cerebellar granule cells from cytokine-induced apoptotic cell death by inhibition of inducible nitric oxide synthase.

    PubMed

    Heneka, M T; Feinstein, D L; Galea, E; Gleichmann, M; Wüllner, U; Klockgether, T

    1999-12-01

    Cerebellar granule cells (CGCs) can express the inducible isoform of nitric oxide synthase (iNOS) in response to inflammatory stimuli. We demonstrate that induction of iNOS in CGCs by bacterial lipopolysaccharide and pro-inflammatory cytokines results in cell death that was potentiated by excess L-arginine and inhibited by the selective iNOS inhibitor, 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine. The NO-mediated cell death was accompanied by increased caspase-3-like activity, DNA fragmentation and positive terminal transferase dUTP nick end labeling (TUNEL), suggesting that apoptosis mediates CGC cell death. Incubation of CGCs with the non-steroidal anti-inflammatory drugs (NSAIDs), ibuprofen or indomethacin, or with 15-deoxy-delta12,14 prostaglandin J2 (PGJ2) downregulates iNOS expression and reduces subsequent cell death. Since in other cell types, both NSAIDs and PGJ2 can activate the peroxisome proliferator-activated receptor-gamma (PPARgamma) and downregulate cytokine levels and iNOS expression, and since CGCs express PPARgamma in vivo and in vitro, our data suggest that activation of CGC PPARgamma mediates iNOS suppression and reduced cell death. Because PPARgamma is expressed in brains of Alzheimer's Disease (AD) patients, in which neuronal iNOS expression and apoptotic cell death have been described, these results may help explain the basis for the beneficial effects of NSAIDs in AD. PMID:10695726

  20. The MSX1 homeobox transcription factor is a downstream target of PHOX2B and activates the Delta-Notch pathway in neuroblastoma

    SciTech Connect

    Revet, Ingrid; Huizenga, Gerda; Chan, Alvin; Koster, Jan; Volckmann, Richard; Sluis, Peter van; Ora, Ingrid; Versteeg, Rogier; Geerts, Dirk

    2008-02-15

    Neuroblastoma is an embryonal tumour of the peripheral sympathetic nervous system (SNS). One of the master regulator genes for peripheral SNS differentiation, the homeobox transcription factor PHOX2B, is mutated in familiar and sporadic neuroblastomas. Here we report that inducible expression of PHOX2B in the neuroblastoma cell line SJNB-8 down-regulates MSX1, a homeobox gene important for embryonic neural crest development. Inducible expression of MSX1 in SJNB-8 caused inhibition of both cell proliferation and colony formation in soft agar. Affymetrix micro-array and Northern blot analysis demonstrated that MSX1 strongly up-regulated the Delta-Notch pathway genes DLK1, NOTCH3, and HEY1. In addition, the proneural gene NEUROD1 was down-regulated. Western blot analysis showed that MSX1 induction caused cleavage of the NOTCH3 protein to its activated form, further confirming activation of the Delta-Notch pathway. These experiments describe for the first time regulation of the Delta-Notch pathway by MSX1, and connect these genes to the PHOX2B oncogene, indicative of a role in neuroblastoma biology. Affymetrix micro-array analysis of a neuroblastic tumour series consisting of neuroblastomas and the more benign ganglioneuromas showed that MSX1, NOTCH3 and HEY1 are more highly expressed in ganglioneuromas. This suggests a block in differentiation of these tumours at distinct developmental stages or lineages.

  1. Structural and Biochemical Basis for the Binding Selectivity of Peroxisome Proliferator-activated Receptor [gamma] to PGC-1[alpha

    SciTech Connect

    Li, Yong; Kovach, Amanda; Suino-Powell, Kelly; Martynowski, Dariusz; Xu, H. Eric

    2008-07-23

    The functional interaction between the peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and its coactivator PGC-1{alpha} is crucial for the normal physiology of PPAR{gamma} and its pharmacological response to antidiabetic treatment with rosiglitazone. Here we report the crystal structure of the PPAR{gamma} ligand-binding domain bound to rosiglitazone and to a large PGC-1{alpha} fragment that contains two LXXLL-related motifs. The structure reveals critical contacts mediated through the first LXXLL motif of PGC-1{alpha} and the PPAR{gamma} coactivator binding site. Through a combination of biochemical and structural studies, we demonstrate that the first LXXLL motif is the most potent among all nuclear receptor coactivator motifs tested, and only this motif of the two LXXLL-related motifs in PGC-1{alpha} is capable of binding to PPAR{gamma}. Our studies reveal that the strong interaction of PGC-1{alpha} and PPAR{gamma} is mediated through both hydrophobic and specific polar interactions. Mutations within the context of the full-length PGC-1{alpha} indicate that the first PGC-1{alpha} motif is necessary and sufficient for PGC-1{alpha} to coactivate PPAR{gamma} in the presence or absence of rosiglitazone. These results provide a molecular basis for specific recruitment and functional interplay between PPAR{gamma} and PGC-1{alpha} in glucose homeostasis and adipocyte differentiation.

  2. Mississippi Delta

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The Mississippi River delta teems with sediment deposited by the river as it flows into the Gulf of Mexico in this true-color image captured by MODIS on October 15, 2001. The sediment, which is marked by brown swirls in the Gulf, provides nutrients for the bloom of phytoplankton visible as blue-green swirls off the coastline. In the high-resolution image the city of Memphis can be seen in the southwest corner of Tennessee, which is just to left of center at the top of the image. The brown coloration that encompasses Memphis and either side of the river, as flows north to south along the left side of the image, is the river's flood plain. Also visible, in the upper-right hand corner of the image is the southern end of the Appalachian Mountains.

  3. Prompt gamma neutron activation analysis of toxic elements in radioactive waste packages.

    PubMed

    Ma, J-L; Carasco, C; Perot, B; Mauerhofer, E; Kettler, J; Havenith, A

    2012-07-01

    The French Alternative Energies and Atomic Energy Commission (CEA) and National Radioactive Waste Management Agency (ANDRA) are conducting an R&D program to improve the characterization of long-lived and medium activity (LL-MA) radioactive waste packages. In particular, the amount of toxic elements present in radioactive waste packages must be assessed before they can be accepted in repository facilities in order to avoid pollution of underground water reserves. To this aim, the Nuclear Measurement Laboratory of CEA-Cadarache has started to study the performances of Prompt Gamma Neutron Activation Analysis (PGNAA) for elements showing large capture cross sections such as mercury, cadmium, boron, and chromium. This paper reports a comparison between Monte Carlo calculations performed with the MCNPX computer code using the ENDF/B-VII.0 library and experimental gamma rays measured in the REGAIN PGNAA cell with small samples of nickel, lead, cadmium, arsenic, antimony, chromium, magnesium, zinc, boron, and lithium to verify the validity of a numerical model and gamma-ray production data. The measurement of a ∼20kg test sample of concrete containing toxic elements has also been performed, in collaboration with Forschungszentrum Jülich, to validate the model in view of future performance studies for dense and large LL-MA waste packages. PMID:22406218

  4. Biochemical composition and antioxidant activities of Arthrospira (Spirulina) platensis in response to gamma irradiation.

    PubMed

    Shabana, Effat Fahmy; Gabr, Mahmoud Ali; Moussa, Helal Ragab; El-Shaer, Enas Ali; Ismaiel, Mostafa M S

    2017-01-01

    Arthrospira (Spirulina) platensis is a blue-green alga, rich with bioactive components and nutrients. To evaluate effect of gamma irradiation, A. platensis was exposed to different doses of 0.0, 0.5, 1.0, 1.5, 2.0 and 2.5kGy. The data showed that the phenolic and proline contents significantly increased with the increase of gamma irradiation doses up to 2.0kGy, above which a reduction was observed. The soluble proteins and malondialdehyde (MDA) contents were stimulated by all tested irradiation doses. Furthermore, the vitamins (A, K and B group) and mineral contents (N, P, Na, K, Ca, Mg and Fe) were stimulated by the irradiation doses compared with the control. The activities of some N-assimilating and antioxidant enzymes were significantly increased with the irradiation doses up to 2.0kGy. This study suggests the possible use of gamma irradiation as a stimulatory agent to raise the nutritive value and antioxidant activity of A. platensis. PMID:27507509

  5. Determination of boron in materials by cold neutron prompt gamma-ray activation analysis.

    PubMed

    Paul, Rick L

    2005-01-01

    An instrument for cold neutron prompt gamma-ray activation analysis (PGAA), located at the NIST Center for Neutron Research (NCNR), has proven useful for the measurement of boron in a variety of materials. Neutrons, moderated by passage through liquid hydrogen at 20 K, pass through a (58)Ni coated guide to the PGAA station in the cold neutron guide hall of the NCNR. The thermal equivalent neutron fluence rate at the sample position is 9 x 10(8) cm(-2) s(-1). Prompt gamma rays are measured by a cadmium- and lead-shielded high-purity germanium detector. The instrument has been used to measure boron mass fractions in minerals, in NIST SRM 2175 (Refractory Alloy MP-35-N) for certification of boron, and most recently in semiconductor-grade silicon. The limit of detection for boron in many materials is <10 ng g(-1). PMID:15614360

  6. Stabilization of prompt gamma-ray neutron activation analysis (PGNAA) spectra from NaI detectors

    NASA Astrophysics Data System (ADS)

    Metwally, W. A.; Gardner, R. P.

    2004-06-01

    NaI detectors are still used frequently in industrial Prompt Gamma-Ray Neutron Activation Analysis applications such as in bulk material analysis. They have the advantages of being efficient for high-energy gamma rays, being relatively rugged, and being able to be used without cooling. When using NaI detectors, and consequently photomultiplier tubes, the quality of the data can drastically deteriorate through gain and zero shifts that result in spectral smearing due to temperature and/or counting rate changes. A new offline approach is presented to stabilize the NaI spectral drift. The approach is not sensitive to the cause of the drift and takes into account the NaI and ADC non-linearities. Peak resolution is improved substantially when this approach is used in the presence of spectral drift.

  7. Relativistic particles and gamma-rays in quasars and active galactic nuclei

    NASA Technical Reports Server (NTRS)

    Protheroe, R. J.; Kazanas, D.

    1983-01-01

    A model for a class of quasars and active galactic nuclei is described in which a shock around a massive black hole randomizes the infall kinetic energy of spherically accreting matter producing a nonthermal spectrum of high energy protons. These protons may be responsible for the secondary production (via tau + or - decay) of the radio emitting high energy electrons and also of high energy gamma rays (via Pi decay and inverse Compton interactions of the electrons). The correlation between radio and gamma ray emission implied by the model is in good agreement with observations of 3C273. Observation of the flux of high energy neutrinos from quasars may provide a test for the model.

  8. Relativistic particles and gamma-ray in quasars and active galactic nuclei

    NASA Technical Reports Server (NTRS)

    Protheroe, R. J.; Kazanas, D.

    1982-01-01

    A model for a class of quasars and active galactic nuclei is described in which a shock around a massive black hole randomizes the infall kinetic energy of spherically accreting matter producing a nonthermal spectrum of high energy protons. These protons may be responsible for the secondary production (via tau + or - decay) of the radio emitting high energy electrons and also of high energy gamma rays (via pi decay and inverse Compton interactions of the electrons). The correlation between radio and gamma ray emission implied by the model is in good agreement with observations of 3C273. Observation of the flux of high energy neutrinos from quasars may provide a test for the model.

  9. A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation.

    PubMed

    Wright, H M; Clish, C B; Mikami, T; Hauser, S; Yanagi, K; Hiramatsu, R; Serhan, C N; Spiegelman, B M

    2000-01-21

    While searching for natural ligands for the peroxisome proliferator-activated receptor (PPAR) gamma, we identified a synthetic compound that binds to this receptor. Bisphenol A diglycidyl ether (BADGE) is a ligand for PPARgamma with a K(d(app)) of 100 microM. This compound has no apparent ability to activate the transcriptional activity of PPARgamma; however, BADGE can antagonize the ability of agonist ligands such as rosiglitazone to activate the transcriptional and adipogenic action of this receptor. BADGE also specifically blocks the ability of natural adipogenic cell lines such as 3T3-L1 and 3T3-F442A cells to undergo hormone-mediated cell differentiation. These results provide the first pharmacological evidence that PPARgamma activity is required for the hormonally induced differentiation of adipogenic cells. PMID:10636887

  10. Peroxisome proliferator-activated receptor {gamma} is expressed in hippocampal neurons and its activation prevents {beta}-amyloid neurodegeneration: role of Wnt signaling

    SciTech Connect

    Inestrosa, Nibaldo C. . E-mail: ninestr@genes.bio.puc.cl; Godoy, Juan A.; Quintanilla, Rodrigo A.; Koenig, Cecilia S.; Bronfman, Miguel

    2005-03-10

    The molecular pathogenesis of Alzheimer's disease (AD) involves the participation of the amyloid-{beta}-peptide (A{beta}), which plays a critical role in the neurodegeneration that triggers the disease. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, which are members of the nuclear receptor family. We report here that (1) PPAR{gamma} is present in rat hippocampal neurons in culture. (2) Activation of PPAR{gamma} by troglitazone and rosiglitazone protects rat hippocampal neurons against A{beta}-induced neurodegeneration, as shown by the 3-[4,5 -2yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay, immunofluorescence using an anti-heavy neurofilament antibody, and quantitative electron microscopy. (3) Hippocampal neurons treated with several PPAR{gamma} agonists, including troglitazone, rosiglitazone, and ciglitazone, prevent the excitotoxic A{beta}-induced rise in bulk-free Ca{sup 2+}. (4) PPAR{gamma} activation results in the modulation of Wnt signaling components, including the inhibition of glycogen synthase kinase-3{beta} (GSK-3{beta}) and an increase of the cytoplasmic and nuclear {beta}-catenin levels. We conclude that the activation of PPAR{gamma} prevents A{beta}-induced neurodegeneration by a mechanism that may involve a cross talk between neuronal PPAR{gamma} and the Wnt signaling pathway. More important, the fact that the activation of PPAR{gamma} attenuated A{beta}-dependent neurodegeneration opens the possibility to fight AD from a new therapeutic perspective.

  11. Activation of mutant protein kinase C{gamma} leads to aberrant sequestration and impairment of its cellular function

    SciTech Connect

    Doran, Graeme; Davies, Kay E.; Talbot, Kevin

    2008-08-01

    Mutations in protein kinase C{gamma} (PKC{gamma}) cause the neurodegenerative disease spinocerebellar ataxia type 14 (SCA14). In this study, expression of an extensive panel of known SCA14-associated PKC{gamma} mutations as fusion proteins in cell culture led to the consistent formation of cytoplasmic aggregates in response to purinoceptor stimulation. Aggregates co-stained with antibodies to phosphorylated PKC{gamma} and the early endosome marker EEA1 but failed to redistribute to the cell membrane under conditions of oxidative stress. These studies suggest that Purkinje cell damage in SCA14 may result from a reduction of PKC{gamma} activity due its aberrant sequestration in the early endosome compartment.

  12. Search for gamma-ray-emitting active galactic nuclei in the Fermi-LAT unassociated sample using machine learning

    SciTech Connect

    Doert, M.; Errando, M. E-mail: errando@astro.columbia.edu

    2014-02-10

    The second Fermi-LAT source catalog (2FGL) is the deepest all-sky survey available in the gamma-ray band. It contains 1873 sources, of which 576 remain unassociated. Machine-learning algorithms can be trained on the gamma-ray properties of known active galactic nuclei (AGNs) to find objects with AGN-like properties in the unassociated sample. This analysis finds 231 high-confidence AGN candidates, with increased robustness provided by intersecting two complementary algorithms. A method to estimate the performance of the classification algorithm is also presented, that takes into account the differences between associated and unassociated gamma-ray sources. Follow-up observations targeting AGN candidates, or studies of multiwavelength archival data, will reduce the number of unassociated gamma-ray sources and contribute to a more complete characterization of the population of gamma-ray emitting AGNs.

  13. Hepatitis B Virus HBx Activates Notch Signaling via Delta-Like 4/Notch1 in Hepatocellular Carcinoma

    PubMed Central

    Kongkavitoon, Pornrat; Tangkijvanich, Pisit; Hirankarn, Nattiya; Palaga, Tanapat

    2016-01-01

    Hepatitis virus B (HBV) infection is one of the major causes of hepatocellular carcinomas (HCC). HBx protein encoded in HBV genome is one of the key viral factors leading to malignant transformation of infected cells. HBx functions by interfering with cellular functions, causing aberration in cellular behaviour and transformation. Notch signalling is a well-conserved pathway involved in cellular differentiation, cell survival and cell death operating in various types of cells. Aberration in the Notch signalling pathways is linked to various tumors, including HCC. The role of HBx on the Notch signalling in HCC, however, is still controversial. In this study, we reported that HBV genome-containing HCC cell line HepG2 (HepG2.2.15) expressed higher Notch1 and Delta-like 4 (Dll4), compared to the control HepG2 without HBV genome. This upregulation coincided with increased appearance of the cleavage of Notch1, indicating constitutively activated Notch signalling. Silencing of HBx specifically reduced the level of Dll4 and cleaved Notch1. The increase in Dll4 level was confirmed in clinical specimens of HCC lesion, in comparison with non-tumor lesions. Using specific signalling pathway inhibitors, we found that MEK1/2, PI3K/AKT and NF-κB pathways are critical for HBx-mediated Dll4 upregulation. Silencing of HBx clearly decreased the level of phosphorylation of Akt and Erk1/2. Upon silencing of Dll4 in HepG2.2.15, decreased cleaved Notch1, increased apoptosis and cell cycle arrest were observed, suggesting a critical role of HBx-Dll4-Notch1 axis in regulating cell survival in HCC. Furthermore, clonogenic assay confirmed the important role of Dll4 in regulating cell survival of HBV-genome containing HCC cell line. Taken together, we reported a link between HBx and the Notch signalling in HCC that affects cell survival of HCC, which can be a potential target for therapy. PMID:26766040

  14. In vitro activation of a transcription factor by gamma interferon requires a membrane-associated tyrosine kinase and is mimicked by vanadate.

    PubMed Central

    Igarashi, K; David, M; Larner, A C; Finbloom, D S

    1993-01-01

    Gamma interferon (IFN-gamma) activates the formation of a DNA-binding protein complex (FcRF gamma) that recognizes the gamma response region (GRR) of the promoter for the human high-affinity Fc gamma receptor. In a membrane-enriched fraction prepared from human peripheral blood monocytes, IFN-gamma activation of FcRF gamma occurred within 1 min and was ATP dependent. Activation of FcRF gamma required a tyrosine kinase activity, and recognition of the GRR sequence by FcRF gamma could be abrogated by treatment with a tyrosine-specific protein phosphatase. Treatment of cells with vanadate alone resulted in the formation of FcRF gamma without the need for IFN-gamma. UV cross-linking and antibody competition experiments demonstrated that the FcRF gamma complex was composed of at least two components: the 91-kDa protein of the IFN-alpha-induced transcription complex ISGF3 and a 43-kDa component that bound directly to the GRR. Therefore, specificity for IFN-induced transcriptional activation of early response genes requires at least two events: (i) ligand-induced activation of membrane-associated protein by tyrosine phosphorylation and (ii) formation of a complex composed of an activated membrane protein(s) and a sequence-specific DNA-binding component. Images PMID:8321205

  15. Diminished self-chaperoning activity of the DeltaF508 mutant of CFTR results in protein misfolding.

    PubMed

    Serohijos, Adrian W R; Hegedus, Tamás; Riordan, John R; Dokholyan, Nikolay V

    2008-02-01

    The absence of a functional ATP Binding Cassette (ABC) protein called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) from apical membranes of epithelial cells is responsible for cystic fibrosis (CF). Over 90% of CF patients carry at least one mutant allele with deletion of phenylalanine at position 508 located in the N-terminal nucleotide binding domain (NBD1). Biochemical and cell biological studies show that the DeltaF508 mutant exhibits inefficient biosynthetic maturation and susceptibility to degradation probably due to misfolding of NBD1 and the resultant misassembly of other domains. However, little is known about the direct effect of the Phe508 deletion on the NBD1 folding, which is essential for rational design strategies of cystic fibrosis treatment. Here we show that the deletion of Phe508 alters the folding dynamics and kinetics of NBD1, thus possibly affecting the assembly of the complete CFTR. Using molecular dynamics simulations, we find that meta-stable intermediate states appearing on wild type and mutant folding pathways are populated differently and that their kinetic accessibilities are distinct. The structural basis of the increased misfolding propensity of the DeltaF508 NBD1 mutant is the perturbation of interactions in residue pairs Q493/P574 and F575/F578 found in loop S7-H6. As a proof-of-principle that the S7-H6 loop conformation can modulate the folding kinetics of NBD1, we virtually design rescue mutations in the identified critical interactions to force the S7-H6 loop into the wild type conformation. Two redesigned NBD1-DeltaF508 variants exhibited significantly higher folding probabilities than the original NBD1-DeltaF508, thereby partially rescuing folding ability of the NBD1-DeltaF508 mutant. We propose that these observed defects in folding kinetics of mutant NBD1 may also be modulated by structures separate from the 508 site. The identified structural determinants of increased misfolding propensity of NBD1-DeltaF508

  16. Spectral evolution of active galactic nuclei: A unified description of the X-ray and gamma

    NASA Technical Reports Server (NTRS)

    Leiter, D.; Boldt, E.

    1982-01-01

    A model for spectral evolution is presented whereby active galactic nuclei (AGN) of the type observed individually emerge from an earlier stage at z approx = 4 in which they are the thermal X-ray sources responsible for most of the cosmic X-ray background (CXB). The conjecture is pursued that these precursor objects are initially supermassive Schwarzschild black holes with accretion disks radiating near the Eddington luminosity limit. It is noted that after approx. 10 to the 8th power years these central black holes are spun-up to a canonical Kerr equilibrium state (A/M = 0.998; Thorne 1974) and shown how they then can lead to spectral evolution involving non-thermal emission extending to gamma rays, at the expense of reduced thermal disk radiation. That major portion of the CXB remaining after the contribution of usual AGN are considered, while a superposition of AGN sources at z 1 can account for the gamma ray background. Extensive X-ray measurements carried out with the HEAO 1 and 2 missions as well as gamma ray and optical data are shown to compare favorably with principal features of this model.

  17. 15-Deoxy-{delta}{sup 12,14}-prostaglandin J{sub 2} down-regulates CXCR4 on carcinoma cells through PPAR{gamma}- and NF{kappa}B-mediated pathways

    SciTech Connect

    Richard, Cynthia Lee; Lowthers, Erica Lauren; Blay, Jonathan

    2007-10-01

    The chemokine receptor CXCR4 plays a key role in the metastasis of colorectal cancer and its growth at metastatic sites. Here, we have investigated the mechanisms by which CXCR4 on cancer cells might be regulated by eicosanoids present within the colorectal tumor microenvironment. We show that prostaglandins PGE{sub 2}, PGA{sub 2}, PGD{sub 2}, PGJ{sub 2} and 15dPGJ{sub 2} each down-regulates CXCR4 receptor expression on human colorectal carcinoma cells to differing degrees. The most potent of these were PGD{sub 2} and its metabolites PGJ{sub 2} and 15dPGJ{sub 2}. Down-regulation was most rapid with the end-product 15dPGJ{sub 2} and was accompanied by a marked reduction in CXCR4 mRNA. 15dPGJ{sub 2} is known to be a ligand for the nuclear receptor PPAR{gamma}. Down-regulation of CXCR4 was also observed with the PPAR{gamma} agonist rosiglitazone, while 15dPGJ{sub 2}-induced CXCR4 down-regulation was substantially diminished by the PPAR{gamma} antagonists GW9662 and T0070907. These data support the involvement of PPAR{gamma}. However, the 15dPGJ{sub 2} analogue CAY10410, which can act on PPAR{gamma} but which lacks the intrinsic cyclopentenone structure found in 15dPGJ{sub 2}, down-regulated CXCR4 substantially less potently than 15dPGJ{sub 2}. The cyclopentenone grouping is known to inhibit the activity of NF{kappa}B. Consistent with an additional role for NF{kappa}B, we found that the cyclopentenone prostaglandin PGA{sub 2} and cyclopentenone itself could also down-regulate CXCR4. Immunolocalization studies showed that the cellular context was sufficient to trigger a focal nuclear pattern of NF{kappa}B p50 and that 15dPGJ{sub 2} interfered with this p50 nuclear localization. These data suggest that 15dPGJ{sub 2} can down-regulate CXCR4 on cancer cells through both PPAR{gamma} and NF{kappa}B. 15dPGJ{sub 2}, present within the tumor microenvironment, may act to down-regulate CXCR4 and impact upon the overall process of tumor expansion.

  18. GABAB receptor-mediated activation of astrocytes by gamma-hydroxybutyric acid

    PubMed Central

    Gould, Timothy; Chen, Lixin; Emri, Zsuzsa; Pirttimaki, Tiina; Errington, Adam C.; Crunelli, Vincenzo; Parri, H. Rheinallt

    2014-01-01

    The gamma-aminobutyric acid (GABA) metabolite gamma-hydroxybutyric acid (GHB) shows a variety of behavioural effects when administered to animals and humans, including reward/addiction properties and absence seizures. At the cellular level, these actions of GHB are mediated by activation of neuronal GABAB receptors (GABABRs) where it acts as a weak agonist. Because astrocytes respond to endogenous and exogenously applied GABA by activation of both GABAA and GABABRs, here we investigated the action of GHB on astrocytes on the ventral tegmental area (VTA) and the ventrobasal (VB) thalamic nucleus, two brain areas involved in the reward and proepileptic action of GHB, respectively, and compared it with that of the potent GABABR agonist baclofen. We found that GHB and baclofen elicited dose-dependent (ED50: 1.6 mM and 1.3 µM, respectively) transient increases in intracellular Ca2+ in VTA and VB astrocytes of young mice and rats, which were accounted for by activation of their GABABRs and mediated by Ca2+ release from intracellular store release. In contrast, prolonged GHB and baclofen exposure caused a reduction in spontaneous astrocyte activity and glutamate release from VTA astrocytes. These findings have key (patho)physiological implications for our understanding of the addictive and proepileptic actions of GHB. PMID:25225100

  19. Transcriptional regulation of the presenilin-1 gene controls gamma-secretase activity.

    PubMed

    Lee, Sebum; Das, Hriday K

    2010-01-01

    Inhibition of basal JNK activity by JNK inhibitor SP600125 or JNK1siRNA repressed presenilin-1 (PS1) expression in SK-N-SH cells by augmenting the level of p53, a repressor of the PS1 gene (1). We now showed that repression of PS1 transcription by JNK inhibitor SP600125 inhibited gamma-secretase mediated processing of amyloid precursor protein (APP) resulting in the accumulation of C99 fragment and the reduction of secreted Abeta40 level without altering the expression of nicastrin (NCT). Co-treatment of cells with SP600125 and p53 inhibitor, pifithrin-alpha, partially nullified the suppressive effects of SP610025 on PS1 expression and secreted Abeta40 level. Suppression of JNK1 by JNK1siRNA also decreased Abeta40 level. Furthermore, overexpression of the repressors p53, ZNF237 and CHD3 of the PS1 gene also suppressed the processing of APP through repression of PS1 transcription by deacetylation of histone at the PS1 promoter. Transcriptional activator Ets2 increased PS1 protein and secreted Abeta40 levels without affecting the expression of NCT by activating PS1 transcription via hyper-acetylation of histone at the PS1 promoter. Therefore, regulation of PS1 transcription modulates gamma-secretase activity. PMID:20036849

  20. Delta III—an evolutionary delta growth

    NASA Astrophysics Data System (ADS)

    Arvesen, R. J.; Simpson, J. S.

    1996-03-01

    In order to remain competitive in the future and expand the McDonnell Douglas Aerospace market share, MDA has developed an expendable launch system strategy that devices cost-effective launch systems from the Delta II with a growth vehicle configuration called Delta III. The Delta III evolves from the Delta II launch system through development of a larger payload fairing (4-meter diameter), new cryogenically propelled upper stage, new first stage fuel tank, and larger strap-on solid rocket motors. We are developing the Delta III using Integrated Product Development Teams that capitalize on the experience base that has led us to a world record breaking mission success of 49 consecutive Delta II missions. The Delta III first-launch capability is currently planned for the spring of 1998 in support of our first spacecraft customer, Hughes Space and Communications International.

  1. Isohumulones, bitter acids derived from hops, activate both peroxisome proliferator-activated receptor alpha and gamma and reduce insulin resistance.

    PubMed

    Yajima, Hiroaki; Ikeshima, Emiko; Shiraki, Maho; Kanaya, Tomoka; Fujiwara, Daisuke; Odai, Hideharu; Tsuboyama-Kasaoka, Nobuyo; Ezaki, Osamu; Oikawa, Shinichi; Kondo, Keiji

    2004-08-01

    The peroxisome proliferator-activated receptors (PPARs) are dietary lipid sensors that regulate fatty acid and carbohydrate metabolism. The hypolipidemic effects of fibrate drugs and the therapeutic benefits of the thiazolidinedione drugs are due to their activation of PPARalpha and -gamma, respectively. In this study, isohumulones, the bitter compounds derived from hops that are present in beer, were found to activate PPARalpha and -gamma in transient co-transfection studies. Among the three major isohumulone homologs, isohumulone and isocohumulone were found to activate PPARalpha and -gamma. Diabetic KK-Ay mice that were treated with isohumulones (isohumulone and isocohumulone) showed reduced plasma glucose, triglyceride, and free fatty acid levels (65.3, 62.6, and 73.1%, respectively, for isohumulone); similar reductions were found following treatment with the thiazolidinedione drug, pioglitazone. Isohumulone treatment did not result in significant body weight gain, although pioglitazone treatment did increase body weight (10.6% increase versus control group). C57BL/6N mice fed a high fat diet that were treated with isohumulones showed improved glucose tolerance and reduced insulin resistance. Furthermore, these animals showed increased liver fatty acid oxidation and a decrease in size and an increase in apoptosis of their hypertrophic adipocytes. A double-blind, placebo-controlled pilot study for studying the effect of isohumulones on diabetes suggested that isohumulones significantly decreased blood glucose and hemoglobin A1c levels after 8 weeks (by 10.1 and 6.4%, respectively, versus week 0). These results suggest that isohumulones can improve insulin sensitivity in high fat diet-fed mice with insulin resistance and in patients with type 2 diabetes. PMID:15178687

  2. RAPID HETEROLOGOUS DESENSITIZATION OF ANTINOCICEPTIVE ACTIVITY BETWEEN MU OR DELTA OPIOID RECEPTORS AND CHEMOKINE RECEPTORS IN RATS

    PubMed Central

    Chen, Xiaohong; Geller, Ellen B.; Rogers, Thomas J.; Adler, Martin W.

    2007-01-01

    Previous studies have shown pretreatment with chemokines CCL5/RANTES (100 ng) or CXCL12/SDF-1alpha (100 ng) injected into the periaqueductal grey (PAG) region of the brain, 30 minutes (min) before the mu opioid agonist DAMGO (400 ng), blocked the antinociception induced by DAMGO in the in vivo cold water tail-flick (CWT) antinociceptive test in rats. In the present experiments, we tested whether the action of other agonists at mu and delta opioid receptors is blocked when CCL5/RANTES or CXCL12/SDF-1alpha is administered into the PAG 30 min before, or co-administered with, opioid agonists in the CWT assay. The results showed that (1) CXCL12/SDF-1alpha (100 ng, PAG) or CCL5/RANTES (100 ng, PAG), given 30 min before the opioid agonist morphine, or selective delta opioid receptor agonist DPDPE, blocked the antinociceptive effect of these drugs; (2) CXCL12/SDF-1alpha (100 ng, PAG) or CCL5/RANTES (100 ng, PAG), injected at the same time as DAMGO or DPDPE, significantly reduced the antinociceptive effect induced by these drugs. These results demonstrate that the heterologous desensitization is rapid between the mu or delta opioid receptors and either CCL5/RANTES receptor CCR5 or CXCL12/SDF-1alpha receptor CXCR4 in vivo, but the effect is greater if the chemokine is administered before the opioid. PMID:17049756

  3. Stimulatory effects of opioid neuropeptides on locomotory activity and conformational changes in invertebrate and human immunocytes: evidence for a subtype of delta receptor.

    PubMed

    Stefano, G B; Cadet, P; Scharrer, B

    1989-08-01

    The presence of opioid neuropeptides was shown to stimulate conformational changes and locomotory activity in immunocytes of two representatives of invertebrates as well as in human leukocytes. Cells were examined by use of phase-contrast and Nomarski optics coupled with a Zeiss Axiophot microscope, and of the Zeiss Videoplan/Vidas Image Analysis system. Immunocompetent blood cells, activated by exogenous opioids or stressful stimuli presumed to engage endogenous opioids, showed flattening, elongation, and formation of pseudopodia. In the mollusc Mytilus edulis, ameboid movements resulted in the formation of cell clusters, an activity not observed in untreated controls, or in immunocytes simultaneously exposed to opioid and naloxone. Tests with nine immunoreactive substances revealed immunocyte stimulation by delta, mu-, kappa-, and epsilon(?)-selective ligands. One of these, [D-Ala2,D-Met5]enkephalinamide (DAMA), active at a concentration of 10 pM, proved to be considerably more effective than the rest. The high pharmacological potency of DAMA, observed in both human and invertebrate immunocytes, sets this opioid apart from the closely related [D-Ala2,D-Leu5]enkephalin, a discrepancy not occurring in the mammalian nervous system. This suggests a specific function for [Met]enkephalin in immunoregulation, mediated perhaps by a special subtype of delta receptor. PMID:2548205

  4. Gamma-ray-spectroscopy following high-flux 14-MeV neutron activation

    SciTech Connect

    Williams, R.E.

    1981-10-12

    The Rotating Target Neutron Source (RTNS-I), a high-intensity source of 14-MeV neutrons at the Lawrence Livermore National Laboratory (LLNL), has been used for applications in activation analysis, inertial-confinement-fusion diagnostic development, and fission decay-heat studies. The fast-neutron flux from the RTNS-I is at least 50 times the maximum fluxes available from typical neutron generators, making these applications possible. Facilities and procedures necessary for gamma-ray spectroscopy of samples irradiated at the RTNS-I were developed.

  5. In vivo Prompt Gamma Neutron Activation Analysis Facility for Total Body Nitrogen and Cd

    SciTech Connect

    Munive, Marco; Revilla, Angel; Solis, Jose L.

    2007-10-26

    A Prompt Gamma Neutron Activation Analysis (PGNAA) system has been designed and constructed to measure the total body nitrogen and Cd for in vivo studies. An aqueous solution of KNO{sub 3} was used as phantom for system calibration. The facility has been used to monitor total body nitrogen (TBN) of mice and found that is related to their diet. Some mice swallowed diluted water with Cl{sub 2}Cd, and the presence of Cd was detected in the animals. The minimum Cd concentration that the system can detect was 20 ppm.

  6. Functions of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) in Gynecologic Disorders

    PubMed Central

    Ren, Ping; Zhang, Yuquan; Huang, Yan; Yang, Yingli; Jiang, Ming

    2015-01-01

    Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of a class of nuclear hormone receptors intimately involved in the regulation of expression of myriad genes that regulate energy metabolism, cell differentiation, apoptosis, and inflammation. Although originally discovered as a pivotal regulator of adipocyte differentiation, the roles that PPARγ plays in gynecological disorders are still unknown. There are a number of studies on the functions of PPARγ and its agonists in gynecological disorders. In this mini-review, we provide a brief summary of the advances in recent years. PMID:25987855

  7. A novel mouse PKC{delta} splice variant, PKC{delta}IX, inhibits etoposide-induced apoptosis

    SciTech Connect

    Kim, Jung D.; Seo, Kwang W.; Lee, Eun A.; Quang, Nguyen N.; Cho, Hong R.; Kwon, Byungsuk

    2011-07-01

    Highlights: {yields} A novel PKC{delta} isoform, named PKC{delta}IX, that lacks the C1 domain and the ATP-binding site is ubiquitously expressed. {yields} PKC{delta}IX inhibits etoposide-induced apoptosis. {yields} PKC{delta}IX may function as an endogenous dominant negative isoform for PKC{delta}. -- Abstract: Protein kinase C (PKC) {delta} plays an important role in cellular proliferation and apoptosis. The catalytic fragment of PKC{delta} generated by caspase-dependent cleavage is essential for the initiation of etoposide-induced apoptosis. In this study, we identified a novel mouse PKC{delta} isoform named PKC{delta}IX (Genebank Accession No. (HQ840432)). PKC{delta}IX is generated by alternative splicing and is ubiquitously expressed, as seen in its full-length PKC{delta}. PKC{delta}IX lacks the C1 domain, the caspase 3 cleavage site, and the ATP binding site but preserves an almost intact c-terminal catalytic domain and a nuclear localization signal (NLS). The structural characteristics of PKC{delta}IX provided a possibility that this PKC{delta} isozyme functions as a novel dominant-negative form for PKC{delta} due to its lack of the ATP-binding domain that is required for the kinase activity of PKC{delta}. Indeed, overexpression of PKC{delta}IX significantly inhibited etoposide-induced apoptosis in NIH3T3 cells. In addition, an in vitro kinase assay showed that recombinant PKC{delta}IX protein could competitively inhibit the kinase activity of PKC{delta}. We conclude that PKC{delta}IX can function as a natural dominant-negative inhibitor of PKC{delta}in vivo.

  8. Study on antibacterial activity of silver nanoparticles synthesized by gamma irradiation method using different stabilizers

    NASA Astrophysics Data System (ADS)

    Van Phu, Dang; Quoc, Le Anh; Duy, Nguyen Ngoc; Lan, Nguyen Thi Kim; Du, Bui Duy; Luan, Le Quang; Hien, Nguyen Quoc

    2014-04-01

    Colloidal solutions of silver nanoparticles (AgNPs) were synthesized by gamma Co-60 irradiation using different stabilizers, namely polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), alginate, and sericin. The particle size measured from TEM images was 4.3, 6.1, 7.6, and 10.2 nm for AgNPs/PVP, AgNPs/PVA, AgNPs/alginate, and AgNPs/sericin, respectively. The influence of different stabilizers on the antibacterial activity of AgNPs was investigated. Results showed that AgNPs/alginate exhibited the highest antibacterial activity against Escherichia coli ( E. coli) among the as-synthesized AgNPs. Handwash solution has been prepared using Na lauryl sulfate as surfactant, hydroxyethyl cellulose as binder, and 15 mg/L of AgNPs/alginate as antimicrobial agent. The obtained results on the antibacterial test of handwash for the dilution to 3 mg AgNPs/L showed that the antibacterial efficiency against E. coli was of 74.6%, 89.8%, and 99.0% for the contacted time of 1, 3, and 5 min, respectively. Thus, due to the biocompatibility of alginate extracted from seaweed and highly antimicrobial activity of AgNPs synthesized by gamma Co-60 irradiation, AgNPs/alginate is promising to use as an antimicrobial agent in biomedicine, cosmetic, and in other fields.

  9. Identification and functional analysis of the genes encoding Delta6-desaturase from Ribes nigrum.

    PubMed

    Song, Li-Ying; Lu, Wan-Xiang; Hu, Jun; Zhang, Yan; Yin, Wei-Bo; Chen, Yu-Hong; Hao, Shan-Ting; Wang, Bai-Lin; Wang, Richard R-C; Hu, Zan-Min

    2010-06-01

    Gamma-linolenic acid (gamma-linolenic acid, GLA; C18:3 Delta(6, 9, 12)) belongs to the omega-6 family and exists primarily in several plant oils, such as evening primrose oil, blackcurrant oil, and borage oil. Delta(6)-desaturase is a key enzyme involved in the synthesis of GLA. There have been no previous reports on the genes encoding Delta(6)-desaturase in blackcurrant (Ribes nigrum L.). In this research, five nearly identical copies of Delta(6)-desaturase gene-like sequences, named RnD8A, RnD8B, RnD6C, RnD6D, and RnD6E, were isolated from blackcurrant. Heterologous expression in Saccharomyces cerevisiae and/or Arabidopsis thaliana confirmed that RnD6C/D/E were Delta(6)-desaturases that could use both alpha-linolenic acids (ALA; C18:3 Delta(9,12,15)) and linoleic acid (LA; C18:2 Delta(9,12)) precursors in vivo, whereas RnD8A/B were Delta(8)-sphingolipid desaturases. Expression of GFP tagged with RnD6C/D/E showed that blackcurrant Delta(6)-desaturases were located in the mitochondrion (MIT) in yeast and the endoplasmic reticulum (ER) in tobacco. GC-MS results showed that blackcurrant accumulated GLA and octadecatetraenoic acids (OTA; C18:4 Delta(6,9,12,15)) mainly in seeds and a little in other organs and tissues. RT-PCR results showed that RnD6C and RnD6E were expressed in all the tissues at a low level, whereas RnD6D was expressed at a high level only in seeds, leading to the accumulation of GLA and OTA in seeds. This research provides new insights to our understanding of GLA synthesis and accumulation in plants and the evolutionary relationship of this class of desaturases, and new clues as to the amino acid determinants which define precise enzyme activity. PMID:20231328

  10. Measured Activities of Al and Ni in gamma-(Ni) and gamma'-(Ni)3Al in the Ni-Al-Pt System

    NASA Technical Reports Server (NTRS)

    Copland, Evan

    2007-01-01

    Adding Pt to Ni-Al coatings is critical to achieving the required oxidation protection of Ni-based superalloys, but the nature of the Pt effect remains unresolved. This research provides a fundamental part of the answer by measuring the influence of Pt on the activities of Al and Ni in gamma-(Ni), gamma prime-(Ni)3Al and liquid in the Ni-Al-Pt system. Measurements have been made at 25 compositions in the Ni-rich corner over the temperature range, T = 1400-1750 K, by the vapor pressure technique with a multiple effusion-cell mass spectrometer (multi-cell KEMS). These measurements clearly show adding Pt (for X(sub Pt) less than 0.25) decreases a(Al) while increasing a(Ni). This solution behavior supports the idea that Pt increases Al transport to an alloy / Al2O3 interface and also limits the interaction between the coating and substrate alloys in the gamma-(Ni) + gamma prime-(Ni)3Al region. This presentation will review the progress of this study.

  11. Production of interferon-gamma by in vivo tumor-sensitized T cells: Association with active antitumor immunity

    SciTech Connect

    Bursuker, I.; Pearce, M.T. )

    1990-02-01

    The state of active immunity to Meth A fibrosarcoma in mice immunized with an admixture of Meth A cells and Propionibacterium acnes is associated with possession by the host of spleen cells capable of producing interferon-gamma (IFN-gamma) upon in vitro restimulation with irradiated tumor cells. The ability of spleen cells from immunized mice to produce IFN-gamma in response to irradiated Meth A cells decays as active antitumor immunity is replaced by a state of immunological memory. The IFN-producing cells are L3T4+Ly2+, cyclophosphamide-sensitive and radiosensitive T cells, as determined by their sensitivity to corresponding monoclonal antibodies and complement. The induction of IFN-gamma production by in vivo tumor-sensitized T cells is tumor specific, in that spleen cells from mice immunized against Meth A fibrosarcoma can produce IFN in response to irradiated Meth A cells but not in response to another syngeneic tumor M109 lung carcinoma.

  12. Radiation does from medical in-vivo prompt gamma-ray activation using a mobile nuclear reactor.

    PubMed

    Chung, C; Chen, C P; Chang, P S

    1988-10-01

    A method of medical diagnosis of toxic elements, using a neutron beam from a mobile nuclear reactor to perform partial-body in-vivo prompt gamma-ray activation technique, has been developed. Both neutron and gamma-ray dose equivalents in an irradiated phantom and around medical researchers were measured and evaluated. Neutron flux at various kinetic energies was measured using an activation foil technique, and the neutron dose equivalents at tissues of risk inside the irradiated phantom were calculated by neutron transport code. Gamma-ray dose equivalents inside the irradiated phantom and around the nuclear reactor were measured by thermoluminescent dosimeters. The risk associated with the neutron and gamma radiation dose equivalents received by both the irradiated phantom and medical researchers were evaluated in detail. The radiation safety of the in-vivo medical diagnosis using the mobile nuclear reactor, under the context of radiation protection guidelines, is discussed. PMID:3170218

  13. Gamma irradiation induced disintegration of waste activated sludge for biological hydrogen production

    NASA Astrophysics Data System (ADS)

    Yin, Yanan; Wang, Jianlong

    2016-04-01

    In this paper, gamma irradiation was applied for the disintegration and dissolution of waste activated sludge produced during the biological wastewater treatment, and the solubilized sludge was used as substrate for bio-hydrogen production. The experimental results sho