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Sample records for alpha 2-macroglobulin implications

  1. Alpha-2-Macroglobulin Is Acutely Sensitive to Freezing and Lyophilization: Implications for Structural and Functional Studies.

    Directory of Open Access Journals (Sweden)

    Amy R Wyatt

    Full Text Available Alpha-2-macroglobulin is an abundant secreted protein that is of particular interest because of its diverse ligand binding profile and multifunctional nature, which includes roles as a protease inhibitor and as a molecular chaperone. The activities of alpha-2-macroglobulin are typically dependent on whether its conformation is native or transformed (i.e. adopts a more compact conformation after interactions with proteases or small nucleophiles, and are also influenced by dissociation of the native alpha-2-macroglobulin tetramer into stable dimers. Alpha-2-macroglobulin is predominately present as the native tetramer in vivo; once purified from human blood plasma, however, alpha-2-macroglobulin can undergo a number of conformational changes during storage, including transformation, aggregation or dissociation. We demonstrate that, particularly in the presence of sodium chloride or amine containing compounds, freezing and/or lyophilization of alpha-2-macroglobulin induces conformational changes with functional consequences. These conformational changes in alpha-2-macroglobulin are not always detected by standard native polyacrylamide gel electrophoresis, but can be measured using bisANS fluorescence assays. Increased surface hydrophobicity of alpha-2-macroglobulin, as assessed by bisANS fluorescence measurements, is accompanied by (i reduced trypsin binding activity, (ii increased chaperone activity, and (iii increased binding to the surfaces of SH-SY5Y neurons, in part, via lipoprotein receptors. We show that sucrose (but not glycine effectively protects native alpha-2-macroglobulin from denaturation during freezing and/or lyophilization, thereby providing a reproducible method for the handling and long-term storage of this protein.

  2. Primary structure of human alpha 2-macroglobulin. V. The complete structure

    DEFF Research Database (Denmark)

    Sottrup-Jensen, Lars; Stepanik, Terrence M; Kristensen, Torsten

    1984-01-01

    The primary structure of the tetrameric plasma glycoprotein human alpha 2-macroglobulin has been determined. The identical subunits contain 1451 amino acid residues. Glucosamine-based oligosaccharide groups are attached to asparagine residues 32, 47, 224, 373, 387, 846, 968, and 1401. Eleven......-SH group of Cys-949 is thiol esterified to the gamma-carbonyl group of Glx-952, thus forming an activatable reactive site which can mediate covalent binding of nucleophiles. A putative transglutaminase cross-linking site is constituted by Gln-670 and Gln-671. The primary sites of proteolytic cleavage......-macroglobulin subunit is discussed. A comparison of stretches of sequences from alpha 2-macroglobulin with partial sequence data for complement components C3 and C4 indicates that these proteins are evolutionary related. The properties of alpha 2-macroglobulin are discussed within the context of proteolytically...

  3. Characterization of binding of human alpha 2-macroglobulin to group G streptococci

    International Nuclear Information System (INIS)

    Chhatwal, G.S.; Mueller, H.P.; Blobel, H.

    1983-01-01

    An interaction was observed between human alpha 2-macroglobulin (alpha 2M) and streptococci belonging to group A, C, and G. Of 27 group C and 19 group G streptococcal cultures, 13 and 14, respectively, bound 125 I-labeled alpha 2M. Some group A streptococci also interacted with alpha 2M. A number of other bacterial species tested did not react with alpha 2M. The binding of 125 I-labeled alpha 2M to group G streptococci was time dependent, saturable, and could be inhibited by unlabeled alpha 2M. Inhibition experiments indicated that the streptococcal binding site for alpha 2M differed from the receptors for immunoglobulin G, fibrinogen, aggregated beta 2-microglobulin, albumin, and fibronectin. The alpha 2M binding activity was remarkably sensitive to trypsin and heat treatment indicating its protein nature. Kinetic analysis indicated a homogenous population of binding sites. The number of binding sites per bacterial cell was estimated to be approximately 20,000

  4. Individual levels of plasma alpha 2-antiplasmin and alpha 2-macroglobulin during the normal menstrual cycle and in women on oral contraceptives low in oestrogen

    DEFF Research Database (Denmark)

    Jespersen, J; Sidelmann, Johannes Jakobsen

    1983-01-01

    Determinations of alpha 2-antiplasmin and alpha 2-macroglobulin were made in plasma samples collected during one normal or hormone induced cycle in 15 normal women and 11 women using oral contraceptives containing 30 micrograms ethinyl oestradiol and 150 micrograms levo-norgestrel. The immediate ...

  5. Mannan-binding protein forms complexes with alpha-2-macroglobulin. A protein model for the interaction

    DEFF Research Database (Denmark)

    Storgaard, P; Holm Nielsen, E; Skriver, E

    1995-01-01

    We report that alpha-2-macroglobulin (alpha 2M) can form complexes with a high molecular weight porcine mannan-binding protein (pMBP-28). The alpha 2M/pMBP-28 complexes was isolated by PEG-precipitation and affinity chromatography on mannan-Sepharose, protein A-Sepharose and anti-IgM Sepharose......-PAGE, which reacted with antibodies against alpha 2M and pMBP-28, respectively, in Western blotting. Furthermore, alpha 2M/pMBP-28 complexes were demonstrated by electron microscopy. Fractionation of pMBP-containing D-mannose eluate from mannan-Sepharose on Superose 6 showed two protein peaks which reacted...... with anti-C1 s antibodies in ELISA, one of about 650-800 kDa, which in addition contained pMBP-28 and anti-alpha 2M reactive material, the other with an M(r) of 100-150 kDa. The latter peak revealed rhomboid molecules (7 x 15 nm) in the electron microscope and a 67 kDa band in SDS-PAGE under reducing...

  6. Human alpha2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3.

    Science.gov (United States)

    Doan, Ninh; Gettins, Peter G W

    2007-10-01

    Human alpha2M (alpha2-macroglobulin) and the complement components C3 and C4 are thiol ester-containing proteins that evolved from the same ancestral gene. The recent structure determination of human C3 has allowed a detailed prediction of the location of domains within human alpha2M to be made. We describe here the expression and characterization of three alpha(2)M domains predicted to be involved in the stabilization of the thiol ester in native alpha2M and in its activation upon bait region proteolysis. The three newly expressed domains are MG2 (macroglobulin domain 2), TED (thiol ester-containing domain) and CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain. Together with the previously characterized RBD (receptor-binding domain), they represent approx. 42% of the alpha2M polypeptide. Their expression as folded domains strongly supports the predicted domain organization of alpha2M. An X-ray crystal structure of MG2 shows it to have a fibronectin type-3 fold analogous to MG1-MG8 of C3. TED is, as predicted, an alpha-helical domain. CUB is a spliced domain composed of two stretches of polypeptide that flank TED in the primary structure. In intact C3 TED interacts with RBD, where it is in direct contact with the thiol ester, and with MG2 and CUB on opposite, flanking sides. In contrast, these alpha2M domains, as isolated species, show negligible interaction with one another, suggesting that the native conformation of alpha2M, and the consequent thiol ester-stabilizing domain-domain interactions, result from additional restraints imposed by the physical linkage of these domains or by additional domains in the protein.

  7. Fast form alpha-2-macroglobulin

    DEFF Research Database (Denmark)

    Biltoft, Daniel; Gram, Jørgen Brodersen; Larsen, Anette

    2017-01-01

    Objectives: Investigation of the blood compatibility requires a number of sensitive assays to quantify the activation of the blood protein cascades and cells induced by biomaterials. A global assay measuring the blood compatibility of biomaterials could be a valuable tool in such regard....... In this study, we investigated whether an enzyme-linked immunosorbent assay (ELISA), that specifically measures the electrophoretic "fast form" of α2-macroglobulin (F-α2M), could be a sensitive and global marker for activation of calcium dependent and in-dependent proteases in plasma exposed to biomaterials...... in vitro. Methods: A F-α2M specific monoclonal antibody was generated and applied in an ELISA setup. Using the F-α2M ELISA, we investigated activation of calcium dependent and in-dependent proteases by polyvinylchloride (n=10), polytetrafluoroethylene (n=10) and silicone (n=10) tubings as well as glass...

  8. Kinetics of the urea-induced dissociation of human plasma alpha-2-macroglobulin as measured by small-angle neutron scattering

    DEFF Research Database (Denmark)

    Sjöberg, B.; Pap, S.; Järnberg, S.-E.

    1991-01-01

    The kinetics of the urea-induced dissociation of human plasma alpha-2-macroglobulin into two half-molecular fragments was investigated at 21.0-degrees-C by using small-angle neutron scattering. The relative change in molecular mass that occurs upon dissociation was monitored by recording the forw...

  9. The rat acute-phase protein {alpha}{sub 2}-macroglobulin plays a central role in amifostine-mediated radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Mirjana, Mihailovic; Goran, Poznanovic; Nevena, Grdovic; Melita, Vidakovic; Svetlana, Dinic; Ilijana, Grigorov; Desanka, Bogojevic, E-mail: mista@ibiss.bg.ac.r [Department of Molecular Biology, Institute for Biological Research ' Sinisa Stankovic' , University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade (Serbia)

    2010-09-15

    Previously we reported that elevated circulating concentrations of the acute-phase (AP) protein {alpha}{sub 2}-macroglobulin ({alpha}{sub 2}M), either as typically occurring in pregnant female rats or after administration to male rats, provides radioprotection, displayed as 100% survival of experimental animals exposed to total-body irradiation with 6.7 Gy (LD{sub 50/30}) x-rays, that is as effective as that afforded by the synthetic radioprotector amifostine. The finding that amifostine administration induces a 45-fold increase in {alpha}{sub 2}M in the circulation led us to hypothesise that {alpha}{sub 2}M assumes an essential role in both natural and amifostine-mediated radioprotection in the rat. In the present work we examined the activation of cytoprotective mechanisms in rat hepatocytes after the exogenous administration of {alpha}{sub 2}M and amifostine. Our results showed that the IL6/JAK/STAT3 hepatoprotective signal pathway, described in a variety of liver-injury models, upregulated the {alpha}{sub 2}M gene in amifostine-pretreated animals. In both {alpha}{sub 2}M- and amifostine-pretreated rats we observed the activation of the Akt signalling pathways that mediate cellular survival. At the cellular level this was reflected as a significant reduction of irradiation-induced DNA damage that allowed for the rapid and complete restoration of liver mass and ultimately at the level of the whole organism the complete restoration of body weight. We conclude that the selective upregulation of {alpha}{sub 2}M plays a central role in amifostine-provided radioprotection.

  10. Active MMPs captured by alpha2Macroglobulin as a marker of disease activity in rheumatoid arthritis

    NARCIS (Netherlands)

    Tchetverikov, I.; Verzijl, N.; Huizinga, T.W.J.; TeKoppele, J.M.; Hanemaaijer, R.; Groot, J. de

    2003-01-01

    Objective. The aim of the present study was to analyze α2Macroglobulin/MMP (α2M/MMP) complex formation and to investigate whether MMP activity in α2M/MMP complexes in serum can be used as a disease marker in rheumatoid arthritis (RA). Methods. High and low molecular weight (H/LMW) substrates and

  11. Determination of the synthesis of uptake of α2-macroglobulin by cultured human glioma cells

    International Nuclear Information System (INIS)

    Druskova, E.; Bizik, J.; Grofova, M.

    1994-01-01

    Using immunological techniques, the synthesis of α 2 -macroglobulin was studied in established cell lines derived from human glioblastomas multiform. α 2 -Macroglobulin was detected in cytoplasm and in the culture medium of the analyzed cell lines. Radioimmunoprecipitation, revealed a protein with Mr corresponding to α 2 -macroglobulin in the medium conditioned by U-118MG and U-343MG cells. On the other hand, using immunoblot analysis, α 2 -macroglobulin was detected in all of the analyzed lines. In immunofluorescence test, α 2 -macroglobulin was determined also in all four cell lines, but with different staining pattern. Conditioned culture medium of U-536MG cells with the lowest level of α 2 -macroglobulin exerted the lowest mitogenic activity for human fibroblasts. (author)

  12. Identification of A/sub 1/ macroglobulin and A/sub 2/ macroglobulin in rat serum by a two-dimensional quantitative immunoelectrophoresis with intermediate gel

    Energy Technology Data Exchange (ETDEWEB)

    Chlebovska, K; Chlebovsky, O [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Katedra Vseobecnej Biologie; Simsa, J [Vojensky Lekarsky Vyzkumny a Doskolovaci Ustav J.E. Purkyne, Hradec Kralove (Czechoslovakia)

    1978-08-01

    A/sub 1/ macroglobulin was identified in rat serum by two-dimensional quantitative immunoelectrophoresis with intermediate gel containing monovalent anti-A/sub 1/M rat serum. A second serum macroglobulin A/sub 2/M antigenically related to A/sub 1/M was identified in turpentine-stimulated or irradiated rats.

  13. Alpha-2-Macroglobulin Levels in Gingival Crevicular Fluid Pre- and Post-scaling and Root Planing with Adjunctive Tetracycline Fibers in Chronic Periodontitis: A Randomized Controlled Trial.

    Science.gov (United States)

    Chhina, Shivjot; Rathore, Ajit Singh; Juneja, Saurabh

    2015-06-01

    This split-mouth clinical study aimed to investigate levels of alpha-2-macroglobulin (a2M) in gingival crevicular fluid (GCF) of chronic periodontitis patients pre- and post-scaling and root planing (SRP) with or without adjunctive use of tetracycline fibers. In 30 patients of chronic periodontitis, samples of GCF were collected from the gingival sulcus before SRP. Recording of clinical parameters was conducted. This was followed by local drug delivery (LDD) of tetracycline fibers in test sites. In control sites, no LDD was done. Second samples of GCF were taken 90 days after treatment. Samples of crevicular fluid were analyzed to determine the levels of a2m. A gain of clinical attachment (CAL) of 3.30 mm for SRP and LDD and for SRP alone was 1.62 mm (p chronic periodontitis.

  14. Purification, characterization and molecular cloning of alpha-2-macroglobulin in cobia, Rachycentron canadum.

    Science.gov (United States)

    Chuang, Wen-Hsiao; Liu, Ping-Chung; Hung, Chia-Yu; Lee, Kuo-Kau

    2014-12-01

    Alpha-2-macroglobulin (α-2-M) is a broad spectrum protease inhibitor which is abundant in the plasma of vertebrates and several invertebrates. The α-2-M was purified from cobia (Rachycentron canadum) plasma by a four-step procedure: poly ethylene glycol fractionation, affinity chromatography, hydrophobic interaction chromatography and ion exchange chromatography on Fast Protein liquid chromatography system in the present study. It migrated as one protein band with a molecular mass of about 360 kDa in the native state, whereas in SDS-PAGE it was about 180 kDa under non-reducing condition. This result revealed that the native protein was a dimer. In addition, it was cleaved into two different fragments of molecular mass about 93 and 87 kDa when reduced by dithiothreitol (DTT). The anti-protease activity of the purified α-2-M was apparently decreased as temperature elevated above 50 °C. The α-2-M exhibited highest protease inhibitory activity at pH 9. The results indicate that the α-2-M is a heat-labile and alkaline protease inhibitor. The purified α-2-M exhibited more than 50% protease inhibitory activity against extracellular products (ECP) of Vibrio alginolytius isolated from diseased cobia. It seems that the protease activities in ECP may be affected by the plasma α-2-M. The protease inhibitory activities of cobia plasma or purified α-2-M were decreased when incubated with 10 mM methylamine for 30 min. The α-2-M cDNA consisted of 4611 bp with an open reading frame of 4374 bp had been cloned from cobia liver. This sequence contained thioester domain (GCGEQ) and thirteen predicted N-linked glycosylation sites. In addition, the amino acid sequence of thioester domain and genes of adjacent regions of cobia α-2-M were further compared with sequences of known fish species in GenBank. The unweighted pair group method using arithmetic average (UPGMA) was employed to construct the phylogenetic trees of α-2-M among different fish species (freshwater fish, sea

  15. Structure of protease-cleaved Escherichia coli α-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment

    International Nuclear Information System (INIS)

    Fyfe, Cameron D.; Grinter, Rhys; Josts, Inokentijs; Mosbahi, Khedidja; Roszak, Aleksander W.; Cogdell, Richard J.; Wall, Daniel M.; Burchmore, Richard J. S.; Byron, Olwyn; Walker, Daniel

    2015-01-01

    The X-ray structure of protease-cleaved E. coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. Bacterial α-2-macroglobulins have been suggested to function in defence as broad-spectrum inhibitors of host proteases that breach the outer membrane. Here, the X-ray structure of protease-cleaved Escherichia coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. In this competitive mechanism, protease cleavage of the bait-region domain results in the untethering of an intrinsically disordered region of this domain which disrupts native interdomain interactions that maintain E. coli α-2-macroglobulin in the inactivated form. The resulting global conformational change results in entrapment of the protease and activation of the thioester bond that covalently links to the attacking protease. Owing to the similarity in structure and domain architecture of Escherichia coli α-2-macroglobulin and human α-2-macroglobulin, this protease-activation mechanism is likely to operate across the diverse members of this group

  16. Structure of protease-cleaved Escherichia coli α-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment

    Energy Technology Data Exchange (ETDEWEB)

    Fyfe, Cameron D.; Grinter, Rhys; Josts, Inokentijs; Mosbahi, Khedidja [University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); Roszak, Aleksander W. [University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); Cogdell, Richard J.; Wall, Daniel M.; Burchmore, Richard J. S.; Byron, Olwyn; Walker, Daniel, E-mail: daniel.walker@glasgow.ac.uk [University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom)

    2015-06-30

    The X-ray structure of protease-cleaved E. coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. Bacterial α-2-macroglobulins have been suggested to function in defence as broad-spectrum inhibitors of host proteases that breach the outer membrane. Here, the X-ray structure of protease-cleaved Escherichia coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. In this competitive mechanism, protease cleavage of the bait-region domain results in the untethering of an intrinsically disordered region of this domain which disrupts native interdomain interactions that maintain E. coli α-2-macroglobulin in the inactivated form. The resulting global conformational change results in entrapment of the protease and activation of the thioester bond that covalently links to the attacking protease. Owing to the similarity in structure and domain architecture of Escherichia coli α-2-macroglobulin and human α-2-macroglobulin, this protease-activation mechanism is likely to operate across the diverse members of this group.

  17. Characterization of a half-molecular fragment obtained by reduction of human α2-macroglobulin with dithiothreitol

    DEFF Research Database (Denmark)

    Sjöberg, B.; Pap, S.; Kjems, Jørgen

    1985-01-01

    A half-molecular fragment of α2-macroglobulin has been prepared by reducing and alkylating the inter-subunit disulfide bonds in the tetrameric α2-macroglobulin molecule with 1 mM dithiothreitol (40 min) and 3 mM iodoacetamide (40 min). Further purification was made by gel chromatography...

  18. Detection of macroglobulins in mammary tissue prior to and following radiotherapy

    International Nuclear Information System (INIS)

    Kozlov, D.V.

    1996-01-01

    Specimens of breast cancer tissue obtained during operation were immunohistochemically examined before and after radiotherapy and compared with fibroadenoma and intact mammary gland. Statistically reliable shifts on the microglobulin protein levels were revealed in fibroadenoma: the content of alpha 2 -microglobulin (AMG) and pregnancy-associated alpha 2 -glycoprotein (PAG) was increased in the parenchyma, whereas in the stroma the level of this latter protein was decreased. In breast cancer the increase of PAG level in the parenchyma and decrease of AMG biosynthesis were still more expressed. Radiotherapy inverted the time course of these protein in cancer parenchyma and stroma. Remembering about the important role of macroglobulins in tumor growth, measurements thereof may be used as additional tests in the diagnosis of breast tumors and in assessment of radiotherapy efficacy [ru

  19. Primary structure of human alpha 2-macroglobulin. I. Isolation of the 26 CNBr fragments, amino acid sequence of 13 small CNBr fragments, amino acid sequence of methionine-containing peptides, and alignment of all CNBr fragments

    DEFF Research Database (Denmark)

    Sottrup-Jensen, Lars; Stepanik, T M; Jones, C M

    1984-01-01

    -775). These fragments account for 603 of the 1451 residues of the subunits of alpha 2-macroglobulin. CB2 contains two glucosamine-based carbohydrate groups attached to Asn-23 and Asn-38, and one internal disulfide bridge connecting Cys-16 with Cys-54. CB6 contains one glucosamine-based carbohydrate group attached...... to Asn-1 and two internal disulfide bridges (Cys-5 bound to Cys-53 and Cys-23 bound to Cys-41, respectively); Cys-32 is bound to Cys-16 in CB8. CB7 contains two glucosamine-based carbohydrate groups attached to Asn-78 and Asn-92, CB8 contains 1 Cys residue (Cys-16), bridged to Cys-32 of CB6. CB11...

  20. Characteristics of Endotoxin-Altering Fractions Derived from Normal Serum III. Isolation and Properties of Horse Serum alpha(2)-Macroglobulin.

    Science.gov (United States)

    Yoshioka, M; Konno, S

    1970-05-01

    The endotoxin-altering activity of fractions isolated from normal horse serum was examined by incubation of Salmonella typhosa strain 0-901 endotoxin (Boivin) in a solution of the fraction, and subsequent quantitation of any diminution in the capacity of endotoxin to be precipitated by specific anti-endotoxin antiserum. The horse serum fraction isolated by precipitation with ammonium sulfate at a concentration between 1.6 and 2.7 m was incubated with Pronase PA and then with trypsin. When this partly digested fraction was passed twice through a Sephadex G-200 column and eluted with 0.2 m tris(hydroxymethyl)aminomethane buffer, most of the endotoxinaltering activity was found in the first protein peak designated F-1a. F-1a was found to be homogeneous and corresponded to an alpha(2)-macroglobulin by the techniques of electrophoresis, immunodiffusion, and ultracentrifugation. Approximately 100-fold more F-1a than endotoxin was needed to reduce the antigenicity of the endotoxin by one-half. Alteration was increased when F-1a was incubated with the endotoxin at acid pH or at 45 C rather than at 37 C and was lost after heating F-1a at 56 C for 30 min. N-ethylmaleimide increased the endotoxin-altering activity of horse serum, F-1a, and human plasma fraction III(0), whereas p-chloromercuribenzoate did not. On the other hand, diazonium-1-H-tetrazole, iodoacetic acid, and benzylchloride suppressed the activity of F-1a. When the interaction of endotoxin and F-1a was examined by immunodiffusion techniques, depolymerization of the endotoxin molecule was indicated. The endotoxin-altering factor of horse serum is discussed in relation to the mechanisms of other known reagents, such as deoxycholate and sodium lauryl sulfate.

  1. IrAM—An .alpha..sub.2./sub.-macroglobulin from the hard tick Ixodes ricinus: Characterization and function in phagocytosis of a potential pathogen Chryseobacterium indologenes

    Czech Academy of Sciences Publication Activity Database

    Burešová, Veronika; Hajdušek, Ondřej; Franta, Zdeněk; Sojka, Daniel; Kopáček, Petr

    2009-01-01

    Roč. 33, č. 4 (2009), s. 489-198 ISSN 0145-305X R&D Projects: GA AV ČR IAA600220603; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : α2-macroglobulin * tick * phagocytosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.290, year: 2009

  2. Analysis of Alpha-2 Macroglobulin from the Long-Lived and Cancer-Resistant Naked Mole-Rat and Human Plasma.

    Science.gov (United States)

    Thieme, René; Kurz, Susanne; Kolb, Marlen; Debebe, Tewodros; Holtze, Susanne; Morhart, Michaela; Huse, Klaus; Szafranski, Karol; Platzer, Matthias; Hildebrandt, Thomas B; Birkenmeier, Gerd

    2015-01-01

    The naked mole-rat (NMR) is a long-lived and cancer resistant species. Identification of potential anti-cancer and age related mechanisms is of great interest and makes this species eminent to investigate anti-cancer strategies and understand aging mechanisms. Since it is known that the NMR expresses higher liver mRNA-levels of alpha 2-macroglobulin than mice, nothing is known about its structure, functionality or expression level in the NMR compared to the human A2M. Here we show a comprehensive analysis of NMR- and human plasma-A2M, showing a different prediction in glycosylation of NMR-A2M, which results in a higher molecular weight compared to human A2M. Additionally, we found a higher concentration of A2M (8.3±0.44 mg/mL vs. and 4.4±0.20 mg/mL) and a lower total plasma protein content (38.7±1.79 mg/mL vs. 61.7±3.20 mg/mL) in NMR compared to human. NMR-A2M can be transformed by methylamine and trypsin resulting in a conformational change similar to human A2M. NMR-A2M is detectable by a polyclonal antibody against human A2M. Determination of tryptic and anti-tryptic activity of NMR and human plasma revealed a higher anti-tryptic activity of the NMR plasma. On the other hand, less proteolytic activity was found in NMR plasma compared to human plasma. We found transformed NMR-A2M binding to its specific receptor LRP1. We could demonstrate lower protein expression of LRP1 in the NMR liver tissue compared to human but higher expression of A2M. This was accompanied by a higher EpCAM protein expression as central adhesion molecule in cancer progression. NMR-plasma was capable to increase the adhesion in human fibroblast in vitro most probably by increasing CD29 protein expression. This is the first report, demonstrating similarities as well as distinct differences between A2M in NMR and human plasma. This might be directly linked to the intriguing phenotype of the NMR and suggests that A2M might probably play an important role in anti-cancer and the anti

  3. Analysis of Alpha-2 Macroglobulin from the Long-Lived and Cancer-Resistant Naked Mole-Rat and Human Plasma.

    Directory of Open Access Journals (Sweden)

    René Thieme

    Full Text Available The naked mole-rat (NMR is a long-lived and cancer resistant species. Identification of potential anti-cancer and age related mechanisms is of great interest and makes this species eminent to investigate anti-cancer strategies and understand aging mechanisms. Since it is known that the NMR expresses higher liver mRNA-levels of alpha 2-macroglobulin than mice, nothing is known about its structure, functionality or expression level in the NMR compared to the human A2M.Here we show a comprehensive analysis of NMR- and human plasma-A2M, showing a different prediction in glycosylation of NMR-A2M, which results in a higher molecular weight compared to human A2M. Additionally, we found a higher concentration of A2M (8.3±0.44 mg/mL vs. and 4.4±0.20 mg/mL and a lower total plasma protein content (38.7±1.79 mg/mL vs. 61.7±3.20 mg/mL in NMR compared to human. NMR-A2M can be transformed by methylamine and trypsin resulting in a conformational change similar to human A2M. NMR-A2M is detectable by a polyclonal antibody against human A2M. Determination of tryptic and anti-tryptic activity of NMR and human plasma revealed a higher anti-tryptic activity of the NMR plasma. On the other hand, less proteolytic activity was found in NMR plasma compared to human plasma.We found transformed NMR-A2M binding to its specific receptor LRP1. We could demonstrate lower protein expression of LRP1 in the NMR liver tissue compared to human but higher expression of A2M. This was accompanied by a higher EpCAM protein expression as central adhesion molecule in cancer progression. NMR-plasma was capable to increase the adhesion in human fibroblast in vitro most probably by increasing CD29 protein expression. This is the first report, demonstrating similarities as well as distinct differences between A2M in NMR and human plasma. This might be directly linked to the intriguing phenotype of the NMR and suggests that A2M might probably play an important role in anti-cancer and the

  4. Mannan-binding protein forms complexes with alpha-2-macroglobulin. A protein model for the interaction

    DEFF Research Database (Denmark)

    Storgaard, P; Holm Nielsen, E; Skriver, E

    1995-01-01

    . The occurrence of alpha 2M/pMBP-28 complexes was further indicated by crossed immunoelectrophoresis and by use of an anti-alpha 2M affinity column and chelating Sepharose loaded with Zn2+. The eluates from these affinity columns showed alpha 2M subunits (94 and 180 kDa) and pMBP subunits (28kDa) in SDS-PAGE...... with anti-C1 s antibodies in ELISA, one of about 650-800 kDa, which in addition contained pMBP-28 and anti-alpha 2M reactive material, the other with an M(r) of 100-150 kDa. The latter peak revealed rhomboid molecules (7 x 15 nm) in the electron microscope and a 67 kDa band in SDS-PAGE under reducing...

  5. PRODUCTION OF PROINFLAMMATORY CYTOKINES AND ALPHA-2-MACROGLOBULIN BY PERIPHERAL BLOOD CELLS IN THE PATIENTS WITH COLORECTAL CANCER

    Directory of Open Access Journals (Sweden)

    V. N. Zorina

    2016-01-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer worldwide, being quite complicated, with respect to diagnostics and postoperative prognosis. Proinflammatory cytokines are shown to be involved into CRC pathogenesis. However, the changes in alpha-2-macroglobulin2-MG, a known regulator of cytokine production, still remain unclear. The aim of this work was to compare contents and production of a2-MG and several pro-inflammatory cytokines in blood serum and supernates from short-term blood cell cultures. The samples were taken from the patients with CRC at initial terms and after surgical removal of the tumor.Studies of cytokines and a2-MG concentrations in serum and supernates of 24-h blood cell cultures from the patients with verified CRC (stages T2-3N0-1M0 and T4N0-1M0 have shown some sufficient differences from healthy volunteers (control group. Pre-surgery IL-6 and TNFα contents in blood of CRC patients was significantly increased agains healthy controls (respectively, 29.9±5.4 and 3.4±1.5 pg/mL versus control group (1.0±0.3 and 0 pg/mL, respectively. Following surgical treatment, the cytokine levels were decreased by 40- 60% after the operation, however, without significant differences from initial values.The supernates of blood cultures stimulated with polyclonal mitogens exhibited significant reduction of IFNγ levels prior to surgery (273±123 pg/ml versus 804±154 pg/mL, and elevated IL-6 levels (14412±2570 pg/mL versus 1970±457 pg/mL. The mean α2-MG concentrations before CRC surgery comprised 1.96±0.11 g/L for blood serum, 0.0304±0.0047 g/L, for non-stimulated blood cell cultures, and 0.0300±0.0052 g/L in mitogen-induced cultures. These parameters did not significantly differ from control values (2.21±0.17 g/L, 0.0328±0.0018 g/L, and 0.0314±0.0019 g/L, respectively. Similar results have been yielded with the samples obtained after surgical treatment of the CRC patients.The obtained data indicate that surgical

  6. Binding of α2-macroglobulin-thrombin complexes and methylamine-treated α2-macroglobulin to human blood monocytes

    International Nuclear Information System (INIS)

    Straight, D.L.; Jakoi, L.; McKee, P.A.; Snyderman, R.

    1988-01-01

    The binding of α 2 -macroglobulin2 M) to human peripheral blood monocytes was investigated. Monocytes, the precursors of tissue macrophages, were isolated from fresh blood by centrifugal elutriation or density gradient centrifugation. Binding studies were performed using 125 I-labeled α 2 M. Cells and bound ligand were separated from free ligand by rapid vacuum filtration. Nonlinear least-squares analysis of data obtained in direct binding studies at 0 0 C showed that monocytes bound the α 2 M-thrombin complex with a K/sub d/ 3.0 +- .09 nM and the monocyte had 1545 +- 153 sitescell. Thrombin alone did not compete for the site. Binding was divalent cation dependent. Direct binding studies also demonstrated that monocytes bound methylamine-treated α 2 M in a manner similar to α 2 M-thrombin. Competitive binding studies showed that α 2 M-thrombin and methylamine-treated α 2 M bound to the same sites on the monocyte. In contrast, native α 2 M did not compete with α 2 M-thrombin for the site. Studies done at 37 0 C suggested that after binding, the monocyte internalized and degraded α 2 M-thrombin and excreted the degradation products. Receptor turnover and degradation of α 2 M-thrombin complexes were blocked in monocytes treated with chloroquine, an inhibitor of lysosomal function. The results indicate that human monocytes have a divalent cation dependent, high-affinity binding site for α 2 M-thrombin and methylamine-treated α 2 M which may function to clear α 2 M-proteinase complexes from the circulation

  7. Expression of the α2-macroglobulin receptor on human neoplastic fibroblastoid cells

    International Nuclear Information System (INIS)

    Grofova, M.; Matoska, J.; Bies, J.; Bizik, J.; Vaheri, A.

    1995-01-01

    The α 2 -macroglobulin membrane-associated receptor ( α 2 MR) has been previously detected on hepatocytes, fibroblast, macrophages, syncytiotrophoblasts and recently on human malignant blood cells of myelomonocytic leukemia. In cells growing in vitro from human germ cell tumors α 2 MR mRNA was detected by Northern blotting. Endocytosis of α 2 MR from culture medium was detected in these cells by indirect immunofluorescence. In cell extracts α 2 MR and its degradation products were detected by immunoblotting. The cells expressing α 2 MR and internalizing α 2 MR were identified as fibroblast both by their morphology and expression of vimentin intermediate filaments. The role and function of α 2 MR receptor in the analyzed neoplastic cells of teratomatous origin is discussed. (author)

  8. Differential Levels of Alpha-2-Macroglobulin, Haptoglobin and Sero-Transferrin as Adjunct Markers for TB Diagnosis and Disease Progression in the Malnourished Tribal Population of Melghat, India.

    Science.gov (United States)

    Bapat, Prachi R; Satav, Ashish R; Husain, Aliabbas A; Shekhawat, Seema D; Kawle, Anuja P; Chu, Justin J; Purohit, Hemant J; Daginawala, Hatim F; Taori, Girdhar M; Kashyap, Rajpal S

    2015-01-01

    Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis.

  9. Leflunomide and methotrexate reduce levels of activated matrix metalloproteinases in complexes with α2 macroglobulin in serum of rheumatoid arthritis patients

    NARCIS (Netherlands)

    Tchetverikov, I.; Kraan, M.C.; El, B. van; Hanemaaijer, R.; Groot, J. de; Huizinga, T.W.J.

    2008-01-01

    Objective: To analyse the effects of leflunomide and methotrexate treatment on matrix metalloproteinase (MMP) activity levels in a2 macroglobulin/MMP (α2M/MMP) complexes in the systemic circulation of rheumatoid arthritis (RA) patients. Methods: A total of 102 RA patients from a prospective,

  10. Crystallization and preliminary X-ray diffraction analysis of eukaryotic α2-macroglobulin family members modified by methylamine, proteases and glycosidases

    DEFF Research Database (Denmark)

    Goulas, T; Garcia-Ferrer, I; García-Piqué, S

    2014-01-01

    α2-Macroglobulin2M) has many functions in vertebrate physiology. To understand the basis of such functions, high-resolution structural models of its conformations and complexes with interacting partners are required. In an attempt to grow crystals that diffract to high or medium resolution, we...

  11. Changes in Zinc metabolism after burns : observations, explanations, clinical implications

    NARCIS (Netherlands)

    Haan, de K.E.C.; de Goeij, J.J.M.; Hamer, van den C.J.A.; Boxma, H.; Groot, de C.J.

    1992-01-01

    Zinc in plasma and urine and serum albumin and alpha 2-macroglobulin were measured in 48 patients with burns. Mean total burned surface area amounted to 18%, ranging from 2 to 55%, and mean hospitalization time amounted to 35 days, ranging from 10 to 124 days. All parameters showed a decrease during

  12. The multiligand α2-macroglobulin receptor/low density lipoprotein receptor-related protein

    DEFF Research Database (Denmark)

    Gliemann, Jørgen; Nykjær, Anders; Petersen, Claus Munck

    1994-01-01

    The fusion of separate lines of research has greatly helped in elucidating the function of the giant members of the low density lipoprotein (LDL) receptor (LDLR) supergene family. The cDNA encoding a large protein structurally closely related to LDLR, and hence named LDLR-related protein (LRP......), was cloned by Herz et al. in 1988.'Evidence was provided demonstrating that LRP can function as a receptor for chylomicron remnants@-migrating very low density lipoproteins (P-VLDL) rich in apolipoprotein E (apoE)?' The a2-macroglobulin (a2M) receptor (a2MR) was purified from rat livep and human p l a~e n t...... from the observation that affinity-purified a2MR/LRP contains a 40-kDa5.8 or 39-kDa6.' protein, designated a2MRAP, in addition to the a2MFULRP a- and P-chains. cDNA cloning" disclosed the 323-residue protein as both the human homologue of mouse heparin binding protein 44 (see reference 11) and...

  13. Human α2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3

    Science.gov (United States)

    Doan, Ninh; Gettins, Peter G. W.

    2007-01-01

    Human α2M (α2-macroglobulin) and the complement components C3 and C4 are thiol ester-containing proteins that evolved from the same ancestral gene. The recent structure determination of human C3 has allowed a detailed prediction of the location of domains within human α2M to be made. We describe here the expression and characterization of three α2M domains predicted to be involved in the stabilization of the thiol ester in native α2M and in its activation upon bait region proteolysis. The three newly expressed domains are MG2 (macroglobulin domain 2), TED (thiol ester-containing domain) and CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain. Together with the previously characterized RBD (receptor-binding domain), they represent approx. 42% of the α2M polypeptide. Their expression as folded domains strongly supports the predicted domain organization of α2M. An X-ray crystal structure of MG2 shows it to have a fibronectin type-3 fold analogous to MG1–MG8 of C3. TED is, as predicted, an α-helical domain. CUB is a spliced domain composed of two stretches of polypeptide that flank TED in the primary structure. In intact C3 TED interacts with RBD, where it is in direct contact with the thiol ester, and with MG2 and CUB on opposite, flanking sides. In contrast, these α2M domains, as isolated species, show negligible interaction with one another, suggesting that the native conformation of α2M, and the consequent thiol ester-stabilizing domain–domain interactions, result from additional restraints imposed by the physical linkage of these domains or by additional domains in the protein. PMID:17608619

  14. Inactivation of viruses by pasteurization at 60 °C for 10 h with and without 40% glucose as stabilizer during a new manufacturing process of α2-Macroglobulin from Cohn Fraction IV.

    Science.gov (United States)

    Huangfu, Chaoji; Ma, Yuyuan; Jia, Junting; Lv, Maomin; Zhu, Fengxuan; Ma, Xiaowei; Zhao, Xiong; Zhang, Jingang

    2017-03-01

    Pasteurization is regularly used to inactivate viruses for the safety of plasma derivatives. Influence of pasteurization at 60 °C for 10 h on α2-Macroglobulin activity and virus inactivation were studied. With 40% sugar as stabilizers more than 70% α2-Macroglobulin activity was reserved after pasteurization compared with 20% in control. Glucose presented a better activity protection effect than sucrose and maltose. By pasteurization without stabilizer the virus titers of pseudorabies virus, Sindbis virus, porcine parvovirus and encephalomyocarditis virus were reduced more than 5.88 log 10 , 7.50 log 10 , 4.88 log 10 , and 5.63 log 10 respectively within 2 h. By pasteurization with 40% glucose vesicular stomatitis virus was inactivated more than 5.88 log 10 within 1 h. Only 2.71 log 10 reduction was achieved for encephalomyocarditis virus after 10 h. 40% glucose protected α2-M activity and viruses simultaneously from pasteurization. Other viral inactivation methods need to be incorporated to ensure viral safety of this manufacturing process of α2-Macroglobulin. Copyright © 2017 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  15. Binding of alpha2ML1 to the low density lipoprotein receptor-related protein 1 (LRP1 reveals a new role for LRP1 in the human epidermis.

    Directory of Open Access Journals (Sweden)

    Marie-Florence Galliano

    Full Text Available BACKGROUND: The multifunctional receptor LRP1 has been shown to bind and internalize a large number of protein ligands with biological importance such as the pan-protease inhibitor alpha2-macroglobulin (alpha2M. We recently identified Alpha2ML1, a new member of the alpha2M gene family, expressed in epidermis. alpha2ML1 might contribute to the regulation of desquamation through its inhibitory activity towards proteases of the chymotrypsin family, notably KLK7. The expression of LRP1 in epidermis as well as its ability to internalize alpha2ML1 was investigated. METHODS AND PRINCIPAL FINDINGS: In human epidermis, LRP1 is mainly expressed within the granular layer of the epidermis, which gathers the most differentiated keratinocytes, as shown by immunohistochemistry and immunofluorescence using two different antibodies. By using various experimental approaches, we show that the receptor binding domain of alpha2ML1 (RBDl is specifically internalized into the macrophage-like cell line RAW and colocalizes with LRP1 upon internalization. Coimmunoprecipitation assays demonstrate that RBDl binds LRP1 at the cell surface. Addition of RAP, a universal inhibitor of ligand binding to LRP1, prevents RBDl binding at the cell surface as well as internalization into RAW cells. Silencing Lrp1 expression with specific siRNA strongly reduces RBDl internalization. CONCLUSIONS AND SIGNIFICANCE: Keratinocytes of the upper differentiated layers of epidermis express LRP1 as well as alpha2ML1. Our study also reveals that alpha2ML1 is a new ligand for LRP1. Our findings are consistent with endocytosis by LRP1 of complexes formed between alpha2ML1 and proteases. LRP1 may thus control desquamation by regulating the biodisponibility of extracellular proteases.

  16. α2-macroglobulin can crosslink multiple Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) molecules and may facilitate adhesion of parasitized erythrocytes

    DEFF Research Database (Denmark)

    Stevenson, Liz; Laursen, Erik; Cowan, Graeme J

    2015-01-01

    -macroglobulin2M), which is both required and sufficient for rosetting mediated by the PfEMP1 protein HB3VAR06 and some other rosette-mediating PfEMP1 proteins. We map the α2M binding site to the C terminal end of HB3VAR06, and demonstrate that α2M can bind at least four HB3VAR06 proteins, plausibly....... Together, our results are evidence that P. falciparum parasites exploit α2M (and IgM) to expand the repertoire of host receptors available for PfEMP1-mediated IE adhesion, such as the erythrocyte carbohydrate moieties that lead to formation of rosettes. It is likely that this mechanism also affects IE...

  17. PSA-alpha-2-macroglobulin complex is enzymatically active in the serum of patients with advanced prostate cancer and can degrade circulating peptide hormones.

    Science.gov (United States)

    Kostova, Maya B; Brennen, William Nathaniel; Lopez, David; Anthony, Lizamma; Wang, Hao; Platz, Elizabeth; Denmeade, Samuel R

    2018-08-01

    Prostate cancer cells produce high levels of the serine protease Prostate-Specific Antigen (PSA). PSA is enzymatically active in the tumor microenvironment but is presumed to be enzymatically inactive in the blood due to complex formation with serum protease inhibitors α-1-antichymotrypsin and α-2-macroglobulin (A2M). PSA-A2M complexes cannot be measured by standard ELISA assays and are also rapidly cleared from the circulation. Thus the exact magnitude of PSA production by prostate cancer cells is not easily measured. The PSA complexed to A2M is unable to cleave proteins but maintains the ability to cleave small peptide substrates. Thus, in advanced prostate cancer, sufficient PSA-A2M may be in circulation to effect total A2M levels, levels of cytokines bound to A2M and hydrolyze small circulating peptide hormones. Total A2M levels in men with advanced prostate cancer and PSA levels above 1000 ng/mL were measured by ELISA and compared to controls. Additional ELISA assays were used to measure levels of IL-6 and TGF-beta which can bind to A2M. The ability of PSA-A2M complexes to hydrolyze protein and peptide substrates was analyzed ± PSA inhibitor. Enzymatic activity of PSA-A2M in serum of men with high PSA levels was also assayed. Serum A2M levels are inversely correlated with PSA levels in men with advanced prostate cancer. Il-6 Levels are significantly elevated in men with PSA >1000 ng/mL compared to controls with PSA PSA-A2M complex in serum of men with PSA levels >1000 ng/mL can hydrolyze small fluorescently labeled peptide substrates but not large proteins that are PSA substrates. PSA can hydrolyze small peptide hormones like PTHrP and osteocalcin. PSA complexed to A2M retains the ability to degrade PTHrP. In advanced prostate cancer with PSA levels >1000 ng/mL, sufficient PSA-A2M is present in circulation to produce enzymatic activity against circulating small peptide hormones. Sufficient PSA is produced in advanced prostate cancer to alter

  18. Changes in blood levels of proteinase inhibitors, pregnancy zone protein, steroid carriers and complement factors induced by oral contraceptives

    DEFF Research Database (Denmark)

    Nielsen, C H; Poulsen, H K; Teisner, B

    1993-01-01

    levels of antithrombin III (AT III), alpha 2-macroglobulin (alpha 2M) alpha 1-antitrypsin (alpha 1at), complement factors (factor B, C3, C4), pregnancy zone protein (PZP), corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG) and albumin were measured before treatment and during...

  19. Spectroscopic and thermodynamic studies on ferulic acid - Alpha-2-macroglobulin interaction

    Science.gov (United States)

    Rehman, Ahmed Abdur; Sarwar, Tarique; Arif, Hussain; Ali, Syed Saqib; Ahsan, Haseeb; Tabish, Mohammad; Khan, Fahim Halim

    2017-09-01

    Ferulic acid is a major phenolic acid found in numerous plant species in conjugated form. It binds to enzymes and oligomeric proteins and modifies their structure and function. This study was designed to examine the interaction of ferulic acid, an active ingredient of some important medicines, with α2M, a key serum proteinase, under physiological conditions. The mechanism of interaction was studied by spectroscopic techniques such as, UV-visible absorption, fluorescence spectroscopy, circular dichroism along with isothermal titration calorimetry. Fluorescence quenching of α2M by ferulic acid demonstrated the formation of α2M-ferulic acid complex by static quenching mechanism. Binding parameters calculated by Stern-Volmer method showed that ferulic acid binds to α2M with moderate affinity of the order of ∼104 M-1. The thermodynamic signatures reveal that binding was enthalpy driven and hydrogen bonding played a major role in ferulic acid-α2M binding. CD spectra analysis suggests very little conformational changes in α2M on ferulic acid binding.

  20. Activated α2-macroglobulin binding to human prostate cancer cells triggers insulin-like responses.

    Science.gov (United States)

    Misra, Uma Kant; Pizzo, Salvatore Vincent

    2015-04-10

    Ligation of cell surface GRP78 by activated α2-macroglobulin2M*) promotes cell proliferation and suppresses apoptosis. α2M*-treated human prostate cancer cells exhibit a 2-3-fold increase in glucose uptake and lactate secretion, an effect similar to insulin treatment. In both α2M* and insulin-treated cells, the mRNA levels of SREBP1-c, SREBP2, fatty-acid synthase, acetyl-CoA carboxylase, ATP citrate lyase, and Glut-1 were significantly increased together with their protein levels, except for SREBP2. Pretreatment of cells with α2M* antagonist antibody directed against the carboxyl-terminal domain of GRP78 blocks these α2M*-mediated effects, and silencing GRP78 expression by RNAi inhibits up-regulation of ATP citrate lyase and fatty-acid synthase. α2M* induces a 2-3-fold increase in lipogenesis as determined by 6-[(14)C]glucose or 1-[(14)C]acetate incorporation into free cholesterol, cholesterol esters, triglycerides, free fatty acids, and phosphatidylcholine, which is blocked by inhibitors of fatty-acid synthase, PI 3-kinase, mTORC, or an antibody against the carboxyl-terminal domain of GRP78. We also assessed the incorporation of [(14)CH3]choline into phosphatidylcholine and observed similar effects. Lipogenesis is significantly affected by pretreatment of prostate cancer cells with fatostatin A, which blocks sterol regulatory element-binding protein proteolytic cleavage and activation. This study demonstrates that α2M* functions as a growth factor, leading to proliferation of prostate cancer cells by promoting insulin-like responses. An antibody against the carboxyl-terminal domain of GRP78 may have important applications in prostate cancer therapy. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Drugs interacting with alpha adrenoceptors

    NARCIS (Netherlands)

    van Zwieten, P. A.

    1989-01-01

    Alpha adrenoceptors should be divided into various subtypes, comprising pre/postsynaptic and alpha 1/alpha 2-subpopulations, respectively. This classification implicates important functional differences between the various alpha-receptor subtypes, including certain differences in signal transduction

  2. Diagnostical meaning acute phase proteins in cerebrospinal liquid in children with neuroinfections

    Directory of Open Access Journals (Sweden)

    L. A. Alekseeva

    2010-01-01

    Full Text Available In the article presented results of the examination of acute phase proteins in cerebrospinal liquid in 237 children with meningitis and encephalitis viral and bacterial etiology. The dependence between the level of acute phase proteins in cerebrospinal liquid and etiology of neuroinfectional process, the severity of brain damage and the process stage was determined. Diagnostic and prognostic efficiency of the acute phase proteins (C-reactive protein, albumin, alpha-1-antitripsin, alpha-2-macroglobulin, gaptoglobin examination in children with neuroinfections was specified. Developed method of express diagnostics of the severity of inflammatory damage of the brain in bacterial meningitis in children by determination in cerebrospinal liquid alpha-2-macroglobulin is described.

  3. New ALPHA-2 magnet

    CERN Multimedia

    Anaïs Schaeffer

    2012-01-01

    On 21 June, members of the ALPHA collaboration celebrated the handover of the first solenoid designed for the ALPHA-2 experiment. The magnet has since been successfully installed and is working well.   Khalid Mansoor, Sumera Yamin and Jeffrey Hangst in front of the new ALPHA-2 solenoid. “This was the first of three identical solenoids that will be installed between now and September, as the rest of the ALPHA-2 device is installed and commissioned,” explains ALPHA spokesperson Jeffrey Hangst. “These magnets are designed to allow us to transfer particles - antiprotons, electrons and positrons - between various parts of the new ALPHA-2 device by controlling the transverse size of the particle bunch that is being transferred.” Sumera Yamin and Khalid Mansoor, two Pakistani scientists from the National Centre for Physics in Islamabad, came to CERN in February specifically to design and manufacture these magnets. “We had the chance to work on act...

  4. ALPHA-2: the sequel

    CERN Multimedia

    Katarina Anthony

    2012-01-01

    While many experiments are methodically planning for intense works over the long shutdown, there is one experiment that is already working at full steam: ALPHA-2. Its final components arrived last month and will completely replace the previous ALPHA set-up. Unlike its predecessor, this next generation experiment has been specifically designed to measure the properties of antimatter.   The ALPHA team lower the new superconducting solenoid magnet into place. The ALPHA collaboration is working at full speed to complete the ALPHA-2 set-up for mid-November – this will give them a few weeks of running before the AD shutdown on 17 December. “We really want to get some experience with this device this year so that, if we need to make any changes, we will have time during the long shutdown in which to make them,” says Jeffrey Hangst, ALPHA spokesperson. “Rather than starting the 2014 run in the commissioning stage, we will be up and running from the get go.&...

  5. Cell survival following alpha particle irradiation: critical sites and implications for carcinogenesis

    International Nuclear Information System (INIS)

    Lloyd, E.L.; Gemmell, M.A.; Henning, C.B.; Gemmell, D.S.; Zabransky, B.J.

    1976-01-01

    In experiments in which mammalian cells were irradiated with 5.6 MeV alpha particles from a Tandem Van de Graaff machine we have confirmed the finding of others that the mean lethal dose (D 0 ) is about 100 rad, but by measurements of the area of the cell nuclei as irradiated we found that this mean lethal dose corresponds not to 1, as expected, but to about 27 alpha particles per cell nucleus. (The exact number appears to change slightly with cell passage number.) This allows for the possibility that the direct action of alpha particles on the nucleus may be the important event in carcinogenesis, a theory which was previously difficult to accept if a single particle hitting the nucleus anywhere was considered to be lethal. Evidence is presented to implicate the nucleolus as a possible critical site for the inhibition of reproductive integrity of the cell

  6. Immunoglobulin classes, metal binding proteins, and trace metals in ...

    African Journals Online (AJOL)

    , IgA and IgM), metal binding proteins (Transferrin, Caeruloplasmin, Alpha-2- Macroglobulin and Haptoglobin) and nutritionally essential trace metals/heavy metals (Zn, Fe, Se, Cu, Mg, Cd and Pb) in Nigerian cassava processors using single ...

  7. Human fat cell alpha-2 adrenoceptors. I. Functional exploration and pharmacological definition with selected alpha-2 agonists and antagonists

    International Nuclear Information System (INIS)

    Galitzky, J.; Mauriege, P.; Berlan, M.; Lafontan, M.

    1989-01-01

    This study was undertaken to investigate more fully the pharmacological characteristics of the human fat cell alpha-2 adrenoceptor. Biological assays were performed on intact isolated fat cells while radioligand binding studies were carried out with [ 3 H]yohimbine in membranes. These pharmacological studies brought: (1) a critical definition of the limits of the experimental conditions required for the exploration of alpha-2 adrenergic responsiveness on human fat cells and membranes; (2) an improvement in the pharmacological definition of the human fat cell postsynaptic alpha-2 adrenoceptor. Among alpha-2 agonists, UK-14,304 was the most potent and the relative order of potency was: UK-14,304 greater than p-aminoclonidine greater than clonidine = B-HT 920 greater than rilmenidine. For alpha-2 antagonists, the potency order was: yohimbine greater than idazoxan greater than SK ampersand F-86,466 much greater than benextramine; (3) a description of the impact of benextramine (irreversible alpha-1/alpha-2 antagonist) on human fat cell alpha-2 adrenergic receptors and on human fat cell function; the drug inactivates the alpha-2 adrenergic receptors with a minor impact on beta adrenergic receptors and without noticeable alterations of fat cell function as assessed by preservation of beta adrenergic and Al-adenosine receptor-mediated lipolytic responses; and (4) a definition of the relationship existing between alpha-2 adrenergic receptor occupancy, inhibition of adenylate cyclase activity and antilipolysis with full and partial agonists. The existence of a receptor reserve must be taken into account when evaluating alpha-2 adrenergic receptor distribution and regulation of human fat cells

  8. Differentiation of the mRNA transcripts originating from the alpha 1- and alpha 2-globin loci in normals and alpha-thalassemics.

    OpenAIRE

    Liebhaber, S A; Kan, Y W

    1981-01-01

    The alpha-globin polypeptide is encoded by two adjacent genes, alpha 1 and alpha 2. In the normal diploid state (alpha alpha/alpha alpha) all four alpha-globin genes are expressed. Loss or dysfunction of one or more of these genes leads to deficient alpha-globin production and results in alpha-thalassemia. We present a technique to differentially assess the steady-state levels of the alpha 1- and alpha-2-globin messenger RNA (mRNA) transcripts and thus delineate the relative level of expressi...

  9. Biochemical characterization of CK2alpha and alpha' paralogues and their derived holoenzymes: evidence for the existence of a heterotrimeric CK2alpha'-holoenzyme forming trimeric complexes

    DEFF Research Database (Denmark)

    Olsen, Birgitte; Rasmussen, Tine; Niefind, Karsten

    2008-01-01

    Altogether 2 holoenzymes and 4 catalytic CK2 constructs were expressed and characterized i.e. CK2alpha (2) (1-335) beta(2); CK2alpha'-derived holoenzyme; CK2alpha(1-335); MBP-CK2alpha'; His-tagged CK2alpha and His-tagged CK2alpha'. The two His-tagged catalytic subunits were expressed in insect...... cells, all others in Escherichia coli. IC(50) studies involving the established CK2 inhibitors DMAT, TBBt, TBBz, apigenin and emodin were carried out and the K(i) values calculated. Although the differences in the K(i) values found were modest, there was a general tendency showing that the CK2...... holoenzymes were more sensitive towards the inhibitors than the free catalytic subunits. Thermal inactivation experiments involving the individual catalytic subunits showed an almost complete loss of activity after only 2 min at 45 degrees C. In the case of the two holoenzymes, the CK2alpha...

  10. Receptor tyrosine phosphatase R-PTP-alpha is tyrosine-phosphorylated and associated with the adaptor protein Grb2

    DEFF Research Database (Denmark)

    Su, J; Batzer, A; Sap, J

    1994-01-01

    Receptor tyrosine phosphatases (R-PTPases) have generated interest because of their suspected involvement in cellular signal transduction. The adaptor protein Grb2 has been implicated in coupling receptor tyrosine kinases to Ras. We report that a ubiquitous R-PTPase, R-PTP-alpha, is tyrosine......-phosphorylated and associated in vivo with the Grb2 protein. This association can be reproduced in stably and transiently transfected cells, as well as in vitro using recombinant Grb2 protein. Association requires the presence of an intact SH2 domain in Grb2, as well as tyrosine phosphorylation of R-PTP-alpha. This observation...... links a receptor tyrosine phosphatase with a key component of a central cellular signalling pathway and provides a basis for addressing R-PTP-alpha function....

  11. Analysis of the binding of pro-urokinase and urokinase-plasminogen activator inhibitor-1 complex to the low density lipoprotein receptor-related protein using a Fab fragment selected from a phage-displayed Fab library

    NARCIS (Netherlands)

    Horn, I. R.; Moestrup, S. K.; van den Berg, B. M.; Pannekoek, H.; Nielsen, M. S.; van Zonneveld, A. J.

    1995-01-01

    The low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) mediates endocytosis of a number of structurally unrelated ligands, including complexes of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) or urokinase plasminogen

  12. Cell motility in chronic lymphocytic leukemia: defective Rap1 and alphaLbeta2 activation by chemokine.

    Science.gov (United States)

    Till, Kathleen J; Harris, Robert J; Linford, Andrea; Spiller, David G; Zuzel, Mirko; Cawley, John C

    2008-10-15

    Chemokine-induced activation of alpha4beta1 and alphaLbeta2 integrins (by conformational change and clustering) is required for lymphocyte transendothelial migration (TEM) and entry into lymph nodes. We have previously reported that chemokine-induced TEM is defective in chronic lymphocytic leukemia (CLL) and that this defect is a result of failure of the chemokine to induce polar clustering of alphaLbeta2; engagement of alpha4beta1 and autocrine vascular endothelial growth factor (VEGF) restore clustering and TEM. The aim of the present study was to characterize the nature of this defect in alphaLbeta2 activation and determine how it is corrected. We show here that the alphaLbeta2 of CLL cells is already in variably activated conformations, which are not further altered by chemokine treatment. Importantly, such treatment usually does not cause an increase in the GTP-loading of Rap1, a GTPase central to chemokine-induced activation of integrins. Furthermore, we show that this defect in Rap1 GTP-loading is at the level of the GTPase and is corrected in CLL cells cultured in the absence of exogenous stimuli, suggesting that the defect is the result of in vivo stimulation. Finally, we show that, because Rap1-induced activation of both alpha4beta1 and alphaLbeta2 is defective, autocrine VEGF and chemokine are necessary to activate alpha4beta1 for ligand binding. Subsequently, this binding and both VEGF and chemokine stimulation are all needed for alphaLbeta2 activation for motility and TEM. The present study not only clarifies the nature of the alphaLbeta2 defect of CLL cells but is the first to implicate activation of Rap1 in the pathophysiology of CLL.

  13. MID1 and MID2 homo- and heterodimerise to tether the rapamycin-sensitive PP2A regulatory subunit, Alpha 4, to microtubules: implications for the clinical variability of X-linked Opitz GBBB syndrome and other developmental disorders

    Directory of Open Access Journals (Sweden)

    Cox Timothy C

    2002-01-01

    Full Text Available Abstract Background Patients with Opitz GBBB syndrome present with a variable array of developmental defects including craniofacial, cardiac, and genital anomalies. Mutations in the X-linked MID1 gene, which encodes a microtubule-binding protein, have been found in ~50% of Opitz GBBB syndrome patients consistent with the genetically heterogeneous nature of the disorder. A protein highly related to MID1, called MID2, has also been described that similarly associates with microtubules. Results To identify protein partners of MID1 and MID2 we undertook two separate yeast two-hybrid screens. Using this system we identified Alpha 4, a regulatory subunit of PP2-type phosphatases and a key component of the rapamycin-sensitive signaling pathway, as a strong interactor of both proteins. Analysis of domain-specific deletions has shown that the B-boxes of both MID1 and MID2 mediate the interaction with Alpha 4, the first demonstration in an RBCC protein of a specific role for the B-box region. In addition, we show that the MID1/2 coiled-coil motifs mediate both homo- and hetero-dimerisation, and that dimerisation is a prerequisite for association of the MID-Alpha 4 complex with microtubules. Conclusions Our findings not only implicate Alpha 4 in the pathogenesis of Opitz GBBB syndrome but also support our earlier hypothesis that MID2 is a modifier of the X-linked phenotype. Of further note is the observation that Alpha 4 maps to Xq13 within the region showing linkage to FG (Opitz-Kaveggia syndrome. Overlap in the clinical features of FG and Opitz GBBB syndromes warrants investigation of Alpha 4 as a candidate for causing FG syndrome.

  14. Barley alpha-amylase/subtilisin inhibitor: structure, biophysics and protein engineering

    DEFF Research Database (Denmark)

    Nielsen, P.K.; Bønsager, Birgit Christine; Fukuda, Kenji

    2004-01-01

    Bifunctional alpha-amylase/subtilisin inhibitors have been implicated in plant defence and regulation of endogenous alpha-amylase action. The barley alpha-amylase/subtilisin inhibitor (BASI) inhibits the barley alpha-amylase 2 (AMY2) and subtilisin-type serine proteases. BASI belongs to the Kunitz...... Ca2+-modulated kinetics of the AMY2/BASl interaction and found that the complex formation involves minimal structural changes. The modulation of the interaction by calcium ions makes it unique among the currently known binding mechanisms of proteinaceous alpha-amylase inhibitors....

  15. Alpha 2-adrenergic receptor turnover in adipose tissue and kidney: irreversible blockade of alpha 2-adrenergic receptors by benextramine

    International Nuclear Information System (INIS)

    Taouis, M.; Berlan, M.; Lafontan, M.

    1987-01-01

    The recovery of post- and extrasynaptic alpha 2-adrenergic receptor-binding sites was studied in vivo in male golden hamsters after treatment with an irreversible alpha-adrenoceptor antagonist benextramine, a tetramine disulfide that possesses a high affinity for alpha 2-binding sites. The kidney alpha 2-adrenergic receptor number was measured with [ 3 H]yohimbine, whereas [ 3 H]clonidine was used for fat cell and brain membrane alpha 2-binding site identification. Benextramine treatment of fat cell, kidney, and brain membranes reduced or completely suppressed, in an irreversible manner, [ 3 H] clonidine and [ 3 H]yohimbine binding without modifying adenosine (A1-receptor) and beta-adrenergic receptor sites. This irreversible binding was also found 1 and 2 hr after intraperitoneal administration of benextramine to the hamsters. Although it bound irreversibly to peripheral and central alpha 2-adrenergic receptors on isolated membranes, benextramine was unable to cross the blood-brain barrier of the hamster at the concentrations used (10-20 mg/kg). After the irreversible blockade, alpha 2-binding sites reappeared in kidney and adipose tissue following a monoexponential time course. Recovery of binding sites was more rapid in kidney than in adipose tissue; the half-lives of the receptor were 31 and 46 hr, respectively in the tissues. The rates of receptor production were 1.5 and 1.8 fmol/mg of protein/hr in kidney and adipose tissue. Reappearance of alpha 2-binding sites was associated with a rapid recovery of function (antilipolytic potencies of alpha 2-agonists) in fat cells inasmuch as occupancy of 15% of [ 3 H]clonidine-binding sites was sufficient to promote 40% inhibition of lipolysis. Benextramine is a useful tool to estimate turnover of alpha 2-adrenergic receptors under normal and pathological situations

  16. Nicotinic {alpha}4{beta}2 receptor imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Pichika, Rama [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Easwaramoorthy, Balasubramaniam [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Collins, Daphne [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Christian, Bradley T. [Department of Nuclear Medicine, Kettering Medical Center, Dayton, OH 45429 (United States); Shi, Bingzhi [Department of Nuclear Medicine, Kettering Medical Center, Dayton, OH 45429 (United States); Narayanan, Tanjore K. [Department of Nuclear Medicine, Kettering Medical Center, Dayton, OH 45429 (United States); Potkin, Steven G. [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States); Mukherjee, Jogeshwar [Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960 (United States)]. E-mail: j.mukherjee@uci.edu

    2006-04-15

    The {alpha}4{beta}2 nicotinic acetylcholine receptor (nAChR) has been implicated in various neurodegenerative diseases. Optimal positron emission tomography (PET) imaging agents are therefore highly desired for this receptor. We report here the development and initial evaluation of 2-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine (nifene). In vitro binding affinity of nifene in rat brain homogenate using {sup 3}H-cytisine exhibited a K {sub i}=0.50 nM for the {alpha}4{beta}2 sites. The radiosynthesis of 2-{sup 18}F-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine ({sup 18}F-nifene) was accomplished in 2.5 h with an overall radiochemical yield of 40-50%, decay corrected. The specific activity was estimated to be approx. 37-185 GBq/{mu}mol. In vitro autoradiography in rat brain slices indicated selective binding of {sup 18}F-nifene to anteroventral thalamic (AVT) nucleus, thalamus, subiculum, striata, cortex and other regions consistent with {alpha}4{beta}2 receptor distribution. Rat cerebellum showed some binding, whereas regions in the hippocampus had the lowest binding. The highest ratio of >13 between AVT and cerebellum was measured for {sup 18}F-nifene in rat brain slices. The specific binding was reduced (>95%) by 300 {mu}M nicotine in these brain regions. Positron emission tomography imaging study of {sup 18}F-nifene (130 MBq) in anesthetized rhesus monkey was carried out using an ECAT EXACT HR+ scanner. PET study showed selective maximal uptake in the regions of the anterior medial thalamus, ventro-lateral thalamus, lateral geniculate, cingulate gyrus, temporal cortex including the subiculum. The cerebellum in the monkeys showed lower binding than the other regions. Thalamus-to-cerebellum ratio peaked at 30-35 min postinjection to a value of 2.2 and subsequently reduced. The faster binding profile of {sup 18}F-nifene indicates promise as a PET imaging agent and thus needs further evaluation.

  17. Actions of alpha2 adrenoceptor ligands at alpha2A and 5-HT1A receptors: the antagonist, atipamezole, and the agonist, dexmedetomidine, are highly selective for alpha2A adrenoceptors.

    Science.gov (United States)

    Newman-Tancredi, A; Nicolas, J P; Audinot, V; Gavaudan, S; Verrièle, L; Touzard, M; Chaput, C; Richard, N; Millan, M J

    1998-08-01

    This study examined the activity of chemically diverse alpha2 adrenoceptor ligands at recombinant human (h) and native rat (r) alpha2A adrenoceptors compared with 5-HT1A receptors. First, in competition binding experiments at h alpha2A and h5-HT1A receptors expressed in CHO cells, several compounds, including the antagonists 1-(2-pyrimidinyl)piperazine (1-PP), (+/-)-idazoxan, benalfocin (SKF 86466), yohimbine and RX 821,002, displayed preference for h alpha2A versus h5-HT1A receptors of only 1.4-, 3.6-, 4-, 10- and 11-fold, respectively (based on differences in pKi values). Clonidine, brimonidine (UK 14304), the benzopyrrolidine fluparoxan and the guanidines guanfacine and guanabenz exhibited intermediate selectivity (22- to 31-fold) for h alpha2A receptors. Only the antagonist atipamezole and the agonist dexmedetomidine (DMT) displayed high preference for alpha2 adrenoceptors (1290- and 91-fold, respectively). Second, the compounds were tested for their ability to induce h5-HT1A receptor-mediated G-protein activation, as indicated by the stimulation of [35S]GTPgammaS binding. All except atipamezole and RX 821,002 exhibited agonist activity, with potencies which correlated with their affinity for h5-HT1A receptors. Relative efficacies (Emax values) were 25-35% for guanabenz, guanfacine, WB 4101 and benalfocin, 50-65% for 1-PP, (+/-)-idazoxan and clonidine, and over 70% for fluparoxan, oxymetazoline and yohimbine (relative to 5-HT = 100%). Yohimbine-induced [35S]GTPgammaS binding was inhibited by the selective 5-HT1A receptor antagonist WAY 100,635. In contrast, RX 821,002 was the only ligand which exhibited antagonist activity at h5-HT1A receptors, inhibiting 5-HT-stimulated [35S]GTPgammaS binding. Atipamezole, which exhibited negligeable affinity for 5-HT1A receptors, was inactive. Third, the affinities for r alpha2A differed considerably from the affinities for h alpha2A receptors whereas the affinities for r5-HT1A differed much less from the affinities for h5-HT

  18. Molecular determinants of desensitization and assembly of the chimeric GABA(A) receptor subunits (alpha1/gamma2) and (gamma2/alpha1) in combinations with beta2 and gamma2

    DEFF Research Database (Denmark)

    Elster, L; Kristiansen, U; Pickering, D S

    2001-01-01

    Two gamma-aminobutyric acid(A) (GABA(A)) receptor chimeras were designed in order to elucidate the structural requirements for GABA(A) receptor desensitization and assembly. The (alpha1/gamma2) and (gamma2/alpha1) chimeric subunits representing the extracellular N-terminal domain of alpha1 or gamma......, as opposed to the staining of the (gamma2/alpha1)-containing receptors, which was only slightly higher than background. To explain this, the (alpha1/gamma2) and (gamma2/alpha1) chimeras may act like alpha1 and gamma2 subunits, respectively, indicating that the extracellular N-terminal segment is important...... for assembly. However, the (alpha1/gamma2) chimeric subunit had characteristics different from the alpha1 subunit, since the (alpha1/gamma2) chimera gave rise to no desensitization after GABA stimulation in whole-cell patch-clamp recordings, which was independent of whether the chimera was expressed...

  19. Impact of experimental endogenous gram-negative peritonitis on the pancreas of the rat as evaluated by cationic trypsin-like immunoreactivity in peritoneal fluid and serum and by electron microscopy of pancreatic tissue

    International Nuclear Information System (INIS)

    Florholmen, J.; Almdahl, S.M.; Myklebust, R.; Burhol, P.G.; Malm, D.; Riepl, R.; Giercksky, K.E.

    1987-01-01

    Endogenous gram-negative peritonitis leading to septic shock was induced in rats by a defined perforation of the coecum. Cationic trypsin-like immunoreactivity (CTLI) was measured in peritoneal fluid and serum by a radioimmunoassay method. 5, 10 and 15 h after the coecal perforation, CTLI in peritoneal fluid was significantly higher than before the coecal perforation and also higher than in the corresponding control rats. Moreover, CTLI in serum was under the same conditions significantly higher 10 and 15 h after the induction of peritonitis. Gel chromatography of peritoneal fluid and serum during peritonitis showed free CTLI and CTLI bound to both alpha-1-antitrypsin and alpha-2-macroglobulin, wheras only free CTLI could be detected in serum from control rats. These findings were accompanied by local ultrastructural changes in the acinar cells as evaluated by electron microscopy. The pathophysiologic implications of the findings are discussed

  20. Energy dependence of event shapes and of $\\alpha_s$ at LEP 2

    CERN Document Server

    Abreu, P; Adye, T; Adzic, P; Albrecht, Z; Alderweireld, T; Alekseev, G D; Alemany, R; Allmendinger, T; Allport, P P; Almehed, S; Amaldi, Ugo; Amapane, N; Amato, S; Anassontzis, E G; Andersson, P; Andreazza, A; Andringa, S; Antilogus, P; Apel, W D; Arnoud, Y; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Bambade, P; Barão, F; Barbiellini, Guido; Barbier, R; Bardin, Dimitri Yuri; Barker, G; Baroncelli, A; Battaglia, Marco; Baubillier, M; Becks, K H; Begalli, M; Behrmann, A; Beillière, P; Belokopytov, Yu A; Belous, K S; Benekos, N C; Benvenuti, Alberto C; Bérat, C; Berggren, M; Bertini, D; Bertrand, D; Besançon, M; Bianchi, F; Bigi, M; Bilenky, S M; Bizouard, M A; Bloch, D; Blom, H M; Bonesini, M; Bonivento, W; Boonekamp, M; Booth, P S L; Borgland, A W; Borisov, G; Bosio, C; Botner, O; Boudinov, E; Bouquet, B; Bourdarios, C; Bowcock, T J V; Boyko, I; Bozovic, I; Bozzo, M; Branchini, P; Brenke, T; Brenner, R A; Brückman, P; Brunet, J M; Bugge, L; Buran, T; Burgsmüller, T; Buschbeck, Brigitte; Buschmann, P; Cabrera, S; Caccia, M; Calvi, M; Camporesi, T; Canale, V; Carena, F; Carroll, L; Caso, Carlo; Castillo-Gimenez, M V; Cattai, A; Cavallo, F R; Chabaud, V; Chapkin, M M; Charpentier, P; Chaussard, L; Checchia, P; Chelkov, G A; Chierici, R; Chliapnikov, P V; Chochula, P; Chorowicz, V; Chudoba, J; Cieslik, K; Collins, P; Contri, R; Cortina, E; Cosme, G; Cossutti, F; Cowell, J H; Crawley, H B; Crennell, D J; Crépé, S; Crosetti, G; Cuevas-Maestro, J; Czellar, S; Davenport, Martyn; Da Silva, W; Deghorain, A; Della Ricca, G; Delpierre, P A; Demaria, N; De Angelis, A; de Boer, Wim; De Clercq, C; De Lotto, B; De Min, A; De Paula, L S; Dijkstra, H; Di Ciaccio, Lucia; Dolbeau, J; Doroba, K; Dracos, M; Drees, J; Dris, M; Duperrin, A; Durand, J D; Eigen, G; Ekelöf, T J C; Ekspong, Gösta; Ellert, M; Elsing, M; Engel, J P; Erzen, B; Espirito-Santo, M C; Falk, E; Fanourakis, G K; Fassouliotis, D; Fayot, J; Feindt, Michael; Fenyuk, A; Ferrari, P; Ferrer, A; Ferrer-Ribas, E; Ferro, F; Fichet, S; Firestone, A; Flagmeyer, U; Föth, H; Fokitis, E; Fontanelli, F; Franek, B J; Frodesen, A G; Frühwirth, R; Fulda-Quenzer, F; Fuster, J A; Galloni, A; Gamba, D; Gamblin, S; Gandelman, M; García, C; Gaspar, C; Gaspar, M; Gasparini, U; Gavillet, P; Gazis, E N; Gelé, D; Ghodbane, N; Gil, I; Glege, F; Gokieli, R; Golob, B; Gómez-Ceballos, G; Gonçalves, P; González-Caballero, I; Gopal, Gian P; Gorn, L; Górski, M; Guz, Yu; Gracco, Valerio; Grahl, J; Graziani, E; Green, C; Grimm, H J; Gris, P; Grosdidier, G; Grzelak, K; Günther, M; Guy, J; Hahn, F; Hahn, S; Haider, S; Hallgren, A; Hamacher, K; Hansen, J; Harris, F J; Hedberg, V; Heising, S; Hernández, J J; Herquet, P; Herr, H; Hessing, T L; Heuser, J M; Higón, E; Holmgren, S O; Holt, P J; Hoorelbeke, S; Houlden, M A; Hrubec, Josef; Huet, K; Hughes, G J; Hultqvist, K; Jackson, J N; Jacobsson, R; Jalocha, P; Janik, R; Jarlskog, C; Jarlskog, G; Jarry, P; Jean-Marie, B; Johansson, E K; Jönsson, P E; Joram, C; Juillot, P; Kapusta, F; Karafasoulis, K; Katsanevas, S; Katsoufis, E C; Keränen, R; Kersevan, Borut P; Khomenko, B A; Khovanskii, N N; Kiiskinen, A P; King, B J; Kinvig, A; Kjaer, N J; Klapp, O; Klein, H; Kluit, P M; Kokkinias, P; Koratzinos, M; Kostyukhin, V; Kourkoumelis, C; Kuznetsov, O; Krammer, Manfred; Kriznic, E; Krstic, J; Krumshtein, Z; Kubinec, P; Kurowska, J; Kurvinen, K L; Lamsa, J; Lane, D W; Langefeld, P; Lapin, V; Laugier, J P; Lauhakangas, R; Leder, Gerhard; Ledroit, F; Lefébure, V; Leinonen, L; Leisos, A; Leitner, R; Lemonne, J; Lenzen, Georg; Lepeltier, V; Lesiak, T; Lethuillier, M; Libby, J; Liko, D; Lipniacka, A; Lippi, I; Lörstad, B; Loken, J G; Lopes, J H; López, J M; López-Fernandez, R; Loukas, D; Lutz, P; Lyons, L; MacNaughton, J N; Mahon, J R; Maio, A; Malek, A; Malmgren, T G M; Maltezos, S; Malychev, V; Mandl, F; Marco, J; Marco, R P; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Martínez-Rivero, C; Martínez-Vidal, F; Martí i García, S; Mastroyiannopoulos, N; Matorras, F; Matteuzzi, C; Matthiae, Giorgio; Masik, J; Mazzucato, F; Mazzucato, M; McCubbin, M L; McKay, R; McNulty, R; McPherson, G; Meroni, C; Meyer, W T; Migliore, E; Mirabito, L; Mitaroff, Winfried A; Mjörnmark, U; Moa, T; Moch, M; Møller, R; Mönig, K; Monge, M R; Moreau, X; Morettini, P; Morton, G A; Müller, U; Münich, K; Mulders, M; Mulet-Marquis, C; Muresan, R; Murray, W J; Muryn, B; Myatt, Gerald; Myklebust, T; Naraghi, F; Nassiakou, M; Navarria, Francesco Luigi; Navas, S; Nawrocki, K; Negri, P; Némécek, S; Neufeld, N; Neumeister, N; Nicolaidou, R; Nielsen, B S; Nikolenko, M; Nomokonov, V P; Normand, Ainsley; Nygren, A; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, Risto; Orazi, G; Österberg, K; Ouraou, A; Paganoni, M; Paiano, S; Pain, R; Paiva, R; Palacios, J; Palka, H; Papadopoulou, T D; Papageorgiou, K; Pape, L; Parkes, C; Parodi, F; Parzefall, U; Passeri, A; Passon, O; Pegoraro, M; Peralta, L; Pernicka, Manfred; Perrotta, A; Petridou, C; Petrolini, A; Phillips, H T; Pierre, F; Pimenta, M; Piotto, E; Podobnik, T; Pol, M E; Polok, G; Poropat, P; Pozdnyakov, V; Privitera, P; Pukhaeva, N; Pullia, Antonio; Radojicic, D; Ragazzi, S; Rahmani, H; Ratoff, P N; Read, A L; Rebecchi, P; Redaelli, N G; Regler, Meinhard; Reid, D; Reinhardt, R; Renton, P B; Resvanis, L K; Richard, F; Rídky, J; Rinaudo, G; Røhne, O M; Romero, A; Ronchese, P; Rosenberg, E I; Rosinsky, P; Roudeau, Patrick; Rovelli, T; Royon, C; Ruhlmann-Kleider, V; Ruiz, A; Saarikko, H; Sacquin, Yu; Sadovskii, A; Sajot, G; Salt, J; Sampsonidis, D; Sannino, M; Schneider, H; Schwemling, P; Schwering, B; Schwickerath, U; Schyns, M A E; Scuri, F; Seager, P; Sedykh, Yu; Segar, A M; Sekulin, R L; Shellard, R C; Sheridan, A; Siebel, M; Simard, L C; Simonetto, F; Sissakian, A N; Smadja, G; Smirnov, N; Smirnova, O G; Smith, G R; Sopczak, André; Sosnowski, R; Spassoff, Tz; Spiriti, E; Sponholz, P; Squarcia, S; Stanescu, C; Stanic, S; Stevenson, K; Stocchi, A; Strub, R; Stugu, B; Szczekowski, M; Szeptycka, M; Tabarelli de Fatis, T; Tegenfeldt, F; Terranova, F; Thomas, J; Timmermans, J; Tinti, N; Tkatchev, L G; Todorova-Nová, S; Tomaradze, A G; Tomé, B; Tonazzo, A; Tortora, L; Tranströmer, G; Treille, D; Tristram, G; Trochimczuk, M; Troncon, C; Tsirou, A L; Turluer, M L; Tyapkin, I A; Tzamarias, S; Ullaland, O; Uvarov, V; Valenti, G; Vallazza, E; Van der Velde, C; van Apeldoorn, G W; van Dam, P; Van Doninck, W K; Van Eldik, J; Van Lysebetten, A; Van Vulpen, I B; Vassilopoulos, N; Vegni, G; Ventura, L; Venus, W A; Verbeure, F; Verlato, M; Vertogradov, L S; Verzi, V; Vilanova, D; Vitale, L; Vlasov, E; Vodopyanov, A S; Vollmer, C F; Voulgaris, G; Vrba, V; Wahlen, H; Walck, C; Weiser, C; Wicke, D; Wickens, J H; Wilkinson, G R; Winter, M; Witek, M; Wolf, G; Yi, J; Yushchenko, O P; Zaitsev, A; Zalewska-Bak, A; Zalewski, Piotr; Zavrtanik, D; Zevgolatakos, E; Zimin, N I; Zucchelli, G C; Zumerle, G

    1999-01-01

    Infrared and collinear safe event shape distributions and their mean values are determined using the data taken at ve di erent centre of mass energies above $M_Z$ with the DELPHI detector at LEP. From the event shapes, the strong coupling $\\alpha_s$ is extracted in $O(\\alpha^2_s)$, NLLA and a combined scheme using hadronisation corrections evaluated with fragmentation model generators as well as using an analytical power ansatz. Comparing these measurements to those obtained at MZ, the energy dependence (running) of $\\alpha_s$ is accessible. The logarithmic energy slope of the inverse strong coupling is measured to be $d\\alpha_{s}^{-1}/d log(E_{cm}) = 1.39 \\pm 0.34(stat) \\pm 0.17(syst)$, in good agreement with the QCD expectation of 1.27.

  1. Synthesis and antimicrobial evaluation of new 3-alkyl/aryl-2-[((alpha,alpha-diphenyl-alpha-hydroxy)acetyl)hydrazono]-5-methyl-4-thiazolidinones.

    Science.gov (United States)

    Güzeldemirci, Nuray Ulusoy; Ilhan, Eser; Küçükbasmaci, Omer; Satana, Dilek

    2010-01-01

    New 4-thiazolidinone derivatives of benzilic acid (alpha,alpha-diphenyl-alpha-hydroxyacetic acid) have been synthesized and evaluated for antibacterial and antifungal activities. The reaction of 1- (alpha,alpha-diphenyl-alpha-hydroxy)acetyl-4-alkyl/arylthiosemicarbazides with ethyl 2-bromopropionate gave 3-alkyl/aryl-2-[((alpha,alpha-diphenyl-alpha-hydroxy)acetyl)hydrazono]-5-methyl-4-thiazolidinone derivatives. Their antibacterial and antifungal activities were evaluated against S. aureus ATCC 29213, P. aeruginosa ATCC 27853, E. coli ATCC 25922, C. albicans ATCC 10231, C. parapsilosis ATCC 22019, C. krusei ATCC 6258, T. mentagrophytes var. erinacei NCPF 375, M. gypseum NCPF 580 and T. tonsurans NCPF 245. 3e, 3f, 3g and 3h showed the highest antibacterial activity. Particularly 3a and 3e showed the highest antifungal activities against C. parapsilosis ATCC 22019, T. tonsurans NCPF 245 and M. gypseum NCPF 580.

  2. α2-Macroglobulin Is a Significant In Vivo Inhibitor of Activated Protein C and Low APC:α2M Levels Are Associated with Venous Thromboembolism.

    Science.gov (United States)

    Martos, Laura; Ramón, Luis Andrés; Oto, Julia; Fernández-Pardo, Álvaro; Bonanad, Santiago; Cid, Ana Rosa; Gruber, Andras; Griffin, John H; España, Francisco; Navarro, Silvia; Medina, Pilar

    2018-04-01

     Activated protein C (APC) is a major regulator of thrombin formation. Two major plasma inhibitors form complexes with APC, protein C inhibitor (PCI) and α 1 -antitrypsin (α 1 AT), and these complexes have been quantified by specific enzyme-linked immunosorbent assays (ELISAs). Also, complexes of APC with α 2 -macroglobulin2 M) have been observed by immunoblotting. Here, we report an ELISA for APC:α 2 M complexes in plasma.  Plasma samples were pre-treated with dithiothreitol and then with iodoacetamide. The detection range of the newly developed APC:α 2 M assay was 0.031 to 8.0 ng/mL of complexed APC. Following infusions of APC in humans and baboons, complexes of APC with α 2 M, PCI and α 1 AT were quantified. These complexes as well as circulating APC were also measured in 121 patients with a history of venous thromboembolism (VTE) and 119 matched controls.  In all the in vivo experiments, α 2 M was a significant APC inhibitor. The VTE case-control study showed that VTE patients had significantly lower APC:α 2 M and APC levels than the controls ( p  APC:α 2 M or the lowest quartile of APC had approximately four times more VTE risk than those in the highest quartile of APC:α 2 M or of APC. The risk increased for individuals with low levels of both parameters.  The APC:α 2 M assay reported here may be useful to help monitor the in vivo fate of APC in plasma. In addition, our results show that a low APC:α 2 M level is associated with increased VTE risk. Schattauer GmbH Stuttgart.

  3. Activated α2 -Macroglobulin Induces Mesenchymal Cellular Migration Of Raw264.7 Cells Through Low-Density Lipoprotein Receptor-Related Protein 1.

    Science.gov (United States)

    Ferrer, Darío G; Dato, Virginia Actis; Fincati, Javier R Jaldín; Lorenc, Valeria E; Sánchez, María C; Chiabrando, Gustavo A

    2017-07-01

    Distinct modes of cell migration contribute to diverse types of cell movements. The mesenchymal mode is characterized by a multistep cycle of membrane protrusion, the formation of focal adhesion, and the stabilization at the leading edge associated with the degradation of extracellular matrix (ECM) components and with regulated extracellular proteolysis. Both α 2 -Macroglobulin2 M) and its receptor, low density lipoprotein receptor-related protein 1 (LRP1), play important roles in inflammatory processes, by controlling the extracellular activity of several proteases. The binding of the active form of α 2 M (α 2 M*) to LRP1 can also activate different signaling pathways in macrophages, thus inducing extracellular matrix metalloproteinase-9 (MMP-9) activation and cellular proliferation. In the present study, we investigated whether the α 2 M*/LRP1 interaction induces cellular migration of the macrophage-derived cell line, Raw264.7. By using the wound-scratch migration assay and confocal microscopy, we demonstrate that α 2 M* induces LRP1-mediated mesenchymal cellular migration. This migration exhibits the production of enlarged cellular protrusions, MT1-MMP distribution to these leading edge protrusions, actin polymerization, focal adhesion formation, and increased intracellular LRP1/β1-integrin colocalization. Moreover, the presence of calphostin-C blocked the α 2 M*-stimulated cellular protrusions, suggesting that the PKC activation is involved in the cellular motility of Raw264.7 cells. These findings could constitute a therapeutic target for inflammatory processes with deleterious consequences for human health, such as rheumatoid arthritis, atherosclerosis and cancer. J. Cell. Biochem. 118: 1810-1818, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Immunodetection of Thyroid Hormone Receptor (Alpha1/Alpha2) in the Rat Uterus and Oviduct

    International Nuclear Information System (INIS)

    Öner, Jale; Öner, Hakan

    2007-01-01

    The aim of this study was to investigate the immunolocalization and the existence of thyroid hormone receptors (THR) (alpha1/alpha2) in rat uterus and oviduct. For this purpose 6 female Wistar albino rats found in estrous period were used. Tissue samples fixed in 10% neutral formalin were examined immunohistochemically. Sections were incubated with primary mouse-monoclonal THR (alpha1/alpha2) antibody. In uterus, THR (alpha1/alpha2) immunoreacted strongly with uterine luminal epithelium, endometrial gland epithelium and endometrial stromal cells and, moderately with myometrial smooth muscle. In oviduct, they were observed moderately in the epithelium of the tube and the smooth muscle cells of the muscular layer. In conclusion, the presence of THR in uterus and oviduct suggests that these organs are an active site of thyroid hormones

  5. Taraxacum officinale induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

    Science.gov (United States)

    Koo, Hyun-Na; Hong, Seung-Heon; Song, Bong-Keun; Kim, Cheorl-Ho; Yoo, Young-Hyun; Kim, Hyung-Min

    2004-01-16

    Taraxacum officinale (TO) has been frequently used as a remedy for women's disease (e.g. breast and uterus cancer) and disorders of the liver and gallbladder. Several earlier studies have indicated that TO exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we investigated the effect of TO on the cytotoxicity and production of cytokines in human hepatoma cell line, Hep G2. Our results show that TO decreased the cell viability by 26%, and significantly increased the tumor necrosis factor (TNF)-alpha and interleukin (IL)-1alpha production compared with media control (about 1.6-fold for TNF-alpha, and 2.4-fold for IL-1alpha, P < 0.05). Also, TO strongly induced apoptosis of Hep G2 cells as determined by flow cytometry. Increased amounts of TNF-alpha and IL-1alpha contributed to TO-induced apoptosis. Anti-TNF-alpha and IL-1alpha antibodies almost abolished it. These results suggest that TO induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

  6. Characteristics of Endotoxin-Altering Fractions Derived from Normal Serum III. Isolation and Properties of Horse Serum α2-Macroglobulin

    Science.gov (United States)

    Yoshioka, Morimasa; Konno, Seishi

    1970-01-01

    The endotoxin-altering activity of fractions isolated from normal horse serum was examined by incubation of Salmonella typhosa strain 0-901 endotoxin (Boivin) in a solution of the fraction, and subsequent quantitation of any diminution in the capacity of endotoxin to be precipitated by specific anti-endotoxin antiserum. The horse serum fraction isolated by precipitation with ammonium sulfate at a concentration between 1.6 and 2.7 m was incubated with Pronase PA and then with trypsin. When this partly digested fraction was passed twice through a Sephadex G-200 column and eluted with 0.2 m tris(hydroxymethyl)aminomethane buffer, most of the endotoxinaltering activity was found in the first protein peak designated F-1a. F-1a was found to be homogeneous and corresponded to an α2-macroglobulin by the techniques of electrophoresis, immunodiffusion, and ultracentrifugation. Approximately 100-fold more F-1a than endotoxin was needed to reduce the antigenicity of the endotoxin by one-half. Alteration was increased when F-1a was incubated with the endotoxin at acid pH or at 45 C rather than at 37 C and was lost after heating F-1a at 56 C for 30 min. N-ethylmaleimide increased the endotoxin-altering activity of horse serum, F-1a, and human plasma fraction III0, whereas p-chloromercuribenzoate did not. On the other hand, diazonium-1-H-tetrazole, iodoacetic acid, and benzylchloride suppressed the activity of F-1a. When the interaction of endotoxin and F-1a was examined by immunodiffusion techniques, depolymerization of the endotoxin molecule was indicated. The endotoxin-altering factor of horse serum is discussed in relation to the mechanisms of other known reagents, such as deoxycholate and sodium lauryl sulfate. Images PMID:16557754

  7. HIF-1alpha and HIF-2alpha are differentially activated in distinct cell populations in retinal ischaemia.

    Directory of Open Access Journals (Sweden)

    Freya M Mowat

    2010-06-01

    Full Text Available Hypoxia plays a key role in ischaemic and neovascular disorders of the retina. Cellular responses to oxygen are mediated by hypoxia-inducible transcription factors (HIFs that are stabilised in hypoxia and induce the expression of a diverse range of genes. The purpose of this study was to define the cellular specificities of HIF-1alpha and HIF-2alpha in retinal ischaemia, and to determine their correlation with the pattern of retinal hypoxia and the expression profiles of induced molecular mediators.We investigated the tissue distribution of retinal hypoxia during oxygen-induced retinopathy (OIR in mice using the bio-reductive drug pimonidazole. We measured the levels of HIF-1alpha and HIF-2alpha proteins by Western blotting and determined their cellular distribution by immunohistochemistry during the development of OIR. We measured the temporal expression profiles of two downstream mediators, vascular endothelial growth factor (VEGF and erythropoietin (Epo by ELISA. Pimonidazole labelling was evident specifically in the inner retina. Labelling peaked at 2 hours after the onset of hypoxia and gradually declined thereafter. Marked binding to Müller glia was evident during the early hypoxic stages of OIR. Both HIF-1alpha and HIF-2alpha protein levels were significantly increased during retinal hypoxia but were evident in distinct cellular distributions; HIF-1alpha stabilisation was evident in neuronal cells throughout the inner retinal layers whereas HIF-2alpha was restricted to Müller glia and astrocytes. Hypoxia and HIF-alpha stabilisation in the retina were closely followed by upregulated expression of the downstream mediators VEGF and EPO.Both HIF-1alpha and HIF-2alpha are activated in close correlation with retinal hypoxia but have contrasting cell specificities, consistent with differential roles in retinal ischaemia. Our findings suggest that HIF-2alpha activation plays a key role in regulating the response of Müller glia to hypoxia.

  8. Alpha1 and Alpha2 Integrins Mediate Invasive Activity of Mouse Mammary Carcinoma Cells through Regulation of Stromelysin-1 Expression

    Energy Technology Data Exchange (ETDEWEB)

    Lochter, Andre; Navre, Marc; Werb, Zena; Bissell, Mina J

    1998-06-29

    Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits {alpha}6 and {beta}1, but not against {alpha}1 and {alpha}2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against {beta}1, but not against a6 or {alpha}2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against {alpha}1 integrins impaired only cell adhesion to type IV collagen. Antibodies against {alpha}1, {alpha}2, {alpha}6, and {beta}1, but not {alpha}5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins {alpha}1 and {alpha}2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against {alpha}1 and {alpha}2, but not {alpha}6 and {beta}1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1. Inhibition of tumor cell invasion by antibodies against {alpha}1 and {alpha}2 was reversed by addition of recombinant stromelysin-1. In contrast, stromelysin-1 could not rescue invasion inhibited by anti-{alpha}6 antibodies. Our data indicate that {alpha}1 and {alpha}2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas {alpha}6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion.

  9. Ubiquitous hazardous metal lead induces TNF-{alpha} in human phagocytic THP-1 cells: Primary role of ERK 1/2

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Mohd Imran [Fiber Toxicology Division, Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), Mahatma Gandhi Marg, P.O Box 80, Lucknow 226001, U.P. (India); Islam, Najmul [Department of Biochemistry, J.N Medical College, Aligarh Muslim University, Aligarh (India); Sahasrabuddhe, Amogh A. [Molecular and Structural Biology Division, Central Drug Research Institute, Lucknow (India); Mahdi, Abbas Ali [Department of Biochemistry, C.S.M. Medical University, Lucknow (India); Siddiqui, Huma; Ashquin, Mohd [Fiber Toxicology Division, Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), Mahatma Gandhi Marg, P.O Box 80, Lucknow 226001, U.P. (India); Ahmad, Iqbal, E-mail: ahmadi@sify.com [Fiber Toxicology Division, Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), Mahatma Gandhi Marg, P.O Box 80, Lucknow 226001, U.P. (India)

    2011-05-15

    Induction of tumor necrosis factor-{alpha} (TNF-{alpha}) in response to lead (Pb) exposure has been implicated in its immunotoxicity. However, the molecular mechanism by which Pb upregulates the level of TNF-{alpha} is wagely known. An attempt was therefore made to elucidate the mechanistic aspect of TNF-{alpha} induction, mainly focusing transcriptional and post transcriptional regulation via mitogen activated protein kinases (MAPKs) activation. We observed that exposure of Pb to human monocytic THP-1 cells resulted in significant enhanced production of TNF-{alpha} m-RNA and protein secretion. Moreover, the stability of TNF-{alpha} m-RNA was also increased as indicated by its half life. Notably, activation of ERK 1/2, p38 and JNK in Pb exposed THP-1 was also evident. Specific inhibitor of ERK1/2, PD 98059 caused significant inhibition in production and stability of TNF-{alpha} m-RNA. However, SB 203580 partially inhibited production and stability of TNF-{alpha} m-RNA. Interestingly, a combined exposure of these two inhibitors completely blocked modulation of TNF-{alpha} m-RNA. Data tends to suggest that expression and stability of TNF-{alpha} induction due to Pb exposure is mainly regulated through ERK. Briefly, these observations are useful in understanding some mechanistic aspects of proinflammatory and immunotoxicity of Pb, a globally acknowledged key environmental contaminant.

  10. Determination of the Crystal Structure of Human Zn-Alpha 2-Gylcoprotein, A Protein Implicated in Breast Cancer

    National Research Council Canada - National Science Library

    Bjorkman, Pamela

    2000-01-01

    Zn-alpha 2-glycoprotein (ZAG) is a 41 kDa soluble protein whose sequence and domain organization are surprisingly similar to those of the membrane glycoproteins of the major histocompatibility complex (MHC...

  11. Implications of alpha-decay for long term storage of advanced heavy water reactor fuels

    International Nuclear Information System (INIS)

    Pencer, J.; McDonald, M.H.; Roubtsov, D.; Edwards, G.W.R.

    2017-01-01

    Highlights: •Alpha decays versus storage time are calculated for examples of advanced heavy water reactor fuels. •Estimates are made for fuel swelling and helium bubble formation as a function of time. •These predictions are compared to predictions for natural uranium fuel. •Higher rates of damage are predicted for advanced heavy water reactor fuels than natural uranium. -- Abstract: The decay of actinides such as 238 Pu, results in recoil damage and helium production in spent nuclear fuels. The extent of the damage depends on storage time and spent fuel composition and has implications for the integrity of the fuels. Some advanced nuclear fuels intended for use in pressurized heavy water pressure tube reactors have high initial plutonium content and are anticipated to exhibit swelling and embrittlement, and to accumulate helium bubbles over storage times as short as hundreds of years. Calculations are performed to provide estimates of helium production and fuel swelling associated with alpha decay as a function of storage time. Significant differences are observed between predicted aging characteristics of natural uranium and the advanced fuels, including increased helium concentrations and accelerated fuel swelling in the latter. Implications of these observations for long term storage of advanced fuels are discussed.

  12. Concentration levels of alpha emitting radionuclides in natural waters. Implications in the use of various radionuclides of reference for the determination of total alpha activity index

    International Nuclear Information System (INIS)

    Corbacho, J. A.; Baeza, A.; Guillen, J.; Valles, I.; Serrano, I.; Camacho, A.; Montana, M.

    2013-01-01

    The present study was carried out a statistical evaluation of the natural radioactive contents of a large number of water samples collected at different points of the Spanish geography, in order to meet its controlling radioactive composition and assessing the implications of total alpha activity index can have in this type of samples. (Author)

  13. Vitreous advanced glycation endproducts and alpha-dicarbonyls in retinal detachment patients with type 2 diabetes mellitus and non-diabetic controls

    NARCIS (Netherlands)

    Fokkens, Bernardina T.; Mulder, Douwe J.; Schalkwijk, Casper G.; Scheijen, Jean L.; Smit, Andries J.; Los, Leonoor I.

    2017-01-01

    Purpose Advanced glycation endproducts (AGEs) and their precursors alpha-dicarbonyls are implicated in the progression of diabetic retinopathy. The purpose of this study was to assess AGEs and a-dicarbonyls in the vitreous of patients with type 2 diabetes mellitus (T2DM) with early stages or absence

  14. Tumor necrosis factor-alpha modulates human in vivo lipolysis

    DEFF Research Database (Denmark)

    Plomgaard, Peter; Fischer, Christian P; Ibfelt, Tobias

    2008-01-01

    CONTEXT: Low-grade systemic inflammation is a feature of most lifestyle-related chronic diseases. Enhanced TNF-alpha concentrations have been implicated in the development of hyperlipidemia. OBJECTIVE: We hypothesized that an acute elevation of TNF-alpha in plasma would cause an increase...... in lipolysis, increasing circulatory free fatty acid (FFA) levels. SUBJECTS AND METHODS: Using a randomized controlled, crossover design, healthy young male individuals (n = 10) received recombinant human (rh) TNF-alpha (700 ng/m(-2).h(-1)) for 4 h, and energy metabolism was evaluated using a combination...... of tracer dilution methodology and arterial-venous differences over the leg. RESULTS: Plasma TNF-alpha levels increased from 0.7 +/- 0.04 to 16.7 +/- 1.8 pg/ml, and plasma IL-6 increased from 1.0 +/- 0.2 to 9.2 +/- 1.0 pg/ml (P alpha infusion. Here, we demonstrate that 4-h rhTNF-alpha...

  15. IFN-alpha antibodies in patients with age-related macular degeneration treated with recombinant human IFN-alpha2a

    DEFF Research Database (Denmark)

    Ross, Christian; Engler, Claus Bødker; Sander, Birgit

    2002-01-01

    We tested for development of binding and neutralizing antibodies to interferon-alpha (IFN-alpha) during IFN-alpha2a therapy of patients with age-related macular degeneration (AMD) of the eyes. Antibodies were investigated retrospectively in sera of 34 patients treated with 3 x 10(6) IU IFN-alpha2...

  16. IFN-alpha antibodies in patients with age-related macular degeneration treated with recombinant human IFN-alpha2a

    DEFF Research Database (Denmark)

    Ross, Christian; Engler, Claus Bødker; Sander, Birgit

    2002-01-01

    We tested for development of binding and neutralizing antibodies to interferon-alpha (IFN-alpha) during IFN-alpha2a therapy of patients with age-related macular degeneration (AMD) of the eyes. Antibodies were investigated retrospectively in sera of 34 patients treated with 3 x 10(6) IU IFN-alpha2a...

  17. Peginterferon alpha-2a versus peginterferon alpha-2b for chronic hepatitis C

    DEFF Research Database (Denmark)

    Hauser, Goran; Awad, Tahany; Thorlund, Kristian

    2014-01-01

    virological response in the blood serum compared with peginterferon alpha-2b (1069/2099 (51%) versus 1327/3075 (43%); RR 1.12, 95% CI 1.06 to 1.18; I(2)= 0%, 12 trials; moderate quality evidence). Trial sequential analyses supported this result. Subgroup analyses based on risk of bias, viral genotype...

  18. Compensatory increase in alpha 1-globin gene expression in individuals heterozygous for the alpha-thalassemia-2 deletion.

    OpenAIRE

    Liebhaber, S A; Cash, F E; Main, D M

    1985-01-01

    alpha-Globin is encoded by the two adjacent genes, alpha 1 and alpha 2. Although it is clearly established that both alpha-globin genes are expressed, their relative contributions to alpha-globin messenger RNA (mRNA) and protein synthesis are not fully defined. Furthermore, changes that may occur in alpha-globin gene activity secondarily to the loss of function of one or more of these genes (alpha-thalassemia [Thal]) have not been directly investigated. This study further defines the expressi...

  19. Inhibition of HIF-2.alpha. heterodimerization with HIF1.beta. (ARNT)

    Science.gov (United States)

    Bruick, Richard K.; Caldwell, Charles G.; Frantz, Doug E.; Gardner, Kevin H.; MacMillan, John B.; Scheuermann, Thomas H.; Tambar, Uttam K.

    2017-09-12

    Provided is a method of inhibiting heterodimerization of HIF-2.alpha. to HIF1.beta. (ARNT) comprising binding certain small molecules to the HIF-2.alpha. PAS-B domain cavity but not to HIF1.alpha. and inhibiting HIF-2.alpha. heterodimerization to HIF1.beta. (ARNT) but not inhibiting HIF1.alpha. heterodimerization to HIF1.beta. (ARNT). Those certain small molecules are also referenced synonymously as HIF2-HDI and HIF2.alpha. heterodimerization inhibitors and also simply as certain small molecules.

  20. Color image enhancement of medical images using alpha-rooting and zonal alpha-rooting methods on 2D QDFT

    Science.gov (United States)

    Grigoryan, Artyom M.; John, Aparna; Agaian, Sos S.

    2017-03-01

    2-D quaternion discrete Fourier transform (2-D QDFT) is the Fourier transform applied to color images when the color images are considered in the quaternion space. The quaternion numbers are four dimensional hyper-complex numbers. Quaternion representation of color image allows us to see the color of the image as a single unit. In quaternion approach of color image enhancement, each color is seen as a vector. This permits us to see the merging effect of the color due to the combination of the primary colors. The color images are used to be processed by applying the respective algorithm onto each channels separately, and then, composing the color image from the processed channels. In this article, the alpha-rooting and zonal alpha-rooting methods are used with the 2-D QDFT. In the alpha-rooting method, the alpha-root of the transformed frequency values of the 2-D QDFT are determined before taking the inverse transform. In the zonal alpha-rooting method, the frequency spectrum of the 2-D QDFT is divided by different zones and the alpha-rooting is applied with different alpha values for different zones. The optimization of the choice of alpha values is done with the genetic algorithm. The visual perception of 3-D medical images is increased by changing the reference gray line.

  1. Flavonoids-induced accumulation of hypoxia-inducible factor (HIF)-1alpha/2alpha is mediated through chelation of iron.

    Science.gov (United States)

    Park, Sung-Soo; Bae, Insoo; Lee, Yong J

    2008-04-15

    Hypoxia-inducible factor-1 alpha (HIF-1alpha) is the regulatory subunit of the heterodimeric transcription factor HIF-1 that is the key regulator of cellular response to low oxygen tension. Under normoxic conditions, HIF-1alpha is continuously degraded by the ubiquitin-proteasome pathway through pVHL (von Hippel-Lindau tumor suppressor protein). Under hypoxic conditions, HIF-1alpha is stabilized and induces the transcription of HIF-1 target genes. Quercetin, a flavonoid with anti-oxidant, anti-inflammatory, and kinase modulating properties, has been found to induce HIF-1alpha accumulation and VEGF secretion in normoxia. In this study, the molecular mechanisms of quercetin-mediated HIF-1alpha accumulation were investigated. Previous studies have shown that, in addition to being induced by hypoxia, HIF-1alpha can be induced through the phosphatidylinositol 3-kinase (PI3K)/Akt and p53 signaling pathways. But our study revealed, through p53 mutant-type as well as p53 null cell lines, that neither the PI3K/Akt nor the p53 signaling pathway is required for quercetin-induced HIF-1alpha accumulation. And we observed that HIF-1alpha accumulated by quercetin is not ubiquitinated and the interaction of HIF-1alpha with pVHL is reduced, compared with HIF-1alpha accumulated by the proteasome inhibitor MG132. The use of quercetin's analogues showed that only quercetin and galangin induce HIF-1/2alpha accumulation and this effect is completely reversed by additional iron ions. This is because quercetin and galangin are able to chelate cellular iron ions that are cofactors of HIF-1/2alpha proline hydroxylase (PHD). These data suggest that quercetin inhibits the ubiquitination of HIF-1/2alpha in normoxia by hindering PHD through chelating iron ions.

  2. Role of alpha2C-adrenoceptor subtype in spatial working memory as revealed by mice with targeted disruption of the alpha2C-adrenoceptor gene.

    Science.gov (United States)

    Tanila, H; Mustonen, K; Sallinen, J; Scheinin, M; Riekkinen, P

    1999-02-01

    The role of the alpha2C-adrenoceptor subtype in mediating the beneficial effect of alpha2-adrenoceptor agonists on spatial working memory was studied in adult mice with targeted inactivation of the alpha2C-receptor gene (KO) and their wild-type controls (WT). A delayed alternation task was run in a T-maze with mixed delays varying from 20 s to 120 s. Dexmedetomidine, a specific but subtype nonselective alpha2-adrenoceptor agonist, dose-dependently decreased the total number of errors. The effect was strongest at the dose of 5 microg/kg (s.c.), and was observed similarly in KO and WT mice. KO mice performed inferior to WT mice due to a higher number of perseverative errors. Dexmedetomidine slowed initiation of the motor response in the start phase at lower doses in WT mice than in KO mice but no such difference was observed in the return phase of the task, suggesting involvement of alpha2C-adrenoceptors in the cognitive aspect of response preparation or in response sequence initiation. According to these findings, enhancement of spatial working memory is best achieved with alpha2-adrenoceptor agonists which have neither agonistic nor antagonistic effects at the alpha2C-adrenoceptor subtype.

  3. Molecular basis for nondeletion alpha-thalassemia in American blacks. Alpha 2(116GAG----UAG).

    OpenAIRE

    Liebhaber, S A; Coleman, M B; Adams, J G; Cash, F E; Steinberg, M H

    1987-01-01

    An American black woman was found to have the phenotype of moderately severe alpha-thalassemia normally associated with the loss of two to three alpha-globin genes despite an alpha-globin gene map that demonstrated the loss of only a single alpha-globin gene (-alpha/alpha alpha). Several individuals in her kindred with normal alpha-globin gene mapping studies (alpha alpha/alpha alpha) had mild alpha-thalassemia hematologic values consistent with the loss of one to two alpha-globin genes. Thes...

  4. Urinary IgG and α2-Macroglobulin Are Powerful Predictors of Outcome and Responsiveness to Steroids and Cyclophosphamide in Idiopathic Focal Segmental Glomerulosclerosis with Nephrotic Syndrome

    Directory of Open Access Journals (Sweden)

    Claudio Bazzi

    2013-01-01

    Full Text Available Objective. To assess whether high-molecular-weight proteins excretion predicts outcome and therapy-responsiveness in patients with FSGS and nephrotic syndrome. Research Design and Methods. Thirty-eight patients measured at biopsy fractional excretion of IgG (FEIgG and urinary α2-macroglobulin/creatinine ratio (α2m/C. Low and high risk groups were defined by cutoffs assessed by ROC analysis. In all patients first-line therapy was with steroids alone or in combination with cyclophosphamide. Results. α2m/C and FEIgG were correlated with segmental sclerosis (r=0.546; r=0.522. Twenty-three patients (61% entered Remission and 9 (24% progressed to ESRD. Comparing low and high risk groups, by univariate analysis remission was predicted by FEIgG (77% versus 25%, P=0.016 and α2m/C (81% versus 17%, P=0.007 and ESRD at best by FEIgG (0% versus 75%, P<0.0001 and α2m/C (4% versus 67%, P<0.0001. By multivariate analysis FEIgG was the only independent predictor of remission and α2m/C the most powerful predictor of ESRD. Low and high risk groups of FEIgG and α2m/C in combination had very high predictive value of sustained remission and ESRD in response to therapy. Conclusions. FEIgG and α2m/C are powerful predictors of outcome and responsiveness to steroids and cyclophosphamide; their predictive value, if validated in prospective studies, may be useful in clinical practice suggesting first-line alternative treatments in high risk patients.

  5. Binding of ADAM12, a marker of skeletal muscle regeneration, to the muscle-specific actin-binding protein, alpha -actinin-2, is required for myoblast fusion

    DEFF Research Database (Denmark)

    Galliano, M F; Huet, C; Frygelius, J

    2000-01-01

    ADAM12 belongs to the transmembrane metalloprotease ADAM ("a disintegrin and metalloprotease") family. ADAM12 has been implicated in muscle cell differentiation and fusion, but its precise function remains unknown. Here, we show that ADAM12 is dramatically up-regulated in regenerated, newly formed...... of differentiation. Using the yeast two-hybrid screen, we found that the muscle-specific alpha-actinin-2 strongly binds to the cytoplasmic tail of ADAM12. In vitro binding assays with GST fusion proteins confirmed the specific interaction. The major binding site for alpha-actinin-2 was mapped to a short sequence...... in a dominant negative fashion by inhibiting fusion of C2C12 cells, whereas expression of a cytosolic ADAM12 lacking the major alpha-actinin-2 binding site had no effect on cell fusion. Our results suggest that interaction of ADAM12 with alpha-actinin-2 is important for ADAM12 function....

  6. Radial-velocity variations in Alpha Ori, Alpha Sco, and Alpha Her

    International Nuclear Information System (INIS)

    Smith, M.A.; Patten, B.M.; Goldberg, L.

    1989-01-01

    Radial-velocity observations of Alpha Ori, Alpha Sco A, and Alpha Her A are used to study radial-velocity periodicities in M supergiants. The data refer to several metallic lines in the H-alpha region and to H-alpha itself. It is shown that Alpha Ori and Alpha Sco A have cycle lengths of about 1 yr and semiamplitudes of 2 km/s. It is suggested that many semiregular red supergiant varibles such as Alpha Ori may be heading toward chaos. All three stars show short-term stochastic flucutations with an amplitude of 1-2 km/s. It is found that the long-term variability of H-alpha velocities may be a consequence of intermittent failed ejections. 58 refs

  7. Expression and characterization of a recombinant maize CK-2 alpha subunit

    DEFF Research Database (Denmark)

    Boldyreff, B; Meggio, F; Dobrowolska, G

    1993-01-01

    to support the immunological data also by biochemical and biophysical experiments the availability of a recombinant CK-2 alpha from maize was a prerequisite. A maize cDNA clone of maize CK-2 alpha was expressed in the bacterial strain BL21 (DE3). The recombinant protein was purified to homogeneity; its......CKIIB, one of the CK-2 like enzymes which have been isolated from maize, has been shown to be a monomeric enzyme that cross-reacts with anti CK-2 alpha specific antibodies suggesting a possible relationship between the two proteins (Dobrowolska et al. (1992) Eur. J. Biochem. 204, 299-303). In order...... molecular mass on one-dimensional SDS PAGE was estimated to be 36.5 kDa. The calculated molecular mass according to the amino acid composition is 39,228 Da (332 amino acids). The recombinant maize CK-2 alpha (rmCK-2 alpha) exhibited mostly the same properties as the recombinant human CK-2 alpha (rhCK-2...

  8. Pancreatic cellular injury after cardiac surgery with cardiopulmonary bypass: frequency, time course and risk factors.

    Science.gov (United States)

    Nys, Monique; Venneman, Ingrid; Deby-Dupont, Ginette; Preiser, Jean-Charles; Vanbelle, Sophie; Albert, Adelin; Camus, Gérard; Damas, Pierre; Larbuisson, Robert; Lamy, Maurice

    2007-05-01

    Although often clinically silent, pancreatic cellular injury (PCI) is relatively frequent after cardiac surgery with cardiopulmonary bypass; and its etiology and time course are largely unknown. We defined PCI as the simultaneous presence of abnormal values of pancreatic isoamylase and immunoreactive trypsin (IRT). The frequency and time evolution of PCI were assessed in this condition using assays for specific exocrine pancreatic enzymes. Correlations with inflammatory markers were searched for preoperative risk factors. One hundred ninety-three patients submitted to cardiac surgery were enrolled prospectively. Blood IRT, amylase, pancreatic isoamylase, lipase, and markers of inflammation (alpha1-protease inhibitor, alpha2-macroglobulin, myeloperoxidase) were measured preoperatively and postoperatively until day 8. The postoperative increase in plasma levels of pancreatic enzymes and urinary IRT was biphasic in all patients: early after surgery and later (from day 4 to 8 after surgery). One hundred thirty-three patients (69%) experienced PCI, with mean IRT, isoamylase, and alpha1-protease inhibitor values higher for each sample than that in patients without PCI. By multiple regression analysis, we found preoperative values of plasma IRT >or=40 ng/mL, amylase >or=42 IU/mL, and pancreatic isoamylase >or=20 IU/L associated with a higher incidence of postsurgery PCI (P < 0.005). In the PCI patients, a significant correlation was found between the 4 pancreatic enzymes and urinary IRT, total calcium, myeloperoxidase, alpha1-protease inhibitor, and alpha2-macroglobulin. These data support a high prevalence of postoperative PCI after cardiac surgery with cardiopulmonary bypass, typically biphasic and clinically silent, especially when pancreatic enzymes were elevated preoperatively.

  9. Canine serum protein patterns using high-resolution electrophoresis (HRE).

    Science.gov (United States)

    Abate, O; Zanatta, R; Malisano, T; Dotta, U

    2000-03-01

    Serum protein values were determined in 26 healthy dogs using agarose gel electrophoresis (SPE), splitting the electrophoretic separation into six regions: albumin, alpha(1), alpha(2), beta(1), beta(2)and gamma globulins. High-resolution electrophoresis (HRE) was used to separate single proteins. Serum proteins from dogs (26 healthy and 20 affected by various diseases) were then characterized by electrophoretic immunofixation (IFE) and Sudan black staining on HRE film. Haemoglobin and normal canine plasma and serum were used to identify haptoglobin and fibrinogen, respectively. In the standard pattern, determined by HRE, the following proteins were identified: albumin, alpha(1)-lipoprotein (alpha(1)-region), haptoglobin and alpha(2)-macroglobulin (alpha(2)-region), beta -lipoprotein and C3 (beta(1)-region), transferrin and IgM (beta(2)-region), IgG (mostly in gamma -region and partly in beta(2)-region). The HRE pattern shown by healthy dogs could be compared with those of dogs affected by various diseases to obtain clinical information. Copyright 2000 Harcourt Publishers Ltd.

  10. Induction of human airway hyperresponsiveness by tumour necrosis factor-alpha.

    Science.gov (United States)

    Anticevich, S Z; Hughes, J M; Black, J L; Armour, C L

    1995-09-15

    Tumour necrosis factor-alpha (TNF alpha) is implicated in the pathogenesis of asthma; however, little is known of its direct effect on smooth muscle reactivity. We investigated the effect of TNF alpha on the responsiveness of human bronchial tissue to electrical field stimulation in vitro. Incubation of non-sensitized tissue with 1 nM, 3 nM and 10 nM TNF alpha significantly increased responsiveness to electrical field stimulation (113 +/- 8, 110 +/- 4 and 112 +/- 2% respectively) compared to control (99 +/- 2%) (P 0.05) nor were responses to exogenous acetylcholine (93 +/- 4% versus 73 +/- 7%, n = 3, P = 0.38). These results show that TNF alpha causes an increase in responsiveness of human bronchial tissue and that this occurs prejunctionally on the parasympathetic nerve pathway. This is the first report of a cytokine increasing human airway tissue responsiveness.

  11. {alpha}-Sb{sub 2}O{sub 4}-induced improvements of the catalytic behavior of MoO{sub 3}-(010) in the oxygen-assisted dehydration of 2-butanol: implications in selective oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Gaigneaux, E.M. [Fonds National de la Recherche Scientifique of Belgium (Belgium); Naeye, M.L.; Dupont, O.; Ruiz, P.; Delmon, B. [Unite de Catalyse et Chimie des Materiaux Divises, Universite Catholique de Louvain, Louvain-La-Neuve (Belgium); Callant, M.; Kartheuser, B. [CERTECH, Senefffe (Belgium)

    1998-12-31

    This article concerns the synergetic effects between an MoO{sub 3} sample composed of crystallites exposing preferentially the (010) basal faces and {alpha}-Sb{sub 2}O{sub 4} in the oxygen-assisted dehydration of 2-butanol at 220 C. The conversion of 2-butanol and the yield to butene improved when MoO{sub 3} was reacted in the presence of {alpha}-Sb{sub 2}O{sub 4}. The origin of the synergism is discussed. When reacted in the absence of {alpha}-Sb{sub 2}O{sub 4}, MoO{sub 3} got over-reduced and fragmented to MoO{sub 2}. MoO{sub 2} is intrinsically less active than MoO{sub 3} thus explaining that the deep reduction of MoO{sub 3} corresponds to its tendency to deactivate. In the presence of {alpha}-Sb{sub 2}O{sub 4}, the formation of MoO{sub 2} is inhibited with, as a consequence, the absence of deactivation. This leads to the synergetic effects obtained with the mechanical mixture of MoO{sub 3} with {alpha}-Sb{sub 2}O{sub 4}. (orig.)

  12. Genomic organization of the rat alpha 2u-globulin gene cluster.

    Science.gov (United States)

    McFadyen, D A; Addison, W; Locke, J

    1999-05-01

    The alpha 2u-globulin are a group of similar proteins, belonging to the lipocalin superfamily of proteins, that are synthesized in a subset of secretory tissues in rats. The many alpha 2u-globulin isoforms are encoded by a multigene family that exhibits extensive homology. Despite a high degree of sequence identity, individual family members show diverse expression patterns involving complex hormonal, tissue-specific, and developmental regulation. Analysis suggests that there are approximately 20 alpha 2u-globulin genes in the rat genome. We have used fluorescence in situ hybridization (FISH) to show that the alpha 2u-globulin genes are clustered at a single site on rat Chromosome (Chr) 5 (5q22-24). Southern blots of rat genomic DNA separated by pulsed field gel electrophoresis indicated that the alpha 2u-globulin genes are contained on two NruI fragments with a total size of 880 kbp. Analysis of three P1 clones containing alpha 2u-globulin genes indicated that the alpha 2u-globulin genes are tandemly arranged in a head-to-tail fashion. The organization of the alpha 2u-globulin genes in the rat as a tandem array of single genes differs from the homologous major urinary protein genes in the mouse, which are organized as tandem arrays of divergently oriented gene pairs. The structure of these gene clusters may have consequences for the proposed function, as a pheromone transporter, for the protein products encoded by these genes.

  13. Assignment of casein kinase 2 alpha sequences to two different human chromosomes

    DEFF Research Database (Denmark)

    Boldyreff, B; Klett, C; Göttert, E

    1992-01-01

    Human casein kinase 2 alpha gene (CK-2-alpha) sequences have been localized within the human genome by in situ hybridization and somatic cell hybrid analysis using a CK-2 alpha cDNA as a probe. By in situ hybridization, the CK-2 alpha cDNA could be assigned to two different loci, one on 11p15.1-ter...

  14. Intraethnic variation in steroid-5-alpha-reductase polymorphisms in ...

    Indian Academy of Sciences (India)

    2015-06-01

    Jun 1, 2015 ... in prostate cancer patients: a potential factor implicated ... reductase alpha polypeptides 1 and 2 in a set of 601 prostate cancer patients from four ..... tion in the key androgen-regulating genes androgen receptor, cytochrome ...

  15. Complete primary structure of rainbow trout type I collagen consisting of alpha1(I)alpha2(I)alpha3(I) heterotrimers.

    Science.gov (United States)

    Saito, M; Takenouchi, Y; Kunisaki, N; Kimura, S

    2001-05-01

    The subunit compositions of skin and muscle type I collagens from rainbow trout were found to be alpha1(I)alpha2(I)alpha3(I) and [alpha1(I)](2)alpha2(I), respectively. The occurrence of alpha3(I) has been observed only for bonyfish. The skin collagen exhibited more susceptibility to both heat denaturation and MMP-13 digestion than the muscle counterpart; the former had a lower denaturation temperature by about 0.5 degrees C than the latter. The lower stability of skin collagen, however, is not due to the low levels of imino acids because the contents of Pro and Hyp were almost constant in both collagens. On the other hand, some cDNAs coding for the N-terminal and/or a part of triple-helical domains of proalpha(I) chains were cloned from the cDNA library of rainbow trout fibroblasts. These cDNAs together with the previously cloned collagen cDNAs gave information about the complete primary structure of type I procollagen. The main triple-helical domain of each proalpha(I) chain had 338 uninterrupted Gly-X-Y triplets consisting of 1014 amino acids and was unique in its high content of Gly-Gly doublets. In particular, the bonyfish-specific alpha(I) chain, proalpha3(I) was characterized by the small number of Gly-Pro-Pro triplets, 19, and the large number of Gly-Gly doublets, 38, in the triple-helical domain, compared to 23 and 22, respectively, for proalpha1(I). The small number of Gly-Pro-Pro and the large number of Gly-Gly in proalpha3(I) was assumed to partially loosen the triple-helical structure of skin collagen, leading to the lower stability of skin collagen mentioned above. Finally, phylogenetic analyses revealed that proalpha3(I) had diverged from proalpha1(I). This study is the first report of the complete primary structure of fish type I procollagen.

  16. Field production and functional evaluation of chloroplast-derived interferon-alpha2b.

    Science.gov (United States)

    Arlen, Philip A; Falconer, Regina; Cherukumilli, Sri; Cole, Amy; Cole, Alexander M; Oishi, Karen K; Daniell, Henry

    2007-07-01

    Type I interferons (IFNs) inhibit viral replication and cell growth and enhance the immune response, and therefore have many clinical applications. IFN-alpha2b ranks third in world market use for a biopharmaceutical, behind only insulin and erythropoietin. The average annual cost of IFN-alpha2b for the treatment of hepatitis C infection is $26,000, and is therefore unavailable to the majority of patients in developing countries. Therefore, we expressed IFN-alpha2b in tobacco chloroplasts, and transgenic lines were grown in the field after obtaining United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) approval. Stable, site-specific integration of transgenes into chloroplast genomes and homoplasmy through several generations were confirmed. IFN-alpha2b levels reached up to 20% of total soluble protein, or 3 mg per gram of leaf (fresh weight). Transgenic IFN-alpha2b had similar in vitro biological activity to commercially produced PEG-Introntrade mark when tested for its ability to protect cells against cytopathic viral replication in the vesicular stomatitis virus cytopathic effect (VSV CPE) assay and to inhibit early-stage human immunodeficiency virus (HIV) infection. The antitumour and immunomodulating properties of IFN-alpha2b were also seen in vivo. Chloroplast-derived IFN-alpha2b increased the expression of major histocompatibility complex class I (MHC I) on splenocytes and the total number of natural killer (NK) cells. Finally, IFN-alpha2b purified from chloroplast transgenic lines (cpIFN-alpha2b) protected mice from a highly metastatic tumour line. This demonstration of high levels of expression of IFN-alpha2b, transgene containment and biological activity akin to that of commercial preparations of IFN-alpha2b facilitated the first field production of a plant-derived human blood protein, a critical step towards human clinical trials and commercialization.

  17. Expression and functional importance of collagen-binding integrins, alpha 1 beta 1 and alpha 2 beta 1, on virus-activated T cells

    DEFF Research Database (Denmark)

    Andreasen, Susanne Ø; Thomsen, Allan R; Koteliansky, Victor E

    2003-01-01

    decreased responses were seen upon transfer of alpha(1)-deficient activated/memory T cells. Thus, expression of alpha(1)beta(1) and alpha(2)beta(1) integrins on activated T cells is directly functionally important for generation of inflammatory responses within tissues. Finally, the inhibitory effect......Adhesive interactions are crucial to cell migration into inflammatory sites. Using murine lymphocytic choriomeningitis virus as an Ag model system, we have investigated expression and function of collagen-binding integrins, alpha(1)beta(1) and alpha(2)beta(1), on activated and memory T cells. Using...... this system and MHC tetramers to define Ag-specific T cells, we demonstrate that contrary to being VLAs, expression of alpha(1)beta(1) and alpha(2)beta(1) can be rapidly induced on acutely activated T cells, that expression of alpha(1)beta(1) remains elevated on memory T cells, and that expression of alpha(1...

  18. Secondary reduction of alpha7B integrin in laminin alpha2 deficient congenital muscular dystrophy supports an additional transmembrane link in skeletal muscle.

    Science.gov (United States)

    Cohn, R D; Mayer, U; Saher, G; Herrmann, R; van der Flier, A; Sonnenberg, A; Sorokin, L; Voit, T

    1999-03-01

    The integrins are a large family of heterodimeric transmembrane cellular receptors which mediate the association between the extracellular matrix (ECM) and cytoskeletal proteins. The alpha7beta1 integrin is a major laminin binding integrin in skeletal and cardiac muscle and is thought to be involved in myogenic differentiation and migration processes. The main binding partners of the alpha7 integrin are laminin-1 (alpha1-beta1-gamma1), laminin-2 (alpha2-beta1-gamma1) and laminin-4 (alpha2-beta2-gamma1). Targeted deletion of the gene for the alpha7 integrin subunit (ITGA7) in mice leads to a novel form of muscular dystrophy. In the present study we have investigated the expression of two alternative splice variants, the alpha7B and beta1D integrin subunits, in normal human skeletal muscle, as well as in various forms of muscular dystrophy. In normal human skeletal muscle the expression of the alpha7 integrin subunit appeared to be developmentally regulated: it was first detected at 2 years of age. In contrast, the beta1D integrin could be detected in immature and mature muscle in the sarcolemma of normal fetal skeletal muscle at 18 weeks gestation. The expression of alpha7B integrin was significantly reduced at the sarcolemma in six patients with laminin alpha2 chain deficient congenital muscular dystrophy (CMD) (age >2 years). However, this reduction was not correlated with the amount of laminin alpha2 chain expressed. In contrast, the expression of the laminin alpha2 chain was not altered in the skeletal muscle of the alpha7 knock-out mice. These data argue in favor that there is not a tight correlation between the expression of the alpha7 integrin subunit and that of the laminin alpha2 chain in either human or murine dystrophic muscle. Interestingly, in dystrophinopathies (Duchenne and Becker muscular dystrophy; DMD/BMD) expression of alpha7B was upregulated irrespective of the level of dystrophin expression as shown by a strong sarcolemmal staining pattern even

  19. PGC-1{alpha} accelerates cytosolic Ca{sup 2+} clearance without disturbing Ca{sup 2+} homeostasis in cardiac myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Min, E-mail: chenminyx@gmail.com [Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871 (China); Yunnan Centers for Diseases Prevention and Control, Kunming 650022 (China); Wang, Yanru [Institute of Molecular Medicine, State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing 100871 (China); Qu, Aijuan [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2010-06-11

    Energy metabolism and Ca{sup 2+} handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1{alpha}) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1{alpha} in cardiac Ca{sup 2+} signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1{alpha} via adenoviral transduction. Our data shows that overexpressing PGC-1{alpha} improved myocyte contractility without increasing the amplitude of Ca{sup 2+} transients, suggesting that myofilament sensitivity to Ca{sup 2+} increased. Interestingly, the decay kinetics of global Ca{sup 2+} transients and Ca{sup 2+} waves accelerated in PGC-1{alpha}-expressing cells, but the decay rate of caffeine-elicited Ca{sup 2+} transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca{sup 2+}-ATPase (SERCA2a), but not Na{sup +}/Ca{sup 2+} exchange (NCX) contribute to PGC-1{alpha}-induced cytosolic Ca{sup 2+} clearance. Furthermore, PGC-1{alpha} induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1{alpha} did not disturb cardiac Ca{sup 2+} homeostasis, because SR Ca{sup 2+} load and the propensity for Ca{sup 2+} waves remained unchanged. These data suggest that PGC-1{alpha} can ameliorate cardiac Ca{sup 2+} cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1{alpha}-calcium handing pathway sheds new light on the role of PGC-1{alpha} in the therapy of cardiac diseases.

  20. Functional labeling of insulin receptor subunits in live cells. Alpha 2 beta 2 species is the major autophosphorylated form

    International Nuclear Information System (INIS)

    Le Marchand-Brustel, Y.; Ballotti, R.; Gremeaux, T.; Tanti, J.F.; Brandenburg, D.; Van Obberghen, E.

    1989-01-01

    Both receptor subunits were functionally labeled in order to provide methods allowing, in live cells and in broken cell systems, concomitant evaluation of the insulin receptor dual function, hormone binding, and kinase activity. In cell-free systems, insulin receptors were labeled on their alpha-subunit with 125I-photoreactive insulin, and on their beta-subunit by autophosphorylation. Thereafter, phosphorylated receptors were separated from the complete set of receptors by means of anti-phosphotyrosine antibodies. Using this approach, a subpopulation of receptors was found which had bound insulin, but which were not phosphorylated. Under nonreducing conditions, receptors appeared in three oligomeric species identified as alpha 2 beta 2, alpha 2 beta, and alpha 2. Mainly the alpha 2 beta 2 receptor species was found to be phosphorylated while insulin was bound to alpha 2 beta 2, alpha 2 beta, and alpha 2 forms. In live cells, biosynthetic labeling of insulin receptors was used. Receptors were first labeled with [35S]methionine. Subsequently, the addition of insulin led to receptor autophosphorylation by virtue of the endogenous ATP pool. The total amount of [35S]methionine-labeled receptors was precipitated with antireceptor antibodies, whereas with anti-phosphotyrosine antibodies, only the phosphorylated receptors were isolated. Using this approach we made the two following key findings: (1) Both receptor species, alpha 2 beta 2 and alpha 2 beta, are present in live cells and in comparable amounts. This indicates that the alpha 2 beta form is not a degradation product of the alpha 2 beta 2 form artificially generated during receptor preparation. (2) The alpha 2 beta 2 species is the prevalently autophosphorylated form

  1. Hemoglobin alpha 2 gene +861 G>A polymorphism in Turkish ...

    African Journals Online (AJOL)

    Thalassemia is an inherited blood disorder which is divided into two groups: alpha and beta. HBA1 and HBA2 are the two genes associated with alpha thalassemia. The aim of this study is to investigate abnormal hemoglobin variants of alpha globin gene in healthy abnormal hemoglobin carrying individuals with intact beta ...

  2. Jet Production in ep Collisions at Low Q^2 and Determination of $\\alpha_{s}$

    CERN Document Server

    Aaron, F.D.; Alexa, C.; Andreev, V.; Antunovic, B.; Backovic, S.; Baghdasaryan, A.; Barrelet, E.; Bartel, W.; Begzsuren, K.; Belousov, A.; Bizot, J.C.; Boudry, V.; Bozovic-Jelisavcic, I.; Bracinik, J.; Brandt, G.; Brinkmann, M.; Brisson, V.; Bruncko, D.; Bunyatyan, A.; Buschhorn, G.; Bystritskaya, L.; Campbell, A.J.; Cantun Avila, K.B.; Cerny, K.; Cerny, V.; Chekelian, V.; Cholewa, A.; Contreras, J.G.; Coughlan, J.A.; Cozzika, G.; Cvach, J.; Dainton, J.B.; Daum, K.; Deak, M.; Delcourt, B.; Delvax, J.; De Wolf, E.A.; Diaconu, C.; Dodonov, V.; Dossanov, A.; Dubak, A.; Eckerlin, G.; Efremenko, V.; Egli, S.; Eliseev, A.; Elsen, E.; Falkiewicz, A.; Favart, L.; Fedotov, A.; Felst, R.; Feltesse, J.; Ferencei, J.; Fischer, D.J.; Fleischer, M.; Fomenko, A.; Gabathuler, E.; Gayler, J.; Ghazaryan, Samvel; Glazov, A.; Glushkov, I.; Goerlich, L.; Gogitidze, N.; Gouzevitch, M.; Grab, C.; Greenshaw, T.; Grell, B.R.; Grindhammer, G.; Habib, S.; Haidt, D.; Helebrant, C.; Henderson, R.C.W.; Hennekemper, E.; Henschel, H.; Herbst, M.; Herrera, G.; Hildebrandt, M.; Hiller, K.H.; Hoffmann, D.; Horisberger, R.; Hreus, T.; Jacquet, M.; Janssen, X.; Jonsson, L.; Jung, A.W.; Jung, H.; Kapichine, M.; Katzy, J.; Kenyon, I.R.; Kiesling, C.; Klein, M.; Kleinwort, C.; Kluge, T.; Knutsson, A.; Kogler, R.; Kosior, E.; Kostka, P.; Kraemer, M.; Krastev, K.; Kretzschmar, J.; Kropivnitskaya, A.; Kruger, K.; Kutak, K.; Landon, M.P.J.; Lange, W.; Lastovicka-Medin, G.; Laycock, P.; Lebedev, A.; Lendermann, V.; Levonian, S.; Li, G.; Lipka, K.; Liptaj, A.; List, B.; List, J.; Loktionova, N.; Lopez-Fernandez, R.; Lubimov, V.; Makankine, A.; Malinovski, E.; Marage, P.; Marti, Ll.; Martyn, H.U.; Maxfield, S.J.; Mehta, A.; Meyer, A.B.; Meyer, H.; Meyer, H.; Meyer, J.; Mikocki, S.; Milcewicz-Mika, I.; Moreau, F.; Morozov, A.; Morris, J.V.; Mozer, M.U.; Mudrinic, M.; Muller, K.; Murin, P.; Naumann, Th.; Newman, P.R.; Niebuhr, C.; Nikiforov, A.; Nikitin, D.; Nowak, G.; Nowak, K.; Olsson, J.E.; Osman, S.; Ozerov, D.; Palichik, V.; Panagoulias, I.; Pandurovic, M.; Papadopoulou, Th.; Pascaud, C.; Patel, G.D.; Pejchal, O.; Perez, E.; Petrukhin, A.; Picuric, I.; Piec, S.; Pitzl, D.; Placakyte, R.; Pokorny, B.; Polifka, R.; Povh, B.; Radescu, V.; Rahmat, A.J.; Raicevic, N.; Raspiareza, A.; Ravdandorj, T.; Reimer, P.; Rizvi, E.; Robmann, P.; Roland, B.; Roosen, R.; Rostovtsev, A.; Rotaru, M.; Tabasco, J.E.Ruiz; Rusakov, S.; Salek, D.; Sankey, D.P.C.; Sauter, M.; Sauvan, E.; Schmitt, S.; Schoeffel, L.; Schoning, A.; Schultz-Coulon, H.C.; Sefkow, F.; Shaw-West, R.N.; Shtarkov, L.N.; Shushkevich, S.; Sloan, T.; Smiljanic, Ivan; Soloviev, Y.; Sopicki, P.; South, D.; Spaskov, V.; Specka, A.; Staykova, Z.; Steder, M.; Stella, B.; Stoicea, G.; Straumann, U.; Sunar, D.; Sykora, T.; Tchoulakov, V.; Thompson, G.; Thompson, P.D.; Toll, T.; Tomasz, F.; Tran, T.H.; Traynor, D.; Trinh, T.N.; Truol, P.; Tsakov, I.; Tseepeldorj, B.; Turnau, J.; Urban, K.; Valkarova, A.; Vallee, C.; Van Mechelen, P.; Trevino, A.Vargas; Vazdik, Y.; Vinokurova, S.; Volchinski, V.; von den Driesch, M.; Wegener, D.; Wissing, Ch.; Wunsch, E.; Zacek, J.; Zalesak, J.; Zhang, Z.; Zhokin, A.; Zimmermann, T.; Zohrabyan, H.; Zomer, F.

    2010-01-01

    The production of jets is studied in deep-inelastic e+p scattering at low negative four momentum transfer squared 52<100 GeV^2 and at inelasticity 0.22-jet and 3-jet cross sections as well as the ratio of 3-jet to 2-jet cross sections are measured as a function of Q^2 and jet transverse momentum. The 2-jet cross section is also measured as a function of the proton momentum fraction xi. The measurements are well described by perturbative quantum chromodynamics at next-to-leading order corrected for hadronisation effects and are subsequently used to extract the strong coupling alpha_s.

  3. TNF-alpha impairs the S-G2/M cell cycle checkpoint and cyclobutane pyrimidine dimer repair in premalignant skin cells: Role of the PI3K-Akt pathway

    DEFF Research Database (Denmark)

    Faurschou, A.; Gniadecki, R.; Calay, D.

    2008-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is induced by UVB radiation and has been implicated in the early stages of skin carcinogenesis. Here, we show that in normal keratinocytes and the transformed keratinocyte cell lines, HaCaT and A431, TNF-alpha stimulates protein kinase B/Akt, which results...... cycling. TNF-alpha enhanced apoptosis less potently and did not increase the level of CPD or stimulate cell cycle progression in normal keratinocytes. Our data suggest that TNF-alpha overrides the G2/M checkpoint in premalignant skin cells and allows for some cells containing unrepaired CPD to enter...... in activation of the survival complex mTORC1 (mammalian target of rapamycin complex 1) and inhibition of the proapoptotic proteins Bad and Fox03a. In UVB-irradiated HaCaT cells (10-20 mJ cm(-2)), TNF-alpha increased the proportion of cycling cells and enhanced the rate of apoptosis. A significantly higher...

  4. Biodistribution analysis of 125I-albumin-IFN-alpha2b fusion protein in rats

    International Nuclear Information System (INIS)

    Zhou Yaoyuan; Zhang Rongjun; Cai Gangming; Gu Xiaobo; Jiang Mengjun; Zhang Bo; Yang Min; Cao Guoxian; Yang Jianliang

    2009-01-01

    125 I-albumin-IFN-alpha2b was prepared with the methods of Ch-T and purified with PD-10 column. The radiochemical purity was measured with TCA (trichloroacetic acid) precipitation. The antiviral activities of 125 I-albumin-IFN-alpha2b and albumin-IFN-alpha2b were compared with WISH/VSV system in vitro. SD rats were injected with 125 I-albumin-IFN-alpha2b subcutaneously and sacrificed at 0.5, 2, 6, 24, 48, 90, 180 and 300 h post-injection. Selected organs were dissected, weighed and their radioactivity was measured using γ-counter. The accumulated radioactivity in the tissues was calculated in terms of percentage of injected dose per gram organ (%ID·g -1 ). The labeling yield was 82.72%. The radiochemical purity of 125 I-albumin-IFN-alpha2b was 95.53%, and its radioactivity was 0.26 MBq/μg. The antiviral bioactivities of albumin-IFN-alpha2b and 125 I-albumin- IFN-alpha2b did not change. Biodistribution analysis of 125 I-albumin-IFN-alpha2b in rats showed that concentrated 125 I-albumin-IFN-alpha2b in blood reached maximum at 6 h post injection, and eliminated slowly. No specific accumulation was seen in other tissues. 125 I-albumin-IFN-alpha2b could maintain in peripheral blood for a long time and it meant albumin-IFN-alpha2b would be an effective long-term interferon. (authors)

  5. Binding of 125I-labeled proteinases to plasma proteins in cystic fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Romeo, G; Parsons, M; Bossen, A; Blessing-Moore, J; Cavalli-Sforza, L L

    1979-09-01

    Samples of plasma or serum from 53 cystic fibrosis (CF) patients, 90 relatives of CF patients, and 159 controls have been incubated with porcine or bovine 125I-trypsin, electrophoresed on polyacrylamide gel, and autoradiographed. In these individuals, the main binding protein for 125I-trypsin has been shown to be alpha 2-macroglobulin (alpha 2M)> Using this method of analysis, no difference in electrophoretic migration of 125I-trypsin-alpha 2M complexes has been observed between CF ad control individuals. However, trypsin binding to IgG has been observed in 80% of CF patients, 30% of their mothers, 3% of controls, and in two patients affected with pancreatitis. Experimental evidence indicates that binding of trypsin to IgG occurs through the Fab portion of the molecule.

  6. Attenuation of alpha2A-adrenergic receptor expression in neonatal rat brain by RNA interference or antisense oligonucleotide reduced anxiety in adulthood.

    Science.gov (United States)

    Shishkina, G T; Kalinina, T S; Dygalo, N N

    2004-01-01

    Brain alpha2-adrenergic receptors (alpha2-ARs) have been implicated in the regulation of anxiety, which is associated with stress. Environmental treatments during neonatal development could modulate the level of brain alpha2-AR expression and alter anxiety in adults, suggesting possible involvement of these receptors in early-life programming of anxiety state. The present study was undertaken to determine whether the reduction of the expression of A subtype of these receptors most abundant in the neonatal brain affects anxiety-related behavior in adulthood. We attenuated the expression of alpha2A-ARs during neonatal life by two different sequence specific approaches, antisense technology and RNA interference. Treatment of rats with the antisense oligodeoxynucleotide or short interfering RNA (siRNA) against alpha2A-ARs on the days 2-4 of their life, produced a marked acute decrease in the levels of both alpha2A-AR mRNA and [3H]RX821002 binding sites in the brainstem into which drugs were injected. The decrease of alpha2A-AR expression in the neonatal brainstem influenced the development of this receptor system in the brain regions as evidenced by the increased number of [3H]RX821002 binding sites in the hypothalamus of adult animals with both neonatal alpha2A-AR knockdown treatments; also in the frontal cortex of antisense-treated, and in the hippocampus of siRNA-treated adult rats. These adult animals also demonstrated a decreased anxiety in the elevated plus-maze as evidenced by an increased number of the open arm entries, greater proportion of time spent in the open arms, and more than a two-fold increase in the number of exploratory head dips. The results provide the first evidence that the reduction in the brain expression of a gene encoding for alpha2A-AR during neonatal life led to the long-term neurochemical and behavioral alterations. The data suggests that alterations in the expression of the receptor-specific gene during critical periods of brain

  7. Effects of central imidazolinergic and alpha2-adrenergic activation on water intake

    Directory of Open Access Journals (Sweden)

    Sugawara A.M.

    2001-01-01

    Full Text Available Non-adrenergic ligands that bind to imidazoline receptors (I-R, a selective ligand that binds to alpha2-adrenoceptors (alpha2-AR and mixed ligands that bind to both receptors were tested for their action on water intake behavior of 24-h water-deprived rats. All drugs were injected into the third cerebral ventricle. Except for agmatine (80 nmol, mixed ligands binding to I-R/alpha2-AR such as guanabenz (40 nmol and UK 14304 (20 nmol inhibited water intake by 65% and up to 95%, respectively. The selective non-imidazoline alpha2-AR agonist, alpha-methylnoradrenaline, produced inhibition of water intake similar to that obtained with guanabenz, but at higher doses (80 nmol. The non-adrenergic I-R ligands histamine (160 nmol, mixed histaminergic and imidazoline ligand and imidazole-4-acetic acid (80 nmol, imidazoline ligand did not alter water intake. The results show that selective, non-imidazoline alpha2-AR activation suppresses water intake, and suggest that the action on imidazoline sites by non-adrenergic ligands is not sufficient to inhibit water intake.

  8. Spent fuel UO2 matrix corrosion behaviour studies through alpha-doped UO2 pellets leaching

    International Nuclear Information System (INIS)

    Muzeau, B.; Jegou, C.; Broudic, V.

    2005-01-01

    Full text of publication follows: The option of direct disposal of spent nuclear fuel in a deep geological formation raises the need to investigate the long-term behaviour of the UO 2 matrix in aqueous media subjected to α-β-γ radiations. The β-γ emitters account for the most of the activity of spent fuel at the moment it is removed from the reactor, but diminish within a millennial time frame by over three orders of magnitude to less than the long-term activity. The latter persist over much longer time periods and must therefore be taken into account over geological disposal scale. In the present investigation the UO 2 matrix corrosion under alpha radiation is studied as a function of different parameters such as: the alpha activity, the carbonates and hydrogen concentrations,.. In order to study the effect of alpha radiolysis of water on the UO 2 matrix, 238/239 Pu doped UO 2 pellets (0.22 %wt. Pu total) were fabricated with different 238 Pu/ 239 Pu ratio to reproduce the alpha activity of a 47 GWd.t HMi -1 UOX spent fuel at different milestones in time (15, 50, 1500, 10000 and 40000 years). Undoped UO 2 pellets were also available as reference sample. Leaching experiments were conducted in deionized or carbonated water (NaHCO 3 1 mM), under Argon (O 2 2 30% gas mixture. Previous experiments conducted in deionized water under argon atmosphere, have shown a good correlation between alpha activity and uranium release for the 15-, 1500- and 40000-years alpha doped UO 2 batches. Besides, uranium release in the leachate is controlled either by the kinetics, or by the thermodynamics. Provided the solubility limit of uranium is not achieved, uranium concentration increases and is only limited by the kinetics, unless precipitation occurs and the uranium concentration remains constant over time. These controls are highly dependant on the solution chemistry (HCO 3 - , pH, Eh,..), the atmosphere (Ar, Ar/H 2 ,..), and the radiolysis strength. The experimental matrix

  9. A network of hydrophobic residues impeding helix alphaC rotation maintains latency of kinase Gcn2, which phosphorylates the alpha subunit of translation initiation factor 2.

    Science.gov (United States)

    Gárriz, Andrés; Qiu, Hongfang; Dey, Madhusudan; Seo, Eun-Joo; Dever, Thomas E; Hinnebusch, Alan G

    2009-03-01

    Kinase Gcn2 is activated by amino acid starvation and downregulates translation initiation by phosphorylating the alpha subunit of translation initiation factor 2 (eIF2alpha). The Gcn2 kinase domain (KD) is inert and must be activated by tRNA binding to the adjacent regulatory domain. Previous work indicated that Saccharomyces cerevisiae Gcn2 latency results from inflexibility of the hinge connecting the N and C lobes and a partially obstructed ATP-binding site in the KD. Here, we provide strong evidence that a network of hydrophobic interactions centered on Leu-856 also promotes latency by constraining helix alphaC rotation in the KD in a manner relieved during amino acid starvation by tRNA binding and autophosphorylation of Thr-882 in the activation loop. Thus, we show that mutationally disrupting the hydrophobic network in various ways constitutively activates eIF2alpha phosphorylation in vivo and bypasses the requirement for a key tRNA binding motif (m2) and Thr-882 in Gcn2. In particular, replacing Leu-856 with any nonhydrophobic residue activates Gcn2, while substitutions with various hydrophobic residues maintain kinase latency. We further provide strong evidence that parallel, back-to-back dimerization of the KD is a step on the Gcn2 activation pathway promoted by tRNA binding and autophosphorylation. Remarkably, mutations that disrupt the L856 hydrophobic network or enhance hinge flexibility eliminate the need for the conserved salt bridge at the parallel dimer interface, implying that KD dimerization facilitates the reorientation of alphaC and remodeling of the active site for enhanced ATP binding and catalysis. We propose that hinge remodeling, parallel dimerization, and reorientation of alphaC are mutually reinforcing conformational transitions stimulated by tRNA binding and secured by the ensuing autophosphorylation of T882 for stable kinase activation.

  10. Effect of alpha irradiation on UO2 surface reactivity in aqueous media

    International Nuclear Information System (INIS)

    Jegou, C.; Muzeau, B.; Broudic, V.; Poulesquen, A.; Roudil, D.; Jorion, F.; Corbel, C.

    2005-01-01

    The option of direct disposal of spent nuclear fuel in a deep geological formation raises the need to investigate the long-term behavior of the UO 2 matrix in aqueous media subjected to α-β-γ radiation. The β-γ emitters account for most of the activity of spent fuel at the moment it is removed from the reactor, but diminish within a millennial time frame by over three orders of magnitude to less than the long-term activity. The latter persists over much longer time periods and must therefore be taken into account over a geological disposal time scale. Leaching experiments with solution renewal were carried out on UO 2 pellets doped with alpha emitters ( 238 Pu and 239 Pu) to quantify the impact of alpha irradiation on UO 2 matrix alteration. Three batches of doped UO 2 pellets with different alpha flux levels (3.30 x 10 4 , 3.30 x 10 5 , and 3.2 x 10 6 α cm -2 s -1 ) were studied. The results obtained in aerated and deaerated media immediately after sample annealing or interim storage in air provide a better understanding of the UO 2 matrix alteration mechanisms under alpha irradiation. Interim storage in air of UO 2 pellets doped with alpha emitters results in variations of the UO 2 surface reactivity, which depends on the alpha particle flux at the interface and on the interim storage duration. The variation in the surface reactivity and the greater uranium release following interim storage cannot be attributed to the effect of alpha radiolysis in aerated media since the uranium release tends toward the same value after several leaching cycles for the doped UO 2 pellet batches and spent fuel. Oxygen diffusion enhanced by alpha irradiation of the extreme surface layer and/or radiolysis of the air could account for the oxidation of the surface UO 2 to UO 2+x . However, leaching experiments performed in deaerated media after annealing the samples and preleaching the surface suggest that alpha radiolysis does indeed affect the dissolution, which varies with the

  11. Effect of alpha irradiation on UO{sub 2} surface reactivity in aqueous media

    Energy Technology Data Exchange (ETDEWEB)

    Jegou, C.; Muzeau, B.; Broudic, V.; Poulesquen, A.; Roudil, D. [Commissariat a l' Energie Atomique (CEA), Rhone Valley Research Center, DIEC/SESC/LMPA, Bagnols-sur-Ceze (France); Jorion, F. [Commissariat a l' Energie Atomique (CEA), Rhone Valley Research Center, DRCP/SE2A/LEMA, Bagnols-sur-Ceze (France); Corbel, C. [Commissariat a l' Energie Atomique (CEA), Saclay Research Center, DSM/DRECAM/SCM, Gif sur Yvette (France)

    2005-07-01

    The option of direct disposal of spent nuclear fuel in a deep geological formation raises the need to investigate the long-term behavior of the UO{sub 2} matrix in aqueous media subjected to {alpha}-{beta}-{gamma} radiation. The {beta}-{gamma} emitters account for most of the activity of spent fuel at the moment it is removed from the reactor, but diminish within a millennial time frame by over three orders of magnitude to less than the long-term activity. The latter persists over much longer time periods and must therefore be taken into account over a geological disposal time scale. Leaching experiments with solution renewal were carried out on UO{sub 2} pellets doped with alpha emitters ({sup 238}Pu and {sup 239}Pu) to quantify the impact of alpha irradiation on UO{sub 2} matrix alteration. Three batches of doped UO{sub 2} pellets with different alpha flux levels (3.30 x 10{sup 4}, 3.30 x 10{sup 5}, and 3.2 x 10{sup 6} {alpha} cm{sup -2} s{sup -1}) were studied. The results obtained in aerated and deaerated media immediately after sample annealing or interim storage in air provide a better understanding of the UO{sub 2} matrix alteration mechanisms under alpha irradiation. Interim storage in air of UO{sub 2} pellets doped with alpha emitters results in variations of the UO{sub 2} surface reactivity, which depends on the alpha particle flux at the interface and on the interim storage duration. The variation in the surface reactivity and the greater uranium release following interim storage cannot be attributed to the effect of alpha radiolysis in aerated media since the uranium release tends toward the same value after several leaching cycles for the doped UO{sub 2} pellet batches and spent fuel. Oxygen diffusion enhanced by alpha irradiation of the extreme surface layer and/or radiolysis of the air could account for the oxidation of the surface UO{sub 2} to UO{sub 2+x}. However, leaching experiments performed in deaerated media after annealing the samples and

  12. alpha2-Adrenergic agonists antagonise the anxiolytic-like effect of antidepressants in the four-plate test in mice.

    Science.gov (United States)

    Massé, Fabienne; Hascoët, Martine; Bourin, Michel

    2005-10-14

    Selective serotonin reuptake inhibitors (SSRIs) and serotonin/noradrenaline reuptake inhibitors (SNRIs) has been reported to be efficient in anxiety disorders. Some animal models have demonstrated an anxiolytic-like effect following acute administration, however, it is not yet known how noradrenergic receptors are implicated in the therapeutic effects of antidepressants (ADs) in anxiety. The effects of two alpha(2)-adrenoceptor agonists (clonidine, guanabenz) on anxiolytic-like effect of two SSRIs (paroxetine and citalopram) and two SNRIs (venlafaxine and milnacipran) were evaluated in the four-plate test (FPT) in mice. Paroxetine (4 mg/kg), citalopram (8 mg/kg), venlafaxine (8 mg/kg), and milnacipran (8 mg/kg) administered intraperitoneally (i.p.) increased the number of punishments accepted by mice in the FPT. Clonidine (0.0039-0.5 mg/kg) and guanabenz (0.03-0.5mg/kg) had no effect on the number of punishments accepted by mice. Clonidine (0.03 and 0.06 mg/kg) and guanabenz (0.125 and 0.5 mg/kg) (i.p. -45 min) reversed the anti-punishment effect of paroxetine, citalopram, venlafaxine and milnacipran (i.p. -30 min). But if the antidepressants are administered 45 min before the test and alpha(2)-adrenoceptor agonists 30 min before the test, alpha(2)-adrenoceptor agonists failed to alter the anti-punishment effect of antidepressants. The results of this present study indicate that alpha(2)-adrenoceptor agonists antagonise the anxiolytic-like effect of antidepressants in mice when they are administered 15 min before the administration of antidepressant suggesting a close inter-regulation between noradrenergic and serotoninergic system in the mechanism of SSRIs and SNRIs in anxiety-like behaviour.

  13. The Structure of Neurexin 1[alpha] Reveals Features Promoting a Role as Synaptic Organizer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Fang; Venugopal, Vandavasi; Murray, Beverly; Rudenko, Gabby (Michigan)

    2014-10-02

    {alpha}-Neurexins are essential synaptic adhesion molecules implicated in autism spectrum disorder and schizophrenia. The {alpha}-neurexin extracellular domain consists of six LNS domains interspersed by three EGF-like repeats and interacts with many different proteins in the synaptic cleft. To understand how {alpha}-neurexins might function as synaptic organizers, we solved the structure of the neurexin 1{alpha} extracellular domain (n1{alpha}) to 2.65 {angstrom}. The L-shaped molecule can be divided into a flexible repeat I (LNS1-EGF-A-LNS2), a rigid horseshoe-shaped repeat II (LNS3-EGF-B-LNS4) with structural similarity to so-called reelin repeats, and an extended repeat III (LNS5-EGF-B-LNS6) with controlled flexibility. A 2.95 {angstrom} structure of n1{alpha} carrying splice insert SS3 in LNS4 reveals that SS3 protrudes as a loop and does not alter the rigid arrangement of repeat II. The global architecture imposed by conserved structural features enables {alpha}-neurexins to recruit and organize proteins in distinct and variable ways, influenced by splicing, thereby promoting synaptic function.

  14. 5alphaDH-DOC (5alpha-dihydro-deoxycorticosterone) activates androgen receptor in castration-resistant prostate cancer.

    Science.gov (United States)

    Uemura, Motohide; Honma, Seijiro; Chung, Suyoun; Takata, Ryo; Furihata, Mutsuo; Nishimura, Kazuo; Nonomura, Norio; Nasu, Yasutomo; Miki, Tsuneharu; Shuin, Taro; Fujioka, Tomoaki; Okuyama, Akihiko; Nakamura, Yusuke; Nakagawa, Hidewaki

    2010-08-01

    Prostate cancer often relapses during androgen-depletion therapy, even under the castration condition in which circulating androgens are drastically reduced. High expressions of androgen receptor (AR) and genes involved in androgen metabolism indicate a continued role for AR in castration-resistant prostate cancers (CRPCs). There is increasing evidence that some amounts of 5alpha-dihydrotestosterone (DHT) and other androgens are present sufficiently to activate AR within CRPC tissues, and enzymes involved in the androgen and steroid metabolism, such as 5alpha-steroid reductases, are activated in CRPCs. In this report, we screened eight natural 5alphaDH-steroids to search for novel products of 5alpha-steroid reductases, and identified 11-deoxycorticosterone (DOC) as a novel substrate for 5alpha-steroid reductases in CRPCs. 11-Deoxycorticosterone (DOC) and 5alpha-dihydro-deoxycorticosterone (5alphaDH-DOC) could promote prostate cancer cell proliferation through AR activation, and type 1 5alpha-steroid reductase (SRD5A1) could convert from DOC to 5alphaDH-DOC. Sensitive liquid chromatography-tandem mass spectrometric analysis detected 5alphaDH-DOC in some clinical CRPC tissues. These findings implicated that under an extremely low level of DHT, 5alphaDH-DOC and other products of 5alpha-steroid reductases within CRPC tissues might activate the AR pathway for prostate cancer cell proliferation and survival under castration.

  15. Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico.

    Science.gov (United States)

    Jhong, Chien-Hung; Riyaphan, Jirawat; Lin, Shih-Hung; Chia, Yi-Chen; Weng, Ching-Feng

    2015-01-01

    The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clinical effects have been observed. The present study seeks an alternative drug that can regulate the hyperglycemia by down-regulating alpha-glucosidase and alpha-amylase activity by molecular docking approach to screen the hyperglycemia antagonist against alpha-glucosidase and alpha-amylase activities from the 47 natural compounds. The docking data showed that Curcumin, 16-hydroxy-cleroda-3,13-dine-16,15-olide (16-H), Docosanol, Tetracosanol, Antroquinonol, Berberine, Catechin, Quercetin, Actinodaphnine, and Rutin from 47 natural compounds had binding ability towards alpha-amylase and alpha-glucosidase as well. Curcumin had a better biding ability of alpha-amylase than the other natural compounds. Analyzed alpha-glucosidase activity reveals natural compound inhibitors (below 0.5 mM) are Curcumin, Actinodaphnine, 16-H, Quercetin, Berberine, and Catechin when compared to the commercial drug Acarbose (3 mM). A natural compound with alpha-amylase inhibitors (below 0.5 mM) includes Curcumin, Berberine, Docosanol, 16-H, Actinodaphnine/Tetracosanol, Catechin, and Quercetin when compared to Acarbose (1 mM). When taken together, the implication is that molecular docking is a fast and effective way to screen alpha-glucosidase and alpha-amylase inhibitors as lead compounds of natural sources isolated from medicinal plants. © 2015 International Union of Biochemistry and Molecular Biology.

  16. Laminin alpha2 deficiency and muscular dystrophy; genotype-phenotype correlation in mutant mice

    DEFF Research Database (Denmark)

    Guo, L T; Zhang, X U; Kuang, W

    2003-01-01

    2, lacking domain VI. Interestingly, all mutants lack laminin alpha2 in peripheral nerve. We have demonstrated previously, that overexpression of the human laminin alpha2 in skeletal muscle in dy(2J)/dy(2J) and dy(W)/dy(W) mice under the control of a striated muscle-specific creatine kinase promoter......Deficiency of laminin alpha2 is the cause of one of the most severe muscular dystrophies in humans and other species. It is not yet clear how particular mutations in the laminin alpha2 chain gene affect protein expression, and how abnormal levels or structure of the protein affect disease. Animal...

  17. Zinc in human serum. Biochemical and clinical aspects. Zink i humant serum. Biokemiske og kliniske aspekter

    Energy Technology Data Exchange (ETDEWEB)

    Kiilerich, S

    1987-01-01

    The zinc ion is essential for the living organism. Many pathological conditions have been described as a consequence of zinc deficiency. As zinc constitutes less than 0.01 percent of the body weight, it conventionally belongs to the group of trace elements. The method of atomic absorption spectrophotometry is used to measure the concentration of zinc in serum and urine from healthy persons. The assumptions of the method is discussed. The importance of protein binding, diet and the diurnal variation of serum zinc concentration is presented. Serum versus plasma zinc concentration is discussed. Reference serum zinc values from 104 normal subjects are given. Zinc in serum is almost entirely bound to proteins. A preliminary model for the estimation of the distribution of zinc between serum albumin and ..cap alpha../sub 2/-macroglobulin is set up. This estimate has been examined by an ultracentrufugation method. The binding of zinc to a ..cap alpha../sup 2/-macroglobulin in normal persons is appoximately 7 percent, in patients with cirrhosis of the liver of alcoholic origin approximately 6 percent, in patients with insulin dependent diabetes mellitus approximately 5 percent, and in patients with chronic renal failure approximately 2 percent. It is concluded, therefore, that for clinical purposes it is sufficient to use the concentration of total serum zinc corrected for the concentration of serum albumin.

  18. Commentary: Are alpha-2 agonist really effective in children with tics with comorbid ADHD? A commentary on Whittington et al. (2016).

    Science.gov (United States)

    Bloch, Michael H

    2016-09-01

    In this issue, Whittington et al. (2016) present a systematic review that reports the efficacy of three primary treatments for children with Tourette syndrome (TS) - (a) α2-adrenergic receptor agonists; (b) antipsychotic medications; and (c) habit reversal training/comprehensive behavioral intervention. In this commentary, we highlight the large degree of heterogeneity observed in the meta-analysis of trials involving alpha-2 agonist medications and present possible explanations for the observed heterogeneity. Among these possible explanations is the possibility that presence of comorbid ADHD may moderate the efficacy of alpha-2 agonists in the treatment of tic disorder with the medications being more effective in patients with both conditions. The commentary reviews the evidence supporting this possible moderating effect of ADHD and discusses the implications for such a relationship. © 2016 Association for Child and Adolescent Mental Health.

  19. alpha-Adducin mutations increase Na/K pump activity in renal cells by affecting constitutive endocytosis: implications for tubular Na reabsorption.

    Science.gov (United States)

    Torielli, Lucia; Tivodar, Simona; Montella, Rosa Chiara; Iacone, Roberto; Padoani, Gloria; Tarsini, Paolo; Russo, Ornella; Sarnataro, Daniela; Strazzullo, Pasquale; Ferrari, Patrizia; Bianchi, Giuseppe; Zurzolo, Chiara

    2008-08-01

    Genetic variation in alpha-adducin cytoskeletal protein is implicated in the polymerization and bundling of actin and alteration of the Na/K pump, resulting in abnormal renal sodium transport and hypertension in Milan hypertensive rats and humans. To investigate the molecular involvement of alpha-adducin in controlling Na/K pump activity, wild-type or mutated rat and human alpha-adducin forms were, respectively, transfected into several renal cell lines. Through multiple experimental approaches (microscopy, enzymatic assays, coimmunoprecipitation), we showed that rat and human mutated forms increased Na/K pump activity and the number of pump units; moreover, both variants coimmunoprecipitate with Na/K pump. The increased Na/K pump activity was not due to changes in its basolateral localization, but to an alteration of Na/K pump residential time on the plasma membrane. Indeed, both rat and human mutated variants reduced constitutive Na/K pump endocytosis and similarly affected transferrin receptor trafficking and fluid-phase endocytosis. In fact, alpha-adducin was detected in clathrin-coated vesicles and coimmunoprecipitated with clathrin. These results indicate that adducin, besides its modulatory effects on actin cytoskeleton dynamics, might play a direct role in clathrin-dependent endocytosis. The constitutive reduction of the Na/K pump endocytic rate induced by mutated adducin variants may be relevant in Na-dependent hypertension.

  20. The determination of $\\alpha_s$ by the ALPHA collaboration

    CERN Document Server

    Bruno, Mattia

    2016-01-01

    We review the ALPHA collaboration strategy for obtaining the QCD coupling at high scale. In the three-flavor effective theory it avoids the use of perturbation theory at $\\alpha > 0.2$ and at the same time has the physical scales small compared to the cutoff $1/a$ in all stages of the computation. The result $\\Lambda_\\overline{MS}^{(3)}=332(14)$~MeV is translated to $\\alpha_\\overline{MS}(m_Z)=0.1179(10)(2)$ by use of (high order) perturbative relations between the effective theory couplings at the charm and beauty quark "thresholds". The error of this perturbative step is discussed and estimated as $0.0002$.

  1. Characterization of the human pH- and PKA-activated ClC-2G(2 alpha) Cl- channel.

    Science.gov (United States)

    Sherry, A M; Stroffekova, K; Knapp, L M; Kupert, E Y; Cuppoletti, J; Malinowska, D H

    1997-08-01

    A ClC-2G(2 alpha) Cl- channel was identified to be present in human lung and stomach, and a partial cDNA for this Cl- channel was cloned from a human fetal lung library. A full-length expressible human ClC-2G(2 alpha) cDNA was constructed by ligation of mutagenized expressible rabbit ClC-2G(2 alpha) cDNA with the human lung ClC-2G(2 alpha) cDNA, expressed in oocytes, and characterized at the single-channel level. Adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) treatment increased the probability of opening of the channel (Po). After PKA activation, the channel exhibited a linear (r = 0.99) current-voltage curve with a slope conductance of 22.1 +/- 0.8 pS in symmetric 800 mM tetraethylammonium chloride (TEACl; pH 7.4). Under fivefold gradient conditions of TEACl, a reversal potential of +21.5 +/- 2.8 mV was measured demonstrating anion-to-cation discrimination. As previously demonstrated for the rabbit ClC-2G(2 alpha) Cl- channel, the human analog, hClC-2G(2 alpha), was active at pH 7.4 as well as when the pH of the extracellular face of the channel (trans side of the bilayer; pHtrans) was asymmetrically reduced to pH 3.0. The extent of PKA activation was dependent on pHtrans. With PKA treatment, Po increased fourfold with a pHtrans of 7.4 and eightfold with a pHtrans of 3.0. Effects of sequential PKA addition followed by pHtrans reduction on the same channel suggested that the PKA- and pH-dependent increases in channel Po were separable and cumulative. Northern analysis showed ClC-2G(2 alpha) mRNA to be present in human adult and fetal lung and adult stomach, and quantitative reverse transcriptase-polymerase chain reaction showed this channel to be present in the adult human lung and stomach at about one-half the level found in fetal lung. The findings of the present study suggest that the ClC-2G(2 alpha) Cl- channel may play an important role in Cl- transport in the fetal and adult human lung.

  2. Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes

    Science.gov (United States)

    Li, Y. P.; Atkins, C. M.; Sweatt, J. D.; Reid, M. B.; Hamilton, S. L. (Principal Investigator)

    1999-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.

  3. No-carrier-added (NCA) synthesis of 6-[{sup 18}F]fluoro-L-DOPA using 3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[6S-(6{alpha}, 8{alpha}, 8{alpha}{beta})]-6,8-methano-2H-1,4-benzoxazin-2-one

    Energy Technology Data Exchange (ETDEWEB)

    Horti, A. [Yale Univ., New Haven, CT (United States). School of Medicine]|[Yale Univ., West Haven, CT (United States). PET Center; Redmond, D.E. Jr. [Yale Univ., New Haven, CT (United States). School of Medicine; Soufer, R. [Yale Univ., West Haven, CT (United States). PET Center

    1995-12-31

    3,5,6,7,8,8a-Hexahydro-7,7,8a-trimethyl-[6S-(6{alpha},8{alpha} , 8{alpha}{beta})]-6,8-methano-2H-1,4-benzoxazino-2-one (2) was investigated as chiral auxiliary for asymmetric NCA nucleophilic synthesis of 6-[{sup 18}F]Fluoro-L-DOPA. Direct condensation of 3,4-dimethoxy-2-[{sup 18}F]fluorobenzaldehyde (1a) or 6-[{sup 18}F]fluoro-piperonal (1b) in the presence of NaH with 2 gave the corresponding [{sup 18}F]-3-[(2-fluorophenyl)methylene]-3,5,6,7,8,8a-hexahydro-7,7,8 a-trimethyl-[6S-(3Z,3{alpha},6{alpha},8{alpha},8{alpha}{beta})]-6, 8-methano-2H-1,4-benzoxazin-2-one derivative 3a or 3b as a single stereoisomer. L-Selectride promoted hydrogenation of the olefinic double bond of these derivatives, in presence of tertbutyl alcohol, afforded the corresponding [{sup 18}F]-3-[(2-fluorophenyl) methyl]-3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[3S-(3{alpha}, 6{alpha}, 8{alpha}8{alpha}{beta})]-6,8-methano-2H-1,4-benzoxazin-2-one derivatives (4a,b) without affecting the orientation of diasterofacial discrimination. Deprotection of the derivatives 4a,b yielded 6-[{sup 18}F]fluoro-L-DOPA (e.e. >90%, 3% radiochemical yield (EOB), total synthesis time 125 min, specific activity >2000 mCi/{mu}mol). Direct deprotection/reduction of the compounds 3a,b provides the enantiomeric mixture of 6-[{sup 18}F]fluoro-D,L-DOPA (10-12% radiochemical yield) and, after chiral separation, 6-[{sup 18}F]fluoro-L-DOPA (e.e. 98%, 4-5% radiochemical yield). (author).

  4. Facile hydrothermal synthesis of alpha manganese sesquioxide ({alpha}-Mn{sub 2}O{sub 3}) nanodumb-bells: Structural, magnetic, optical and photocatalytic properties

    Energy Technology Data Exchange (ETDEWEB)

    Gnanam, S., E-mail: gnanam.nanoscience@gmail.com [Department of Physics, Presidency College, Chennai 600005, Tamilnadu (India); Rajendran, V. [Department of Physics, Presidency College, Chennai 600005, Tamilnadu (India)

    2013-02-15

    Highlights: Black-Right-Pointing-Pointer {alpha}-Mn{sub 2}O{sub 3} nanoparticles sizes of 35-42 nm have been prepared by hydrothermal process. Black-Right-Pointing-Pointer Shapes of {alpha}-Mn{sub 2}O{sub 3}: Dumb-bell, Cauliflower, spherical with rod, spherical with wires. Black-Right-Pointing-Pointer The strong UV emission can be attributed to high purity and perfect crystallinity. Black-Right-Pointing-Pointer Photocatalytic activity of {alpha}-Mn{sub 2}O{sub 3} was studied by degradation of Remazol red B dye. - Abstract: Nanometer scale cubic bixbyite {alpha}-Mn{sub 2}O{sub 3} has been synthesized by a facile hydrothermal method, at a temperature of 450 Degree-Sign C in the presence of various surfactants. The X-ray diffraction (XRD) analysis shows that the average crystallite size of the sample is {approx}35-42 nm. The shapes of the {alpha}-Mn{sub 2}O{sub 3} nanoparticles include: Dumb-bell-like (anionic surfactant), Cauliflower-like (nonionic surfactant), spherical with rods (cationic surfactant) and spherical with wires (surface modifier). The shapes of {alpha}-Mn{sub 2}O{sub 3} nanoparticles depend on the type of surfactant used in the synthesis. The magnetic property of the anionic surfactant assisted sample was primarily studied, using the vibrating sample magnetometer (VSM). The optical absorption spectra confirmed the effectiveness of the selected capping agents, as the anionic capped {alpha}-Mn{sub 2}O{sub 3} colloids absorbed at shorter wavelength than the other agents, indicating a much smaller crystallite size. The property of strong UV emissions may be attributed to the high purity and perfect crystallinity of the as-prepared {alpha}-Mn{sub 2}O{sub 3}. The surfactants-assisted catalyst was tested for its photocatalytic activity towards the photodegradation of the harmful organic dye Remazol Red B, using a multilamp photo reactor. Possible formation mechanisms have also been proposed for the as-synthesized anionic surfactant assisted samples.

  5. 40 CFR 721.5356 - Ethanol, 2,22″-nitrilotris-, compound with alpha-2,4,6-tris (1-phenylethyl)phenyl]-omega...

    Science.gov (United States)

    2010-07-01

    ...-, compound with alpha-2,4,6-tris (1-phenylethyl)phenyl]-omega-hydroxypoly (oxy-1,2-ethanediyl) phosphate. 721...]-omega-hydroxypoly (oxy-1,2-ethanediyl) phosphate. (a) Chemical substance and significant new uses... alpha-[2,4,6-tris(1-phenylethyl)phenyl]-omega-hydroxypoly (oxy-1,2-ethanediyl) phosphate (PMN P-98-185...

  6. Combinations of ERK and p38 MAPK inhibitors ablate tumor necrosis factor-alpha (TNF-alpha ) mRNA induction. Evidence for selective destabilization of TNF-alpha transcripts.

    Science.gov (United States)

    Rutault, K; Hazzalin, C A; Mahadevan, L C

    2001-03-02

    Tumor necrosis factor-alpha (TNF-alpha) is a potent proinflammatory cytokine whose synthesis and secretion are implicated in diverse pathologies. Hence, inhibition of TNF-alpha transcription or translation and neutralization of its protein product represent major pharmaceutical strategies to control inflammation. We have studied the role of ERK and p38 mitogen-activated protein (MAP) kinase in controlling TNF-alpha mRNA levels in differentiated THP-1 cells and in freshly purified human monocytes. We show here that it is possible to produce virtually complete inhibition of lipopolysaccharide-stimulated TNF-alpha mRNA accumulation by using a combination of ERK and p38 MAP kinase inhibitors. Furthermore, substantial inhibition is achievable using combinations of 1 microm of each inhibitor, whereas inhibitors used individually are incapable of producing complete inhibition even at high concentrations. Finally, addressing mechanisms involved, we show that inhibition of p38 MAP kinase selectively destabilizes TNF-alpha transcripts but does not affect degradation of c-jun transcripts. These results impinge on the controversy in the literature surrounding the mode of action of MAP kinase inhibitors on TNF-alpha mRNA and suggest the use of combinations of MAP kinase inhibitors as an effective anti-inflammatory strategy.

  7. Fabrication, characterization, and photocatalytic property of {alpha}-Fe{sub 2}O{sub 3}/graphene oxide composite

    Energy Technology Data Exchange (ETDEWEB)

    Li Hong; Zhao Qidong; Li Xinyong, E-mail: xinyongli@hotmail.com [School of Environmental Science and Technology, Dalian University of Technology, State Key Laboratory of Fine Chemical, Key Laboratory of Industrial Ecology and Environmental Engineering (MOE) (China); Zhu Zhengru [Research Center of Hydrology and Engineering, Academy of City and Environment, Liaoning Normal University (China); Tade, Moses; Liu Shaomin, E-mail: shaomin.liu@curtin.edu.au [Curtin University, Department of Chemical Engineering (Australia)

    2013-06-15

    Spindle-shaped microstructure of {alpha}-Fe{sub 2}O{sub 3} was successfully synthesized by a simple hydrothermal method. The {alpha}-Fe{sub 2}O{sub 3}/graphene oxide (GO) composites was prepared using a modified Hummers' strategy. The properties of the samples were systematically investigated by X-ray powder diffraction (XRD), UV-Vis diffuse reflectance spectrophotometer, transmission electron microscope, atomic force microscope, X-ray photoelectron spectroscopy, and Raman spectroscopy (Raman) techniques. GO nanosheets act as supporting materials for anchoring the {alpha}-Fe{sub 2}O{sub 3} particles. The average crystallite sizes of the {alpha}-Fe{sub 2}O{sub 3} and {alpha}-Fe{sub 2}O{sub 3}/GO samples are ca. 27 and 24 nm, respectively. The possible growth of {alpha}-Fe{sub 2}O{sub 3} onto GO layers led to a higher absorbance capacity for visible light by {alpha}-Fe{sub 2}O{sub 3}/GO than {alpha}-Fe{sub 2}O{sub 3} composite. The photocatalytic degradation of toluene over the {alpha}-Fe{sub 2}O{sub 3} and {alpha}-Fe{sub 2}O{sub 3}/GO samples under xenon-lamp irradiation was comparatively studied by in situ FTIR technique. The results indicate that the {alpha}-Fe{sub 2}O{sub 3}/GO sample synthesized exhibited a higher capacity for the degradation of toluene. The composite of {alpha}-Fe{sub 2}O{sub 3}/GO could be promisingly applied in photo-driven air purification.

  8. Characteristics of chemical binding to alpha 2u-globulin in vitro--evaluating structure-activity relationships

    International Nuclear Information System (INIS)

    Borghoff, S.J.; Miller, A.B.; Bowen, J.P.; Swenberg, J.A.

    1991-01-01

    alpha 2u-Globulin (alpha 2u) has been shown to accumulate in the kidneys of male rats treated with 2,2,4-trimethylpentane (TMP). 2,4,4-Trimethyl-2-pentanol (TMP-2-OH), a metabolite of TMP, is found reversibly bound to alpha 2u isolated from the kidneys of these treated rats. The objectives of the following study were to characterize the ability of [3H]TMP-2-OH to bind to alpha 2u in vitro and to determine whether other compounds that cause this protein to accumulate have the same binding characteristics. Although compounds that have been shown to cause the accumulation of alpha 2u in male rat kidneys compete in vitro with [3H]TMP-2-OH for binding to alpha 2u, they do so to varying degrees. The binding affinity (Kd) of the [3H]TMP-2-OH-alpha 2u complex was calculated to be on the order of 10(-7) M. The inhibition constant values (Ki) determined for d-limonene, 1,4-dichlorobenzene, and 2,5-dichlorophenol were all in the range 10(-4) M, whereas the Ki values for isophorone, 2,4,4- or 2,2,4-trimethyl-1-pentanol, and d-limonene oxide were determined to be in the range 10(-6) and 10(-7) M, respectively. TMP and 2,4,4- and 2,2,4-trimethylpentanoic acid did not compete for binding. This suggests that other factors, besides binding, are involved in the accumulation of alpha 2u. In this study the ability of a chemical to bind to alpha 2u was used as a measure of biological activity to assess structure-activity relationships among the chemicals tested and known to cause the accumulation of alpha 2u. The results so far suggest that binding is dependent on both hydrophobic interactions and hydrogen bonding

  9. Central alpha2 adrenergic receptors in the rat cerebral cortex: repopulation kinetics and receptor reserve

    International Nuclear Information System (INIS)

    Adler, C.H.

    1986-01-01

    The alpha 2 adrenergic receptor subtype is thought to play a role in the mechanism of action of antidepressant and antihypertensive drugs. This thesis has attempted to shed light on the regulation of central alpha 2 adrenergic receptors in the rat cerebral cortex. Repopulation kinetics analysis allows for the determination of the rate of receptor production, rate constant of degradation, and half-life of the receptor. This analysis was carried out using both radioligand binding and functional receptor assays at various times following the irreversible inactivation of central alpha 2 adrenergic receptors by in vivo administration of N-ethoxycarbonyl-2-ethyoxy-1,2-dihydroquinoline (EEDQ). Both alpha 2 agonist and antagonist ligand binding sites recovered with a t/sub 1/2/ equal to approximately 4 days. The function of alpha 2 adrenergic autoreceptors, which inhibit stimulation-evoked release of 3 H-norepinephrine ( 3 H-NE) and alpha 2 adrenergic heteroreceptors which inhibit stimulation-evoked release of 3 H-serotonin ( 3 H-5-HT) were assayed. The t/sub 1/2/ for recovery of maximal autoreceptor and heteroreceptor function was 2.4 days and 4.6 days, respectively. The demonstration of a receptor reserve is critical to the interpretation of past and future studies of the alpha 2 adrenergic receptor since it demonstrates that: (1) alterations in the number of alpha 2 adrenergic receptor binding sites cannot be extrapolated to the actual function of the alpha 2 adrenergic receptor; and (2) alterations in the number of alpha 2 receptors is not necessarily accompanied by a change in the maximum function being studied, but may only result in shifting of the dose-response curve

  10. Acute lymphoid and gastrointestinal toxicity induced by selective p38alpha map kinase and map kinase-activated protein kinase-2 (MK2) inhibitors in the dog.

    Science.gov (United States)

    Morris, Dale L; O'Neil, Shawn P; Devraj, Rajesh V; Portanova, Joseph P; Gilles, Richard W; Gross, Cindy J; Curtiss, Sandra W; Komocsar, Wendy J; Garner, Debra S; Happa, Fernando A; Kraus, Lori J; Nikula, Kristen J; Monahan, Joseph B; Selness, Shaun R; Galluppi, Gerald R; Shevlin, Kimberly M; Kramer, Jeffrey A; Walker, John K; Messing, Dean M; Anderson, David R; Mourey, Robert J; Whiteley, Laurence O; Daniels, John S; Yang, Jerry Z; Rowlands, Philip C; Alden, Carl L; Davis, John W; Sagartz, John E

    2010-06-01

    Exposure to moderately selective p38alpha mitogen-activated protein kinase (MAPK) inhibitors in the Beagle dog results in an acute toxicity consisting of mild clinical signs (decreased activity, diarrhea, and fever), lymphoid necrosis and depletion in the gut-associated lymphoid tissue (GALT), mesenteric lymph nodes and spleen, and linear colonic and cecal mucosal hemorrhages. Lymphocyte apoptosis and necrosis in the GALT is the earliest and most prominent histopathologic change observed, followed temporally by neutrophilic infiltration and acute inflammation of the lymph nodes and spleen and multifocal mucosal epithelial necrosis and linear hemorrhages in the colon and cecum. These effects are not observed in the mouse, rat, or cynomolgus monkey. To further characterize the acute toxicity in the dog, a series of in vivo, in vitro, and immunohistochemical studies were conducted to determine the relationship between the lymphoid and gastrointestinal (GI) toxicity and p38 MAPK inhibition. Results of these studies demonstrate a direct correlation between p38alpha MAPK inhibition and the acute lymphoid and gastrointestinal toxicity in the dog. Similar effects were observed following exposure to inhibitors of MAPK-activated protein kinase-2 (MK2), further implicating the role of p38alpha MAPK signaling pathway inhibition in these effects. Based on these findings, the authors conclude that p38alpha MAPK inhibition results in acute lymphoid and GI toxicity in the dog and is unique among the species evaluated in these studies.

  11. Synthesis and electrochemical properties of {alpha}-MnO{sub 2} microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Wang Hongen [College of Chemistry and Chemical Engineering, Central South University, Changsha 410083 (China); Zhengzhou Research Institute of CHALCO, Zhengzhou Research Institute of Light Metals, Zhengzhou 450041 (China); Qian Dong [College of Chemistry and Chemical Engineering, Central South University, Changsha 410083 (China)], E-mail: qiandong6@yahoo.com.cn

    2008-06-15

    We report the synthesis of {alpha}-MnO{sub 2} microspheres by a low-temperature hydrothermal method involving no templates or catalysts. The products were characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), Energy-dispersive X-ray spectrum (EDX), transmission electron microscopy (TEM), Fourier transform infrared spectrum (FT-IR), and Brunauer-Emmett-Teller (BET). The results show that the as-synthesized products are mainly composed of large quantities of {alpha}-MnO{sub 2} microspheres having a sea-urchin shape and a few microspheres constructed of small nanorods. Electrochemical characterization indicates that the resulting {alpha}-MnO{sub 2} microspheres display promising discharge properties than the commercial electrolytic manganese dioxides (EMD) when used as cathodes in alkaline Zn-MnO{sub 2} batteries.

  12. alpha-MSH and its receptors in regulation of tumor necrosis factor-alpha production by human monocyte/macrophages.

    Science.gov (United States)

    Taherzadeh, S; Sharma, S; Chhajlani, V; Gantz, I; Rajora, N; Demitri, M T; Kelly, L; Zhao, H; Ichiyama, T; Catania, A; Lipton, J M

    1999-05-01

    The hypothesis that macrophages contain an autocrine circuit based on melanocortin [ACTH and alpha-melanocyte-stimulating hormone (alpha-MSH)] peptides has major implications for neuroimmunomodulation research and inflammation therapy. To test this hypothesis, cells of the THP-1 human monocyte/macrophage line were stimulated with lipopolysaccharide (LPS) in the presence and absence of alpha-MSH. The inflammatory cytokine tumor necrosis factor (TNF)-alpha was inhibited in relation to alpha-MSH concentration. Similar inhibitory effects on TNF-alpha were observed with ACTH peptides that contain the alpha-MSH amino acid sequence and act on melanocortin receptors. Nuclease protection assays indicated that expression of the human melanocortin-1 receptor subtype (hMC-1R) occurs in THP-1 cells; Southern blots of RT-PCR product revealed that additional subtypes, hMC-3R and hMC-5R, also occur. Incubation of resting macrophages with antibody to hMC-1R increased TNF-alpha concentration; the antibody also markedly reduced the inhibitory influence of alpha-MSH on TNF-alpha in macrophages treated with LPS. These results in cells known to produce alpha-MSH at rest and to increase secretion of the peptide when challenged are consistent with an endogenous regulatory circuit based on melanocortin peptides and their receptors. Targeting of this neuroimmunomodulatory circuit in inflammatory diseases in which myelomonocytic cells are prominent should be beneficial.

  13. Protein-energy malnutrition developing after global brain ischemia induces an atypical acute-phase response and hinders expression of GAP-43.

    Science.gov (United States)

    Smith, Shari E; Figley, Sarah A; Schreyer, David J; Paterson, Phyllis G

    2014-01-01

    Protein-energy malnutrition (PEM) is a common post-stroke problem. PEM can independently induce a systemic acute-phase response, and pre-existing malnutrition can exacerbate neuroinflammation induced by brain ischemia. In contrast, the effects of PEM developing in the post-ischemic period have not been studied. Since excessive inflammation can impede brain remodeling, we investigated the effects of post-ischemic malnutrition on neuroinflammation, the acute-phase reaction, and neuroplasticity-related proteins. Male, Sprague-Dawley rats were exposed to global forebrain ischemia using the 2-vessel occlusion model or sham surgery. The sham rats were assigned to control diet (18% protein) on day 3 after surgery, whereas the rats exposed to global ischemia were assigned to either control diet or a low protein (PEM, 2% protein) diet. Post-ischemic PEM decreased growth associated protein-43, synaptophysin and synaptosomal-associated protein-25 immunofluorescence within the hippocampal CA3 mossy fiber terminals on day 21, whereas the glial response in the hippocampal CA1 and CA3 subregions was unaltered by PEM. No systemic acute-phase reaction attributable to global ischemia was detected in control diet-fed rats, as reflected by serum concentrations of alpha-2-macroglobulin, alpha-1-acid glycoprotein, haptoglobin, and albumin. Acute exposure to the PEM regimen after global brain ischemia caused an atypical acute-phase response. PEM decreased the serum concentrations of albumin and haptoglobin on day 5, with the decreases sustained to day 21. Serum alpha-2-macroglobulin concentrations were significantly higher in malnourished rats on day 21. This provides the first direct evidence that PEM developing after brain ischemia exerts wide-ranging effects on mechanisms important to stroke recovery.

  14. Conformational analysis of a Chlamydia-specific disaccharide {alpha}-Kdo-(2{sup {yields}}8)-{alpha}-Kdo-(2{sup {yields}}O)-allyl in aqueous solution and bound to a monoclonal antibody: Observation of intermolecular transfer NOEs

    Energy Technology Data Exchange (ETDEWEB)

    Sokolowski, Tobias; Haselhorst, Thomas; Scheffler, Karoline [Medizinische Universitaet, Institut fuer Chemie (Germany); Weisemann, Ruediger [Bruker Analytik GmbH, Silberstreifen (Germany); Kosma, Paul [Institut fuer Chemie der Universitaet fuer Bodenkultur Wien (Austria); Brade, Helmut; Brade, Lore [Forschungszentrum Borstel, Zentrum fuer Medizin und Biowissenschaften Parkallee 22 (Germany); Peters, Thomas [Medizinische Universitaet, Institut fuer Chemie (Germany)

    1998-07-15

    The disaccharide {alpha}-Kdo-(2{sup {yields}}8)-{alpha}-Kdo (Kdo: 3-deoxy-d-manno-oct-2-ulosonic acid) represents a genus-specific epitope of the lipopolysaccharide of the obligate intracellular human pathogen Chlamydia. The conformation of the synthetically derived disaccharide {alpha}-Kdo-(2{sup {yields}}8)-{alpha}-Kdo-(2{sup {yields}}O)-allyl was studied in aqueous solution, and complexed to a monoclonal antibody S25-2. Various NMR experiments based on the detection of NOEs (or transfer NOEs) and ROEs (or transfer ROEs) were performed. A major problem was the extensive overlap of almost all {sup 1}H NMR signals of {alpha}-Kdo-(2{sup {yields}}8)-{alpha}-Kdo-(2{sup {yields}}O)-allyl. To overcome this difficulty, HMQC-NOESY and HMQC-trNOESY experiments were employed. Spin diffusion effects were identified using trROESY experiments, QUIET-trNOESY experiments and MINSY experiments. It was found that protein protons contribute to the observed spin diffusion effects. At 800 MHz, intermolecular trNOEs were observed between ligand protons and aromatic protons in the antibody binding site. From NMR experiments and Metropolis Monte Carlo simulations, it was concluded that {alpha}-Kdo-(2{sup {yields}}8)-{alpha}-Kdo-(2{sup {yields}}O)-allyl in aqueous solution exists as a complex conformational mixture. Upon binding to the monoclonal antibody S25-2, only a limited range of conformations is available to {alpha}-Kdo-(2{sup {yields}}8)-{alpha}-Kdo-(2{sup {yields}}O)-allyl. These possible bound conformations were derived from a distance geometry analysis using transfer NOEs as experimental constraints. It is clear that a conformation is selected which lies within a part of the conformational space that is highly populated in solution. This conformational space also includes the conformation found in the crystal structure. Our results provide a basis for modeling studies of the antibody-disaccharide complex.

  15. Interaction of molybdenum with blood serum proteins in vitro

    International Nuclear Information System (INIS)

    Bibr, B.; Kselikova, M.; Lener, J.

    1985-01-01

    The interaction of pentavalent and hexavalent 99 Mo compounds with rat and human serum was monitored in vitro by paper electrophoresis after incubation for one hour at 37 0 C. Hexavalent 99 Mo is not capable of interaction and, via sulfur ligands, forms unstable and unspecific bonds to the whole spectrum of serum proteins, in particular to albumin. Pentavalent 99 Mo binds strongly to alpha-2-macroglobulin in a ratio of 2 : 1; according to the nature of the ligand, it forms somewhat unstable bonds to albumin, beta-1-globulin and gamma-2-globulin. (author)

  16. Staurosporine, but not Ro 31-8220, induces interleukin 2 production and synergizes with interleukin 1alpha in EL4 thymoma cells.

    Science.gov (United States)

    Mahon, T M; Matthews, J S; O'Neill, L A

    1997-07-01

    Protein kinase C (PKC) has been implicated in interleukin 1 (IL1) signal transduction in a number of cellular systems, either as a key event in IL1 action or as a negative regulator. Here we have examined the effects of two PKC inhibitors, staurosporine and the more selective agent Ro 31-8220, on IL1 responses in the murine thymoma line EL4.NOB-1. A 1 h pulse of staurosporine was found to strongly potentiate the induction of IL2 by IL1alpha in these cells. In contrast, neither a pulse nor prolonged incubation with Ro 31-8220 affected the response to IL1alpha. Both agents blocked the response to PMA, however. A 1 h pulse of staurosporine was also found to induce IL2 production on its own, activate the transcription factor nuclear factor kappaB (NFkappaB) and increase the expression of a NFkappaB-linked reporter gene. It synergized with IL1alpha in all of these responses. Ro 31-8220 was again without effect, although both staurosporine and Ro 31-8220 blocked the activation of NFkappaB by PMA. Finally, staurosporine caused the translocation of PKC-alpha and -epsilon, and to a lesser extent PKC-beta, but not PKC-θ or -zeta, from the cytosol to the membrane, although a similar effect was observed with Ro 31-8220. The results suggest that PKC is not involved in IL1alpha signalling in EL4 cells. Furthermore, the potentiating effect of staurosporine on IL1alpha action does not involve PKC inhibition, and is likely to be at the level of NFkappaB activation.

  17. Structure of the T cell receptor in a Ti alpha V beta 2, alpha V beta 8-positive T cell line

    DEFF Research Database (Denmark)

    Hou, X; Dietrich, J; Kuhlmann, J

    1994-01-01

    not known; however, it has been suggested that each TcR contains two Ti dimers. To gain insight into the structure of the TcR we constructed a Ti alpha V beta 2, alpha V beta 8-positive T cell line which expressed the endogenous human TiV beta 8 and the transfected mouse TiV beta 2 both in association......The T cell receptor (TcR) is composed of at least six different polypeptide chains consisting of the clonotypic Ti heterodimer (Ti alpha beta or Ti gamma delta) and the noncovalently associated CD3 chains (CD3 gamma delta epsilon zeta). The exact number of subunits constituting the TcR is still...... with the endogenous Ti alpha and CD3 chains at the cell surface. Preclearing experiments with radioiodinated cell lysate prepared with digitonin lysis buffer demonstrated that depleting the lysate of Ti alpha V beta 8 by immunoprecipitation with anti V beta 8 monoclonal antibody (mAb) did not reduce the amount of Ti...

  18. Microstructure and gas sensitive properties of alpha-Fe2O3-MO2 (M: Sn and Ti) materials prepared by ball milling

    DEFF Research Database (Denmark)

    Jiang, Jianzhong; Lin, R.; Mørup, Steen

    1998-01-01

    Metastable alpha-Fe2O3-MO2 (M: Sn and Ti) solid solutions can be synthesized by mechanical alloying. The alloy formation, microstructure, and gas sensitive properties of mechanically milled alpha-Fe2O3-SnO2 materials are discussed. Tin ions in alpha-Fe2O3 are found to occupy the empty octahedral...... holes in the alpha-Fe2O3 lattice. This interstitial model can also describe the structure of alpha-Fe2O3-TiO2 solid solutions. Finally, a correlation of gas sensitive properties with microstructure of alpha-Fe2O3-SnO2 materials is presented....

  19. In vitro bioactivity of 17alpha-estradiol.

    Science.gov (United States)

    Sievernich, André; Wildt, Ludwig; Lichtenberg-Fraté, Hella

    2004-12-01

    A miniaturised short-term in vitro assay based on the activation of the human estrogen receptor alpha and genetically modified yeast (Saccharomyces cerevisiae) cells was performed to explore the capacity of this system to monitor the bioactivity of estrogenic compounds, particularly 17alpha- and 17beta-estradiol. Together with the human estrogen receptor (hER)-alpha plasmid, the reporter plasmid containing a yeast-optimised version of the green fluorescent protein (yEGFP) linked to three repeats of the cis-acting estrogen hormone-responsive element (ERE) were expressed in a strain being deleted in the pleiotropic drug resistance transporters Pdr5, Snq2 and Yor1, known to facilitate efflux of organic compounds including steroids and chemotherapeutics. Agonists that bind to hER in vitro trigger estrogen receptor-mediated transcriptional activation of the GFP reporter gene monitored by fluorescence emission at 535 nm. The sensitivity of the assay was tested with various 17alpha- and 17beta-estradiol concentrations, yielding a detection limit of 5 pg/ml (0.018 nM) for the agonist 17beta-E2 in solvent and in human charcoal-stripped serum using a S. cerevisiae pdr5, snq2 and yor1 mutant strain. For 17alpha-estradiol only, at approximately 1500 pg/ml a similar fluorescence response compared to 100 pg/ml 17beta-E2 was observed implicating a much weaker potency of this stereoisomer. The specificity of the system was tested by expression of a truncated hER lacking the ligand-binding domain E and by administration of the androgen, 4-androsten 3,17 dione. Both controls did not yield an increase in fluorescence emission. This fluorescence emission assay enables detection of estrogenic biological activity induced by direct agonists, such as 17beta-E2 at concentrations similar to those found in human sera or by estrogen-like chemicals.

  20. Spent fuel UO{sub 2} matrix corrosion behaviour studies through alpha-doped UO{sub 2} pellets leaching

    Energy Technology Data Exchange (ETDEWEB)

    Muzeau, B.; Jegou, C.; Broudic, V. [CEA-Valrho DEN/DTCD/SECM Laboratoire des Materiaux et Procedes Actifs BP 17171 F-30207 Bagnols-sur-Ceze cedex (France)

    2005-07-01

    Full text of publication follows: The option of direct disposal of spent nuclear fuel in a deep geological formation raises the need to investigate the long-term behaviour of the UO{sub 2} matrix in aqueous media subjected to {alpha}-{beta}-{gamma} radiations. The {beta}-{gamma} emitters account for the most of the activity of spent fuel at the moment it is removed from the reactor, but diminish within a millennial time frame by over three orders of magnitude to less than the long-term activity. The latter persist over much longer time periods and must therefore be taken into account over geological disposal scale. In the present investigation the UO{sub 2} matrix corrosion under alpha radiation is studied as a function of different parameters such as: the alpha activity, the carbonates and hydrogen concentrations,.. In order to study the effect of alpha radiolysis of water on the UO{sub 2} matrix, {sup 238/239}Pu doped UO{sub 2} pellets (0.22 %wt. Pu total) were fabricated with different {sup 238}Pu/{sup 239}Pu ratio to reproduce the alpha activity of a 47 GWd.t{sub HMi}{sup -1} UOX spent fuel at different milestones in time (15, 50, 1500, 10000 and 40000 years). Undoped UO{sub 2} pellets were also available as reference sample. Leaching experiments were conducted in deionized or carbonated water (NaHCO{sub 3} 1 mM), under Argon (O{sub 2} < 0.1 ppm), or Ar/H{sub 2} 30% gas mixture. Previous experiments conducted in deionized water under argon atmosphere, have shown a good correlation between alpha activity and uranium release for the 15-, 1500- and 40000-years alpha doped UO{sub 2} batches. Besides, uranium release in the leachate is controlled either by the kinetics, or by the thermodynamics. Provided the solubility limit of uranium is not achieved, uranium concentration increases and is only limited by the kinetics, unless precipitation occurs and the uranium concentration remains constant over time. These controls are highly dependant on the solution chemistry

  1. The anti-tumorigenic activity of A2M-A lesson from the naked mole-rat.

    Science.gov (United States)

    Kurz, Susanne; Thieme, René; Amberg, Ronny; Groth, Marco; Jahnke, Heinz-Georg; Pieroh, Philipp; Horn, Lars-Christian; Kolb, Marlen; Huse, Klaus; Platzer, Matthias; Volke, Daniela; Dehghani, Faramarz; Buzdin, Anton; Engel, Kathrin; Robitzki, Andrea; Hoffmann, Ralf; Gockel, Ines; Birkenmeier, Gerd

    2017-01-01

    Cancer resistance is a major cause for longevity of the naked mole-rat. Recent liver transcriptome analysis in this animal compared to wild-derived mice revealed higher expression of alpha2-macroglobulin (A2M) and cell adhesion molecules, which contribute to the naked mole-rat's cancer resistance. Notably, A2M is known to dramatically decrease with age in humans. We hypothesize that this might facilitate tumour development. Here we found that A2M modulates tumour cell adhesion, migration and growth by inhibition of tumour promoting signalling pathways, e.g. PI3K / AKT, SMAD and up-regulated PTEN via down-regulation of miR-21, in vitro and in tumour xenografts. A2M increases the expression of CD29 and CD44 but did not evoke EMT. Transcriptome analysis of A2M-treated tumour cells, xenografts and mouse liver demonstrated a multifaceted regulation of tumour promoting signalling pathways indicating a less tumorigenic environment mediated by A2M. By virtue of these multiple actions the naturally occurring A2M has strong potential as a novel therapeutic agent.

  2. Cloning and sequencing of the casein kinase 2 alpha subunit from Zea mays

    DEFF Research Database (Denmark)

    Dobrowolska, G; Boldyreff, B; Issinger, O G

    1991-01-01

    The nucleotide sequence of the cDNA coding for the alpha subunit of casein kinase 2 of Zea mays has been determined. The cDNA clone contains an open reading frame of 996 nucleotides encoding a polypeptide comprising 332 amino acids. The primary amino acid sequence exhibits 75% identity to the alpha...... subunit and 71% identity to the alpha' subunit of human casein kinase 2....

  3. A transmembrane polar interaction is involved in the functional regulation of integrin alpha L beta 2.

    Science.gov (United States)

    Vararattanavech, Ardcharaporn; Chng, Choon-Peng; Parthasarathy, Krupakar; Tang, Xiao-Yan; Torres, Jaume; Tan, Suet-Mien

    2010-05-14

    Integrins are heterodimeric transmembrane (TM) receptors formed by noncovalent associations of alpha and beta subunits. Each subunit contains a single alpha-helical TM domain. Inside-out activation of an integrin involves the separation of its cytoplasmic tails, leading to disruption of alphabeta TM packing. The leukocyte integrin alpha L beta 2 is required for leukocyte adhesion, migration, proliferation, cytotoxic function, and antigen presentation. In this study, we show by mutagenesis experiments that the packing of alpha L beta 2 TMs is consistent with that of the integrin alpha IIb beta 3 TMs. However, molecular dynamics simulations of alpha L beta 2 TMs in lipids predicted a polar interaction involving the side chains of alpha L Ser1071 and beta2 Thr686 in the outer-membrane association clasp (OMC). This is supported by carbonyl vibrational shifts observed in isotope-labeled alpha L beta 2 TM peptides that were incorporated into lipid bilayers. Molecular dynamics studies simulating the separation of alpha L beta 2 tails showed the presence of polar interaction during the initial perturbation of the inner-membrane association clasp. When the TMs underwent further separation, the polar interaction was disrupted. OMC polar interaction is important in regulating the functions of beta2 integrins because mutations that disrupt the OMC polar interaction generated constitutively activated alpha L beta 2, alpha M beta 2, and alpha X beta 2 in 293T transfectants. We also show that the expression of mutant beta2 Thr686Gly in beta2-deficient T cells rescued cell adhesion to intercellular adhesion molecule 1, but the cells showed overt elongated morphologies in response to chemokine stromal-cell-derived factor 1 alpha treatment as compared to wild-type beta2-expressing cells. These two TM polar residues are totally conserved in other members of the beta2 integrins in humans and across different species. Our results provide an example of the stabilizing effect of polar

  4. Delirium after interleukin-2 and alpha-interferon therapy for renal cell carcinoma

    NARCIS (Netherlands)

    Van Steijn, JHM; Nieboer, P; Hospers, GAP; De Vries, EGE; Mulder, NH

    2001-01-01

    A 55-year-old man receiving alpha-interferon and interieukin-2 therapy for renal cell carcinoma presented with seizures and delirium. A CT-scan of the cerebrum did not reveal any disorder. Both alpha-interferon and interleukin-2 were stopped Treatment with steroids led to complete regression of

  5. Regular endurance training reduces the exercise induced HIF-1alpha and HIF-2alpha mRNA expression in human skeletal muscle in normoxic conditions

    DEFF Research Database (Denmark)

    Lundby, Carsten; Gassmann, Max; Pilegaard, Henriette

    2005-01-01

    and 2 (HIFs) are clearly related heterodimeric transcription factors that consist of an oxygen-depended alpha-subunit and a constitutive beta-subunit. With hypoxic exposure, HIF-1alpha and HIF-2alpha protein are stabilized. Upon heterodimerization, HIFs induce the transcription of a variety of genes......Regular exercise induces a variety of adaptive responses that enhance the oxidative and metabolic capacity of human skeletal muscle. Although the physiological adjustments of regular exercise have been known for decades, the underlying mechanisms are still unclear. The hypoxia inducible factors 1...... including erythropoietin (EPO), transferrin and its receptor, as well as vascular endothelial growth factor (VEGF) and its receptor. Considering that several of these genes are also induced with exercise, we tested the hypothesis that the mRNA level of HIF-1alpha and HIF-2alpha subunits increases...

  6. Protective effects of an aptamer inhibitor of neutrophil elastase in lung inflammatory injury

    DEFF Research Database (Denmark)

    Bless, N M; Smith, D; Charlton, J

    1997-01-01

    Neutrophils play an important part in the development of acute inflammatory injury. Human neutrophils contain high levels of the serine protease elastase, which is stored in azurophilic granules and is secreted in response to inflammatory stimuli. Elastase is capable of degrading many components...... of extracellular matrix [1-4] and has cytotoxic effects on endothelial cells [5-7] and airway epithelial cells. Three types of endogenous protease inhibitors control the activity of neutrophil elastase, including alpha-1 protease inhibitor (alpha-1PI), alpha-2 macroglobulin and secreted leukoproteinase inhibitor...... (SLPI) [8-10]. A disturbed balance between neutrophil elastase and these inhibitors has been found in various acute clinical conditions (such as adult respiratory syndrome and ischemia-reperfusion injury) and in chronic diseases. We investigated the effect of NX21909, a selected oligonucleotide (aptamer...

  7. Silencing alpha-fetoprotein inhibits VEGF and MMP-2/9 production in human hepatocellular carcinoma cell.

    Science.gov (United States)

    Meng, Wenbo; Li, Xun; Bai, Zhongtian; Li, Yan; Yuan, Jinqiu; Liu, Tao; Yan, Jun; Zhou, Wence; Zhu, Kexiang; Zhang, Hui; Li, Yumin

    2014-01-01

    Alpha-fetoprotein not only serves as a diagnostic marker for liver cancer, but also posses a variety of biological functions. However, the role of Alpha-fetoprotein on tumor angiogenesis and cell invasion remains incompletely understood. In this study, we aimed to evaluate if Alpha-fetoprotein can regulate the major angiogenic factors and matrix metalloproteinases in human liver cancer cells. Alpha-fetoprotein silencing was achieved by Stealth RNAi. Expression of Alpha-fetoprotein was examined by a full-automatic electrochemistry luminescence immunity analyzer. Expression of VEGF, VEGFR-2, MMP-9, and MMP-2 was examined by Western blot and immunocytochemistry. Apoptosis was detected by TUNEL assay. Angiogenesis was detected by in vitro angiogenesis assay kit. Silencing of Alpha-fetoprotein led to an increased apoptosis, which was associated with a decreased expression of vascular endothelial growth factor, vascular endothelial growth factor receptor 2, matrix metalloproteinases-2/9. These results suggest that Alpha-fetoprotein may play a regulatory role on angiogenesis and cell invasion during liver cancer development.

  8. Regulation and function of the alpha2 adrenergic autoreceptor in the central nervous system

    International Nuclear Information System (INIS)

    Spengler, R.N.

    1987-01-01

    The purpose of this investigation was to determine whether changes observed in the number of alpha 2 adrenergic receptors in the brain as measured by radioligand binding experiments reflect changes in the function of alpha 2 autoregulatory receptors which are located on noradrenergic nerve terminals. Inhibition by clonidine of field stimulated 3 H-norepinephrine ( 3 H-NE) release from rat hippocampal slices before and after several drug treatments was analyzed to investigate changes in alpha 2 adrenergic receptor function. Clonidine in a concentration-dependent manner inhibited 3 H-NE release. The effect of clonidine was blocked by the specific alpha 2 adrenergic receptor antagonist, idazoxan. The cumulative administration of clonidine generated a smooth and well-fitted log-concentration-effect curve. Results are presented which demonstrate that this technique can be employed to investigate the role of changes in the function of the alpha 2 autoregulatory receptor. The present investigation also examined representatives of four drug classes which have been shown to alter the specific binding of 3 H-clonidine to neural membranes to determine whether changes in the alpha 2 autoregulatory receptor function also occur

  9. Platelet alpha-2 adrenergic receptor-mediated phosphoinositide responses in endogenous depression

    International Nuclear Information System (INIS)

    Mori, Hideki; Koyama, Tsukasa; Yamashita, Itaru

    1991-01-01

    We have previously indicated that epinephrine stimulates phosphoinositide (PI) hydrolysis by activating alpha-2 adrenergic receptors in human platelets. This method involves the measurement of the accumulation of [ 3 H]-inositol-1-phosphate (IP-1) as an index of Pl hydrolysis; lithium is added to inhibit the metabolism of IP-1, thus giving an enhanced signal. In the present study, we assessed the platelet alpha-2 adrenergic receptor-mediated PI responses in samples from 15 unmedicated patients with endogenous depression and 15 age- and sex-matched control subjects. The responses to epinephrine in the depressed patients were significantly higher than those of the controls, whereas the basal values did not differ significantly. These results support the hypothesis that platelet alpha-2 adrenergic receptors may be supersensitive in patients with endogenous depression

  10. Alternative splicing of T cell receptor (TCR) alpha chain transcripts containing V alpha 1 or V alpha 14 elements.

    Science.gov (United States)

    Mahotka, C; Hansen-Hagge, T E; Bartram, C R

    1995-10-01

    Human acute lymphoblastic leukemia cell lines represent valuable tools to investigate distinct steps of the complex regulatory pathways underlying T cell receptor recombination and expression. A case in point are V delta 2D delta 3 and subsequent V delta 2D delta 3J alpha rearrangements observed in human leukemic pre-B cells as well as in normal lymphopoiesis. The functional expression of these unusual (VD) delta (JC) alpha hybrids is almost exclusively prevented by alternative splicing events. In this report we show that alternative splicing at cryptic splice donor sites within V elements is not a unique feature of hybrid TCR delta/alpha transcripts. Among seven V alpha families analyzed by RT-PCR, alternatively spliced products were observed in TCR alpha recombinations containing V alpha 1 or V alpha 14 elements. In contrast to normal peripheral blood cells and thymocytes, the leukemia cell line JM expressing functional V alpha 1J alpha 3C alpha transcripts lacked evidence of aberrant TCR alpha RNA species.

  11. AMPK alpha1 activation is required for stimulation of glucose uptake by twitch contraction, but not by H2O2, in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Schjerling, Peter; Viollet, Benoit

    2008-01-01

    into muscle by certain stimuli. In contrast, no clear function has yet been determined for alpha(1) AMPK in skeletal muscle, possibly due to alpha-AMPK isoform signaling redundancy. By applying low-intensity twitch-contraction and H(2)O(2) stimulation to activate alpha(1) AMPK, but not alpha(2) AMPK......, in wildtype and alpha-AMPK transgenic mouse muscles, this study aimed to define conditions where alpha(1) AMPK is required to increase muscle glucose uptake. METHODOLOGY/PRINCIPAL FINDINGS: Following stimulation with H(2)O(2) (3 mM, 20 min) or twitch-contraction (0.1 ms pulse, 2 Hz, 2 min), signaling and 2......-deoxyglucose uptake were measured in incubated soleus muscles from wildtype and muscle-specific kinase-dead AMPK (KD), alpha(1) AMPK knockout or alpha(2) AMPK knockout mice. H(2)O(2) increased the activity of both alpha(1) and alpha(2) AMPK in addition to Akt phosphorylation, and H(2)O(2)-stimulated glucose...

  12. Comparative first-principles analysis of undoped and Co{sup 2+}-doped {alpha}-ZnAl{sub 2}S{sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Brik, M.G., E-mail: brik@fi.tartu.ee [Institute of Physics, University of Tartu, Riia 142, Tartu 51014 (Estonia); Nazarov, M. [School of Materials and Mineral Resources Engineering, Universiti Sains Malaysia, 14300 Nibong Tebal, Penang (Malaysia); Institute of Applied Physics, Academiei Street 5, Chisinau MD-2028, Republic of Moldova (Moldova, Republic of); Ahmad Fauzi, M.N. [School of Materials and Mineral Resources Engineering, Universiti Sains Malaysia, 14300 Nibong Tebal, Penang (Malaysia); Kulyuk, L.; Anghel, S. [Institute of Applied Physics, Academiei Street 5, Chisinau MD-2028, Republic of Moldova (Moldova, Republic of); Sushkevich, K. [Moldova State University, Mateevici Street 60, Chisinau MD-2009, Republic of Moldova (Moldova, Republic of); Boulon, G. [Physical Chemistry of Luminescent Materials, Claude Bernard Lyon 1 University, UMR 5620 CNRS, La Doua, 69622 Villeurbanne (France)

    2013-02-15

    Highlights: Black-Right-Pointing-Pointer Structural, electronic, and optical properties of {alpha}-ZnAl{sub 2}S{sub 4}:Co{sup 2+} were calculated. Black-Right-Pointing-Pointer Ab initio and crystal field methods were used in all calculations. Black-Right-Pointing-Pointer Position of the Co{sup 2+} energy levels in the host band gap was estimated. - Abstract: The experimental and theoretical studies of the optical properties of pure {alpha}-ZnAl{sub 2}S{sub 4} and {alpha}-ZnAl{sub 2}S{sub 4}:Co{sup 2+} crystals were carried out. The ab initio and crystal field calculations of the structural and optical properties of {alpha}-ZnAl{sub 2}S{sub 4}:Co{sup 2+} were compared with the corresponding experimental data. It was shown that the lowest cobalt 3d states are located at about 0.5 eV above the valence band's top. The complete energy level scheme of the {alpha}-ZnAl{sub 2}S{sub 4}:Co{sup 2+} system, which includes the host's electronic band structure and impurity ion's energy levels, was suggested on the basis of the performed calculations.

  13. Radiological hazards of alpha-contaminated waste

    International Nuclear Information System (INIS)

    Rodgers, J.C.

    1982-01-01

    The radiological hazards of alpha-contaminated wastes are discussed in this overview in terms of two components of hazard: radiobiological hazard, and radioecological hazard. Radiobiological hazard refers to human uptake of alpha-emitters by inhalation and ingestion, and the resultant dose to critical organs of the body. Radioecological hazard refers to the processes of release from buried wastes, transport in the environment, and translocation to man through the food chain. Besides detailing the sources and magnitude of hazards, this brief review identifies the uncertainties in their estimation, and implications for the regulatory process

  14. Estrogen increases smooth muscle expression of alpha2C-adrenoceptors and cold-induced constriction of cutaneous arteries.

    Science.gov (United States)

    Eid, A H; Maiti, K; Mitra, S; Chotani, M A; Flavahan, S; Bailey, S R; Thompson-Torgerson, C S; Flavahan, N A

    2007-09-01

    Raynaud's phenomenon, which is characterized by intense cold-induced constriction of cutaneous arteries, is more common in women compared with men. Cold-induced constriction is mediated in part by enhanced activity of alpha(2C)-adrenoceptors (alpha(2C)-ARs) located on vascular smooth muscle cells (VSMs). Experiments were therefore performed to determine whether 17beta-estradiol regulates alpha(2C)-AR expression and function in cutaneous VSMs. 17beta-Estradiol (0.01-10 nmol/l) increased expression of the alpha(2C)-AR protein and the activity of the alpha(2C)-AR gene promoter in human cultured dermal VSMs, which was assessed following transient transfection of the cells with a promoter-reporter construct. The effect of 17beta-estradiol was associated with increased accumulation of cAMP and activation of the cAMP-responsive Rap2 GTP-binding protein. Transient transfection of VSMs with a dominant-negative mutant of Rap2 inhibited the 17beta-estradiol-induced activation of the alpha(2C)-AR gene promoter, whereas a constitutively active mutant of Rap2 increased alpha(2C)-AR promoter activity. The effects of 17beta-estradiol were inhibited by the estrogen receptor (ER) antagonist, ICI-182780 (1 micromol/l), and were mimicked by a cell-impermeable form of the hormone (estrogen:BSA) or by the selective ER-alpha receptor agonist 4,4',4'''-(4-propyl-[(1)H]-pyrazole-1,3,5-triyl)tris-phenol (PPT; 10 nmol/l) or the selective ER-beta receptor agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; 10 nmol/l). Therefore, 17beta-estradiol increased expression of alpha(2C)-ARs by interacting with cell surface receptors to cause a cAMP/Rap2-dependent increase in alpha(2C)-AR transcription. In mouse tail arteries, 17beta-estradiol (10 nmol/l) increased alpha(2C)-AR expression and selectively increased the cold-induced amplification of alpha(2)-AR constriction, which is mediated by alpha(2C)-ARs. An estrogen-dependent increase in expression of cold-sensitive alpha(2C)-ARs may contribute

  15. The T alpha 2 nuclear protein binding site from the human T cell receptor alpha enhancer functions as both a T cell-specific transcriptional activator and repressor

    OpenAIRE

    1990-01-01

    T cell-specific expression of the human T cell receptor alpha (TCR- alpha) gene is regulated by the interaction of variable region promoter elements with a transcriptional enhancer that is located 4.5 kb 3' of the TCR-alpha constant region (C alpha) gene segment. The minimal TCR- alpha enhancer is composed of two nuclear protein binding sites, T alpha 1 and T alpha 2, that are both required for the T cell-specific activity of the enhancer. The T alpha 1 binding site contains a consensus cAMP ...

  16. On the rutile alpha-PbO"2-type phase boundary of TiO"2

    DEFF Research Database (Denmark)

    Olsen, J.S.; Gerward, Leif; Jiang, Jianzhong

    1999-01-01

    The high-pressure, high-temperature phase quilibria of TiO"2 have been studied with special emphasis on the rutile and alpha-PbO"2-type phases. It is found that the phase boundary, when plotted in a pressure-temperature diagram, changes from having a negative to having a positive slope...... with increasing temperature at about 6GPa and 850^oC. For nanophase material, the phase boundary is shifted towards lower pressure. The room-temperature bulk moduli are 210(120)GPa, 258(8)GPa and 290(20)GPa for rutile, the alpha-PbO"2-type phase and the baddeleyite-type phase, respectively....

  17. Antimicrobial actions of the human epididymis 2 (HE2 protein isoforms, HE2alpha, HE2beta1 and HE2beta2

    Directory of Open Access Journals (Sweden)

    French Frank S

    2004-08-01

    Full Text Available Abstract Background The HE2 gene encodes a group of isoforms with similarities to the antimicrobial beta-defensins. We demonstrated earlier that the antimicrobial activity of HE2 proteins and peptides is salt resistant and structure dependent and involves permeabilization of bacterial membranes. In this study, we further characterize the antimicrobial properties of HE2 peptides in terms of the structural changes induced in E. coli and the inhibition of macromolecular synthesis. Methods E. coli treated with 50 micro g/ml of HE2alpha, HE2beta1 or HE2beta2 peptides for 30 and 60 min were visualized using transmission and scanning electron microscopy to investigate the impact of these peptides on bacterial internal and external structure. The effects of HE2alpha, HE2beta1 and HE2beta2 on E. coli macromolecular synthesis was assayed by incubating the bacteria with 2, 10 and 25 micro g/ml of the individual peptides for 0–60 min and measuring the incorporation of the radioactive precursors [methyl-3H]thymidine, [5-3H]uridine and L-[4,5-3H(N]leucine into DNA, RNA and protein. Statistical analyses using Student's t-test were performed using Sigma Plot software. Values shown are Mean ± S.D. Results E. coli treated with HE2alpha, HE2beta1 and HE2beta2 peptides as visualized by transmission electron microscopy showed extensive damage characterized by membrane blebbing, thickening of the membrane, highly granulated cytoplasm and appearance of vacuoles in contrast to the smooth and continuous membrane structure of the untreated bacteria. Similarly, bacteria observed by scanning electron microscopy after treating with HE2alpha, HE2beta1 or HE2beta2 peptides exhibited membrane blebbing and wrinkling, leakage of cellular contents, especially at the dividing septa, and external accumulation of fibrous materials. In addition, HE2alpha, HE2beta1 and HE2beta2 peptides inhibited E. coli DNA, RNA and protein synthesis. Conclusions The morphological changes observed

  18. Fluorogenic MMP activity assay for plasma including MMPs complexed to α2-macroglobulin

    NARCIS (Netherlands)

    Beekman, B.; Drijfhout, J.W.; Ronday, H.K.; TeKoppele, J.M.

    1999-01-01

    Elevated MMP activities are implicated in tissue degradation in, e.g., arthritis and cancer. The present study was designed to measure MMP enzyme activity in plasma. Free active MMP is unlikely to be present in plasma: upon entering the circulation, active MMP is expected to be captured by the

  19. Human cancers converge at the HIF-2alpha oncogenic axis.

    Science.gov (United States)

    Franovic, Aleksandra; Holterman, Chet E; Payette, Josianne; Lee, Stephen

    2009-12-15

    Cancer development is a multistep process, driven by a series of genetic and environmental alterations, that endows cells with a set of hallmark traits required for tumorigenesis. It is broadly accepted that growth signal autonomy, the first hallmark of malignancies, can be acquired through multiple genetic mutations that activate an array of complex, cancer-specific growth circuits [Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57-70; Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control. Nat Med 10:789-799]. The superfluous nature of these pathways is thought to severely limit therapeutic approaches targeting tumor proliferation, and it has been suggested that this strategy be abandoned in favor of inhibiting more systemic hallmarks, including angiogenesis (Ellis LM, Hicklin DJ (2008) VEGF-targeted therapy: Mechanisms of anti-tumor activity. Nat Rev Cancer 8:579-591; Stommel JM, et al. (2007) Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science 318:287-290; Kerbel R, Folkman J (2002) Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2:727-739; Kaiser J (2008) Cancer genetics: A detailed genetic portrait of the deadliest human cancers. Science 321:1280-1281]. Here, we report the unexpected observation that genetically diverse cancers converge at a common and obligatory growth axis instigated by HIF-2alpha, an element of the oxygen-sensing machinery. Inhibition of HIF-2alpha prevents the in vivo growth and tumorigenesis of highly aggressive glioblastoma, colorectal, and non-small-cell lung carcinomas and the in vitro autonomous proliferation of several others, regardless of their mutational status and tissue of origin. The concomitant deactivation of select receptor tyrosine kinases, including the EGFR and IGF1R, as well as downstream ERK/Akt signaling, suggests that HIF-2alpha exerts its proliferative effects by endorsing these major pathways. Consistently

  20. Tocopherol metabolites 2, 5, 7, 8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC) and 2, 7, 8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC) in human serum after a single dose of natural vitamin E.

    Science.gov (United States)

    Radosavac, Dragan; Graf, Peter; Polidori, M Cristina; Sies, Helmut; Stahl, Wilhelm

    2002-06-01

    alpha- and gamma-Tocopherol are vitamin E compounds in human blood and tissues. alpha-CEHC (2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman) and gamma-CEHC (2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman) have been identified as water-soluble metabolites which are excreted with the urine in humans. To assess over-time changes of serum levels of alpha- and gamma-CEHC in humans after a single dose of vitamin E from a natural source. Twenty-one healthy subjects ingested a single dose of vitamin E (306 mg of RRR-alpha-tocopherol and 1.77 mg of gamma-tocopherol). Blood was collected before (baseline) and 2, 6, 12, 24, 35, 50, and 74 h after ingestion. Serum was separated and levels of alpha- and gamma-tocopherol and alpha- and gamma-CEHC were determined by HPLC. After vitamin E ingestion, a statistically significant increase was observed for alpha-tocopherol and alpha-CEHC. Maximum serum levels for both compounds were measured 12 h after application (33.3 +/- 11.1 micromol alpha-toco-pherol /L and 42.4 +/- 18.3 nmol alpha-CEHC /L); baseline values were reached again after 72 h. While gamma-tocopherol levels decreased during the study period, an increase in the metabolite gamma-CEHC was observed. The optical isomer formed in the metabolism of RRR-alpha-tocopherol was assigned as S-alpha-CEHC. alpha-CEHC levels increase after administration of a single dose of natural vitamin E in humans. The appearance of the metabolite in blood parallels that of the parent compound. The gamma-tocopherol analog appears to be metabolized more efficiently than alpha-tocopherol.

  1. Alpha-2 adrenergic stimulation triggers Achilles tenocyte hypercellularity: Comparison between two model systems.

    Science.gov (United States)

    Backman, L J; Andersson, G; Fong, G; Alfredson, H; Scott, A; Danielson, P

    2013-12-01

    The histopathology of tendons with painful tendinopathy is often tendinosis, a fibrosis-like condition of unclear pathogenesis characterized by tissue changes including hypercellularity. The primary tendon cells (tenocytes) have been shown to express adrenoreceptors (mainly alpha-2A) as well as markers of catecholamine production, particularly in tendinosis. It is known that adrenergic stimulation can induce proliferation in other cells. The present study investigated the effects of an exogenously administered alpha-2 adrenergic agonist in an established in vivo Achilles tendinosis model (rabbit) and also in an in vitro human tendon cell culture model. The catecholamine producing enzyme tyrosine hydroxylase and the alpha-2A-adrenoreceptor (α2A AR) were expressed by tenocytes, and alpha-2 adrenergic stimulation had a proliferative effect on these cells, in both models. The proliferation was inhibited by administration of an α2A AR antagonist, and the in vitro model further showed that the proliferative alpha-2A effect was mediated via a mitogenic cell signaling pathway involving phosphorylation of extracellular-signal-regulated kinases 1 and 2. The results indicate that catecholamines produced by tenocytes in tendinosis might contribute to the proliferative nature of the pathology through stimulation of the α2A AR, pointing to a novel target for future therapies. The study furthermore shows that animal models are not necessarily required for all aspects of this research. © 2013 The Authors. Scand J Med Sci Sports published by John Wiley & Sons Ltd.

  2. The alpha-cell as target for type 2 diabetes therapy

    DEFF Research Database (Denmark)

    Christensen, Mikkel; Bagger, Jonatan I; Vilsboll, Tina

    2011-01-01

    for type 2 diabetes. Several lines of preclinical evidence have paved the way for the development of drugs, which suppress glucagon secretion or antagonize the glucagon receptor. In this review, the physiological actions of glucagon and the role of glucagon in type 2 diabetic pathophysiology are outlined...... antagonists are confronted with several safety issues. At present, available pharmacological agents based on the glucose-dependent glucagonostatic effects of GLP-1 represent the most favorable way to apply constraints to the alpha-cell in type 2 diabetes.......-coupled receptors in the hepatocytes. Type 2 diabetic patients are characterized by elevated glucagon levels contributing decisively to hyperglycemia in these patients. Accumulating evidence demonstrates that targeting the pancreatic alpha-cell and its main secretory product glucagon is a possible treatment...

  3. Inhibition of K+ permeability diminishes alpha 2-adrenoceptor mediated effects on norepinephrine release

    International Nuclear Information System (INIS)

    Zimanyi, I.; Folly, G.; Vizi, E.S.

    1988-01-01

    The effect of two different potassium channel blockers, 4-aminopyridine (4-AP) and quinine, on the alpha 2-adrenoceptor mediated modulation of norepinephrine (NE) release was investigated. Pairs of mouse vasa deferentia were loaded with 3 H-norepinephrine ( 3 H-NE), superfused continuously, and stimulated electrically. 4-AP (5.3 x 10(-4) M), and quinine (10(-5) M) enhanced the stimulation-evoked release of tritium significantly. The electrically induced release of radioactivity was reduced by alpha 2-adrenoceptor agonists (1-NE and xylazine) and enhanced by the alpha 2-adrenoceptor antagonist yohimbine. Both effects were affected markedly by 4-AP or quinine: the depressant action of 1-NA and xylazine was partially antagonized and the facilitatory effect of yohimbine was completely abolished during the blockade of the potassium channels. It is suggested that the blockade of the potassium permeability counteracts negative feedback modulation; therefore, it seems likely that the stimulation of alpha 2-adrenoceptors leads to an enhanced potassium permeability and hyperpolarization of varicose axon terminals

  4. [(35)S]-GTPgammaS autoradiography reveals alpha(2) adrenoceptor-mediated G-protein activation in amygdala and lateral septum.

    Science.gov (United States)

    Newman-Tancredi, A; Chaput, C; Touzard, M; Millan, M J

    2000-04-03

    alpha(2)-adrenoceptor-mediated G-protein activation was examined by [(35)S]-GTPgammaS autoradiography. In alpha(2)-adrenoceptor-rich regions (amygdala, lateral septum), noradrenaline stimulated [(35)S]-GTPgammaS binding. These actions were abolished by the selective alpha(2) antagonist, atipamezole. Conversely, in caudate nucleus, which expresses few alpha(2) receptors, noradrenaline-induced stimulation was not inhibited by atipamezole, suggesting that it is not mediated by alpha(2)-adrenoceptors.

  5. Canine placental prostaglandin E2 synthase: expression, localization, and biological functions in providing substrates for prepartum PGF2alpha synthesis.

    Science.gov (United States)

    Gram, Aykut; Fox, Barbara; Büchler, Urs; Boos, Alois; Hoffmann, Bernd; Kowalewski, Mariusz P

    2014-12-01

    The prepartum output of PGF2alpha in the bitch is associated with increased placental PGE2-synthase (PTGES) mRNA levels. Contrasting with this is a decreased expression of PGF2alpha-synthase (PGFS/AKR1C3) in uteroplacental compartments during prepartum luteolysis, suggesting an involvement of alternative synthetic pathways in PGF2alpha synthesis, for example, conversion of PGE2 to PGF2alpha. However, because the expression and possible functions of the respective PTGES proteins remained unknown, no further conclusion could be drawn. Therefore, a canine-specific PTGES antibody was generated and used to investigate the expression, cellular localization, and biochemical activities of canine uteroplacental PTGES throughout pregnancy and at prepartum luteolysis. Additionally, the biochemical activities of these tissues involved in the conversion of PGE2 to PGF2alpha were investigated. The endometrial PTGES was localized in the uterine surface epithelium at preimplantation and in superficial and deep uterine glands, endothelial cells, and myometrium throughout pregnancy and at parturition. Placental signals were mostly in the trophoblast. The biochemical properties of recombinant PTGES protein were confirmed. Additionally, expression of two PGE2-receptors, PTGER2/EP2 and PTGER4/EP4, revealed their decreasing expression during luteolysis. In contrast, the uteroplacental expression of prostaglandin transporter (PGT) was strongly elevated prior to parturition. These localization patterns resembled that of PTGES. The increased expression of PTGES and PGT at parturition, together with the accompanying decreased levels of PGE2-receptors and the capability of canine uterine and placental homogenates to take part in the conversion of PGE2 to PGF2alpha, as found in this study, suggest that PGE2 could be used locally as a substrate for prepartum PGF2alpha synthesis in the dog. © 2014 by the Society for the Study of Reproduction, Inc.

  6. Clustering of galaxies near damped Lyman-alpha systems with (z) = 2.6

    Science.gov (United States)

    Wolfe, A. M

    1993-01-01

    The galaxy two-point correlation function, xi, at (z) = 2.6 is determined by comparing the number of Ly-alpha-emitting galaxies in narrowband CCD fields selected for the presence of damped L-alpha absorption to their number in randomly selected control fields. Comparisons between the presented determination of (xi), a density-weighted volume average of xi, and model predictions for (xi) at large redshifts show that models in which the clustering pattern is fixed in proper coordinates are highly unlikely, while better agreement is obtained if the clustering pattern is fixed in comoving coordinates. Therefore, clustering of Ly-alpha-emitting galaxies around damped Ly-alpha systems at large redshifts is strong. It is concluded that the faint blue galaxies are drawn from a parent population different from normal galaxies, the presumed offspring of damped Ly-alpha systems.

  7. Cytotoxic T-Lymphocyte Antigen-2 alpha participates in axial ...

    African Journals Online (AJOL)

    Cytotoxic T-lymphocyte antigen-2 alpha (CTLA-2α) has been discovered and expressed in mouse activated T-cells and mast cells. Structurally, it is homologous to the proregion of mouse cathepsin L, a lysosomal cystein proteinase. Expressed recombinant CTLA-2α is shown to exhibit selective inhibition to cathepsin L and ...

  8. Neutron transition multipole moment for /sup 88/Sr(. cap alpha. ,. cap alpha. ')/sup 88/Sr (2/sup +/, 1. 84 MeV)

    Energy Technology Data Exchange (ETDEWEB)

    Datta, S.K.; Ray, S.; Majumdar, H.; Ghosh, S.K.; Samanta, C.; Dasgupta, P.; Chintalapudi, S.N.; Banerjee, S.R.

    1989-04-01

    The neutron transition multipole moment, M/sub n/, for (0/sup +/..-->..2/sup +/, 1.84 MeV) transition is inferred by measuring the (..cap alpha..,..cap alpha..') angular distribution at E/sub ..cap alpha../ = 50 MeV and comparing it with a microscopic distorted-wave Born approximation calculation. Proton transition densities are taken from electron scattering data. M/sub n//M/sub p/ is found to be substantially less than N/Z in agreement with the (p,p') result.

  9. Scattering of alpha particles from /sup 12/C and the /sup 12/C(. cap alpha. ,. gamma. )/sup 16/O stellar reaction rate

    Energy Technology Data Exchange (ETDEWEB)

    Plaga, R.; Becker, H.W.; Redder, A.; Rolfs, C.; Trautvetter, H.P.; Langanke, K.

    1987-04-06

    The elastic scattering of alpha particles from /sup 12/C has been investigated for 35 angles in the range theta/sub lab/ = 22/sup 0/ to 163/sup 0/ and for 51 energies at E/sub ..cap alpha../ = 1.0 to 6.6 MeV. The extracted phase shifts for l=0 to 6 partial waves have been parametrized in terms of the multilevel R-matrix formalism. Information on the deduced parameters of states in /sup 16/O is reported. The data reveal reduced ..cap alpha..-particle widths for the 6.92 and 7.12 MeV subthreshold states consistent with recent work. The implications for the stellar reaction rate of /sup 12/C(..cap alpha..,..gamma..)/sup 16/O are discussed.

  10. Alpha-tocopheryl phosphate: a novel, natural form of vitamin E.

    Science.gov (United States)

    Gianello, Robert; Libinaki, Roksan; Azzi, Angelo; Gavin, Paul D; Negis, Yesim; Zingg, Jean-Marc; Holt, Phillip; Keah, Hooi-Hong; Griffey, Annike; Smallridge, Andrew; West, Simon M; Ogru, Esra

    2005-10-01

    We have detected alpha-tocopheryl phosphate in biological tissues including liver and adipose tissue, as well as in a variety of foods, suggesting a ubiquitous presence in animal and plant tissue. Alpha-tocopheryl phosphate is a water-soluble molecule that is resistant to both acid and alkaline hydrolysis, making it undetectable using standard assays for vitamin E. A new method was therefore developed to allow the extraction of both alpha-tocopheryl phosphate and alpha-tocopherol from a single specimen. We used ESMS to detect endogenous alpha-tocopheryl phosphate in biological samples that also contained alpha-tocopherol. Due to the significance of these findings, further proof was required to unequivocally demonstrate the presence of endogenous alpha-tocopheryl phosphate in biological samples. Four independent methods of analysis were examined: HPLC, LCMS, LCMS/MS, and GCMS. Alpha-tocopherol phosphate was identified in all instances by comparison between standard alpha-tocopheryl phosphate and extracts of biological tissues. The results show that alpha-tocopheryl phosphate is a natural form of vitamin E. The discovery of endogenous alpha-tocopheryl phosphate has implications for the expanding knowledge of the roles of alpha-tocopherol in biological systems.

  11. Alpha- and beta-adrenoceptors in hypertension. II. Platelet alpha 2- and lymphocyte beta 2-adrenoceptors in children of parents with essential hypertension. A model for the pathogenesis of the genetically determined hypertension

    NARCIS (Netherlands)

    Michel, M. C.; Galal, O.; Stoermer, J.; Bock, K. D.; Brodde, O. E.

    1989-01-01

    To study whether changes in alpha- and beta-adrenoceptors in human essential hypertension (EHT) might be genetically determined, we assessed platelet alpha 2- and lymphocyte beta 2-adrenoceptor density in 48 normotensive children of normotensive parents (NT) and in 41 normotensive children with one

  12. Basic residues in the 74-83 and 191-198 segments of protein kinase CK2 catalytic subunit are implicated in negative but not in positive regulation by the beta-subunit

    DEFF Research Database (Denmark)

    Sarno, S; Vaglio, P; Marin, O

    1997-01-01

    by the beta-subunit many fold more than that of alpha wild type, while extrastimulation by beta mutant D55L56E57A, observable with alpha wild type, is abolished with these mutants. These data support the conclusion that down regulation by the acidic residues clustered in the N-terminal moiety of beta...... is mediated by basic residues in the 74-83 and in the 191-198 sequences of the alpha-subunit. These are also implicated in substrate recognition consistent with the concept that the N-terminal acidic region of the beta subunit operates as a pseudosubstrate. In contrast, another CK2alpha mutant, V66A, is more...

  13. Extrasynaptic location of alpha-2 and noninnervated beta-2 adrenoceptors in the vascular system of the pithed normotensive rat

    NARCIS (Netherlands)

    Wilffert, B.; Timmermans, P.B.M.W.M.; Van Zwieten, P.A.

    1982-01-01

    The receptors involved in the pressor and tachycardic effects of catecholamines applied systemically or released from sympathetic nerve endings were compared. Intravenously administered (-)-epinephrine activated alpha-1, alpha-2, beta-1 and beta-2 adrenoceptors as demonstrated in pithed rats, using

  14. Alcohol depletes coenzyme-Q10 associated with increased TNF-alpha secretion to induce cytotoxicity in HepG2 cells

    International Nuclear Information System (INIS)

    Vidyashankar, Satyakumar; Nandakumar, Krishna S.; Patki, Pralhad S.

    2012-01-01

    Highlights: ► Ethanol induced cytotoxicity in HepG2 cells in absence of lipogenesis. ► Ethanol inhibited HMG-CoA reductase activity. ► Ethanol induced HMG-CoA reductase inhibition is due to decreased cell viability. ► Incubation with mevalonate could not increase the cholesterol. ► Cytotoxicity brought about by CoQ10 depletion and increased TNF-alpha. -- Abstract: Alcohol consumption has been implicated to cause severe hepatic steatosis which is mediated by alcohol dehydrogenase (ADH) activity and CYP 450 2E1 expression. In this context, the effect of ethanol was studied for its influence on lipogenesis in HepG2 cell which is deficient of ADH and does not express CYP 450 2E1. The results showed that ethanol at 100 mM concentration caused 40% cytotoxicity at 72 h as determined by MTT assay. The incorporation of labeled [2- 14 C] acetate into triacylglycerol and phospholipid was increased by 40% and 26% respectively upon 24 h incubation, whereas incorporation of labeled [2- 14 C] acetate into cholesterol was not significantly increased. Further, ethanol inhibited HMG-CoA reductase which is a rate-limiting enzyme in the cholesterol biosynthesis. It was observed that, HMG-CoA reductase inhibition was brought about by ethanol as a consequence of decreased cell viability, since incubation of HepG2 cells with mevalonate could not increase the cholesterol content and increase the cell viability. Addition of ethanol significantly increased TNF-alpha secretion and depleted mitochondrial coenzyme-Q 10 which is detrimental for cell viability. But vitamin E (10 mM) could partially restore coenzyme-Q 10 and glutathione content with decreased TNF-alpha secretion in ethanol treated cells. Further, lipid peroxidation, glutathione peroxidase and superoxide dismutase enzyme activities remained unaffected. Ethanol decreased glutathione content while, GSH/GSSG ratio was significantly higher compared to other groups showing cellular pro-oxidant and antioxidant balance remained

  15. 2-Azido-( sup 32 P)NAD+, a photoactivatable probe for G-protein structure: Evidence for holotransducin oligomers in which the ADP-ribosylated carboxyl terminus of alpha interacts with both alpha and gamma subunits

    Energy Technology Data Exchange (ETDEWEB)

    Vaillancourt, R.R.; Dhanasekaran, N.; Johnson, G.L.; Ruoho, A.E. (Univ. of Wisconsin Medical School, Madison (USA))

    1990-05-01

    A radioactive and photoactivatable derivative of NAD+, 2-azido-(adenylate-32P)NAD+, has been synthesized and used with pertussis toxin to ADP-ribosylate Cys347 of the alpha subunit (alpha T) of GT, the retinal guanine nucleotide-binding protein. ADP-ribosylation of alpha T followed by light activation of the azide moiety of 2-azido-(adenylate-32P)ADP-ribose produced four crosslinked species involving the alpha and gamma subunits of the GT heterotrimer: an alpha trimer (alpha-alpha-alpha), and alpha-alpha-gamma crosslink, an alpha dimer (alpha-alpha), and an alpha-gamma crosslink. The alpha trimer, alpha-alpha-gamma complex, alpha dimer, and alpha-gamma complexes were immunoreactive with alpha T antibodies. The alpha-alpha-gamma and the alpha-gamma complexes were immunoreactive with antisera recognizing gamma subunits. No evidence was found for crosslinking of alpha T to beta T subunits. Hydrolysis of the thioglycosidic bond between Cys347 and 2-azido-(adenylate-32P)ADP-ribose using mercuric acetate resulted in the transfer of radiolabel from Cys347 of alpha T in the crosslinked oligomers to alpha monomers, indicative of intermolecular photocrosslinking, and to gamma monomers, indicative of either intermolecular crosslinked complexes (between heterotrimers) or intramolecular crosslinked complexes (within the heterotrimer). These results demonstrate that GT exists as an oligomer and that ADP-ribosylated Cys347, which is four residues from the alpha T-carboxyl terminus, is oriented toward and in close proximity to the gamma subunit.

  16. Pancreatic elastase in human serum. Determination by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Geokas, M.C. (Univ. of California, Davis); Brodrick, J.W.; Johnson, J.H.; Largman, C.

    1977-01-10

    This study demonstrates that a serine endopeptidase of pancreatic origin (elastase 2) circulates in human blood. A specific and highly sensitive radioimmunoassay has been developed for pancreatic elastase 2 in human serum. The inactivation of elastase 2 employed as radioiodinated tracer with an active site-specific reagent (phenylmethanesulfonyl fluoride) was necessary to prevent its binding by serum ..cap alpha../sub 1/-antitrypsin and ..cap alpha../sub 2/-macroglobulin while maintaining its immunoreactivity. The assay is based upon competition of standard human pancreatic elastase 2 with /sup 125/I-labeled phenylmethanesulfonyl elastase 2 for specific antibody binding sites, after which a second antibody precipitation step is used to separate bound from free /sup 125/I-labeled phenylmethanesulfonyl elastase 2. The minimum detectable concentration of elastase 2 was 0.9 ng/ml. The average normal fasting serum level determined was 71 ng/ml, approximately 80-fold greater than the minimum detectable amount.

  17. ALPHA/AMPU, Radionuclide Radioactivity from Alpha Spectrometer Measurements

    International Nuclear Information System (INIS)

    Sill, D.S.

    1990-01-01

    1 - Description of program or function: The two computer programs, ALPHA and AMPU, take raw data obtained from alpha spectrometry and from these calculate activities and uncertainties of the radionuclides present in the sample. ALPHA determines activities of any alpha emitter in a sample that has been directly precipitated with NdF 3 . AMPU determines the Pu-239, Pu-238,and Am-241 activities using Pu-236 and Am-243 tracers. 2 - Method of solution: These programs propagate all random and systematic uncertainties, found anywhere in the experimental process, to the final result. The result is rounded and is in decimal agreement with the uncertainty. 3 - Restrictions on the complexity of the problem: In ALPHA, a chemical yield of 98% is assumed

  18. IMMUNOMODULATING THERAPY BY RECOMBINANT ALPHA-2B INTERFERON AMONG CHILDREN WITH TIMOMEGALIA

    Directory of Open Access Journals (Sweden)

    L.A. Nikulin

    2007-01-01

    Full Text Available The study of the enlarged thymus gland syndrome is extremely important for understanding of the immune system formation and functioning mechanisms. the purpose of this study is to conduct clinical and immunological analysis of the children, suffering from the syndrome of the enlarged thymus gland II and III degrees, who received recombinant alpha2b interferon (in suppositories. The revealed changes in the immune sys tem during timomegalia are complex and conducive to the development of the infectious and inflammatory diseases among infants, thus, determining the necessity for the adequate immune correction. The application of the recombinant alpha 2b interferon among such children allows one to uncover the immunomodulating effects, normalizing the imbalances in the immune system of children with timomegalia.Key words: timomegalia, alpha 2b interferon, immunity, immune correction, children.

  19. Effects of a single administration of prostaglandin F2alpha, or a combination of prostaglandin F2alpha and prostaglandin E2, or placebo on fertility variables in dairy cows 3-5 weeks post partum, a randomized, double-blind clinical trial.

    Science.gov (United States)

    Hirsbrunner, Gaby; Burkhardt, Heinz W; Steiner, Adrian

    2006-12-21

    Delayed uterine involution has negative effects on the fertility of cows; use of prostaglandin F2alpha alone as a single treatment has not been shown to consistently improve fertility. Combined administration of PGF2alpha and PGE2 increased uterine pressure in healthy cows. We hypothesized, that the combination of both prostaglandins would accelerate uterine involution and have, therefore, a positive effect on fertility variables. In commercial dairy farming, the benefit of a single post partum combined prostaglandin treatment should be demonstrated. 383 cows from commercial dairy farms were included in this study. Uterine size and secretion were evaluated at treatment 21-35 days post partum and 14 days later. Cows were randomly allocated to one of three treatment groups: PGF2alpha and PGE2, PGF2alpha or placebo. For every animal participating in the study, the following reproduction variables were recorded: Interval from calving to first insemination, days open, number of artificial inseminations (AI) to conception; subsequent treatment of uterus, subsequent treatment of ovaries. Plasma progesterone level at time of treatment was used as a covariable. For continuous measurements, analysis of variance was performed. Fisher's exact test for categorical non-ordered data and exact Kruskal-Wallis test for ordered data were used; pairwise group comparisons with Bonferroni adjustment of significance level were performed. There was no significant difference among treatment groups in uterine size. Furthermore, there was no significant difference among treatments concerning days open, number of AI, and subsequent treatment of uterus and ovaries. Days from calving to first insemination tended to be shorter for cows with low progesterone level given PGF2alpha and PGE2 in combination than for the placebo-group (P = 0.024). The results of this study indicate that the administration of PGF2alpha or a combination of PGF2alpha and PGE2 21 to 35 days post partum had no beneficial

  20. Alpha 2-adrenoceptor blockade, pituitary-adrenal hormones, and agonistic interactions in rats.

    Science.gov (United States)

    Haller, J; Barna, I; Kovács, J L

    1994-08-01

    The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. Alpha 2 adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an alpha 2 adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different alpha 2 adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the alpha 2 adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed.

  1. POLARIZED EXTENDED Ly{alpha} EMISSION FROM A z = 2.3 RADIO GALAXY

    Energy Technology Data Exchange (ETDEWEB)

    Humphrey, A. [Centro de Astrofisica da Universidade do Porto, Rua das Estrelas, 4150-762 Porto (Portugal); Vernet, J.; Fosbury, R. A. E. [European Southern Observatory, Karl-Schwarzschild-Strasse 2, D-85748 Garching (Germany); Villar-Martin, M. [Centro de Astrobiologia (INTA-CSIC), Carretera de Ajalvir, km 4, E-28850 Torrejon de Ardoz, Madrid (Spain); Di Serego Alighieri, S. [INAF-Osservatorio Astrofisico di Arcetri, L.go E. Fermi 5, I-50125 Firenze (Italy); Cimatti, A., E-mail: andrew.humphrey@astro.up.pt [Dipartimento di Astronomia, Universita di Bologna, Via Ranzani 1, I-40127 Bologna (Italy)

    2013-05-01

    We present spatially resolved spectropolarimetric measurements of the 100 kpc scale gaseous environment of the z = 2.34 radio galaxy TXS 0211-122. The polarization level of the narrow Ly{alpha} emission is low centrally (P < 5%), but rises to P = 16.4% {+-} 4.6% in the eastern part of the nebula, indicating that the nebula is at least partly powered by the scattering of Ly{alpha} photons by H I. Not only is this the first detection of polarized Ly{alpha} around a radio-loud active galaxy, it is also the second detection to date for any kind of Ly{alpha} nebula. We also detect a pair of diametrically opposed UV continuum sources along the slit, at the outer edges of the Ly{alpha} nebula, which we suggest may be the limb of a dusty shell, related to the large-scale H I absorbers often associated with high-z radio galaxies.

  2. Cathepsin D inhibitors

    Directory of Open Access Journals (Sweden)

    M. Gacko

    2007-11-01

    Full Text Available Inhibitors of cathepsin D belong to chemical compounds that estrify carboxyl groups of the Asp33 and Asp231residues of its catalytic site, penta-peptides containing statin, i.e. the amino acid similar in structure to the tetraedric indirectproduct, and polypeptides found in the spare organs of many plants and forming permanent noncovalent complexes withcathepsin. Cathepsin D activity is also inhibited by alpha2-macroglobulin and antibodies directed against this enzyme.Methods used to determine the activity and concentration of these inhibitors and their analytical, preparative and therapeuticapplications are discussed.

  3. A discrepancy between platelet alpha 2-receptor density and functional circulatory changes in hypertensives

    International Nuclear Information System (INIS)

    Mores, N.; Martire, M.; Pistritto, G.; Cardillo, C.; Folli, G.

    1990-01-01

    To investigate whether differences exist in peripheral alpha 2-adrenoceptors between normotensive and hypertensive subjects, we determined platelet alpha 2-adrenoceptor density in 10 (7 males) untreated essential hypertensives (mean age of 51.1 years, range of 44-59 years) and in 10 age- and sex-matched normotensive controls. Moreover, in hypertensive patients, we examined the relationship between receptor density and cardiovascular reactivity to mental arithmetic, static handgrip, and bicycle exercise, to verify the hypothesis that alpha 2-adrenoceptors might play a role in modulation of hemodynamic response to sympathetic stimuli. alpha 2-Adrenoceptor density, as calculated by binding of [3H]yohimbine to platelets, was significantly higher in essential hypertensives (314.8 +/- 38.7 fmol/mg) than in normotensive subjects (213.6 +/- 34.7 fmol/mg) (p less than 0.05), whereas receptor affinity was similar in both groups (4.0 +/- 0.5 nM hypertensives, 4.3 +/- 0.5 nM normotensives; p greater than 0.05). Mental arithmetic increased mean arterial pressure (MAP) by 21.5% from basal values and heart rate (HR) by 13.2%. During isometric exercise, MAP increased by 38.1% and HR by 24.7%, while during bicycle ergometry, mean increases in MAP and HR from baseline were of 27.2 and 54.3%, respectively. No correlation was found between platelet alpha 2-adrenoceptor density and percent changes in MAP induced by all tests, or between adrenoceptors and absolute basal and peak MAP values. Our findings suggest that in hypertensive patients, peripheral alpha 2-adrenoceptors are increased with respect to matched normotensives, but these receptors seem not to be involved in the modulation of cardiovascular adaptation to enhanced sympathetic activity

  4. The anti-tumorigenic activity of A2M-A lesson from the naked mole-rat.

    Directory of Open Access Journals (Sweden)

    Susanne Kurz

    Full Text Available Cancer resistance is a major cause for longevity of the naked mole-rat. Recent liver transcriptome analysis in this animal compared to wild-derived mice revealed higher expression of alpha2-macroglobulin (A2M and cell adhesion molecules, which contribute to the naked mole-rat's cancer resistance. Notably, A2M is known to dramatically decrease with age in humans. We hypothesize that this might facilitate tumour development. Here we found that A2M modulates tumour cell adhesion, migration and growth by inhibition of tumour promoting signalling pathways, e.g. PI3K / AKT, SMAD and up-regulated PTEN via down-regulation of miR-21, in vitro and in tumour xenografts. A2M increases the expression of CD29 and CD44 but did not evoke EMT. Transcriptome analysis of A2M-treated tumour cells, xenografts and mouse liver demonstrated a multifaceted regulation of tumour promoting signalling pathways indicating a less tumorigenic environment mediated by A2M. By virtue of these multiple actions the naturally occurring A2M has strong potential as a novel therapeutic agent.

  5. Spin reorientation in α-Fe2O3 nanoparticles induced by interparticle exchange interactions in alpha-Fe2O3/NiO nanocomposites

    DEFF Research Database (Denmark)

    Frandsen, Cathrine; Lefmann, Kim; Lebech, Bente

    2011-01-01

    We report that the spin structure of alpha-Fe2O3 nanoparticles rotates coherently out of the basal (001) plane at low temperatures when interacting with thin plate-shaped NiO nanoparticles. The observed spin reorientation (up to similar to 70 degrees) in alpha-Fe2O3 nanoparticles has, in appearan......, similarities to the Morin transition in bulk alpha-Fe2O3, but its origin is different-it is caused by exchange coupling between aggregated nanoparticles of alpha-Fe2O3 and NiO with different directions of easy axes of magnetization.......We report that the spin structure of alpha-Fe2O3 nanoparticles rotates coherently out of the basal (001) plane at low temperatures when interacting with thin plate-shaped NiO nanoparticles. The observed spin reorientation (up to similar to 70 degrees) in alpha-Fe2O3 nanoparticles has, in appearance...

  6. Stromal cell-derived factor-1 alpha (SDF-1 alpha) improves neural recovery after spinal cord contusion in rats

    NARCIS (Netherlands)

    Zendedel, A.; Nobakht, M.; Bakhtiyari, M.; Beyer, C.; Kipp, M.; Baazm, M.; Joghataie, M.T.

    2012-01-01

    Stromal cell-derived factor-1 alpha (SDF-1α) is an important cytokine, implicated in the control of stem cell trafficking and bone marrow-derived stem cell mobilization. Generally, SDF-1α regulates multiple physiological processes such as embryonic development and organ homeostasis. There is also

  7. Novel P2 promoter-derived HNF4{alpha} isoforms with different N-terminus generated by alternate exon insertion

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jianmin, E-mail: jmhuang@partners.org [Pediatric Endocrine Unit, MassGeneral Hospital for Children and Harvard Medical School, Boston, Massachusetts, 02114-2696 (United States); Levitsky, Lynne L. [Pediatric Endocrine Unit, MassGeneral Hospital for Children and Harvard Medical School, Boston, Massachusetts, 02114-2696 (United States); Rhoads, David B., E-mail: rhoads@helix.mgh.harvard.edu [Pediatric Endocrine Unit, MassGeneral Hospital for Children and Harvard Medical School, Boston, Massachusetts, 02114-2696 (United States)

    2009-04-15

    Hepatocyte nuclear factor 4{alpha} (HNF4{alpha}) is a critical transcription factor for pancreas and liver development and functions in islet {beta} cells to maintain glucose homeostasis. Mutations in the human HNF4A gene lead to maturity onset diabetes of the young (MODY1) and polymorphisms are associated with increased risk for type 2 diabetes mellitus (T2DM). Expression of six HNF4{alpha} variants, three each from two developmentally regulated promoters, has been firmly established. We have now detected a new set of HNF4{alpha} variants designated HNF4{alpha}10-12 expressed from distal promoter P2. These variants, generated by inclusion of previously undetected exon 1E (human = 222 nt, rodent = 136 nt) following exon 1D have an altered N-terminus but identical remaining reading frame. HNF4{alpha}10-{alpha}12 are expressed in pancreatic islets (and liver) and exhibit transactivation potentials similar to the corresponding {alpha}7-{alpha}9 isoforms. DNA-binding analyses implied much higher protein levels of HNF4{alpha}10-{alpha}12 in liver than expected from the RT-PCR data. Our results provide evidence for a more complex expression pattern of HNF4{alpha} than previously appreciated. We recommend inclusion of exon 1E and nearby DNA sequences in screening for HNF4{alpha} mutations and polymorphisms in genetic analyses of MODY1 and T2DM.

  8. Increased virulence and competitive advantage of a/alpha over a/a or alpha/alpha offspring conserves the mating system of Candida albicans.

    Science.gov (United States)

    Lockhart, Shawn R; Wu, Wei; Radke, Joshua B; Zhao, Rui; Soll, David R

    2005-04-01

    The majority of Candida albicans strains in nature are a/alpha and must undergo homozygosis to a/a or alpha/alpha to mate. Here we have used a mouse model for systemic infection to test the hypothesis that a/alpha strains predominate in nature because they have a competitive advantage over a/a and alpha/alpha offspring in colonizing hosts. Single-strain injection experiments revealed that a/alpha strains were far more virulent than either their a/a or alpha/alpha offspring. When equal numbers of parent a/alpha and offspring a/a or alpha/alpha cells were co-injected, a/alpha always exhibited a competitive advantage at the time of extreme host morbidity or death. When equal numbers of an engineered a/a/alpha2 strain and its isogenic a/a parent strain were co-injected, the a/a/alpha2 strain exhibited a competitive advantage at the time of host morbidity or death, suggesting that the genotype of the mating-type (MTL) locus, not associated genes on chromosome 5, provides a competitive advantage. We therefore propose that heterozygosity at the MTL locus not only represses white-opaque switching and genes involved in the mating process, but also affects virulence, providing a competitive advantage to the a/alpha genotype that conserves the mating system of C. albicans in nature.

  9. The alpha(2a)-adrenergic receptor plays a protective role in mouse behavioral models of depression and anxiety.

    Science.gov (United States)

    Schramm, N L; McDonald, M P; Limbird, L E

    2001-07-01

    The noradrenergic system is involved in the regulation of many physiological and psychological processes, including the modulation of mood. The alpha(2)-adrenergic receptors (alpha(2)-ARs) modulate norepinephrine release, as well as the release of serotonin and other neurotransmitters, and are therefore potential targets for antidepressant and anxiolytic drug development. The current studies were undertaken to examine the role of the alpha(2A) subtype of alpha(2)-AR in mouse behavioral models of depression and anxiety. We have observed that the genetic knock-out of the alpha(2A)-AR makes mice less active in a modified version of Porsolt's forced swim test and insensitive to the antidepressant effects of the tricyclic drug imipramine in this paradigm. Furthermore, alpha(2A)-AR knock-out mice appear more anxious than wild-type C57 Bl/6 mice in the rearing and light-dark models of anxiety after injection stress. These findings suggest that the alpha(2A)-AR may play a protective role in some forms of depression and anxiety and that the antidepressant effects of imipramine may be mediated by the alpha(2A)-AR.

  10. Involvement of prostaglandins F/sub 2. cap alpha. / and E/sub 1/ with rabbit endometrium

    Energy Technology Data Exchange (ETDEWEB)

    Orlicky, D.J.

    1985-01-01

    Several growth factors and hormones are thought to play a role in the growth control of endometrial cells. The authors have shown that prostaglandin F/sub 2..-->../ (PGF/sub 2..cap alpha../) is a growth factor for primary cultures of rabbit endometrium cultured in chemically-defined serum-free medium and that prostaglandin E/sub 1/ (PGE/sub 1/) antagonizes the PGF/sub 2..-->../ induction of growth. Both (/sup 3/H)PGF/sub 2..cap alpha../ and (/sup 3/H)PGE/sub 1/ bind in a time and temperature dependent, dissociable, saturable and specific manner. The binding of (/sup 3/H)PGF/sub 2..cap alpha../ and (/sup 3/H)PGE/sub 1/ can be both down and up regulated and is enzyme sensitive. PGE /sub 1/ stimulates intracellular cAMP synthesis and accumulation in a time and concentration dependent manner. PGF/sub 2..cap alpha../ probably exerts its effects through an amiloride-sensitive intermediate. Both PGF/sub 2..cap alpha../ and PGE/sub 1/ are constitutively synthesized by these primary cultures, and they have shown this synthesis to be both drug and hormone sensitive. They hypothesize that it is the ratio, rather than the absolute quantities, of PGF/sub 2..cap alpha../ and PGE/sub 1/ which is of more importance in the regulation of endometrial cell growth. Furthermore, they believe this regulation of endometrial growth plays a role in control of proliferation during the decidual response and that a derangement in the ratio of these prostaglandins may lead to either infertility or hyperplasia. The ability of these cultures to synthesize prostaglandins in a hormonally regulatable manner may be of importance in the study of dysmenorrhea and uterine cramping as caused by the myometrial contracting prostaglandin, PGF/sub 2..cap alpha../.

  11. Alpha2-adrenoceptor modulation of long-term potentiation elicited in vivo in rat occipital cortex.

    Science.gov (United States)

    Mondaca, Mauricio; Hernández, Alejandro; Pérez, Hernán; Valladares, Luis; Sierralta, Walter; Fernández, Victor; Soto-Moyano, Rubén

    2004-09-24

    Pretreatment with the alpha(2)-adrenoceptor agonist clonidine (31.25, 62.5, or 125 microg/kg, i.p.) dose-dependently reduced long-term potentiation (LTP) elicited in vivo in the occipital cortex of anesthetized rats, whereas pretreatment with the alpha(2)-adrenoceptor antagonist yohimbine (0.133, 0.4, or 1.2 mg/kg, i.p.) increased neocortical LTP in a dose-dependent fashion. These effects could be related to the reported disruptive and facilitatory actions induced on memory formation by pretreatment with alpha(2)-adrenoceptor agonists and antagonists, respectively.

  12. Contribution to the study of alpha-alpha interaction; Contribution a l'etude de l'interaction alpha - alpha

    Energy Technology Data Exchange (ETDEWEB)

    Darriulai, P [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1965-03-01

    Two sets of measurements of the {alpha}-{alpha} elastic scattering differential cross section are presented. The first set - angular distributions from 50 up to 120 MeV - shows two new resonances, 6{sup +} and 8{sup +}, at 25 and 57 MeV. Complex phase shifts are extracted from the data and a phenomenological potential is given. A description of the 3 {alpha}-particle 0{sup +} states in C{sup 12} is made with this interaction potential. The second set - excitation curves between 20 and 50 MeV - allows investigation of the Be{sup 8} level structure within this energy range - It identifies the 16.6 and 16.9 MeV states as 2{sup +}, but the rise of inelastic processes at higher energies makes further identification of spins and parities more and more difficult. (author) [French] Deux series de mesures de la section efficace differentielle de diffusion {alpha}-{alpha} sont presentees. La premiere - distributions angulaires entre 50 et 120 MeV - fait apparaitre deux nouvelles resonances, 6{sup +} et 8{sup +}, a 25 et 57 MeV d'excitation. Des dephasages complexes en sont extraits et un potentiel phenomenologique est presente. Une etude des etats 0{sup +} a parentage (3{alpha}) de {sup 12}C est faite a partir de ce potentiel. La seconde - courbes d'excitation s'etendant de 20 a 50 MeV - met en evidence la structure de {sup 8}Be dans cette region. Elle montre que les niveaux a 16,6 et 16,9 MeV sont des 2{sup +} mais l'importance des processus inelastiques rend difficile l'identification des niveaux d'excitation plus elevee. (auteur)

  13. Treatment profile of hepatitis C patients - a comparison of interferon alpha 2a and 2b treatment regimes

    International Nuclear Information System (INIS)

    Aziz, S.; Rajper, J.; Nafay, S.; Imran, K.; Khan, M.H.

    2010-01-01

    To compare the side effects, cost, end treatment response (ETR) and Sustained viral response (SVR) with combination therapy of either interferon alpha 2a or 2b in combination with Ribavarin. Study Design: Randomized Control Clinical Trial (RCCT). Place and Duration of Study: The study was conducted at Sarwar Zuberi Liver Centre (SZLC), Civil Hospital Karachi (CHK), from May 2004 to July 2009. Methodology: Patients positive for qualitative HCV ribonucleic acid (RNA) by Polymerase chain reaction (PCR) and genotype 3 were included. Patients with decompensated cirrhosis, severe depressive illness, autoimmune hepatitis, hyperthyroidism, pregnancy, heart failure, uncontrolled diabetes, obstructive pulmonary disease, children less than three years and patients who had previously received treatment were excluded. Single blind randomization using computerized randomization list was done and patients divided into groups A and B, those requiring treatment were given injection Interferon 3 million units (MU) subcutaneously (SC) three times/week and Ribavarin 1000 mg per day (weight greater or equal to 75kg) and 1200 mg/day (weight > 75kg) orally with either interferon alpha 2a (group A; FDA approved products) or alpha 2b (group B; non FDA approved product). Demographics, side effects, ETR and SVR were noted. ETR was defined as absence of virus at the end of treatment and SVR was taken as absence of HCV RNA at 6 months after completion of treatment. Results: There were a total 310 patients with mean age of 34.07 +- 9.38 years including 52.4% males, (n=162). Majority of the patients were from North Pakistan. There were 155 patients each in group A and group B respectively. The cost of treatment for interferon alpha for a single patient for 6 months was Rs 60,000, while for Interferon alpha 2b was Rs 30,000. Side effects (fever initially, followed by fatigue, headache, musculoskeletal pain, depression, alopecia, insomnia, and anorexia) were more prominent in group B when compared

  14. hnRNP L regulates differences in expression of mouse integrin alpha2beta1.

    Science.gov (United States)

    Cheli, Yann; Kunicki, Thomas J

    2006-06-01

    There is a 2-fold variation in platelet integrin alpha2beta1 levels among inbred mouse strains. Decreased alpha2beta1 in 4 strains carrying Itga2 haplotype 2 results from decreased affinity of heterogeneous ribonucleoprotein L (hnRNP L) for a 6 CA repeat sequence (CA6) within intron 1. Seven strains bearing haplotype 1 and a 21 CA repeat sequence at this position (CA21) express twice the level of platelet alpha2beta1 and exhibit an equivalent gain of platelet function in vitro. By UV crosslinking and immunoprecipitation, hnRNP L binds more avidly to CA21, relative to CA6. By cell-free, in vitro mRNA splicing, decreased binding of hnRNP L results in decreased splicing efficiency and an increased proportion of alternatively spliced product. The splicing enhancer activity of CA21 in vivo is abolished by prior treatment with hnRNP L-specific siRNA. Thus, decreased surface alpha2beta1 results from decreased Itga2 pre-mRNA splicing regulated by hnRNP L and depends on CA repeat length at a specific site in intron 1.

  15. Microstructure and phase morphology during thermochemical processing of {alpha}{sub 2}-based titanium aluminide castings

    Energy Technology Data Exchange (ETDEWEB)

    Saqib, M. [Wright State Univ., Dayton, OH (United States). Dept. of Mechanical and Materials Engineering; Apgar, L.S. [Dayton Univ., OH (United States). Graduate Materials Engineering; Eylon, D. [Dayton Univ., OH (United States). Graduate Materials Engineering; Weiss, I. [Wright State Univ., Dayton, OH (United States). Dept. of Mechanical and Materials Engineering

    1995-12-31

    Changes in the microstructure, volume fraction and distribution of phases during different stages of thermochemical processing of Ti-25Al-10Nb-3V-1Mo (at.%) castings were investigated. Up to 14.5 at.% (0.35 wt.%) of hydrogen was introduced into the material by gas charging at temperatures between 650 and 980 C for times up to 20 h. The material was subsequently dehydrogenated by vacuum annealing at 650 C for 48 h. Investment cast Ti-25Al-10Nb-3V-1Mo alloy, hot isostatically pressed (HIP) at 1175 C at 260 MPa for 6 h, was used as the starting material. The microstructure of the as-HIP material consists of {alpha}{sub 2}, B2 and orthorhombic phases. The {alpha}{sub 2} phase exists in equiaxed, Widmanstaeten and cellular morphologies. The B2 phase is observed mainly along {alpha}{sub 2}/{alpha}{sub 2} boundaries. Some {alpha}{sub 2} Widmanstaeten also contain very fine orthorhombic phase in a plate-like morphology. Hydrogenation of the material modified the microstructure; however, the morphology of the {alpha}{sub 2} and B2 phases did not change. Furthermore, hydride precipitation and a higher volume fraction of the orthorhombic phase were observed compared with the as-HIP material. Following dehydrogenation, the hydrogen level in the material was found to be less than 0.1 at.% (0.0025wt.%). Transmission electron microscopy of the dehydrogenated material did not reveal the presence of hydride precipitates; however, the high volume fraction of the orthorhombic phase was found to persist following dehydrogenation. (orig.)

  16. Imidazoline2 (I2) receptor- and alpha2-adrenoceptor-mediated modulation of hypothalamic-pituitary-adrenal axis activity in control and acute restraint stressed rats.

    Science.gov (United States)

    Finn, David P; Hudson, Alan L; Kinoshita, Hiroshi; Coventry, Toni L; Jessop, David S; Nutt, David J; Harbuz, Michael S

    2004-03-01

    Central noradrenaline regulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the neuroendocrine response to stress. alpha2-adrenoceptors and imidazoline2 (I2) receptors modulate the activity of the central noradrenergic system. The present set of experiments investigated the role of alpha2-adrenoceptors and I2 receptors in the regulation of HPA axis activity under basal conditions and during exposure to the acute psychological stress of restraint. Three separate experiments were carried out in which rats were given an i.p. injection of either saline vehicle, the combined alpha2-adrenoceptor antagonist and I2 receptor ligand idazoxan (10 mg/kg), the selective I2 receptor ligand BU224 (2.5 or 10 mg/kg) or the selective alpha2-adrenoceptor antagonist RX821002 (2.5 mg/kg) with or without restraint stress. Drugs were administered immediately prior to restraint of 60 min duration. Blood was sampled pre-injection, 30, 60 and 240 min post-injection and plasma corticosterone was measured by radioimmunoassay. In experiment 1, idazoxan increased plasma corticosterone levels in naive animals and potentiated the corticosterone response to acute restraint stress. In experiment 2, BU224 administration increased plasma corticosterone levels in a dose-related manner in naive rats. The results of experiment 3 indicated that RX821002 also elevated plasma corticosterone levels in naive rats, however, only BU224 potentiated the corticosterone response to restraint stress. These studies suggest that both alpha2-adrenoceptors and I2 receptors play a role in modulating basal HPA axis activity and that I2 receptors may play a more important role than alpha2-adrenoceptors in modulating the HPA axis response to the acute psychological stress of restraint.

  17. THE LYMAN ALPHA REFERENCE SAMPLE: EXTENDED LYMAN ALPHA HALOS PRODUCED AT LOW DUST CONTENT

    Energy Technology Data Exchange (ETDEWEB)

    Hayes, Matthew [Universite de Toulouse, UPS-OMP, IRAP, Toulouse (France); Oestlin, Goeran; Duval, Florent; Guaita, Lucia; Melinder, Jens; Sandberg, Andreas [Department of Astronomy, Oskar Klein Centre, Stockholm University, AlbaNova University Centre, SE-106 91 Stockholm (Sweden); Schaerer, Daniel [CNRS, IRAP, 14, avenue Edouard Belin, F-31400 Toulouse (France); Verhamme, Anne; Orlitova, Ivana [Geneva Observatory, University of Geneva, 51 Chemin des Maillettes, CH-1290 Versoix (Switzerland); Mas-Hesse, J. Miguel; Oti-Floranes, Hector [Centro de Astrobiologia (CSIC-INTA), Departamento de Astrofisica, POB 78, 28691 Villanueva de la Canada (Spain); Adamo, Angela [Max Planck Institute for Astronomy, Koenigstuhl 17, D-69117 Heidelberg (Germany); Atek, Hakim [Laboratoire d' Astrophysique, Ecole Polytechnique Federale de Lausanne (EPFL), Observatoire, CH-1290 Sauverny (Switzerland); Cannon, John M. [Department of Physics and Astronomy, Macalester College, 1600 Grand Avenue, Saint Paul, MN 55105 (United States); Herenz, E. Christian [Leibniz-Institut fuer Astrophysik (AIP), An der Sternwarte 16, D-14482 Potsdam (Germany); Kunth, Daniel [Institut d' Astrophysique de Paris, UMR 7095 CNRS and UPMC, 98 bis Bd Arago, F-75014 Paris (France); Laursen, Peter, E-mail: matthew@astro.su.se [Dark Cosmology Centre, Niels Bohr Institute, University of Copenhagen, Juliane Maries Vej 30, DK-2100 Copenhagen (Denmark)

    2013-03-10

    We report on new imaging observations of the Lyman alpha emission line (Ly{alpha}), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028 < z < 0.18 in continuum-subtracted Ly{alpha}, H{alpha}, and the far ultraviolet continuum. We show that Ly{alpha} is emitted on scales that systematically exceed those of the massive stellar population and recombination nebulae: as measured by the Petrosian 20% radius, R{sub P20}, Ly{alpha} radii are larger than those of H{alpha} by factors ranging from 1 to 3.6, with an average of 2.4. The average ratio of Ly{alpha}-to-FUV radii is 2.9. This suggests that much of the Ly{alpha} light is pushed to large radii by resonance scattering. Defining the Relative Petrosian Extension of Ly{alpha} compared to H{alpha}, {xi}{sub Ly{alpha}} = R {sup Ly{alpha}}{sub P20}/R {sup H{alpha}}{sub P20}, we find {xi}{sub Ly{alpha}} to be uncorrelated with total Ly{alpha} luminosity. However, {xi}{sub Ly{alpha}} is strongly correlated with quantities that scale with dust content, in the sense that a low dust abundance is a necessary requirement (although not the only one) in order to spread Ly{alpha} photons throughout the interstellar medium and drive a large extended Ly{alpha} halo.

  18. Clebopride enhances contractility of the guinea pig stomach by blocking peripheral D2 dopamine receptor and alpha-2 adrenoceptor.

    Science.gov (United States)

    Takeda, K; Taniyama, K; Kuno, T; Sano, I; Ishikawa, T; Ohmura, I; Tanaka, C

    1991-05-01

    The mechanism of action of clebopride on the motility of guinea pig stomach was examined by the receptor binding assay for bovine brain membrane and by measuring gastric contractility and the release of acetylcholine from the stomach. The receptor binding assay revealed that clebopride bound to the D2 dopamine receptor with a high affinity and to the alpha-2 adrenoceptor and 5-HT2 serotonin receptor with relatively lower affinity, and not to D1 dopamine, alpha-1 adrenergic, muscarinic acetylcholine, H1 histamine, or opioid receptor. In strips of the stomach, clebopride at 10(-8) M to 10(-5) M enhanced the electrical transmural stimulation-evoked contraction and the release of acetylcholine. This enhancement was attributed to the blockade of the D2 dopamine receptor and alpha-2 adrenoceptor because: 1) Maximum responses obtained with specific D2 dopamine receptor antagonist, domperidone, and with specific alpha-2 adrenoceptor antagonist, yohimbine, were smaller than that with clebopride, and the sum of the effects of these two specific receptor antagonists is approximately equal to the effect of clebopride. 2) The facilitatory effect of clebopride was partially eliminated by pretreatment of the sample with domperidone or yohimbine, and the facilitatory effect of clebopride was not observed in preparations treated with the combination of domperidone and yohimbine. Clebopride also antagonized the inhibitory effects of dopamine and clonidine on the electrical transmural stimulation-evoked responses. These results indicate that clebopride acts on post ganglionic cholinergic neurons at D2 and alpha-2 receptors in this preparation to enhance enteric nervous system stimulated motility.

  19. Clebopride enhances contractility of the guinea pig stomach by blocking peripheral D2 dopamine receptor and alpha-2 adrenoceptor

    International Nuclear Information System (INIS)

    Takeda, K.; Taniyama, K.; Kuno, T.; Sano, I.; Ishikawa, T.; Ohmura, I.; Tanaka, C.

    1991-01-01

    The mechanism of action of clebopride on the motility of guinea pig stomach was examined by the receptor binding assay for bovine brain membrane and by measuring gastric contractility and the release of acetylcholine from the stomach. The receptor binding assay revealed that clebopride bound to the D2 dopamine receptor with a high affinity and to the alpha-2 adrenoceptor and 5-HT2 serotonin receptor with relatively lower affinity, and not to D1 dopamine, alpha-1 adrenergic, muscarinic acetylcholine, H1 histamine, or opioid receptor. In strips of the stomach, clebopride at 10 - 8 M to 10 - 5 M enhanced the electrical transmural stimulation-evoked contraction and the release of acetylcholine. This enhancement was attributed to the blockade of the D2 dopamine receptor and alpha-2 adrenoceptor because: (1) Maximum responses obtained with specific D2 dopamine receptor antagonist, domperidone, and with specific alpha-2 adrenoceptor antagonist, yohimbine, were smaller than that with clebopride, and the sum of the effects of these two specific receptor antagonists is approximately equal to the effect of clebopride. (2) The facilitatory effect of clebopride was partially eliminated by pretreatment of the sample with domperidone or yohimbine, and the facilitatory effect of clebopride was not observed in preparations treated with the combination of domperidone and yohimbine. Clebopride also antagonized the inhibitory effects of dopamine and clonidine on the electrical transmural stimulation-evoked responses. These results indicate that clebopride acts on post ganglionic cholinergic neurons at D2 and alpha-2 receptors in this preparation to enhance enteric nervous system stimulated motility

  20. Coefficient alpha and interculture test selection.

    Science.gov (United States)

    Thurber, Steven; Kishi, Yasuhiro

    2014-04-01

    The internal consistency reliability of a measure can be a focal point in an evaluation of the potential adequacy of an instrument for adaptation to another cultural setting. Cronbach's alpha (α) coefficient is often used as the statistical index for such a determination. However, alpha presumes a tau-equivalent test and may constitute an inaccurate population estimate for multidimensional tests. These notions are expanded and examined with a Japanese version of a questionnaire on nursing attitudes toward suicidal patients, originally constructed in Sweden using the English language. The English measure was reported to have acceptable internal consistency (α) albeit the dimensionality of the questionnaire was not addressed. The Japanese scale was found to lack tau-equivalence. An alternative to alpha, "composite reliability," was computed and found to be below acceptable standards in magnitude and precision. Implications for research application of the Japanese instrument are discussed. © The Author(s) 2012.

  1. Dissecting cross-reactivity in hymenoptera venom allergy by circumvention of alpha-1,3-core fucosylation.

    Science.gov (United States)

    Seismann, Henning; Blank, Simon; Braren, Ingke; Greunke, Kerstin; Cifuentes, Liliana; Grunwald, Thomas; Bredehorst, Reinhard; Ollert, Markus; Spillner, Edzard

    2010-01-01

    Hymenoptera venom allergy is known to cause life-threatening and sometimes fatal IgE-mediated anaphylactic reactions in allergic individuals. About 30-50% of patients with insect venom allergy have IgE antibodies that react with both honeybee and yellow jacket venom. Apart from true double sensitisation, IgE against cross-reactive carbohydrate determinants (CCD) are the most frequent cause of multiple reactivities severely hampering the diagnosis and design of therapeutic strategies by clinically irrelevant test results. In this study we addressed allergenic cross-reactivity using a recombinant approach by employing cell lines with variant capacities of alpha-1,3-core fucosylation. The venom hyaluronidases, supposed major allergens implicated in cross-reactivity phenomena, from honeybee (Api m 2) and yellow jacket (Ves v 2a and its putative isoform Ves v 2b) as well as the human alpha-2HS-glycoprotein as control, were produced in different insect cell lines. In stark contrast to production in Trichoplusia ni (HighFive) cells, alpha-1,3-core fucosylation was absent or immunologically negligible after production in Spodoptera frugiperda (Sf9) cells. Consistently, co-expression of honeybee alpha-1,3-fucosyltransferase in Sf9 cells resulted in the reconstitution of CCD reactivity. Re-evaluation of differentially fucosylated hyaluronidases by screening of individual venom-sensitised sera emphasised the allergenic relevance of Api m 2 beyond its carbohydrate epitopes. In contrast, the vespid hyaluronidases, for which a predominance of Ves v 2b could be shown, exhibited pronounced and primary carbohydrate reactivity rendering their relevance in the context of allergy questionable. These findings show that the use of recombinant molecules devoid of CCDs represents a novel strategy with major implications for diagnostic and therapeutic approaches. Copyright 2010 Elsevier Ltd. All rights reserved.

  2. The tree-alpha Faddeev calculation on 12C bound states with a Pauli correct alpha-alpha potential

    International Nuclear Information System (INIS)

    Kamada, Hiroyuki; Oryu, Shinsho

    1986-01-01

    The three-alpha model of 12 C is investigated by the Faddeev formalism with the UIM alpha-alpha potential, in which the Pauli effect between two-alpha system was taken into account adequately. The potential can reproduce the on- and off-shell effects of the alpha-alpha interaction by the rank-4 separable type for the S-wave, the rank-3 one for the D-wave, and the rank-2 one for the G-wave, in which two of the ranks in the S-wave, and one in the D-wave are prepared to eliminate the Pauli forbidden states. We obtained three even states J π = 0 + , 2 + , 4 + , and two odd states 1 - , 3 - , below the alpha- 8 Be(0 + g.s) threshold energy. The even parity states gain larger binding energies than those which have been obtained by former Faddeev calculation with the rank-1 Kukulin and Neudatchin (KN) potential. On the other hand, for the odd parity states, we obtained smaller binding energies than the former one. It is found that our Faddeev calculation with the UIM potential does not miss any important low-lying levels of 12 C, in which any spurious states do not appear. (author)

  3. Alpha-particle irradiation induced defects in SiO2 films of Si-SiO2 structures

    International Nuclear Information System (INIS)

    Koman, B.P.; Gal'chynskyy, O.V.; Kovalyuk, R.O.; Shkol'nyy, A.K.

    1996-01-01

    The aim of the work was to investigate alpha-particle irradiation induced defects in Si-SiO 2 structures by means of the thermostimulated discharge currents (TSDC) analysis. The object of investigation were (p-Si)-SiO 2 structures formed by a combined oxidation of the industrial p-Si wafers in dry and wet oxygen at temperature of 1150 C. The TSD currents were investigated in the temperature range between 90 and 500 K under linear heating rate. Pu 238 isotopes were the source of alpha-particles with an energy of 4-5 MeV and a density of 5.10 7 s -1 cm -2 . The TSD current curves show two peculiar maxima at about 370 and 480 K. Alpha-particle irradiation doesn't affect the general shape of the TSDC curves but leads to a shift of the maximum at 370 K and reduces the total electret charge which is accumulated in the Si-SiO 2 structures during polarization. The energy distribution function of the defects which are involved in SiO 2 polarization has been calculated. It showes that defects with activation energies of about 0.8 and 1.0 eV take part in forming the electret state, and these activation energies have certain energy distributions. It has been found that the TSDC maximum at 370 K has space charge nature and is caused by migration of hydrogen ions. In irradiated samples hydrogen and natrium ions localize on deeper trapping centres induced by alpha-particle irradiation. (orig.)

  4. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2012-02-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  5. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2009-08-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  6. Alpha oscillation neurofeedback modulates amygdala complex connectivity and arousal in posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Andrew A. Nicholson

    2016-01-01

    Conclusion: These findings have significant implications for developing targeted non-invasive treatment interventions for PTSD patients that utilize alpha oscillatory neurofeedback, showing evidence of neuronal reconfiguration between areas highly implicated in the disorder, in addition to acute symptom alleviation.

  7. Alpha-2-macroglobulin and albumin are useful serum proteins to detect subclinical peritonitis in the rat

    NARCIS (Netherlands)

    van Westrhenen, Roos; Westra, Wytske M.; van den Born, Jacob; Krediet, Raymond T.; Keuning, Eelco D.; Hiralall, Johan; Dragt, Cindy; Hekking, Liesbeth H. P.

    2006-01-01

    BACKGROUND: In experimental peritoneal dialysis (PD) studies, the occurrence of peritonitis is a confounder in the interpretation of effects of chronic peritoneal exposure to dialysis solutions. Since fluid cannot be drained in most experimental PD models in the rat, it is impossible to diagnose

  8. Survival of Acholeplasma laidlawii, strain S2 after irradiation with alpha particles of /sup 241/Americium

    Energy Technology Data Exchange (ETDEWEB)

    Liska, B.; Drasil, V.; Brza, I. (Ceskoslovenska Akademie Ved, Brno. Biofysikalni Ustav)

    1985-05-23

    A thin layer of dry Acholeplasma laidlawii, strain S2 cells was irradiated with /sup 241/Am alpha particles. D/sub 0/ was 2.54 x 10/sup 7/ - 2.63 x 10/sup 7/ alpha particles/mm/sup 2/ (48 - 50 minutes, 409 - 422 Gy). The extrapolation number was 1.05 - 3.1. The effective cross section at D/sub 0/ was 0.038 - 0.039 ..mu..m/sup 2//alpha particle. A method of preparing thin dry layers of Acholeplasma cells was developed.

  9. Synthesis and characterization of arylamine derivatives of rauwolscine as molecular probes for alpha 2-adrenergic receptors

    International Nuclear Information System (INIS)

    Lanier, S.M.; Graham, R.M.; Hess, H.J.; Grodski, A.; Repaske, M.G.; Nunnari, J.M.; Limbird, L.E.; Homcy, C.J.

    1987-01-01

    The selective alpha 2-adrenergic receptor antagonist rauwolscine was structurally modified to yield a series of arylamine carboxamide derivatives, which were investigated as potential molecular probes for the localization and structural characterization of alpha 2-adrenergic receptors. The arylamine carboxamides differ in the number of carbon atoms separating the reactive phenyl moiety from the fused ring structure of the parent compound, rauwolscine carboxylate. Competitive inhibition studies with [ 3 H]rauwolscine in rat kidney membranes indicate that the affinity for the carboxamide derivatives is inversely related to the length of the carbon spacer arm with rauwolscine 4-aminophenyl carboxamide exhibiting the highest affinity (Kd = 2.3 +/- 0.2 nM). Radioiodination of rau-AMPC yields a ligand, 125 I-rau-AMPC, which binds to rat kidney alpha 2-adrenergic receptors with high affinity, as determined by both kinetic analysis (Kd = k2/k1 = 0.016 min-1/2.1 X 10(7) M-1 min-1 = 0.76 nM) and equilibrium binding studies (Kd = 0.78 +/- 0.16 nM). 125 I-rau-AMPC was quantitatively converted to the photolabile arylazide derivative 17 alpha-hydroxy-20 alpha-yohimban-16 beta-(N-4-azido-3-[ 125 I]iodophenyl) carboxamide ( 125 I-rau-AZPC). In a partially purified receptor preparation from porcine brain, this compound photolabels a major (Mr = 62,000) peptide. The labeling of this peptide is inhibited by adrenergic agonists and antagonists with a rank order of potency consistent with an alpha 2-adrenergic receptor binding site. Both 125 I-rau-AMPC and the photolabile arylazide derivative, 125 I-rau-AZPC, should prove useful as molecular probes for the structural and biochemical characterization of alpha 2-adrenergic receptors

  10. Sterol synthesis. A novel reductive rearrangement of an alpha,beta-unsaturated steroidal epoxide; a new chemical synthesis of 5alpha-cholest-8(14)-en-3beta, 15alpha-diol.

    Science.gov (United States)

    Parish, E J; Schroepfer, G J

    1977-04-01

    Reduction of 3beta-benzoyloxy-14alpha,15alpha-epoxy-5alpha-cholest-7-ene with either lithium triethylboro-hydride or lithium aluminum hydride (4 molar excess) gave 5-alpha-cholest-8(14)-en-3beta,15alpha-diol in high yield. Reduction of the epoxy ester with lithium triethylborodeuteride or lithium aluminum deuteride (4 molar excess) gave [7alpha-2-H]-5alpha-cholest-8(14)-en-3beta,15alpha-diol. Reduction of 2beta-benzoyloxy-14alpha,15alpha-epoxy-5alpha-cholest-7-ene with a large excess (24 molar excess) of lithium aluminum hydride gave, in addition to the expected 5alpha-cholest-8(14)-en-3beta,15alpha-diol, a significant yield (33%) of 5alpha-cholest-8(14)-en-3beta-o1. Reduction of the epoxy ester with a large excess (24 molar excess) of lithium aluminum deuteride gave [7alpha-2H]-5alpha-cholest-8(14)-en-3beta,15alpha-diol and 5alpha-cholest-8(14)-en-3beta-o1 which contained two atoms of stably bound deuterium.

  11. EMMPRIN promotes melanoma cells malignant properties through a HIF-2alpha mediated up-regulation of VEGF-receptor-2.

    Directory of Open Access Journals (Sweden)

    Faten Bougatef

    Full Text Available EMMPRIN's expression in melanoma tissue was reported to be predictive of poor prognosis. Here we demonstrate that EMMPRIN up-regulated VEGF receptor-2 (VEGFR-2 in two different primary melanoma cell lines and consequently increased migration and proliferation of these cells while inhibiting their apoptosis. SiRNA inhibition of VEGFR-2 expression abrogated these EMMPRIN effects. EMMPRIN regulation of VEGFR-2 was mediated through the over-expression of HIF-2alpha and its translocation to the nucleus where it forms heterodimers with HIF-1beta. These results were supported by an in vivo correlation between the expression of EMMPRIN with that of VEGFR-2 in human melanoma tissues as well as with the extent of HIF-2alpha localization in the nucleus. They demonstrate a novel mechanism by which EMMPRIN promotes tumor progression through HIF-2alpha/VEGFR-2 mediated mechanism, with an autocrine role in melanoma cell malignancy. The inhibition of EMMPRIN in cancer may thus simultaneously target both the VEGFR-2/VEGF system and the matrix degrading proteases to block tumor cell growth and invasion.

  12. Aqueous suspensions of {alpha}Al{sub 2}O{sub 3}/SiC mixed systems

    Energy Technology Data Exchange (ETDEWEB)

    Pagnoux, C.; Baklouti, S.; Chartier, T.; Baumard, J.F. [ENSCI, Limoges (France). LMCTS

    1997-12-31

    The preparation of aqueous {alpha}-Al{sub 2}O{sub 3}, {alpha}-SiO{sub 2} and {alpha}-SiC suspensions with polyelectrolytes, respectively the NH{sub 4}{sup +} salt of polymethacrylic acid (PMA-NH{sub 4}{sup +}) and acidic form polyethylene imine (PEI-H{sup +}) is investigated. It is based on the adsorption of these polyelectrolytes which in turn depends mainly on the nature of the polyelectrolyte, and the charge density which develops on the powder surface in water. Good dispersion and stability of dispersions are then obtained through electrostatic and steric stabilization. As an application, the preparation of an Al{sub 2}O{sub 3}-SiC aqueous mixed slurry was investigated as a preliminary step for processing of Al{sub 2}O{sub 3}/SiC nanocomposites. (orig.) 2 refs.

  13. Jet Production in ep Collisions at High $Q^2$ and Determination of $\\alpha_s$

    CERN Document Server

    Aaron, F.D.; Alimujiang, K.; Andreev, V.; Antunovic, B.; Asmone, A.; Backovic, S.; Baghdasaryan, A.; Barrelet, E.; Bartel, W.; Begzsuren, K.; Belousov, A.; Bizot, J.C.; Boudry, V.; Bozovic-Jelisavcic, I.; Bracinik, J.; Brandt, G.; Brinkmann, M.; Brisson, V.; Bruncko, D.; Bunyatyan, A.; Buschhorn, G.; Bystritskaya, L.; Campbell, A.J.; Cantun Avila, K.B.; Cassol-Brunner, F.; Cerny, K.; Cerny, V.; Chekelian, V.; Cholewa, A.; Contreras, J.G.; Coughlan, J.A.; Cozzika, G.; Cvach, J.; Dainton, J.B.; Daum, K.; Deak, M.; de Boer, Y.; Delcourt, B.; Del Degan, M.; Delvax, J.; De Roeck, A.; De Wolf, E.A.; Diaconu, C.; Dodonov, V.; Dossanov, A.; Dubak, A.; Eckerlin, G.; Efremenko, V.; Egli, S.; Eliseev, A.; Elsen, E.; Falkiewicz, A.; Faulkner, P.J.W.; Favart, L.; Fedotov, A.; Felst, R.; Feltesse, J.; Ferencei, J.; Fischer, D.-J.; Fleischer, M.; Fomenko, A.; Gabathuler, E.; Gayler, J.; Ghazaryan, Samvel; Glazov, A.; Glushkov, I.; Goerlich, L.; Gogitidze, N.; Gouzevitch, M.; Grab, C.; Greenshaw, T.; Grell, B.R.; Grindhammer, G.; Habib, S.; Haidt, D.; Helebrant, C.; Henderson, R.C.W.; Hennekemper, E.; Henschel, H.; Herbst, M.; Herrera, G.; Hildebrandt, M.; Hiller, K.H.; Hoffmann, D.; Horisberger, R.; Hreus, T.; Jacquet, M.; Janssen, M.E.; Janssen, X.; Jemanov, V.; Jonsson, L.; Jung, Andreas Werner; Jung, H.; Kapichine, M.; Katzy, J.; Kenyon, I.R.; Kiesling, C.; Klein, M.; Kleinwort, C.; Kluge, T.; Knutsson, A.; Kogler, R.; Korbel, V.; Kostka, P.; Kraemer, M.; Krastev, K.; Kretzschmar, J.; Kropivnitskaya, A.; Kruger, K.; Kutak, K.; Landon, M.P.J.; Lange, W.; Lastovicka-Medin, G.; Laycock, P.; Lebedev, A.; Leibenguth, G.; Lendermann, V.; Levonian, S.; Li, G.; Lipka, K.; Liptaj, A.; List, B.; List, J.; Loktionova, N.; Lopez-Fernandez, R.; Lubimov, V.; Lytkin, L.; Makankine, A.; Malinovski, E.; Marage, P.; Marti, Ll.; Martyn, H.-U.; Maxfield, S.J.; Mehta, A.; Meyer, A.B.; Meyer, H.; Meyer, H.; Meyer, J.; Michels, V.; Mikocki, S.; Milcewicz-Mika, I.; Moreau, F.; Morozov, A.; Morris, J.V.; Mozer, Matthias Ulrich; Mudrinic, M.; Muller, K.; Murin, P.; Naroska, B.; Naumann, Th.; Newman, P.R.; Niebuhr, C.; Nikiforov, A.; Nowak, G.; Nowak, K.; Nozicka, M.; Olivier, B.; Olsson, J.E.; Osman, S.; Ozerov, D.; Palichik, V.; Panagoulias, I.; Pandurovic, M.; Papadopoulou, Th.; Pascaud, C.; Patel, G.D.; Pejchal, O.; Perez, E.; Petrukhin, A.; Picuric, I.; Piec, S.; Pitzl, D.; Placakyte, R.; Pokorny, B.; Polifka, R.; Povh, B.; Preda, T.; Radescu, V.; Rahmat, A.J.; Raicevic, N.; Raspiareza, A.; Ravdandorj, T.; Reimer, P.; Rizvi, E.; Robmann, P.; Roland, B.; Roosen, R.; Rostovtsev, A.; Rotaru, M.; Ruiz Tabasco, J.E.; Rurikova, Z.; Rusakov, S.; Salek, D.; Sankey, D.P.C.; Sauter, M.; Sauvan, E.; Schmitt, S.; Schmitz, C.; Schoeffel, L.; Schoning, A.; Schultz-Coulon, H.-C.; Sefkow, F.; Shaw-West, R.N.; Sheviakov, I.; Shtarkov, L.N.; Shushkevich, S.; Sloan, T.; Smiljanic, Ivan; Soloviev, Y.; Sopicki, P.; South, D.; Spaskov, V.; Specka, Arnd E.; Staykova, Z.; Steder, M.; Stella, B.; Stoicea, G.; Straumann, U.; Sunar, D.; Sykora, T.; Tchoulakov, V.; Thompson, G.; Thompson, P.D.; Toll, T.; Tomasz, F.; Tran, T.H.; Traynor, D.; Trinh, T.N.; Truol, P.; Tsakov, I.; Tseepeldorj, B.; Turnau, J.; Urban, K.; Valkarova, A.; Vallee, C.; Van Mechelen, P.; Vargas Trevino, A.; Vazdik, Y.; Vinokurova, S.; Volchinski, V.; von den Driesch, M.; Wegener, D.; Wissing, Ch.; Wunsch, E.; Zacek, J.; Zalesak, J.; Zhang, Z.; Zhokin, A.; Zimmermann, T.; Zohrabyan, H.; Zomer, F.; Zus, R.

    2010-01-01

    The production of jets is studied in deep-inelastic ep scattering at large negative four momentum transfer squared 1502<15000 GeV^2 using HERA data taken in 1999-2007, corresponding to an integrated luminosity of 395 pb^-1. Inclusive jet, 2-jet and 3-jet cross sections, normalised to the neutral current deep-inelastic scattering cross sections, are measured as functions of Q^2, jet transverse momentum and proton momentum fraction. The measurements are well described by perturbative QCD calculations at next-to-leading order corrected for hadronisation effects. The strong coupling as determined from these measurements is alpha_s(M_Z) = 0.1168 +/-0.0007 (exp.) +0.0046/-0.0030 (th.) +/-0.0016(pdf).

  14. Alpha - Skew Pi - Armendariz Rings

    Directory of Open Access Journals (Sweden)

    Areej M Abduldaim

    2018-03-01

    Full Text Available In this article we introduce a new concept called Alpha-skew Pi-Armendariz rings (Alpha - S Pi - ARas a generalization of the notion of Alpha-skew Armendariz rings.Another important goal behind studying this class of rings is to employ it in order to design a modern algorithm of an identification scheme according to the evolution of using modern algebra in the applications of the field of cryptography.We investigate general properties of this concept and give examples for illustration. Furthermore, this paperstudy the relationship between this concept and some previous notions related to Alpha-skew Armendariz rings. It clearly presents that every weak Alpha-skew Armendariz ring is Alpha-skew Pi-Armendariz (Alpha-S Pi-AR. Also, thisarticle showsthat the concepts of Alpha-skew Armendariz rings and Alpha-skew Pi- Armendariz rings are equivalent in case R is 2-primal and semiprime ring.Moreover, this paper proves for a semicommutative Alpha-compatible ringR that if R[x;Alpha] is nil-Armendariz, thenR is an Alpha-S Pi-AR. In addition, if R is an Alpha - S Pi -AR, 2-primal and semiprime ring, then N(R[x;Alpha]=N(R[x;Alpha]. Finally, we look forwardthat Alpha-skew Pi-Armendariz rings (Alpha-S Pi-ARbe more effect (due to their properties in the field of cryptography than Pi-Armendariz rings, weak Armendariz rings and others.For these properties and characterizations of the introduced concept Alpha-S Pi-AR, we aspire to design a novel algorithm of an identification scheme.

  15. Zinc alpha-2 glycoprotein is overproduced in Cushing's syndrome.

    Science.gov (United States)

    Escoté, Xavier; Aranda, Gloria B; Mora, Mireia; Casals, Gregori; Enseñat, Joaquim; Vidal, Oscar; Esteban, Yaiza; Halperin, Irene; Hanzu, Felicia A

    2017-01-01

    Cushing syndrome (CS), an endogenous hypercortisolemic condition with increased cardiometabolic morbidity, leads to development of abdominal obesity, insulin resistance, diabetes and proatherogenic dyslipidemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized lipolytic adipokine implicated in regulation of adipose tissue metabolism and fat distribution. In vitro and animal studies suggest that glucocorticoids interact with ZAG secretion and action. To assess the relationship between ZAG and glucocorticoids in a human model of hypercortisolism, circulating ZAG levels were tested in patients with CS and its counterpart controls. An observational, cross-sectional study on 39 women, 13 with active CS and 26 controls matched by age and body mass index. Plasma ZAG levels (μg/ml) were measured by ELISA and correlated with hypercortisolism, metabolic, and phenotypic parameters. Plasma ZAG levels were significantly higher in patients with CS compared to controls (64.3±16.6 vs. 44.0±16.1, p=0.002). In a univariate analysis, ZAG levels positively correlated to 24-h urinary free cortisol (p=0.001), body mass index (p=0.02), non-esterified fatty acids (p=0.05), glucose (p=0.003), LDL-C (p=0.028), and type 2 diabetes mellitus (p=0.016), and were inversely related to total adiponectin levels (p=0.035). In a multivariate analysis, after adjusting for CS, ZAG levels only correlated with body mass index (p=0.012), type 2 diabetes mellitus (p=0.004), and glucose (p<0.001). This study provides initial evidence that plasma ZAG levels are higher in patients with CS as compared to controls. The close relationship of ZAG with metabolic and phenotypic changes in CS suggests that ZAG may play a significant role in adipose tissue changes in hypercortisolism. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. The Ar{sup 17+} Ly{sub {alpha}2}/Ly{sub {alpha}1} ratio in Alcator C-Mod tokamak plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Rice, J E; Reinke, M L; Ince-Cushman, A C; Podpaly, Y A [Plasma Science and Fusion Center, MIT, Cambridge, MA (United States); Ashbourn, J M A [Mathematical Institute, University of Oxford, Oxford (United Kingdom); Gu, M F [SSL, University of California Berkeley, CA (United States); Bitter, M; Hill, K [Princeton Plasma Physics Laboratory, Princeton, NJ (United States); Rachlew, E, E-mail: rice@psfc.mit.edu [KTH, Stockholm (Sweden)

    2011-08-28

    High-quality spectra of hydrogen-like Ar{sup 17+} have been obtained from Alcator C-Mod tokamak plasmas using a spatially imaging high-resolution x-ray spectrometer system in an extensive study of the underlying high-n satellite lines. The ratio of Ly{sub {alpha}2} (1S{sub 1/2}-2P{sub 1/2}) to Ly{sub {alpha}1} (1S{sub 1/2}-2P{sub 3/2}) was found to be {approx}0.52 regardless of plasma parameters, which is somewhat greater than the ratio of the statistical weights of the upper n = 2 levels, 0.5. This difference is mainly due to the effects of collisional excitation of fine-structure sub-levels. For the observations presented here, electron densities were in an extended range from 3x10{sup 19} to 4x10{sup 20} m{sup -3} with electron and ion temperatures between 1 and 4 keV. Experimental results are compared to calculations from COLRAD, a collisional-radiative modelling code, and good agreement is shown.

  17. Rapid synthesis and catalytic performance of {alpha}-Mn{sub 2}O{sub 3} single-crystal nanowires

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Xinsong; Hu, Xingming; Zhu, Jinmiao; Dong, Huaze; Wang, Yanping [Department of Chemistry and Chemical Engineering, Hefei Normal University, Hefei 230061 (China); Yang, Baojun [Anhui Key Laboratory of Controllable Chemistry Reaction and Material Chemical Engineering, School of Chemical Engineering, Hefei University of Technology, Hefei 230009 (China); Hao, Jianwen [Department of Chemical Engineering, Anhui Vocational and Technical College, Hefei 230051 (China)

    2011-12-15

    Single-crystal {alpha}-Mn{sub 2}O{sub 3} nanowires were prepared via a ''self-sacrificing template'' route, simply by calcining the prepared {alpha}-MnO{sub 2} nanowire precursors at 550 C for 1.5 h. XRD, TEM, SEM and HRTEM characterizations show that the as-prepared {alpha}-Mn{sub 2}O{sub 3} samples are all phase pure and the nanowires have uniform diameters of approximately 15-30 nm and lengths up to several micrometers. The catalytic performances of the prepared {alpha}-Mn{sub 2}O{sub 3} nanowires were studied in the degradation of coking wastewater with H{sub 2}O{sub 2} as the oxidant, and the technological conditions were optimized by single-factor and orthogonal experiments. (copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  18. Three-Dimensional Conformal Radiotherapy in Prostate Cancer Patients: Rise in Interleukin 6 (IL-6) but not IL-2, IL-4, IL-5, Tumor Necrosis Factor-{alpha}, MIP-1-{alpha}, and LIF Levels

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira Lopes, Carlos [Universidade do Vale do Paraiba, Centro de Oncologia Radioterapica do Vale do Paraiba, Universidade do Vale do Paraiba Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraiba, Sao Jose dos Campos, Sao Paulo (Brazil); Callera, Fernando, E-mail: fcallera@gmail.com [Centro de Hematologia Onco-hematologia e Transplantes de Medula Ossea do Vale do Paraiba, Sao Paulo (Brazil)

    2012-03-15

    Purpose: To investigate the effect of radiotherapy (RT) on serum levels of interleukin-2 (IL-2), IL-4, IL-5, IL-6, tumor necrosis factor alpha (TNF-{alpha}), macrophage inflammatory protein-1-alpha (MIP-1-{alpha}) and leukemia inhibitory factor (LIF) in patients with prostate cancer. Methods and Materials: Forty eight patients with prostate cancer received three-dimensional conformal blocking radiation therapy with a linear accelerator. IL-2, IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were measured by the related immunoassay kit 1 day before the beginning of RT and during RT at days 15 and 30. Results: The mean IL-2 values were elevated before and during the RT in contrast with those of IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF, which were within the normal range under the same conditions. Regarding markers IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF, comparisons among the three groups (before treatment and 15 and 30 days during RT) did not show significant differences. Although values were within the normal range, there was a significant rise in IL-6 levels at day 15 of RT (p = 0.0049) and a decline at day 30 to levels that were similar to those observed before RT. Conclusions: IL-6 appeared to peak after 15 days of RT before returning to pre-RT levels. In contrast, IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were not sensitive to irradiation. The increased levels of IL-6 following RT without the concurrent elevation of other cytokines involved in the acute phase reaction did not suggest a classical inflammatory response to radiation exposure. Further studies should be designed to elucidate the role of IL-6 levels in patients with prostate cancer treated with RT.

  19. In situ observation of transformation in alpha-Fe sub 2 O sub 3 under hydrogen implantation

    CERN Document Server

    Watanabe, Y; Ishikawa, N; Furuya, K; Kato, M

    2002-01-01

    An in situ observation of the alpha-Fe sub 2 O sub 3 -to-Fe sub 3 O sub 4 transformation has been performed using a dual-ion-beam accelerator interfaced with a transmission electron microscope (TEM). During the hydrogen-ion implantation of alpha-Fe sub 2 O sub 3 , transformation into the new phase (gamma-Fe sub 2 O sub 3 or Fe sub 3 O sub 4) was observed. It was also found that the orientation relationship between alpha-Fe sub 2 O sub 3 and the new phase (gamma-Fe sub 2 O sub 3 or Fe sub 3 O sub 4) satisfies the Shoji-Nishiyama relationship, in agreement with previous experiments. It was also found that the nearest interatomic distance does not vary by the implantation until the re-stacked phase appears, although when the re-stacked phase is formed, the lattice expansion is observed in the transformed (re-stacked) phase. Judging from these results, we have concluded that the alpha-Fe sub 2 O sub 3 to Fe sub 3 O sub 4 transformation is induced during the hydrogen ion implantation of alpha-Fe sub 2 O sub 3.

  20. The heavy quarkonium spectrum at order $m\\alpha_{s}^{5}\\ln\\alpha_{s}$

    CERN Document Server

    Brambilla, Nora; Soto, Joan; Vairo, Antonio

    1999-01-01

    We compute the complete leading-log terms of the next-to-next-to-next-to-leading-order corrections to potential NRQCD. As a by-product we obtain the leading logs at $O(m\\alpha_s^5)$ in the heavy quarkonium spectrum. These leading logs, when $\\Lambda_{QCD} \\ll m\\alpha_s^2$, give the complete $O(m\\alpha_s^5 \\ln \\alpha_s)$ corrections to the heavy quarkonium spectrum.

  1. The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Klapper, Maja [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany); Boehme, Mike [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany); Nitz, Inke [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany); Doering, Frank [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany)

    2007-04-27

    The cytosolic human intestinal fatty acid binding protein (hFABP2) is proposed to be involved in intestinal absorption of long-chain fatty acids. The aim of this study was to investigate the regulation of hFABP2 by the endodermal hepatocyte nuclear factor 4{alpha} (HNF-4{alpha}), involved in regulation of genes of fatty acid metabolism and differentiation. Electromobility shift assays demonstrated that HNF-4{alpha} binds at position -324 to -336 within the hFABP2 promoter. Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells. In HeLa cells, this mutation reduced the activation of the hFABP2 promoter by HNF-4{alpha} by about 50%. Thus, binding element at position -336/-324 essentially determines the transcriptional activity of promoter and may be important in control of hFABP2 expression by dietary lipids and differentiation. Studying genotype interactions of hFABP2 and HNF-4{alpha}, that are both candidate genes for diabetes type 2, may be a powerful approach.

  2. The 2.0-A resolution structure of soybean beta-amylase complexed with alpha-cyclodextrin.

    Science.gov (United States)

    Mikami, B; Hehre, E J; Sato, M; Katsube, Y; Hirose, M; Morita, Y; Sacchettini, J C

    1993-07-13

    New crystallographic findings are presented which offer a deeper understanding of the structure and functioning of beta-amylase, the first known exo-type starch-hydrolyzing enzyme. A refined three-dimensional structure of soybean beta-amylase, complexed with the inhibitor alpha-cyclodextrin, has been determined at 2.0-A resolution with a conventional R-value of 17.5%. The model contains 491 amino acid residues, 319 water molecules, 1 sulfate ion, and 1 alpha-cyclodextrin molecule. The protein consists of a core with an (alpha/beta)8 supersecondary structure, plus a smaller globular region formed by long loops (L3, L4, and L5) extending from beta-strands beta 3, beta 4, and beta 5. Between the two regions is a cleft that opens into a pocket whose floor contains the postulated catalytic center near the carboxyl group of Glu 186. The annular alpha-cyclodextrin binds in (and partly projects from) the cleft with its glucosyl O-2/O-3 face abutting the (alpha/beta)8 side and with its alpha-D(1 --> 4) glucosidic linkage progression running clockwise as viewed from that side. The ligand does not bind deeply enough to interact with the carboxyl group of Glu 186. Rather, it occupies most of the cleft entrance, strongly suggesting that alpha-cyclodextrin inhibits catalysis by blocking substrate access to the more deeply located reaction center. Of the various alpha-cyclodextrin interactions with protein residues in loops L4, L5, L6, and L7, most notable is the shallow inclusion complex formed with Leu 383 (in L7, on the core side of the cleft) through contacts of its methyl groups with the C-3 atoms of four of the ligand's D-glucopyranosyl residues. All six residues of the bound alpha-cyclodextrin are of 4C1 conformation and are joined by alpha-1,4 linkages with similar torsional angles to form a nearly symmetrical torus as reported for crystalline inclusion complexes with alpha-cyclodextrin. We envision a significant role for the methyl groups of Leu 383 at the cleft entrance

  3. Alpha 2-adrenergic receptor stimulation of phospholipase A2 and of adenylate cyclase in transfected Chinese hamster ovary cells is mediated by different mechanisms

    International Nuclear Information System (INIS)

    Jones, S.B.; Halenda, S.P.; Bylund, D.B.

    1991-01-01

    The effect of alpha 2-adrenergic receptor activation on adenylate cyclase activity in Chinese hamster ovary cells stably transfected with the alpha 2A-adrenergic receptor gene is biphasic. At lower concentrations of epinephrine forskolin-stimulated cyclic AMP production is inhibited, but at higher concentrations the inhibition is reversed. Both of these effects are blocked by the alpha 2 antagonist yohimbine but not by the alpha 1 antagonist prazosin. Pretreatment with pertussis toxin attenuates inhibition at lower concentrations of epinephrine and greatly potentiates forskolin-stimulated cyclic AMP production at higher concentrations of epinephrine. alpha 2-Adrenergic receptor stimulation also causes arachidonic acid mobilization, presumably via phospholipase A2. This effect is blocked by yohimbine, quinacrine, removal of extracellular Ca2+, and pretreatment with pertussis toxin. Quinacrine and removal of extracellular Ca2+, in contrast, have no effect on the enhanced forskolin-stimulated cyclic AMP production. Thus, it appears that the alpha 2-adrenergic receptor in these cells can simultaneously activate distinct signal transduction systems; inhibition of adenylate cyclase and stimulation of phospholipase A2, both via G1, and potentiation of cyclic AMP production by a different (pertussis toxin-insensitive) mechanism

  4. Alpha 2-adrenergic receptor stimulation of phospholipase A2 and of adenylate cyclase in transfected Chinese hamster ovary cells is mediated by different mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Jones, S.B.; Halenda, S.P.; Bylund, D.B. (Univ. of Missouri-Columbia (USA))

    1991-02-01

    The effect of alpha 2-adrenergic receptor activation on adenylate cyclase activity in Chinese hamster ovary cells stably transfected with the alpha 2A-adrenergic receptor gene is biphasic. At lower concentrations of epinephrine forskolin-stimulated cyclic AMP production is inhibited, but at higher concentrations the inhibition is reversed. Both of these effects are blocked by the alpha 2 antagonist yohimbine but not by the alpha 1 antagonist prazosin. Pretreatment with pertussis toxin attenuates inhibition at lower concentrations of epinephrine and greatly potentiates forskolin-stimulated cyclic AMP production at higher concentrations of epinephrine. alpha 2-Adrenergic receptor stimulation also causes arachidonic acid mobilization, presumably via phospholipase A2. This effect is blocked by yohimbine, quinacrine, removal of extracellular Ca2+, and pretreatment with pertussis toxin. Quinacrine and removal of extracellular Ca2+, in contrast, have no effect on the enhanced forskolin-stimulated cyclic AMP production. Thus, it appears that the alpha 2-adrenergic receptor in these cells can simultaneously activate distinct signal transduction systems; inhibition of adenylate cyclase and stimulation of phospholipase A2, both via G1, and potentiation of cyclic AMP production by a different (pertussis toxin-insensitive) mechanism.

  5. Measurement of {alpha} particle energy loss in biological tissue below 2 MeV

    Energy Technology Data Exchange (ETDEWEB)

    Stella, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy); National Institute of Nuclear Physics (INFN), Pavia (Italy); Bortolussi, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy); National Institute of Nuclear Physics (INFN), Pavia (Italy)], E-mail: silva.bortolussi@pv.infn.it; Bruschi, P.; Portella, C. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy); Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy); National Institute of Nuclear Physics (INFN), Pavia (Italy)

    2009-09-01

    The energy loss of {alpha} particles crossing biological tissue at energies between 0.8 and 2.2 MeV has been measured. This energy range is very important for boron neutron capture therapy, based on the {sup 10}B(n,{alpha}){sup 7}Li reaction, which emits {alpha} particles with energies of 1.78 and 1.47 MeV. One of the methods used for the measurement of the boron concentration in tissue is based on the deconvolution of the {alpha} spectra obtained from neutron irradiation of thin (70 {mu}m) tissue samples. For this technique, a knowledge of the behaviour of the energy loss of the particles in the irradiated tissue is of critical importance. In particular, the curve of the residual energy as a function of the distance travelled in the tissue must be known. In this paper, the results of an experiment carried out with an {sup 241}Am source and a series of cryostatic sections of rat-lung tissue are presented. The experimental measurements are compared with the results of Monte Carlo calculations performed with the MCNPX code.

  6. Plasma proteins in a standardised skin mini-erosion (I: permeability changes as a function of time

    Directory of Open Access Journals (Sweden)

    Ryan Terence J

    2002-02-01

    Full Text Available Abstract Background A standardised technique using a suction-induced mini-erosion that allows serial sampling of dermal interstitial fluid (IF for 5 to 6 days has been described. In the present study, we studied permeability changes as a function of time. Methods We examined IF concentrations of total protein concentration and the concentration of insulin (6.6 kDa, prealbumin (55 kDa, albumin (66 kDa, transferrin (80 kDa, IgG (150 kDa and alpha-2-macroglobulin (720 kDa as a function of time, using an extraction pressure of 200 mmHg below atmospheric. Results At 0 h after forming the erosion, mean total IF protein content (relative to plasma was 26 ± 13% (SD. For the individual proteins, the relative mean concentrations were 65 ± 36% for insulin, 48 ± 12% for albumin, 30 ± 19% for transferrin, 31 ± 15%for IgG and 19.5 ± 10% for alpha-2-macroglobulin. At 24 h, the total IF protein content was higher than at 0 h (56 ± 26% vs 26 ± 13%; p Conclusions The results indicate that fluid sampled at 0 h after forming the erosion represents dermal IF before the full onset of inflammation. From 24 h onward, the sampled fluid reflects a steady state of increased permeability induced by inflammation. This technique is promising as a tool for clinically sampling substances that are freely distributed in the body and as a model for studying inflammation and vascular permeability.

  7. Endocytic activity of Sertoli cells grown in bicameral culture chambers

    International Nuclear Information System (INIS)

    Dai, R.X.; Djakiew, D.; Dym, M.

    1987-01-01

    Immature rat Sertoli cells were cultured for 7 to 14 days on Millipore filters impregnated with a reconstituted basement membrane extract in dual-environment (bicameral) culture chambers. Electron microscopy of the cultured cells revealed the presence of rod-shaped mitochondria, Golgi apparatus, rough endoplasmic reticulum, and Sertoli-Sertoli tight junctions, typical of these cells in vivo. The endocytic activity of both the apical and basal surfaces of the Sertoli cells was examined by either adding alpha 2-macroglobulin (alpha 2-M) conjugated to 20 nm gold particles to the apical chamber or by adding 125 I labeled alpha 2-M to the basal chamber. During endocytosis from the apical surface of Sertoli cells, the alpha 2-M-gold particles were bound initially to coated pits and then internalized into coated vesicles within 5 minutes. After 10 minutes, the alpha 2-M-gold was found in multi-vesicular bodies (MVBs) and by 30 minutes it was present in the lysosomes. The proportion of alpha 2-M-gold found within endocytic cell organelles after 1 hour of uptake was used to estimate the approximate time that this ligand spent in each type of organelle. The alpha 2-M-gold was present in coated pits, coated vesicles, multivesicular bodies, and lysosomes for approximately 3, 11, 22, and 24 minutes, respectively. This indicates that the initial stages of endocytosis are rapid, whereas MVBs and lysosomes are relatively long-lived

  8. Effects of a single administration of prostaglandin F2alpha, or a combination of prostaglandin F2alpha and prostaglandin E2, or placebo on fertility variables in dairy cows 3–5 weeks post partum, a randomized, double-blind clinical trial

    Directory of Open Access Journals (Sweden)

    Steiner Adrian

    2006-12-01

    Full Text Available Abstract Background Delayed uterine involution has negative effects on the fertility of cows; use of prostaglandin F2alpha alone as a single treatment has not been shown to consistently improve fertility. Combined administration of PGF2alpha and PGE2 increased uterine pressure in healthy cows. We hypothesized, that the combination of both prostaglandins would accelerate uterine involution and have, therefore, a positive effect on fertility variables. In commercial dairy farming, the benefit of a single post partum combined prostaglandin treatment should be demonstrated. Methods 383 cows from commercial dairy farms were included in this study. Uterine size and secretion were evaluated at treatment 21–35 days post partum and 14 days later. Cows were randomly allocated to one of three treatment groups: PGF2alpha and PGE2, PGF2alpha or placebo. For every animal participating in the study, the following reproduction variables were recorded: Interval from calving to first insemination, days open, number of artificial inseminations (AI to conception; subsequent treatment of uterus, subsequent treatment of ovaries. Plasma progesterone level at time of treatment was used as a covariable. For continuous measurements, analysis of variance was performed. Fisher's exact test for categorical non-ordered data and exact Kruskal-Wallis test for ordered data were used; pairwise group comparisons with Bonferroni adjustment of significance level were performed. Results There was no significant difference among treatment groups in uterine size. Furthermore, there was no significant difference among treatments concerning days open, number of AI, and subsequent treatment of uterus and ovaries. Days from calving to first insemination tended to be shorter for cows with low progesterone level given PGF2alpha and PGE2 in combination than for the placebo-group (P = 0.024. Conclusion The results of this study indicate that the administration of PGF2alpha or a combination

  9. Effects of a single administration of prostaglandin F2alpha, or a combination of prostaglandin F2alpha and prostaglandin E2, or placebo on fertility variables in dairy cows 3–5 weeks post partum, a randomized, double-blind clinical trial

    Science.gov (United States)

    Hirsbrunner, Gaby; Burkhardt, Heinz W; Steiner, Adrian

    2006-01-01

    Background Delayed uterine involution has negative effects on the fertility of cows; use of prostaglandin F2alpha alone as a single treatment has not been shown to consistently improve fertility. Combined administration of PGF2alpha and PGE2 increased uterine pressure in healthy cows. We hypothesized, that the combination of both prostaglandins would accelerate uterine involution and have, therefore, a positive effect on fertility variables. In commercial dairy farming, the benefit of a single post partum combined prostaglandin treatment should be demonstrated. Methods 383 cows from commercial dairy farms were included in this study. Uterine size and secretion were evaluated at treatment 21–35 days post partum and 14 days later. Cows were randomly allocated to one of three treatment groups: PGF2alpha and PGE2, PGF2alpha or placebo. For every animal participating in the study, the following reproduction variables were recorded: Interval from calving to first insemination, days open, number of artificial inseminations (AI) to conception; subsequent treatment of uterus, subsequent treatment of ovaries. Plasma progesterone level at time of treatment was used as a covariable. For continuous measurements, analysis of variance was performed. Fisher's exact test for categorical non-ordered data and exact Kruskal-Wallis test for ordered data were used; pairwise group comparisons with Bonferroni adjustment of significance level were performed. Results There was no significant difference among treatment groups in uterine size. Furthermore, there was no significant difference among treatments concerning days open, number of AI, and subsequent treatment of uterus and ovaries. Days from calving to first insemination tended to be shorter for cows with low progesterone level given PGF2alpha and PGE2 in combination than for the placebo-group (P = 0.024). Conclusion The results of this study indicate that the administration of PGF2alpha or a combination of PGF2alpha and PGE2 21 to

  10. A biallelic RFLP of the human. alpha. 2-C4 adrenergic receptor gene (ADRA2RL2) localized on the short arm of chromosome 4 and encoding the putative. alpha. 2B receptor is identified with Bsu 36 L using a 1. 5 kb probe (p ADRA2RL2)

    Energy Technology Data Exchange (ETDEWEB)

    Hoeche, M.R.; Berrettini, W.H. (Clinical Neurogenetics Branch, Bethesda, MD (USA)); Regan, J.W. (Duke Univ. Medical Center, Durham, NC (USA))

    1989-12-11

    A 1.5 kb Eco RI cDNA fragment representing the human alpha2-C4 adrenergic receptor (AR) gene encoding the putative alpha2B-AR, containing approximately 1270 bp of the coding and 240 bp of the 3{prime}flanking region, inserted into pSP65, was used as a probe (p ADRA2RL2). This clone was obtained by screening a human kidney lambda GT10 cDNA library with the 0.95 kb Pst I restriction fragment derived from the coding block of the gene for the human platelet alpha2-AR. Hybridization of human genomic DNA digested with Bsu 36 I identifies a two allele polymorphism with bands at 12 kb and 5.8 kb. 20 unrelated North American caucasian subjects were evaluated with frequencies of: A allele, 0.45; B allele, 0.55, heterozygosity (obs), 0.5. This alpha2-AR gene has been mapped in a separation effort in 59 CEPH reference pedigrees to the tip of the short arm of chromosome 4 just proximal to GB (4p 16.3) reported to be linked to the Huntingston's disease gene. Codominant inheritance was observed in seven families with two and three generations, respectively. The number of meioses scored was 95.

  11. HNF1 alpha activates the aminopeptidase N promoter in intestinal (Caco-2) cells

    DEFF Research Database (Denmark)

    Olsen, Jørgen; Laustsen, Lotte; Troelsen, J

    1994-01-01

    The importance of HNF1 binding proteins for intestinal aminopeptidase N expression was investigated using the Caco-2 cell-line. Aminopeptidase N promoter activity in Caco-2 cells depends on the HNF1 element (positions -85 to -58) and co-transfection with an HNF1 alpha expression vector demonstrates...... a direct activation of the promoter by HNF1 alpha through this element. Electrophoretic mobility shift assays using nuclear extracts from Caco-2 cells show the presence of high amounts of HNF1 binding proteins irrespective of their state of differentiation....

  12. Nitrated alpha-synuclein immunity accelerates degeneration of nigral dopaminergic neurons.

    Directory of Open Access Journals (Sweden)

    Eric J Benner

    2008-01-01

    Full Text Available The neuropathology of Parkinson's disease (PD includes loss of dopaminergic neurons in the substantia nigra, nitrated alpha-synuclein (N-alpha-Syn enriched intraneuronal inclusions or Lewy bodies and neuroinflammation. While the contribution of innate microglial inflammatory activities to disease are known, evidence for how adaptive immune mechanisms may affect the course of PD remains obscure. We reasoned that PD-associated oxidative protein modifications create novel antigenic epitopes capable of peripheral adaptive T cell responses that could affect nigrostriatal degeneration.Nitrotyrosine (NT-modified alpha-Syn was detected readily in cervical lymph nodes (CLN from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP intoxicated mice. Antigen-presenting cells within the CLN showed increased surface expression of major histocompatibility complex class II, initiating the molecular machinery necessary for efficient antigen presentation. MPTP-treated mice produced antibodies to native and nitrated alpha-Syn. Mice immunized with the NT-modified C-terminal tail fragment of alpha-Syn, but not native protein, generated robust T cell proliferative and pro-inflammatory secretory responses specific only for the modified antigen. T cells generated against the nitrated epitope do not respond to the unmodified protein. Mice deficient in T and B lymphocytes were resistant to MPTP-induced neurodegeneration. Transfer of T cells from mice immunized with N-alpha-Syn led to a robust neuroinflammatory response with accelerated dopaminergic cell loss.These data show that NT modifications within alpha-Syn, can bypass or break immunological tolerance and activate peripheral leukocytes in draining lymphoid tissue. A novel mechanism for disease is made in that NT modifications in alpha-Syn induce adaptive immune responses that exacerbate PD pathobiology. These results have implications for both the pathogenesis and treatment of this disabling neurodegenerative disease.

  13. New evidence from the Lyman-alpha forest concerning the formation of galaxies

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe, A M

    1986-12-17

    A new type of survey for galaxies with z > 2 is described. The idea is to search for the spectroscopic imprint that the H1 disc of a foreground galaxy leaves on radiation emitted by a background QSO; namely, a Lyman-..cap alpha.. absorption line broadened by radiation damping. A continuing survey has revealed the presence of 15 damped L..cap alpha.. lines with redshifts between 1.8 and 2.8 in the spectra of 68 QSOs. In comparison, no more than three discs with the properties of nearby galaxies should have been detected. Furthermore, the mean column density of the 15 absorbers, = 1.4 x 10/sup 21/cm/sup -2/, is much larger than expected for the outskirts of H1 discs. The statistical and physical evidence accumulated suggests that the damped L..cap alpha.. systems are a distinct population of absorbers with properties reminiscent of H1 discs. It is concluded that the progenitors of the baryon content of nearby galaxies have been detected. The implications for theories of galaxy formations of the discovery of this damped population of absorbers are explained.

  14. The management and disposal of alpha-contaminated waste

    International Nuclear Information System (INIS)

    Duclos, J.; Farges, L.; Lavie, J.M.; Marque, Y.

    1981-01-01

    The establishment of the French National Agency for Radioactive Waste Management (ANDRA) in November 1979 marked the beginning of industrial management of this type of waste in France. The organization of this Agency is sufficiently flexible to reconcile the need for the assumption of responsibility by the public authorities for a matter having considerable long-term implications; the importance of making available to all radioactive-waste producers the benefits of the research carried out by large national entities; (Commissariat a l'energie atomique, Electricite de France, etc.) and the obligation to satisfy all the scientific and financial requirements regarding optimal radioactive-waste management. The Centre de stockage de la Manche (CSM) is at present concerned with the special requirements relating to alpha waste. These are being analysed, together with their implications for technical specifications and industrial management. A strategy for alpha waste storage is defined in the light of the forecasts of waste deliveries for the next 20 years. (author)

  15. Effects of low dose radiation on differential expression of serum protein in mice

    International Nuclear Information System (INIS)

    Chen Wei; He Ying; Shen Xianrong

    2014-01-01

    The aim is to find out the key proteins related with low dose radiation (Ld) by parametric technology, which provided the theory foundation for LDR protection Two-dimensional electrophoresis (2-DE) was performed on serum protein Differential expression proteins were identified by matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and database analysis Compared with the control group, 7 altered proteins was definite in terms of apolipoprotein C-Ⅲ, beta-globin parotid secretory protein alpha-2-macroglobulin precursor, mouse transthyretin, C1qc protein and clusterin. Some proteins related with LDR are found. It may provide some new explanations for the mechanism of LDR. (authors)

  16. First Accurate Normalization of the $\\beta$-delayed $\\alpha$ Decay of $^{16}$N and Implications for the $^{12}$C$(\\alpha,\\gamma)^{16}$O Astrophysical Reaction Rate arXiv

    CERN Document Server

    Kirsebom, O.S.; Lica, R.; Munch, M.; Riisager, K.; Fynbo, H.O.U.; Borge, M.J.G.; Madurga, M.; Marroquin, I.; Andreyev, A.N.; Berry, T.A.; Christensen, E.R.; Fernández, P. Díaz; Doherty, D.T.; Van Duppen, P.; Fraile, L.M.; Gallardo, M.C.; Greenlees, P.T.; Harkness-Brennan, L.J.; Hubbard, N.; Huyse, M.; Jensen, J.H.; Johansson, H.; Jonson, B.; Judson, D.S.; Konki, J.; Lazarus, I.; Lund, M.V.; Marginean, N.; Marginean, R.; Perea, A.; Mihai, C.; Negret, A.; Page, R.D.; Pucknell, V.; Rahkila, P.; Sorlin, O.; Sotty, C.; Swartz, J.A.; Sørensen, H.B.; Törnqvist, H.; Vedia, V.; Warr, N.; De Witte, H.

    The $^{12}$C$(\\alpha,\\gamma)^{16}$O reaction plays a central role in astrophysics, but its cross section at energies relevant for astrophysical applications is only poorly constrained by laboratory data. The reduced $\\alpha$ width, $\\gamma_{11}$, of the bound $1^-$ level in $^{16}$O is particularly important to determine the cross section. The magnitude of $\\gamma_{11}$ is determined via sub-Coulomb $\\alpha$-transfer reactions or the $\\beta$-delayed $\\alpha$ decay of $^{16}$N, but the latter approach is presently hampered by the lack of sufficiently precise data on the $\\beta$-decay branching ratios. Here we report improved branching ratios for the bound $1^-$ level and for $\\beta$-delayed $\\alpha$ emission. In the case of the $\\beta$-delayed $\\alpha$ branch, we find a $5\\sigma$ deviation from the literature value. With our new branching ratios, the constraints imposed on $\\gamma_{11}$ by the $\\beta\\alpha$-decay and $\\alpha$-transfer data are of similar precision and, for the first time, in good agreement. Th...

  17. Monte Carlo simulation of the alpha-amylolysis of amylopectin potato starch. 2. alpha-amylolysis of amylopectin

    NARCIS (Netherlands)

    Marchal, L.M.; Ulijn, R.V.; Gooijer, de C.D.; Franke, G.T.; Tramper, J.

    2003-01-01

    A model is presented that describes all the saccharides that are produced during the hydrolysis of starch by an alpha-amylase. Potato amylopectin, the substrate of the hydrolysis reaction, was modeled in a computer matrix. The four different subsite maps presented in literature for alpha-amylase

  18. Alpha/beta(gamma ray) discrimination and spillover quantification with a BaF2 scintillator

    International Nuclear Information System (INIS)

    DeVol, T.A.; Fjeld, R.A.

    1994-01-01

    A simple pulse shape discrimination technique was used to separate alpha and beta(gamma ray) interactions in a BaF 2 scintillator. The separation was not ideal, resulting in a 5.1% spillover of alpha interactions into the beta(gamma ray) channel and 11.9% spillover of beta(gamma ray) interactions into the alpha channel for a set pulse shape discriminator. The misclassification of events was reduced by post-processing the data using either a simple analytical technique or a more complex linear least squares technique. Both techniques typically reduced the difference between the expected and calculated interaction rates to <10% when the ratio of beta(gamma ray) to alpha count rate was less than 100 : 1. ((orig.))

  19. Endocytosis of GPI-linked membrane folate receptor-alpha.

    Science.gov (United States)

    Rijnboutt, S; Jansen, G; Posthuma, G; Hynes, J B; Schornagel, J H; Strous, G J

    1996-01-01

    GPI-linked membrane folate receptors (MFRs) have been implicated in the receptor-mediated uptake of reduced folate cofactors and folate-based chemotherapeutic drugs. We have studied the biosynthetic transport to and internalization of MFR isoform alpha in KB-cells. MFR-alpha was synthesized as a 32-kD protein and converted in a maturely glycosylated 36-38-kD protein 1 h after synthesis. 32-kD MFR-alpha was completely soluble in Triton X-100 at 0 degree C. In contrast, only 33% of the 36-38-kD species could be solubilized at these conditions whereas complete solubilization was obtained in Triton X-100 at 37 degrees C or in the presence of saponin at 0 degree C. Similar solubilization characteristics were found when MFR-alpha at the plasma membrane was labeled with a crosslinkable 125I-labeled photoaffinity-analog of folic acid as a ligand. Triton X-100-insoluble membrane domains containing MFR-alpha could be separated from soluble MFR-alpha on sucrose flotation gradients. Only Triton X-100 soluble MFR-alpha was internalized from the plasma membrane. The reduced-folate-carrier, an integral membrane protein capable of translocating (anti-)folates across membranes, was completely excluded from the Triton X-100-resistant membrane domains. Internalized MFR-alpha recycled slowly to the cell surface during which it remained soluble in Triton X-100 at 0 degree C. Using immunoelectron microscopy, we found MFR-alpha along the entire endocytic pathway: in clathrin-coated buds and vesicles, and in small and large endosomal vacuoles. In conclusion, our data indicate that a large fraction, if not all, of internalizing MFR-alpha bypasses caveolae.

  20. Simultaneous evaluation of the pre- and postsynaptic interactions of alpha-2 adrenergic agents in the phenoxybenzamine-treated dog saphenous vein

    International Nuclear Information System (INIS)

    Buckner, S.; Morse, P.; DeBernardis, J.; Kyncyl, J.

    1986-01-01

    Functional alpha-2 adrenergic receptors can be demonstrated on both the neuronal and muscular sides of the sympathetic synapse in the superfused, electrically stimulated, 3 H-NE-loaded dog saphenous vein (DSV). Selective alkylation of the alpha-1 subtype in this tissue by phenoxybenzamine produced a preparation which contained functional alpha adrenergic receptors of only the alpha-2 subtype at both locations and provided an experimental model suitable for differentiating alpha-2 selective compounds according to their pre- vs postsynaptic preference. A number of standard alpha-2 selective agonists and antagonists were tested in this model. None of these agents exhibited any significant degree of presynaptic or postsynaptic selectivity

  1. The alpha2-delta protein: an auxiliary subunit of voltage-dependent calcium channels as a recognized drug target.

    Science.gov (United States)

    Thorpe, Andrew J; Offord, James

    2010-07-01

    Currently, there are two drugs on the market, gabapentin (Neurontin) and pregabalin (Lyrica), that are proposed to exert their therapeutic effect through binding to the alpha2-delta subunit of voltage-sensitive calcium channels. This activity was unexpected, as the alpha2-delta subunit had previously been considered not to be a pharmacological target. In this review, the role of the alpha2-delta subunits is discussed and the mechanism of action of the alpha2-delta ligands in vitro and in vivo is summarized. Finally, new insights into the mechanism of drugs that bind to this protein are discussed.

  2. Secretion of alpha 2-plasmin inhibitor is impaired by amino acid deletion in a small region of the molecule.

    Science.gov (United States)

    Toyota, S; Hirosawa, S; Aoki, N

    1994-02-01

    Alpha 2-plasmin inhibitor (alpha 2PI) deficiency Okinawa results from defective secretion of the inhibitor from the liver and appears to be a direct consequence of the deletion of Glu137 in the amino acid sequence of alpha 2PI. To examine the effects of replacing the amino acid occupying position 137 or deleting its neighboring amino acid on alpha 2PI secretion, we used oligonucleotide-directed mutagenesis of alpha 2PI cDNA to change the codon specifying Glu137 or delete a codon specifying its neighboring amino acid. The effects were determined by pulse-chase experiments and by enzyme-linked immunosorbent assay of media from transiently transfected COS-7 cells. Replacement of Glu137 with an amino acid other than Cys had little effect on alpha 2PI secretion. In contrast, deletion of an amino acid in a region spanning a sequence of less than 30 amino acids including positions 127 and 137 severely impaired the secretion. The results suggest that structural integrity of the region, rather than its component amino acids, is important for the intracellular transport and secretion of alpha 2PI.

  3. Alpha-2 receptor agonists for the treatment of posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Molly R Belkin

    2017-09-01

    Full Text Available Clonidine and guanfacine are alpha-2 receptor agonists that decrease sympathetic outflow from the central nervous system. Posttraumatic stress disorder (PTSD is an anxiety disorder that is theorized to be related to a hyperactive sympathetic nervous system. Currently, the only US Food and Drug Administration (FDA-approved medications for PTSD are the selective serotonin reuptake inhibitors (SSRIs sertraline and paroxetine. Sometimes use of the SSRIs may not lead to full remission and symptoms of hyperarousal often persist. This article specifically reviews the literature on alpha-2 receptor agonist use for the treatment of PTSD and concludes that while the evidence base is limited, these agents might be considered useful when SSRIs fail to treat symptoms of agitation and hyperarousal in patients with PTSD.

  4. Conditioning of alpha bearing wastes

    International Nuclear Information System (INIS)

    1991-01-01

    Alpha bearing wastes are generated during the reprocessing of spent fuel, mixed oxide fuel fabrication, decommissioning and other activities. The safe and effective management of these wastes is of particular importance owing to the radiotoxicity and long lived characteristics of certain transuranic (TRU) elements. The management of alpha bearing wastes involves a number of stages which include collection, characterization, segregation, treatment, conditioning, transport, storage and disposal. This report describes the currently available matrices and technologies for the conditioning of alpha wastes and relates them to their compatibility with the other stages of the waste management process. The selection of a specific immobilization process is dependent on the waste treatment state and the subsequent handling, transport, storage and disposal requirements. The overall objectives of immobilization are similar for all waste producers and processors, which are to produce: (a) Waste forms with sufficient mechanical, physical and chemical stability to satisfy all stages of handling, transport and storage (referred to as the short term requirements), and (b) Waste forms which will satisfy disposal requirements and inhibit the release of radionuclides to the biosphere (referred to as the long term requirements). Cement and bitumen processes have already been successfully applied to alpha waste conditioning on the industrial scale in many of the IAEA Member States. Cement systems based on BFS and pozzolanic cements have emerged as the principal encapsulation matrices for the full range of alpha bearing wastes. Alternative technologies, such as polymers and ceramics, are being developed for specific waste streams but are unlikely to meet widespread application owing to cost and process complexity. The merits of alpha waste conditioning are improved performance in transport, storage and disposal combined with enhanced public perception of waste management operations. These

  5. cPLA2alpha-evoked formation of arachidonic acid and lysophospholipids is required for exocytosis in mouse pancreatic beta-cells

    DEFF Research Database (Denmark)

    Juhl, Kirstine; Høy, Marianne; Olsen, Hervør L

    2003-01-01

    Using capacitance measurements, we investigated the effects of intracellularly applied recombinant human cytosolic phospholipase A2 (cPLA2alpha) and its lipolytic products arachidonic acid and lysophosphatidylcholine on Ca2+-dependent exocytosis in single mouse pancreatic beta-cells. cPLA2alpha...... from 70-80 to 280-300. cPLA2alpha-stimulated exocytosis was antagonized by the specific cPLA2 inhibitor AACOCF3. Ca2+-evoked exocytosis was reduced by 40% in cells treated with AACOCF3 or an antisense oligonucleotide against cPLA2alpha. The action of cPLA2alpha was mimicked by a combination...... of arachidonic acid and lysophosphatidylcholine (470% stimulation) in which each compound alone doubled the exocytotic response. Priming of insulin-containing secretory granules has been reported to involve Cl- uptake through ClC-3 Cl- channels. Accordingly, the stimulatory action of cPLA2alpha was inhibited...

  6. Circulating sex hormones and gene expression of subcutaneous adipose tissue oestrogen and alpha-adrenergic receptors in HIV-lipodystrophy: implications for fat distribution

    DEFF Research Database (Denmark)

    Andersen, Ove; Pedersen, Steen B; Svenstrup, Birgit

    2007-01-01

    of alpha2A-adrenergic-receptor correlated positively with expression of oestrogen-receptor-alpha. CONCLUSIONS: The results fit the hypothesis that sex hormones play a role in altered fat distribution and insulin sensitivity of male patients with HIV-lipodystrophy. The effect of oestradiol...... patients, correlated positively with both plasma oestradiol and testosterone (n = 31). Glycerol concentration during clamp (a marker of lipolysis) correlated inversely with expression of alpha2A-adrenergic-receptor, ratio of subcutaneous to total abdominal fat mass, and limb fat, respectively. Expression...

  7. Monovalent cation and amiloride analog modulation of adrenergic ligand binding to the unglycosylated alpha 2B-adrenergic receptor subtype

    International Nuclear Information System (INIS)

    Wilson, A.L.; Seibert, K.; Brandon, S.; Cragoe, E.J. Jr.; Limbird, L.E.

    1991-01-01

    The unglycosylated alpha 2B subtype of the alpha 2-adrenergic receptor found in NG-108-15 cells possesses allosteric regulation of adrenergic ligand binding by monovalent cations and 5-amino-substituted amiloride analogs. These findings demonstrate that allosteric modulation of adrenergic ligand binding is not a property unique to the alpha 2A subtype. The observation that amiloride analogs as well as monovalent cations can modulate adrenergic ligand binding to the nonglycosylated alpha 2B subtype indicates that charge shielding due to carbohydrate moieties does not play a role in this allosteric modulation but, rather, these regulatory effects result from interactions of cations and amiloride analogs with the protein moiety of the receptor. Furthermore, the observation that both alpha 2A and alpha 2B receptor subtypes are modulated by amiloride analogs suggests that structural domains that are conserved between the two are likely to be involved in this allosteric modulation

  8. Muscarinic cholinergic and alpha 2-adrenergic receptors in the epithelium and muscularis of the human ileum

    International Nuclear Information System (INIS)

    Lepor, H.; Rigaud, G.; Shapiro, E.; Baumann, M.; Kodner, I.J.; Fleshman, J.W.

    1990-01-01

    The aim of this study was to characterize the binding and functional properties of muscarinic cholinergic (MCh) and alpha 2-adrenergic receptors in the human ileum to provide insight into pharmacologic strategies for managing urinary and fecal incontinence after bladder and rectal replacement with intestinal segments. MCh and alpha 2-adrenergic binding sites were characterized in the epithelium and muscularis of eight human ileal segments with 3H-N-methylscopolamine and 3H-rauwolscine, respectively. The dissociation constant for 3H-N-methylscopolamine in the epithelium and muscularis was 0.32 +/- 0.07 nmol/L and 0.45 +/- 0.10 nmol/L, respectively (p = 0.32). The MCh receptor content was approximately eightfold greater in the muscularis compared with the epithelium (p = 0.008). The dissociation constant for 3H-rauwolscine in the muscularis and epithelium was 2.55 +/- 0.42 nmol/L and 2.03 +/- 0.19 nmol/L, respectively (p = 0.29). The alpha 2-adrenoceptor density was twofold greater in the epithelium compared with the muscularis (p = 0.05). Noncumulative concentration-response experiments were performed with carbachol, an MCh agonist, and UK-14304, a selective alpha 2-adrenergic agonist. The epithelium did not contract in the presence of high concentrations of carbachol and UK-14304. The muscularis preparations were responsive only to carbachol. The muscularis contains primarily MCh receptors mediating smooth muscle contraction. The alpha 2-adrenoceptors are localized primarily to the epithelium and may regulate water secretion in the intestine. The distribution and functional properties of ileal MCh and alpha 2-adrenergic receptors provide a theoretic basis for the treatment of incontinence after bladder and rectal replacement with intestinal segments

  9. A model for the stepwise radiation inactivation of the alpha 2-dimer of Na,K-ATPase

    International Nuclear Information System (INIS)

    Norby, J.G.; Jensen, J.

    1989-01-01

    This study is a direct continuation of Jensen, J., and Norby. A new model in which we propose that the in situ organization of the Na,K-ATPase alpha-subunit is an alpha 2-dimer and which describes the stepwise degradation by radiation inactivation of this assembly is presented on the basis of the following findings. Radiation inactivation size for alpha-peptide integrity, normal nucleotide, vanadate and ouabain binding, and K-pNPPase activity is close to m(alpha) = 112 kDa; for Na-ATPase activity it is 135 kDa and for Na,K-ATPase activity it increases from 140 to about 195 kDa with increasing assay ATP concentration (equal to increasing average turnover). Normal Tl+ occlusion had the same radiation inactivation size as Vmax for Na,K-ATPase, i.e. about 195 kDa. The binding experiments disclosed radiation-produced molecules with active binding sites but with a lower than normal affinity. Radiation inactivation size for the total binding capacity of ADP and ouabain was therefore smaller than the size of an alpha-peptide, namely about 70 kDa, and for total Tl+ occlusion it was down to 40 kDa. We can explain all these observations by using a new approach to target size analysis and by assuming a dimeric organization of the alpha-subunit. Each alpha-peptide is degraded stepwise by first destruction of either a 42- or a 70-kDa domain, and the partly damaged peptide may retain biochemical activity. We conclude that there is no role for the beta-subunit in catalysis and that the alpha-peptide is organized as an alpha 2-dimer in the membrane with each alpha-subunit being able to perform complete catalytic cycles (and probably also active transport), provided that it is stabilized by an adjacent alpha-peptide or a sufficiently large fragment thereof

  10. A model for the stepwise radiation inactivation of the alpha 2-dimer of Na,K-ATPase

    Energy Technology Data Exchange (ETDEWEB)

    Norby, J.G.; Jensen, J. (Univ. of Aarhus (Denmark))

    1989-11-25

    This study is a direct continuation of Jensen, J., and Norby. A new model in which we propose that the in situ organization of the Na,K-ATPase alpha-subunit is an alpha 2-dimer and which describes the stepwise degradation by radiation inactivation of this assembly is presented on the basis of the following findings. Radiation inactivation size for alpha-peptide integrity, normal nucleotide, vanadate and ouabain binding, and K-pNPPase activity is close to m(alpha) = 112 kDa; for Na-ATPase activity it is 135 kDa and for Na,K-ATPase activity it increases from 140 to about 195 kDa with increasing assay ATP concentration (equal to increasing average turnover). Normal Tl+ occlusion had the same radiation inactivation size as Vmax for Na,K-ATPase, i.e. about 195 kDa. The binding experiments disclosed radiation-produced molecules with active binding sites but with a lower than normal affinity. Radiation inactivation size for the total binding capacity of ADP and ouabain was therefore smaller than the size of an alpha-peptide, namely about 70 kDa, and for total Tl+ occlusion it was down to 40 kDa. We can explain all these observations by using a new approach to target size analysis and by assuming a dimeric organization of the alpha-subunit. Each alpha-peptide is degraded stepwise by first destruction of either a 42- or a 70-kDa domain, and the partly damaged peptide may retain biochemical activity. We conclude that there is no role for the beta-subunit in catalysis and that the alpha-peptide is organized as an alpha 2-dimer in the membrane with each alpha-subunit being able to perform complete catalytic cycles (and probably also active transport), provided that it is stabilized by an adjacent alpha-peptide or a sufficiently large fragment thereof.

  11. NF-kappaB is involved in SHetA2 circumvention of TNF-alpha resistance, but not induction of intrinsic apoptosis.

    Science.gov (United States)

    Chengedza, Shylet; Benbrook, Doris Mangiaracina

    2010-03-01

    Treatment of cancer with tumor necrosis factor-alpha (TNF-alpha) is hindered by resistance and toxicity. The flexible heteroarotinoid, SHetA2, sensitizes resistant ovarian cancer cells to TNF-alpha-induced extrinsic apoptosis, and also induces intrinsic apoptosis as a single agent. This study tested the hypothesis that nuclear factor-kappaB (NF-kappaB) is involved in SHetA2-regulated intrinsic and extrinsic apoptosis. SHetA2 inhibited basal and TNF-alpha-induced or hydrogen peroxide-induced NF-kappaB activity through counter-regulation of upstream kinase (IkappaB kinase) activity, inhibitor protein (IkappaB-alpha) phosphorylation, and p-65 NF-kappaB subunit nuclear translocation, but independently of reactive oxygen species generation. Ectopic over-expression of p-65, or treatment with TNF-alpha receptor 1 (TNFR1) small interfering RNA or a caspase-8 inhibitor, each attenuated synergistic apoptosis by SHetA2 and TNF-alpha, but did not affect intrinsic apoptosis caused by SHetA2. In conclusion, NF-kappaB repression is involved in SHetA2 circumvention of resistance to TNF-alpha-induced extrinsic apoptosis, but not in SHetA2 induction of intrinsic apoptosis.

  12. Study of alpha-case depth in Ti-6Al-2Sn-4Zr-2Mo and Ti-6Al-4V

    International Nuclear Information System (INIS)

    Gaddam, R; Sefer, B; Pederson, R; Antti, M-L

    2013-01-01

    At temperatures exceeding 480°C titanium alloys generally oxidises and forms a hard and brittle layer enriched with oxygen, which is called alpha case. This layer has negative effects on several mechanical properties and lowers the tensile ductility and the fatigue resistance. Therefore any alpha-case formed on titanium alloys during various manufacturing processes, such as heat treatment procedures, must be removed before the final part is mounted in an engine. In addition, long time exposure at elevated temperatures during operation of an engine could possibly also lead to formation of alpha-case on actual parts, therefore knowledge and understanding of the alpha-case formation and its effect on mechanical properties is important. Factors that contribute for growth of alpha-case are: presence of oxygen, exposure time, temperature and pressure. In the present study, isothermal oxidation experiments in air were performed on forged Ti-6Al-2Sn-4Zr-2Mo at 500°C and 593°C up to 500 hours. Similar studies were also performed on Ti-6Al-4V plate at 593°C and 700°C. Alpha-case depth for both alloys was quantified using metallography techniques and compared

  13. Olfactory Bulb [alpha][subscript 2]-Adrenoceptor Activation Promotes Rat Pup Odor-Preference Learning via a cAMP-Independent Mechanism

    Science.gov (United States)

    Shakhawat, Amin MD.; Harley, Carolyn W.; Yuan, Qi

    2012-01-01

    In this study, three lines of evidence suggest a role for [alpha][subscript 2]-adrenoreceptors in rat pup odor-preference learning: olfactory bulb infusions of the [alpha][subscript 2]-antagonist, yohimbine, prevents learning; the [alpha][subscript 2]-agonist, clonidine, paired with odor, induces learning; and subthreshold clonidine paired with…

  14. Different responses of spontaneous and stimulus-related alpha activity to ambient luminance changes.

    Science.gov (United States)

    Benedetto, Alessandro; Lozano-Soldevilla, Diego; VanRullen, Rufin

    2017-12-04

    Alpha oscillations are particularly important in determining our percepts and have been implicated in fundamental brain functions. Oscillatory activity can be spontaneous or stimulus-related. Furthermore, stimulus-related responses can be phase- or non-phase-locked to the stimulus. Non-phase-locked (induced) activity can be identified as the average amplitude changes in response to a stimulation, while phase-locked activity can be measured via reverse-correlation techniques (echo function). However, the mechanisms and the functional roles of these oscillations are far from clear. Here, we investigated the effect of ambient luminance changes, known to dramatically modulate neural oscillations, on spontaneous and stimulus-related alpha. We investigated the effect of ambient luminance on EEG alpha during spontaneous human brain activity at rest (experiment 1) and during visual stimulation (experiment 2). Results show that spontaneous alpha amplitude increased by decreasing ambient luminance, while alpha frequency remained unaffected. In the second experiment, we found that under low-luminance viewing, the stimulus-related alpha amplitude was lower, and its frequency was slightly faster. These effects were evident in the phase-locked part of the alpha response (echo function), but weaker or absent in the induced (non-phase-locked) alpha responses. Finally, we explored the possible behavioural correlates of these modulations in a monocular critical flicker frequency task (experiment 3), finding that dark adaptation in the left eye decreased the temporal threshold of the right eye. Overall, we found that ambient luminance changes impact differently on spontaneous and stimulus-related alpha expression. We suggest that stimulus-related alpha activity is crucial in determining human temporal segmentation abilities. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. Expression of biologically active human interferon alpha 2 in aloe vera

    Science.gov (United States)

    We have developed a system for transgenic expression of proteins in Aloe Vera. Using this approach we have generated plants expressing the human gene interferon alpha 2, IFNa2. IFNa2 is a small secreted cytokine that plays a vital role in regulating the body’s immune response to viral infections a...

  16. In vivo administration of interferon alpha and interleukin 2 induces proliferation of lymphoid cells in the organs of mice

    International Nuclear Information System (INIS)

    Puri, R.K.; Travis, W.D.; Rosenberg, S.A.

    1990-01-01

    We have previously shown that interleukin 2 (IL-2) synergizes with interferon alpha (IFN-alpha) in mediating the regression of established pulmonary and hepatic metastases and the reduction of intradermal tumor in various murine tumor models. To understand the mechanism of synergy, we have examined lymphoid cell proliferation in various organs of mice in response to IL-2 and IFN-alpha administration. We have utilized a technique for labeling newly synthesized DNA in vivo with 5-[125I]iodo-2'-deoxyuridine to examine proliferation of endogenous cells in response to IL-2 and IL-2 plus IFN-alpha. A proliferation index was calculated by dividing cpm in the tissues treated with cytokines by cpm obtained in corresponding tissues of control mice. After 4 days of IL-2 administration, a significant uptake of 5-[125I]iodo-2'-deoxyuridine was observed in the lungs, liver, kidneys, and spleen (proliferation index of 13, 10.3, 3.6, and 3.2, respectively). IFN-alpha alone mediated very little incorporation of radiolabel but when administered in combination with IL-2 a reduction of IL-2-induced proliferation was seen on day 4. For example 19,272 +/- 4,556 cpm (mean +/- SE) were obtained in the liver of IL-2-treated mice, compared to 8,103 +/- 2,111 cpm in livers of IL-2 plus IFN-alpha-treated mice (P less than 0.05). Similar inhibition of IL-2-induced proliferation was observed in the lungs, kidneys, and spleen. In contrast, on days 7 or 8, higher uptake of radiolabel was obtained in IFN-alpha plus IL-2-treated lungs, liver, and kidneys, compared to organs of mice treated with IL-2 alone or IFN-alpha alone. A proliferation index of 30.5, 9.8, and 10 was obtained in the lungs, liver, and kidneys of IL-2- plus IFN-alpha-treated animals, compared to 9.6, 3.6, and 5.5 in the corresponding organs of IL-2-treated mice

  17. Combination of Reduced Levels of Serum Albumin and Αlpha-2 ...

    African Journals Online (AJOL)

    Pulmonary tuberculosis (PTB) is global disease affecting about one third of the world's population with its attendant mortality and morbidity. Acute phase proteins have been used in monitoring the progression of infections but not in relation to PTB in this environment. The levels of total protein, albumin, α-2-macroglobulin, ...

  18. Effect of alpha 2-adrenoceptor agonists on gastric pepsin and acid secretion in the rat.

    Science.gov (United States)

    Tazi-Saad, K.; Chariot, J.; Del Tacca, M.; Rozé, C.

    1992-01-01

    1. The purpose of the present study was to analyze the effects of the alpha 2-adrenoceptor agonists clonidine, guanabenz, detomidine and medetomidine on pepsin secretion in conscious rats provided with gastric chronic fistula and to compare this with acid secretion. 2. Basal interdigestive gastric secretion, which is mainly neurally driven in the rat, and the secretion directly stimulated by the two main stimulants of chief cells, cholecystokinin octapeptide (CCK8) and methacholine, were studied. 3. Basal secretion of pepsin and acid was inhibited by all four drugs with comparable EC50S. 4. CCK-stimulated pepsin and acid secretion was less sensitive than basal pepsin and acid secretion to alpha 2-adrenoceptor inhibition. 5. Methacholine-stimulated pepsin and acid secretion was not changed by clonidine and guanabenz; methacholine-stimulated acid was even marginally increased by clonidine. 6. These results do not favour the presence of alpha 2-receptors on chief cells in the rat stomach. They rather suggest that pepsin inhibition by alpha 2-adrenoceptor agonists is indirect and due to central or peripheral inhibition of the discharge of nerve fibres activating pepsin secretion. PMID:1356566

  19. Murine muscular dystrophy caused by a mutation in the laminin alpha 2 (Lama2) gene

    DEFF Research Database (Denmark)

    Xu, H; Wu, X R; Wewer, U M

    1994-01-01

    The classic murine muscular dystrophy strain, dy, was first described almost 40 years ago. We have identified the molecular basis of an allele of dy, called dy2J, by detecting a mutation in the laminin alpha 2 chain gene--the first identified mutation in laminin-2. The G to A mutation in a splice...

  20. In-situ Long-range Alpha Particles and X-ray Detection for Thin-film Pd Cathodes During Electrolysis in Li_2SO_4/H_2O

    Science.gov (United States)

    Lipson, A. G.; Roussetski, A. S.; Castano, C. H.; S-O, Kim; Miley, G. H.

    2002-03-01

    Measurements of long-range alpha and soft X-ray emissions have been performed using cyclotron calibrated CR-39 plastic track and LiF/Al_2O_3:C-Thermo-Luminescent (TLD) detectors. Application of CR-39 and TLD detectors to the surface of the thin Pd film-cathodes sputtered on the insulator substrate (glass, Al_2O_3, PMMA) allows detection of both alpha and soft X-ray emissions simultaneously with excess heat measurements during electrolysis using 1 Molar Li_2SO_4/H_20 electrolyte. The alpha particles in the range of 8.0 d> 6.0 μm) were detected upon the electrolysis. Those alpha-tracks are quite unique, never having been observed during CR-39 exposure with trans-uranium alpha -sources (Am^241, Pu^239). The TLD measurement shows generation of the low intensity 5.0-10.0 keV X-ray quanta (Φx < 5.0 s -1*cm-2) accompanying the alpha emission.

  1. Peroxisome proliferator-activated receptor {alpha} agonists modulate Th1 and Th2 chemokine secretion in normal thyrocytes and Graves' disease

    Energy Technology Data Exchange (ETDEWEB)

    Antonelli, Alessandro, E-mail: a.antonelli@med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Ferrari, Silvia Martina, E-mail: sm.ferrari@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Frascerra, Silvia, E-mail: lafrasce@gmail.com [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Corrado, Alda, E-mail: dala_res@hotmail.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Pupilli, Cinzia, E-mail: c.pupilli@dfc.unifi.it [Endocrinology Unit, Azienda Ospedaliera Careggi and University of Florence, Viale Morgagni 85, I-50134, Florence (Italy); Bernini, Giampaolo, E-mail: g.bernini@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Benvenga, Salvatore, E-mail: s.benvenga@me.nettuno.it [Department of Clinical and Experimental Medicine, Section of Endocrinology, University of Messina, Piazza Pugliatti 1, I-98122, Messina (Italy); Ferrannini, Ele, E-mail: eferrannini@med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy); Fallahi, Poupak, E-mail: poupak@int.med.unipi.it [Department of Internal Medicine, University of Pisa-School of Medicine, Via Roma 67, I-56100, Pisa (Italy)

    2011-07-01

    Until now, no data are present about the effect of peroxisome proliferator-activated receptor (PPAR){alpha} activation on the prototype Th1 [chemokine (C-X-C motif) ligand (CXCL)10] (CXCL10) and Th2 [chemokine (C-C motif) ligand 2] (CCL2) chemokines secretion in thyroid cells. The role of PPAR{alpha} and PPAR{gamma} activation on CXCL10 and CCL2 secretion was tested in Graves' disease (GD) and control primary thyrocytes stimulated with interferon (IFN){gamma} and tumor necrosis factor (TNF){alpha}. IFN{gamma} stimulated both CXCL10 and CCL2 secretion in primary GD and control thyrocytes. TNF{alpha} alone stimulated CCL2 secretion, while had no effect on CXCL10. The combination of IFN{gamma} and TNF{alpha} had a synergistic effect both on CXCL10 and CCL2 chemokines in GD thyrocytes at levels comparable to those of controls. PPAR{alpha} activators inhibited the secretion of both chemokines (stimulated with IFN{gamma} and TNF{alpha}) at a level higher (for CXCL10, about 60-72%) than PPAR{gamma} agonists (about 25-35%), which were confirmed to inhibit CXCL10, but not CCL2. Our data show that CCL2 is modulated by IFN{gamma} and TNF{alpha} in GD and normal thyrocytes. Furthermore we first show that PPAR{alpha} activators inhibit the secretion of CXCL10 and CCL2 in thyrocytes, suggesting that PPAR{alpha} may be involved in the modulation of the immune response in the thyroid.

  2. Next-to-next-to-leading order O({alpha}{sup 2}{alpha}{sup 2}{sub s}) results for top quark pair production in photon-photon collisions. The loop-by-loop contribution

    Energy Technology Data Exchange (ETDEWEB)

    Koerner, J.G. [Johannes Gutenberg Univ., Mainz (Germany). Inst. fuer Phys.; Merebashvili, Z. [Tbilisi State Univ. (Georgia). Inst. of High Energy Physics and Informatization; Rogal, M. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany)

    2006-08-15

    We calculate the so-called loop-by-loop contributions to the next-to-next-to-leading order O({alpha}{sup 2}{alpha}{sup 2}{sub s}) radiative QCD corrections for the production of heavy quark pairs in the collisions of unpolarized on-shell photons. In particular, we present analytical results for the squared matrix elements that correspond to the product of the one-loop amplitudes. All results of the perturbative calculation are given in the dimensional regularization scheme. These results represent the Abelian part of the corresponding gluon-induced next-to-next-to-leading order cross section for heavy quark pair hadroproduction. (orig.)

  3. Computer modeling of siRNA knockdown effects indicates an essential role of the Ca2+ channel alpha2delta-1 subunit in cardiac excitation-contraction coupling.

    Science.gov (United States)

    Tuluc, Petronel; Kern, Georg; Obermair, Gerald J; Flucher, Bernhard E

    2007-06-26

    L-type Ca(2+) currents determine the shape of cardiac action potentials (AP) and the magnitude of the myoplasmic Ca(2+) signal, which regulates the contraction force. The auxiliary Ca(2+) channel subunits alpha(2)delta-1 and beta(2) are important regulators of membrane expression and current properties of the cardiac Ca(2+) channel (Ca(V)1.2). However, their role in cardiac excitation-contraction coupling is still elusive. Here we addressed this question by combining siRNA knockdown of the alpha(2)delta-1 subunit in a muscle expression system with simulation of APs and Ca(2+) transients by using a quantitative computer model of ventricular myocytes. Reconstitution of dysgenic muscle cells with Ca(V)1.2 (GFP-alpha(1C)) recapitulates key properties of cardiac excitation-contraction coupling. Concomitant depletion of the alpha(2)delta-1 subunit did not perturb membrane expression or targeting of the pore-forming GFP-alpha(1C) subunit into junctions between the outer membrane and the sarcoplasmic reticulum. However, alpha(2)delta-1 depletion shifted the voltage dependence of Ca(2+) current activation by 9 mV to more positive potentials, and it slowed down activation and inactivation kinetics approximately 2-fold. Computer modeling revealed that the altered voltage dependence and current kinetics exert opposing effects on the function of ventricular myocytes that in total cause a 60% prolongation of the AP and a 2-fold increase of the myoplasmic Ca(2+) concentration during each contraction. Thus, the Ca(2+) channel alpha(2)delta-1 subunit is not essential for normal Ca(2+) channel targeting in muscle but is a key determinant of normal excitation and contraction of cardiac muscle cells, and a reduction of alpha(2)delta-1 function is predicted to severely perturb normal heart function.

  4. The influence of nifedipine and pertussis toxin (PTX) on vascular responsiveness to alpha1- and alpha2-adrenergic stimulation of isolated femoral arteries

    Czech Academy of Sciences Publication Activity Database

    Líšková, Silvia; Kuneš, Jaroslav; Paulis, Ĺudovít; Zicha, Josef

    2006-01-01

    Roč. 48, č. 4 (2006), s. 769-769 ISSN 0194-911X. [Annual Meeting of the European Council for Cardiovascular Research (ECCR) /11./. 29.09.2006-01.10.2006, La Colle sur Loup] R&D Projects: GA MZd NR7786 Institutional research plan: CEZ:AV0Z50110509 Keywords : nifedipine * pertussis toxin * vascular responsiveness * alpha1- and alpha2-adrenergic stimulation * femorel arteria Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  5. Involvement of reversible binding to alpha 2u-globulin in 1,4-dichlorobenzene-induced nephrotoxicity.

    Science.gov (United States)

    Charbonneau, M; Strasser, J; Lock, E A; Turner, M J; Swenberg, J A

    1989-06-01

    Similarly to unleaded gasoline, 1,4-dichlorobenzene (1,4-DCB) administered for 2 years caused a dose-related increase in the incidence of renal tumors in male but not in female rats or in either sex of mice. Unleaded gasoline and 2,2,4-trimethylpentane (TMP), a component of unleaded gasoline, increased protein droplet formation and cell proliferation in male but not in female rat kidneys. These protein droplets contained, alpha 2u-globulin, a male rat-specific low-molecular-weight protein and 2,4,4-trimethyl-2-pentanol, a metabolite of TMP that was reversibly bound to this protein. Studies were undertaken to determine if 1,4-DCB produced similar effects; 1,2-DCB was used for comparison since it did not produce renal carcinogenesis in male rats. Gel filtration chromatography of a 116,000g supernatant prepared from kidneys of 1,4-[14C]DCB-treated rats showed that radiolabel coeluted with alpha 2u-globulin as one sharp peak as opposed to a multipeak pattern observed for 1,2-[14C]DCB; the maximal quantity of radiolabel for 1,4-DCB was twice that for 1,2-DCB. Equilibrium dialysis of kidney cytosol in the presence or absence of sodium dodecyl sulfate demonstrated that the radiolabel was reversibly bound to alpha 2u-globulin; the amount for 1,4-[14C]DCB-treated rats was almost twice as much as that for 1,2-[14C]DCB-treated rats. 1,2-DCB was also shown to be covalently bound to renal alpha 2u-globulin, and covalently bound to liver and plasma high-molecular-weight proteins. 1,4-DCB and, to a minor extent, 2,5-dichlorophenol, the major metabolite of 1,4-DCB, were reversibly bound to renal alpha 2u-globulin from 1,4-DCB-treated rats. 1,4-DCB increased protein droplet formation in male but not in female rat kidneys, whereas equimolar doses of 1,2-DCB showed no effect in either sex. Renal cell proliferation, measured by [3H]thymidine incorporation into renal DNA, was increased after 1,4-DCB but not after 1,2-DCB treatment. Nephrotoxicity and biochemical alterations induced by

  6. Influence of fast alpha diffusion and thermal alpha buildup on tokamak reactor performance

    International Nuclear Information System (INIS)

    Uckan, N.A.; Tolliver, J.S.; Houlberg, W.A.; Attenberger, S.E.

    1988-01-01

    The effect of fast alpha diffusion and thermal alpha accumulation on the confinement capability of a candidate Engineering Test Reactor plasma (Tokamak Ignition/Burn Experimental Reactor) in achieving ignition and steady-state driven operation has been assessed using both global and 1-1/2-dimensional transport models. Estimates are made of the threshold for radial diffusion of fast alphas and thermal alpha buildup. It is shown that a relatively low level of radial transport, when combined with large gradients in the fast alpha density, leads to a significant radial flow with a deleterious effect on plasma performance. Similarly, modest levels of thermal alpha concentration significantly influence the ignition and steady-state burn capability

  7. Characterization of the alpha and beta subunits of casein kinase 2 by far-UV CD spectroscopy

    DEFF Research Database (Denmark)

    Issinger, O G; Brockel, C; Boldyreff, B

    1992-01-01

    Although Chou-Fasman calculations of the secondary structure of recombinant casein kinase 2 subunits alpha and beta suggest they have a similar overall conformation, circular dichroism (CD) studies show that substantial differences in the conformation of the two subunits exist. In addition......, no changes in the far-UV CD spectrum of the alpha subunit are observed in the presence of casein or the synthetic decapeptide substrate RRRDDDSDDD. Furthermore, the alpha-helical structure of the alpha subunit (but not the beta subunit) can be increased in the presence of stoichiometric amounts of heparin...

  8. Effect of ascorbic acid and alpha-tocopherol supplementations on serum leptin, tumor necrosis factor alpha, and serum amyloid A levels in individuals with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Mostafa Jamalan

    2015-10-01

    Full Text Available Objective: Diabetes mellitus Type 2 is one of the most widespread chronic metabolic diseases. In most cases, this type of diabetes is associated with alterations in levels of some inflammatory cytokines and hormones. Considering anti-inflammatory properties of plant extracts rich in ascorbic acid (vitamin C and alpha-tocopherol (vitamin E, anti-diabetic properties of these two well-known antioxidant vitamins were investigated through measurement of serum levels of high-sensitivity C-reactive protein (hs-CRP, insulin, leptin, tumor necrosis factor alpha (TNF-α, and serum amyloid A (SAA in patients with diabetes mellitus type 2. Methods: Male patients (n=80 were randomly divided into two groups each consisted of 40 subjects. Test groups were supplemented with ascorbic acid (1000 mg/day or alpha-tocopherol (300 mg/day orally during four weeks. Before and after treatment, serum biochemical factors of subjects were measured and compared. Results: Our results showed that both ascorbic acid and alpha-tocopherol could induce significant anti-inflammatory effects by decreasing the level of inflammatory factors such as TNF-α, SAA, and hs-CRP in diabetes mellitus type 2 patients. Effects of alpha-tocopherol and ascorbic acid in decreasing serum leptin level were similar. Ascorbic acid in contrast to alpha-tocopherol diminished fasting insulin and HOMA index but had no effect on LDL serum level. Conclusion: Concerning the obtained results, it is concluded that consumption of supplementary vitamins C and E could decrease induced inflammatory response in patients with diabetes mellitus type 2.  It is also possible that vitamin C and vitamin E supplementation can attenuate incidence of some proposed pathological effects of diabetes mellitus.

  9. Alpha-contingent EEG feedback reduces SPECT rCBF variability

    DEFF Research Database (Denmark)

    McLaughlin, Thomas; Steinberg, Bruce; Mulholland, Thomas

    2005-01-01

    EEG feedback methods, which link the occurrence of alpha to the presentation of repeated visual stimuli, reduce the relative variability of subsequent, alpha-blocking event durations. The temporal association between electro-cortical field activation and regional cerebral blood flow (rCBF) led us...... to investigate whether the reduced variability of alpha-blocking durations with feedback is associated with a reduction in rCBF variability. Reduced variability in the rCBF response domain under EEG feedback control might have methodological implications for future brain-imaging studies. Visual stimuli were...... to quantify the variance-reducing effects of ACS across multiple, distributed areas of the brain. Both EEG and rCBF measures demonstrated decreased variability under ACS. This improved control was seen for localized as well as anatomically distributed rCBF measures....

  10. Temporary increase in serum beta 2-microglobulin during treatment with interferon-alpha for AIDS-associated Kaposi's sarcoma

    NARCIS (Netherlands)

    de Wit, R.; Bakker, P. J.; Reiss, P.; Hoek, F. J.; Lange, J. M.; Goudsmit, J.; Veenhof, K. H.

    1990-01-01

    Beta 2-microglobulin (beta 2-M) levels were determined in the serum of 24 patients treated with high-dose human recombinant interferon-alpha (IFN alpha) for AIDS-associated Kaposi's sarcoma. There was a significant increase in serum beta 2-M levels, irrespective of the response to treatment.

  11. GAS MOTION STUDY OF Ly{alpha} EMITTERS AT z {approx} 2 USING FUV AND OPTICAL SPECTRAL LINES {sup ,}

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Takuya; Shimasaku, Kazuhiro; Nakajima, Kimihiko [Department of Astronomy, Graduate School of Science, The University of Tokyo, Tokyo 113-0033 (Japan); Ouchi, Masami; Ono, Yoshiaki [Institute for Cosmic Ray Research, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8582 (Japan); Rauch, Michael; Janice Lee [Observatories of the Carnegie Institution of Washington, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); Okamura, Sadanori, E-mail: thashimoto@astron.s.u-tokyo.ac.jp [Department of Advanced Sciences, Faculty of Science and Engineering, Hosei University, 3-7-2 Kajino-cho, Koganei-shi, Tokyo 184-8584 (Japan)

    2013-03-01

    We present the results of Magellan/MMIRS and Keck/NIRSPEC spectroscopy for five Ly{alpha} emitters (LAEs) at z {approx_equal} 2.2 for which high-resolution FUV spectra from Magellan/MagE are available. We detect nebular emission lines including H{alpha} on the individual basis and low-ionization interstellar (LIS) absorption lines in a stacked FUV spectrum, and measure average offset velocities of the Ly{alpha} line, {Delta}v {sub Ly{alpha}}, and LIS absorption lines, {Delta}v {sub abs}, with respect to the systemic velocity defined by the nebular lines. For a sample of eight z {approx} 2-3 LAEs without active galactic nucleus from our study and the literature, we obtain {Delta}v {sub Ly{alpha}} = 175 {+-} 35 km s{sup -1}, which is significantly smaller than that of Lyman-break Galaxies (LBGs), {Delta}v {sub Ly{alpha}} {approx_equal} 400 km s{sup -1}. The stacked FUV spectrum gives {Delta}v {sub abs} = -179 {+-} 73 km s{sup -1}, comparable to that of LBGs. These positive {Delta}v {sub Ly{alpha}} and negative {Delta}v {sub abs} suggest that LAEs also have outflows. In contrast to LBGs, however, the LAEs' {Delta}v {sub Ly{alpha}} is as small as |{Delta}v {sub abs}|, suggesting low neutral hydrogen column densities. Such a low column density with a small number of resonant scattering may cause the observed strong Ly{alpha} emission of LAEs. We find an anti-correlation between Ly{alpha} equivalent width (EW) and {Delta}v {sub Ly{alpha}} in a compilation of LAE and LBG samples. Although its physical origin is not clear, this anti-correlation result appears to challenge the hypothesis that a strong outflow, by means of a reduced number of resonant scattering, produces a large EW. If LAEs at z > 6 have similarly small {Delta}v {sub Ly{alpha}} values, constraints on the reionization history derived from the Ly{alpha} transmissivity may need to be revised.

  12. Gating at the mouth of the acetylcholine receptor channel: energetic consequences of mutations in the alphaM2-cap.

    Directory of Open Access Journals (Sweden)

    Pallavi A Bafna

    2008-06-01

    Full Text Available Gating of nicotinic acetylcholine receptors from a C(losed to an O(pen conformation is the initial event in the postsynaptic signaling cascade at the vertebrate nerve-muscle junction. Studies of receptor structure and function show that many residues in this large, five-subunit membrane protein contribute to the energy difference between C and O. Of special interest are amino acids located at the two transmitter binding sites and in the narrow region of the channel, where CO gating motions generate a lowhigh change in the affinity for agonists and in the ionic conductance, respectively. We have measured the energy changes and relative timing of gating movements for residues that lie between these two locations, in the C-terminus of the pore-lining M2 helix of the alpha subunit ('alphaM2-cap'. This region contains a binding site for non-competitive inhibitors and a charged ring that influences the conductance of the open pore. alphaM2-cap mutations have large effects on gating but much smaller effects on agonist binding, channel conductance, channel block and desensitization. Three alphaM2-cap residues (alphaI260, alphaP265 and alphaS268 appear to move at the outset of channel-opening, about at the same time as those at the transmitter binding site. The results suggest that the alphaM2-cap changes its secondary structure to link gating motions in the extracellular domain with those in the channel that regulate ionic conductance.

  13. Selective alpha autoradiography for monitoring thorium distribution in UO2-ThO2 fuel pellets

    International Nuclear Information System (INIS)

    Shriwastwa, B.B.; Raghunath, B.; Ghosh, J.K.

    1992-01-01

    Although natural uranium and thorium decay with similar alpha energies (4.20 and 3.98 MeV), their daughter products have different alpha characteristics. This has been exploited for selective alpha autoradiography for thoria in urania-thoria mixed nuclear fuel pellets. Difficulties in getting sufficient track density in alpha sensitive films due to the very low specific activity of natural uranium and thorium material were overcome by using a special film with annealing and pre-etching treatment. (orig./HP) [de

  14. Alpha-gamma pulse shape discrimination in CsI:Tl, CsI:Na and BaF sub 2 scintillators

    CERN Document Server

    Dinca, L E; Haas, J; Bom, V R; Eijk, C W E

    2002-01-01

    Some scintillating materials offer the possibility of measuring well separated alpha and gamma scintillation response using a single crystal. Eventually aiming at thermal neutron detection using sup 6 Li or sup 1 sup 0 B admixture, pulse shape discrimination measurements were made on three scintillators: CsI:Tl, CsI:Na and pure BaF sub 2 crystals. A very good alpha/gamma discrimination was obtained using sup 2 sup 2 Na, sup 2 sup 4 sup 1 Am (gamma) and sup 2 sup 4 sup 4 Cm (alpha) radioactive sources.

  15. Prostaglandin E1 and prostaglandin F2 alpha in exudate in nickel allergy

    DEFF Research Database (Denmark)

    Lerche, A; Bisgaard, H; Kassis, V

    1989-01-01

    Ten nickel-allergic patients and 5 healthy control subjects participated in a study of the kinetics of the flux and concentration of migrated leukocytes and extracellular PGE1 and PGF2 alpha during a 48 h period, using a skin chamber technique. The patients were provided with two skin chambers, one...... with and one without nickel challenge. A higher flux of leukocytes, PGE1 and PGF2 alpha was observed during the second day of allergen exposure, while the concentrations probably due to dilution were unchanged or diminished, indicating an unspecific role of the prostaglandins during the contact allergic...

  16. Ultrastructural studies of human and rabbit alpha-M-globulins.

    Science.gov (United States)

    Bloth, B; Chesebro, B; Svehag, S E

    1968-04-01

    Electron micrographs of isolated human alpha(2)M-molecules, obtained by the negative contrast technique, revealed morphologically homogenous structures resembling a graceful monogram of the two letters H and I. The modal values for the length and width of the alpha(2)M particles were 170 A and 100 A, respectively. Purified rabbit alphamacroglobulins contained about 80% alpha(1)M- and 20% alpha(2)M-globulins. The isolated rabbit alpha(1)M- and alpha(2)M-molecules were morphologically indistinguishable from one another and from human alpha(2)M-molecules. Preliminary immunoprecipitation studies demonstrated that the two rabbit alphaM-globulins were antigenically different. Sedimentation constant determinations gave s(20, w) values of 18.8 and 18.2 for rabbit alpha(1)M and alpha(2)M, respectively.

  17. Isolation and characterization of a monoclonal anti CK-2 alpha subunit antibody of the IgG1 subclass

    DEFF Research Database (Denmark)

    Schmidt-Spaniol, I; Boldyreff, B; Issinger, O G

    1992-01-01

    A monoclonal antibody was produced against the recombinant human alpha subunit of CK-2. The antibody was of the IgG1 subclass and it was isolated from serum-free cell culture media and purified by affinity chromatography on Protein G Sepharose. The antibody can be used to detect specifically the CK......-2 alpha subunit in immunoblots from tissue extracts. An ELISA detection test was also established which also allows the identification of the CK-2 alpha subunit....

  18. Co-{alpha}Al{sub 2}O{sub 3}-Cu as shaped catalyst in NaBH{sub 4} hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Chamoun, R. [Universite Lyon 1, CNRS, UMR 5615, Laboratoire des Multimateriaux et Interfaces, 43 boulevard du 11 Novembre 1918, F-69622 Villeurbanne (France); Universite Libanaise, Faculte des Sciences II, Laboratoire de physique appliquee, 90656 Jdeidet El Metn (Lebanon); Demirci, U.B.; Miele, P. [Universite Lyon 1, CNRS, UMR 5615, Laboratoire des Multimateriaux et Interfaces, 43 boulevard du 11 Novembre 1918, F-69622 Villeurbanne (France); Zaatar, Y.; Khoury, A. [Universite Libanaise, Faculte des Sciences II, Laboratoire de physique appliquee, 90656 Jdeidet El Metn (Lebanon)

    2010-07-15

    A study about catalytic films of Co-supported-over-{alpha}Al{sub 2}O{sub 3} fabricated by electrophoretic deposition (EPD) is reported, the as-prepared shaped catalysts being intended to catalyze NaBH{sub 4} hydrolysis. Co-{alpha}Al{sub 2}O{sub 3} supported over Cu substrate can be prepared by a 2-step route: (i) preparation of the supported catalyst Co-{alpha}Al{sub 2}O{sub 3} (in powder form) by wet impregnation of CoCl{sub 2} over {alpha}Al{sub 2}O{sub 3}, followed by a reduction, and (ii) fabrication of Co-{alpha}Al{sub 2}O{sub 3}-Cu (thin film over Cu) by EPD. Both types of catalysts, whatever their form, are highly efficient in hydrolyzing NaBH{sub 4}, conversions of 100% and HGRs of tens of mL(H{sub 2}) min{sup -1} being achieved at 60-80 C. The Co-{alpha}Al{sub 2}O{sub 3}-Cu catalysts are even more reactive than the Co-{alpha}Al{sub 2}O{sub 3} catalysts because the surface of the former materials becomes much more acid than that of the latter ones in the course of the EPD process. The respective rate laws and reaction kinetics have been determined. Independently on the catalyst form, apparent activation energies of about 52 kJ mol{sup -1} and positive reaction orders versus the initial NaBH{sub 4} concentration (i.e. 0.3-0.7) were calculated, suggesting that the EPD does not affect the reaction mechanisms. Besides, it is showed that the hydrolysis is really catalytic as well as typical of a heterogeneous process. For example, an apparent reaction order versus the Co content of 0.9 was calculated. All of these results among others are reported and discussed in the present article. (author)

  19. Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI as biomarkers of recovery.

    Directory of Open Access Journals (Sweden)

    Valentina Peta

    Full Text Available There is a clear need for better biomarkers of drug-induced-liver-injury (DILI.We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI.We analyzed cases and controls included in the IMI-SAFE-T-DILI European project, from which serum samples had been stored in a dedicated biobank. The analyses of ActiTest and FibroTest had been prospectively scheduled. The primary objective was to analyze the performance (AUROC of ActiTest components as predictors of recovery outcome defined as an ALT <2x the upper limit of normal (ULN, and BILI <2x ULN.After adjudication, 154 patients were considered to have DILI and 22 were considered to have acute liver injury without DILI. A multivariate regression analysis (ActiTest-DILI patent pending combining the ActiTest components without BILI and ALT (used as references, apolipoprotein-A1, haptoglobin, alpha-2-macroglobulin and GGT, age and gender, resulted in a significant prediction of recovery with 67.0% accuracy (77/115 and an AUROC of 0.724 (P<0.001 vs. no prediction 0.500. Repeated apolipoprotein-A1 and haptoglobin remained significantly higher in the DILI cases that recovered (n = 65 versus those that did not (n = 16, at inclusion, at 4-8 weeks and at 8-12 weeks. The same results were observed after stratification on APAP cases and non-APAP cases.We identified that apolipoprotein-A1 and haptoglobin had significant predictive values for the prediction of recovery at 12 weeks in DILI, enabling the construction of a new prognostic panel, the DILI-ActiTest, which needs to be independently validated.

  20. Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2alpha phosphorylation.

    Science.gov (United States)

    Mazroui, Rachid; Sukarieh, Rami; Bordeleau, Marie-Eve; Kaufman, Randal J; Northcote, Peter; Tanaka, Junichi; Gallouzi, Imed; Pelletier, Jerry

    2006-10-01

    Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2alpha phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2alpha phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2alpha to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2alpha phosphorylation-dependent and -independent pathways that target translation initiation.

  1. TFTR alpha extraction and measurement: Development and testing of advanced alpha detectors: Final report

    International Nuclear Information System (INIS)

    Wehring, B.W.

    1988-01-01

    Advanced alpha-particle detectors made of heavy elements were investigated as alternatives to silicon surface-barrier detectors for the ''foil-neutralization technique'' of alpha-particle diagnostics in fusion reactors with high neutron backgrounds. From an extensive literature review, it was decided that HgI 2 would make a more suitable detector for alpha-particle diagnostics than other heavy element detectors such as CdTe. Thus, HgI 2 detectors were designed and fabricated. Experimental tests were performed to determine detector characteristics and detector responses to alpha particles. Radiation noise measurements were also performed using the North Carolina State University PULSTAR nuclear reactor for both the HgI 2 detectors and commercial Si(Au) surface barrier detectors. 15 refs., 1 fig

  2. Alpha-amino acid derivatives and alpha-fluoro ketones by enantioselective decarboxylation

    OpenAIRE

    Baur, Markus A.

    2003-01-01

    Die Methode der enantioselektiven Decarboxylierung wurde angewendet, um Enantiomeren-angereicherte alpha-Aminosäurederivate und alpha-Fluorketone zu erhalten. Als Substrate wurden 2-N-Acetylamino-2-alkylmalonsäuremonoethylester beziehungsweise beta-Keto-benzylester verwendet. China-Alkaloide und Derivate davon wurden als Katalysatoren eingesetzt. Die besten erhaltenen Ergebnisse waren N-Acetyl-L-phenylalaninethylester mit 70% Enantiomerenüberschuß unter Verwendung der katalytisch aktiven Base...

  3. Cytosolic phospholipase A2 alpha amplifies early cyclooxygenase-2 expression, oxidative stress and MAP kinase phosphorylation after cerebral ischemia in mice

    Directory of Open Access Journals (Sweden)

    Koehler Raymond C

    2010-07-01

    Full Text Available Abstract Background The enzyme cytosolic phospholipase A2 alpha (cPLA2α has been implicated in the progression of cerebral injury following ischemia and reperfusion. Previous studies in rodents suggest that cPLA2α enhances delayed injury extension and disruption of the blood brain barrier many hours after reperfusion. In this study we investigated the role of cPLA2α in early ischemic cerebral injury. Methods Middle cerebral artery occlusion (MCAO was performed on cPLA2α+/+ and cPLA2α-/- mice for 2 hours followed by 0, 2, or 6 hours of reperfusion. The levels of cPLA2α, cyclooxygenase-2, neuronal morphology and reactive oxygen species in the ischemic and contralateral hemispheres were evaluated by light and fluorescent microscopy. PGE2 content was compared between genotypes and hemispheres after MCAO and MCAO and 6 hours reperfusion. Regional cerebral blood flow was measured during MCAO and phosphorylation of relevant MAPKs in brain protein homogenates was measured by Western analysis after 6 hours of reperfusion. Results Neuronal cPLA2α protein increased by 2-fold immediately after MCAO and returned to pre-MCAO levels after 2 hours reperfusion. Neuronal cyclooxygenase-2 induction and PGE2 concentration were greater in cPLA2α+/+ compared to cPLA2α-/- ischemic cortex. Neuronal swelling in ischemic regions was significantly greater in the cPLA2α+/+ than in cPLA2α-/- brains (+/+: 2.2 ± 0.3 fold vs. -/-: 1.7 ± 0.4 fold increase; P 2α+/+ ischemic core than in cPLA2α-/- (+/+: 7.12 ± 1.2 fold vs. -/-: 3.1 ± 1.4 fold; P 2α+/+, but not cPLA2α-/-, had disruption of neuron morphology and decreased PGE2 content. Phosphorylation of the MAPKs-p38, ERK 1/2, and MEK 1/2-was significantly greater in cPLA2a+/+ than in cPLA2α-/- ischemic cortex 6 hours after reperfusion. Conclusions These results indicate that cPLA2α modulates the earliest molecular and injury responses after cerebral ischemia and have implications for the potential clinical

  4. KECK SPECTROSCOPY OF LYMAN-BREAK GALAXIES AND ITS IMPLICATIONS FOR THE UV-CONTINUUM AND Ly{alpha} LUMINOSITY FUNCTIONS AT z > 6

    Energy Technology Data Exchange (ETDEWEB)

    Jiang Linhua; Egami, Eiichi; Walth, Gregory [Steward Observatory, University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721 (United States); Kashikawa, Nobunari [Optical and Infrared Astronomy Division, National Astronomical Observatory, Mitaka, Tokyo 181-8588 (Japan); Matsuda, Yuichi [Department of Physics, Durham University, South Road, Durham DH1 3LE (United Kingdom); Shimasaku, Kazuhiro [Department of Astronomy, University of Tokyo, Hongo, Tokyo 113-0033 (Japan); Nagao, Tohru [Research Center for Space and Cosmic Evolution, Ehime University, Bunkyo-cho, Matsuyama 790-8577 (Japan); Ota, Kazuaki [Department of Astronomy, Kyoto University, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Ouchi, Masami [Institute for Cosmic Ray Research, University of Tokyo, 5-1-5 Kashiwa-no-Ha, Kashiwa City, Chiba 77-8582 (Japan)

    2011-12-10

    We present Keck spectroscopic observations of z > 6 Lyman-break galaxy (LBG) candidates in the Subaru Deep Field (SDF). The candidates were selected as i'-dropout objects down to z' = 27 AB magnitudes from an ultra-deep SDF z'-band image. With the Keck spectroscopy we identified 19 LBGs with prominent Ly{alpha} emission lines at 6 {<=} z {<=} 6.4. The median value of the Ly{alpha} rest-frame equivalent widths (EWs) is {approx}50 A, with four EWs >100 A. This well-defined spectroscopic sample spans a UV-continuum luminosity range of -21.8 {<=} M{sub UV} {<=} -19.5 (0.6 {approx} 5 L*{sub UV}) and a Ly{alpha} luminosity range of (0.3-3) Multiplication-Sign 10{sup 43} erg s{sup -1} (0.3-3 L*{sub Ly{alpha}}). We derive the UV and Ly{alpha} luminosity functions (LFs) from our sample at (z) {approx} 6.2 after we correct for sample incompleteness. We find that our measurement of the UV LF is consistent with the results of previous studies based on photometric LBG samples at 5 < z < 7. Our Ly{alpha} LF is also generally in agreement with the results of Ly{alpha}-emitter surveys at z {approx} 5.7 and 6.6. This study shows that deep spectroscopic observations of LBGs can provide unique constraints on both the UV and Ly{alpha} LFs at z > 6.

  5. Targeted Alpha Therapy: From Alpha to Omega

    International Nuclear Information System (INIS)

    Allen, Barry J; Clarke, Raymond; Huang Chenyu

    2013-01-01

    This review covers the broad spectrum of Targeted Alpha Therapy (TAT) research in Australia; from in vitro and in vivo studies to clinical trials. The principle of tumour anti-vascular alpha therapy (TAVAT) is discussed in terms of its validation by Monte Carlo calculations of vascular models and the potential role of biological dosimetry is examined. Summmary of this review is as follows: 1. The essence of TAT 2. Therapeutic objectives 3. TAVAT and Monte Carlo microdosimetry 4. Biological dosimetry 5. Preclinical studies 6. Clinical trials 7. What next? 8. Obstacles. (author)

  6. Radiolytic oxidation of UO{sub 2} pellets doped with alpha-emitters ({sup 238/239}Pu)

    Energy Technology Data Exchange (ETDEWEB)

    Muzeau, B. [Commissariat a l' Energie Atomique, Rhone Valley Research Center DTCD/SECM/LMPA, BP 17 171, 30207 Bagnols-sur-Ceze Cedex (France); Jegou, C. [Commissariat a l' Energie Atomique, Rhone Valley Research Center DTCD/SECM/LMPA, BP 17 171, 30207 Bagnols-sur-Ceze Cedex (France)], E-mail: christophe.jegou@cea.fr; Delaunay, F. [Commissariat a l' Energie Atomique, Valduc Research Center, 21120 Is-sur-Tille (France); Broudic, V. [Commissariat a l' Energie Atomique, Rhone Valley Research Center DTCD/SECM/LMPA, BP 17 171, 30207 Bagnols-sur-Ceze Cedex (France); Brevet, A. [Commissariat a l' Energie Atomique, Valduc Research Center, 21120 Is-sur-Tille (France); Catalette, H. [Electricite de France, Les Renardieres Research Center, Route de Sens Ecuelles, 77250 Moret-sur-Loing (France); Simoni, E. [Institut de Physique Nucleaire, Bat. 100, 91406 Orsay Cedex (France); Corbel, C. [Laboratoire des Solides Irradies, UMR 7642-CNRS-CEA-Ecole Polytechnique, Ecole Polytechnique, 91128 Palaiseau Cedex (France)

    2009-01-07

    To assess the impact of alpha radiolysis of water on the oxidative dissolution of UO{sub 2} under anoxic conditions, two series of plutonium-doped samples (specific alpha activity 385 and 18 MBqg{sub UO{sub 2}}{sup -1}) were fabricated, characterized and leached in water of varying complexity (pure water, carbonated water, dissolved hydrogen). Given the very high reactivity of these samples in the presence of air and in order to minimize any prior surface oxidation, a strict experimental protocol was developed based on high-temperature annealing in Ar + 4% H{sub 2} with preleaching cycles. Failure to follow this protocol prevents absolute quantification of oxidation of the UO{sub 2} surface by water radiolysis in solutions. Preoxidation of the pellet surface can lead to uranium release in solution that is dependent on the alpha particle flux, revealing initial oxidation by radiolysis in air including potential traces of water. This makes difficult the accurate quantification of the radiolytic oxidation in water solutions. Controlling the initial surface condition of the samples finally allowed us to demonstrate that radiolytic oxidation in water-saturated media is governed by several threshold effects for which the main parameters are the sample alpha activity and the hydrogen concentration.

  7. In vitro study of alpha 2-adrenoceptor turnover and metabolism using the adenocarcinoma cell line HT29

    International Nuclear Information System (INIS)

    Paris, H.; Taouis, M.; Galitzky, J.

    1987-01-01

    The biosynthesis rate of the receptor was studied in postconfluent HT29 cells, when its density expressed as fmol/mg of cell membrane protein is constant, by following the recovery of the receptor binding capacity after blockade with the non-reversible alpha-adrenergic antagonist benextramine. Study of the inhibition of [ 3 H]yohimbine and [ 3 H]UK-14,304 binding showed that benextramine was a more potent antagonist at alpha 2-adrenoceptor than phenoxybenzamine. The incubation of intact HT29 cells for 30 min in the presence of 10(-5) M benextramine irreversibly blocked more than 95% of the alpha 2-adrenoceptors and totally suppressed the inhibitory effect of UK-14,304 on cyclic AMP production. The blockade appeared specific, since benextramine effects were prevented by alpha 2-adrenergic agents. Moreover, neither vasoactive intestinal polypeptide responsiveness nor other tested aspects of the regulation of the adenylate cyclase was altered by the treatment. Study of the time course of receptor recovery after irreversible blockade indicated that alpha 2-adrenoceptors reappeared in the cells with a monoexponential kinetic. The linearization of the repopulation curve obtained with the labeled antagonist [ 3 H]yohimbine allowed the determination of the rate constant for receptor degradation (k = 0.0268 +/- 0.0025 hr-1) and the rate of receptor synthesis (6.91 +/- 0.64 fmol/mg of cell membrane protein/hr) corresponding to the synthesis of about 500 receptors/cell/hr. The alpha 2-adrenoceptor half-life was 26 +/- 3 hr. Measurement of the biological effects associated to the alpha-adrenoceptor stimulation during the course of receptor recovery indicated a relationship between the number of cell receptors and the percentage of inhibition of the cyclic AMP accumulation induced by forskolin

  8. Facile synthesis and characterization of ZnFe{sub 2}O{sub 4}/{alpha}-Fe{sub 2}O{sub 3} composite hollow nanospheres

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Yu [Key Laboratory of Industrial Ecology and Environmental Engineering and State Key Laboratory of Fine Chemical, School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024 (China); School of Environmental and Chemical Engineering, Dalian Jiaotong University, Dalian 116028 (China); Li, Xinyong, E-mail: xyli@dlut.edu.cn [Key Laboratory of Industrial Ecology and Environmental Engineering and State Key Laboratory of Fine Chemical, School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024 (China); Department of Chemical Engineering, Curtin University, Perth, WA 6845 (Australia); Zhao, Qidong; Hou, Yang [Key Laboratory of Industrial Ecology and Environmental Engineering and State Key Laboratory of Fine Chemical, School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024 (China); Tade, Moses [Department of Chemical Engineering, Curtin University, Perth, WA 6845 (Australia); Liu, Shaomin, E-mail: Shaomin.Liu@curtin.edu.au [Department of Chemical Engineering, Curtin University, Perth, WA 6845 (Australia)

    2011-12-15

    Highlights: Black-Right-Pointing-Pointer ZnFe{sub 2}O{sub 4}/{alpha}-Fe{sub 2}O{sub 3} composite hollow nanospheres were successfully synthesized via a facile method. Black-Right-Pointing-Pointer Detailed structural, morphology and the phase composition were studied. Black-Right-Pointing-Pointer The incorporation of ZnFe{sub 2}O{sub 4} and {alpha}-Fe{sub 2}O{sub 3} gives an appropriate band gap value to utilize solar energy. -- Abstract: ZnFe{sub 2}O{sub 4}/{alpha}-Fe{sub 2}O{sub 3} composite hollow nanospheres were successfully fabricated via a facile one-pot solvothermal method, utilizing polyethylene glycol as soft template. X-ray diffraction and scanning electron microscopy analysis revealed that the prepared nanospheres with cubic spinel and rhombohedra composite structure had a uniform diameter of about 370 nm, and the hollow structure could be further confirmed by transmission electron microscopy. Energy dispersive X-ray, X-ray photoelectron spectroscopy and Fourier transform infrared techniques were also applied to characterize the elemental composition and chemical bonds in the hollow nanospheres. The ZnFe{sub 2}O{sub 4}/{alpha}-Fe{sub 2}O{sub 3} composite hollow nanospheres show attractive light absorption property for potential applications in electronics, optics, and catalysis.

  9. In vitro cytotoxicity of human recombinant tumor necrosis factor alpha in association with radiotherapy in a human ovarian carcinoma cell line

    International Nuclear Information System (INIS)

    Manetta, A.; Lucci, J.; Soopikian, J.; Granger, G.; Berman, M.L.; DiSaia, P.J.

    1990-01-01

    It has been speculated that tumor necrosis factor alpha (TNF-alpha) may decrease the cytotoxicity of radiotherapy by increasing the scavenging of toxic superoxide radicals. Because of the possible clinical implications, the cytotoxicity of TNF-alpha in combination with radiotherapy (RT) was compared with that of RT alone in a human ovarian cancer cell line. NIH:OVCAR-3 cells were incubated with TNF-alpha at 10.0, 1.0, 0.1, and 0.01 microgram/ml. Plates were divided into two groups; one received 150 cGy of radiotherapy and the other received no further therapy. Seventy-two hours later, supernatants were aspirated and viable cells were stained with a 1% solution of crystal violet. Survival of cells treated with RT plus TNF-alpha was expressed as a percentage of surviving irradiated controls. Analysis of results revealed minimal additive cell killing effect between TNF-alpha and radiotherapy at all concentrations of tumor necrosis factor, with the greatest difference noted in the group treated with 10 micrograms/ml TNF-alpha. A continued radiotherapy dose-response study with TNF-alpha showed a similar additive, not radioprotective, effect. This may have implication as a potentiator of RT in some human tumors

  10. Transformation of mouse embryo (C3H 10T1/2) cells by alpha particles

    International Nuclear Information System (INIS)

    Lloyd, E.L.; Gemmell, A.; Henning, C.B.; Gemmell, D.S.; Zabransky, B.J.

    1977-01-01

    Mammalian cells in culture (C3H mouse 10T1/2 cells) have been shown here for the first time to be transformed by alpha irradiation when cells were irradiated with 5.6 MeV alpha particles from a Tandem Van de Graaff machine. Malignant tumors were induced following inoculation of the transformed cells into syngeneic hosts. Unirradiated control cells injected at the same concentration have, so far, failed to produce tumors. The morphology of the transformed foci was remarkably similar to that obtained by x rays and chemicals but different from virally transformed cells. When the cells were seeded at low density in the exponential growth phase, the transformation frequency per surviving cell increased approximately as the cube of the dose and peaked at an alpha particle fluence between 1.5 and 2.5 x 10 7 alpha particles per cm 2 (205 to 342 rads). The frequency of the transformation was found to be greatly dependent on the number of cells per dish irradiated. Irradiation of larger numbers resulted in much lower frequencies of transformation. The maximum transformation frequency observed in nine separate experiments was 4 percent of the surviving cells. At doses greater than 200 rads the transformation frequency per surviving cell remained constant. The present results permit us to conclude that alpha irradiation may, indeed, be able to exert a direct effect on the genome of the cell to produce malignancy without any external immunological or hormonal influences

  11. Absorption and transport of deuterium-substituted 2R,4'R,8'R-alpha-tocopherol in human lipoproteins

    International Nuclear Information System (INIS)

    Traber, M.G.; Ingold, K.U.; Burton, G.W.; Kayden, H.J.

    1988-01-01

    Oral administration of a single dose of tri- or hexadeuterium substituted 2R,4'R,8'R-alpha-tocopheryl acetate (d3- or d6-alpha-T-Ac) to humans was used to follow the absorption and transport of vitamin E in plasma lipoproteins. Three hr after oral administration of d3-alpha-T-Ac (15 mg) to 2 subjects, plasma levels of d3-alpha-T were detectable; these increased up to 10 hr, reached a plateau at 24 hr, then decreased. Following administration of d6-alpha-T-Ac (15-16 mg) to 2 subjects, the percentage of deuterated tocopherol relative to the total tocopherol in chylomicrons increased more rapidly than the corresponding percentage in whole plasma. Chylomicrons and plasma lipoproteins were isolated from 2 additional subjects following administration of d3-alpha-T-Ac (140 or 60 mg). The percentage of deuterated tocopherol relative to the total tocopherol increased most rapidly in chylomicrons, then in very low density lipoproteins (VLDL), followed by essentially identical increases in low and high density lipoproteins (LDL and HDL, respectively) and lastly, in the red blood cells. This pattern of appearance of deuterated tocopherol is consistent with the concept that newly absorbed vitamin E is secreted by the intestine into chylomicrons; subsequently, chylomicron remnants are taken up by the liver from which the vitamin E is secreted in VLDL. The metabolism of VLDL in the circulation results in the simultaneous delivery of vitamin E into LDL and HDL

  12. Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

    DEFF Research Database (Denmark)

    Larsen, Thomas Stauffer; Bjerrum, O W; Pallisgaard, N

    2008-01-01

    Quantitative assessment of the JAK2 V617F allele burden during disease evolution and ongoing myelosuppressive treatment is likely to be implemented in the future clinical setting. Interferon alpha has demonstrated efficacy in treatment of both chronic myeloid leukemia and the Philadelphia chromos...... with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response....

  13. A study of genetic markers in the South African Blesbok (Damaliscus Dorcas Phillipsi

    Directory of Open Access Journals (Sweden)

    D. R Osterhoff

    1972-12-01

    Full Text Available During culling operations on blesbok from the Rietvlei Nature Reserve, 198 blood samples were obtained for study of genetic markers including haemoglobins, transferrins, amylases, albumins and carbonic anhydrases. All animals exhibited the same pattern. Blood typing was performed by using goat reagents. These reagents could possibly be used to establish the relationship between the blesbok and the bontebok. Immunoelectrophoresis was used to detect any immunological differences; 123 blesbok samples were tested against antibovine serum prepared in rabbits. The animals could be grouped into four distinguishable types according to the shape and presence of the alpha-2-macroglobulin and the "horizontal55 band.

  14. Alpha Background Discrimination in the MAJORANA DEMONSTRATOR

    Science.gov (United States)

    Gruszko, Julieta; Majorana Collaboration

    2017-09-01

    The Majorana Demonstrator (MJD) searches for neutrinoless double-beta decay of 76Ge using arrays of high-purity germanium detectors. If observed, this process would have implications for grand-unification and the predominance of matter over antimatter in the universe. A problematic background in such large granular detector arrays is posed by alpha particles. In MJD, potential background events that are consistent with energy-degraded alphas originating on the passivated detector surface have been observed. We have studied these events by scanning the passivated surface of a P-type point contact detector like those used in MJD with a collimated alpha source. We observe that surface alpha events exhibit high charge-trapping, with a significant fraction of the trapped charge being re-released slowly. This leads to both a reduced prompt signal and a measurable change in slope of the tail of a recorded pulse. In this contribution we discuss the characteristics of these events and the filter developed to identify the occurrence of this delayed charge recovery, allowing for the efficient rejection of passivated surface alpha events while retaining 99.8% of bulk events. We also discuss the impact of this filter on the sensitivity of MJD. This material is based upon work supported by the U.S. DOE, Office of Science, Office of Nuclear Phys., the Particle Astrophys. and Nuclear Phys. Programs of the NSF, and SURF. Additional support from the NSFGRFP under Grant No. 1256082.

  15. Effect of dietary protein on the excretion of. cap alpha. /sub 2u/, the sex-dependent protein of the adult male rat

    Energy Technology Data Exchange (ETDEWEB)

    Neuhaus, O W; Flory, W

    1975-01-01

    Adult male rates were maintained on normal (20 percent casein), protein-free (0 percent casein), high protein (50 percent casein), deficient protein (20 percent zein), and a supplemented, deficient protein (20 percent zein plus L-lysine and L-tryptophan) diets. Rats on a protein-free diet excreted approximately 1 mg ..cap alpha../sub 2u//24 h compared with a normal of 10-15 mg/24 h. Depleted rats placed on the normal diet showed a rapid restoration of the normal ..cap alpha../sub 2u/ excretion as well as total urinary proteins. Accumulation of ..cap alpha../sub 2u/ in the blood serum was measured in nephrectomized rats. Rats on the protein free diet accumulated only 30 percent of the ..cap alpha../sub 2u/ compared to normals. On a 50 precent casein diet, rats excreted 30-50 mg ..cap alpha../sub 2u//24 h. However, the accumulation was normal in the serum of nephrectomized rats. A high protein diet did not stimulate ..cap alpha../sub 2u/ synthesis but probably increased the renal loss of all urinary proteins. The excretion of ..cap alpha../sub 2u/ on a zein diet was reduced to the same degree as with the protein-free diet. Supplementation with lysine and tryptophan restored the capacity to eliminate ..cap alpha../sub 2u/ to near normal levels. Accumulation of ..cap alpha../sub 2u/ in the serum of nephrectomized rats kept on the zein diets showed that the effect was to suppress the synthesis of the ..cap alpha../sub 2u/. Supplementation restored the biosynthesis of ..cap alpha../sub 2u/. It is concluded that the effect of dietary protein on the excretion of urinary proteins in the adult male rat is caused in a large part by an influence on the hepatic biosynthesis of ..cap alpha../sub 2u/. The biosynthesis of this protein, which represents approximately 30 percent of the total urinary proteins, is dependent on an adequate supply of dietary protein.

  16. Synthesis and evaluation of phytotoxic activity of {alpha}-Santonin derivatives; Sintese e avaliacao da atividade fitotoxica de derivados da {alpha}-Santonina

    Energy Technology Data Exchange (ETDEWEB)

    Alvarenga, Elson S.; Barbosa, Luiz C.A.; Saliba, William A.; Arantes, Francisco F.P.; Demuner, Antonio J. [Universidade Federal de Vicosa (UFV), MG (Brazil). Dept. de Quimica]. E-mail: elson@ufv.br; Silva, Antonio A. [Universidade Federal de Vicosa (UFV), MG (Brazil). Dept. de Fitotecnia

    2009-07-01

    Mixtures of {alpha}-Santonin and various solvents were irradiated by either high or low pressure mercury lamps. The photochemical reactions afforded lumisantonin (11) (76% in acetonitrile), (3 S,3a S,9{beta}S)-3,6,6-trimethyl-3,3a,4,5-tetrahydronafto[1,2-b]furan-2,7({eta}6,9{beta}{eta}) dione (12) (100% in acetonitrile), 10{alpha}-acetoxy-3-oxo-1,7{alpha}H{eta},6,11{alpha}a{eta}-guaia-4-en-6,12-oli= de (8) (26% in acetic acid), 10{alpha}-hydroxy-3-oxo-1,7{alpha}a{eta},6,11{alpha}{eta}-guaia-4-en-6,12-olid= e (10) (32%) and (E)-3-((3 S,3a S,7{alpha}S)-3-methyl-2-oxo-6-(propan-2-ylidene)hexahydrobenzofuran- 7 - (7{alpha}{eta})-ylidene)propanoic acid (9) (44%) (in water/ acetic acid 1:1, v/v). Lactone 12 was also prepared by irradiation of lumisantonin in diethyl ether. Lactones 8 and 10 were converted, respectively, into the 10 {alpha}-acetoxy-3{alpha}-hydroxy-1,7{alpha}H,6,11{alpha}H-guaia-4-en-6,12-olid= e (13) (87%) and 3a,10a-dihydroxy-1,7{alpha}H,6,11{alpha}H-guaia-4-en-6,12-olide (14) (75%) by sodium borohydride reduction. The effects of the compounds on the development of radicle of Sorghum bicolor and Cucumis sativus were evaluated. (author)

  17. Calculation of subLAMBDA sup 9 Be in an alpha-alpha-LAMBDA three-body model using the Faddeev equations

    CERN Document Server

    Oryu, S; Yamashita, H; Nakazawa, M; Kamada, H

    2000-01-01

    The hypernucleus subLAMBDA sup 9 Be is investigated in an alpha-alpha-LAMBDA three-body model using the Faddeev formalism. We use an alpha-alpha interaction in which the Pauli-forbidden states are correctly taken into account and we employ some phenomenological potentials between the alpha and LAMBDA particles. We obtained two bound states for J suppi = 1/2 sup + and 3/2 sup + , and three resonance states of (3/2) sub 1 sup - , (3/2) sub 2 sup - , (3/2) sub 3 sup -. We studied the properties of these states by calculating the components and the expectation values of the potential for each partial wave. It is found that a few channels dominate in the 1/2 sup + and 3/2 sup + states, so that the alpha-clusters or the sup 8 Be core are still alive in the nucleus. In a case were the two alpha particles are fixed on an axis the contour plots of the distribution of the LAMBDA particle are shown. With the assistence of these plots one can visually understand that some of them are shell-model-like states while others ...

  18. Effects of medicinal cake-separated moxibustion on plasma 6-keto-PGF1alpha and TXB2 contents in the rabbit of hyperlipemia.

    Science.gov (United States)

    Xiaorong, Chang; Jie, Yan; Zenghui, Yue; Jing, Shen; Yaping, Lin; Shouxiang, Yi; Xiangping, Cao

    2005-06-01

    Hyperlipemia rabbit models established with high cholesterol and fat diet were treated with direct moxibustion and medicinal cake-separated moxibustion. The post-treatment plasma 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) and thromboxane B2 (TXB2) contents were determined by radioimmunoassay. Results indicated that the plasma 6-keto-PGF1alpha content significantly increased, the TXB2 level decreased (P keto-PGF1alpha ratio also decreased (P 0.05), suggesting that both the medicinal cake-separated moxibustion and direct moxibustion can regulate the plasma 6-keto-PGF1alpha and TXB2 contents, and the TXB2/6-keto-PGF1alpha ratio with similar actions, and have a certain protective action on endothelial cells of the aorta in the rabbit of hyperlipemia.

  19. Platelet alpha 2-adrenergic receptors in major depressive disorder. Binding of tritiated clonidine before and after tricyclic antidepressant drug treatment

    International Nuclear Information System (INIS)

    Garcia-Sevilla, J.A.; Zis, A.P.; Hollingsworth, P.J.; Greden, J.F.; Smith, C.B.

    1981-01-01

    The specific binding of tritiated (3H)-clonidine, an alpha 2-adrenergic receptor agonist, to platelet membranes was measured in normal subjects and in patients with major depressive disorder. The number of platelet alpha 2-adrenergic receptors from the depressed group was significantly higher than that found in platelets obtained from the control population. Treatment with tricyclic antidepressant drugs led to significant decreases in the number of platelet alpha 2-adrenergic receptors. These results support the hypothesis that the depressive syndrome is related to an alpha 2-adrenergic receptor supersensitivity and that the clinical effectiveness of tricyclic antidepressant drugs is associated with a decrease in the number of these receptors

  20. Binding of benzo(a)pyrene and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo(a)pyrene to histones

    International Nuclear Information System (INIS)

    Sculley, T.B.; Zytkovicz, T.H.

    1983-01-01

    AKR-2B mouse embryo cells were incubated for 24 hr with [3H]benzo(a)pyrene, and the histones were isolated and analyzed using one- and two-dimensional gel electrophoresis and autoradiography. The results revealed that (a) histones H1, H2A, and H3 incorporated significant amounts of label whereas little or no label was associated with histones H2B and H4 and (b) electrophoresis of the histones in the Triton: acid: urea gel system caused labeled histones to have a slower migration than did the corresponding unlabeled histones. Additional studies such as incubation of (+/-)-7 beta,8 alpha-[3H]dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene with nuclei resulted in radioactive labeling of histones H1, H2A, H2B, and H3 and of high-mobility-group proteins HMG1 and HMG2. The low levels of label associated with histone H4 in the whole-cell and nuclear studies were further investigated by incubating isolated histones with (+/-)-7 beta,8 alpha-[3H]dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene. Under these conditions, negligible amounts of radioactivity were associated with H4, while significant labeling of H1, H2A, H2B, and H3 and other nuclear proteins was observed. The results suggest that factors other than the presence of suitable nucleophilic acceptor sites on the histones may be necessary for carcinogen binding

  1. Thermal degradation of {alpha}- and {beta}-PbO{sub 2} and its relationship to capacity loss

    Energy Technology Data Exchange (ETDEWEB)

    Fitas, R.; Zerroual, L.; Chelali, N.; Djellouli, B. [Univ. Ferhat ABBAS, Setif (Algeria). Inst. de Chimie Industrielle

    2000-01-01

    The thermal degradation of {alpha} and {beta} PbO{sub 2} and its relationship to capacity loss was studied using galvanostatic discharge and voltamperometry. The results clearly demonstrate the dramatic effect of the thermal treatment of the capacity of the PAM. The variation of proton diffusion with temperature was determined for both {alpha}- and {beta}-PbO{sub 2}. The two forms of PbO{sub 2} exhibit different behaviour with regard to water loss. (orig.)

  2. Cytosolic phospholipase A2-alpha expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours.

    LENUS (Irish Health Repository)

    Caiazza, F

    2012-02-01

    BACKGROUND: The eicosanoid signalling pathway promotes the progression of malignancies through the production of proliferative prostaglandins (PGs). Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) activity provides the substrate for cyclooxygenase-dependent PG release, and we have previously found that cPLA(2)alpha expression correlated with EGFR\\/HER2 over-expression in a small number of breast cancer cell lines. METHODS: The importance of differential cPLA(2)alpha activity in clinical breast cancer was established by relating the expression of cPLA(2)alpha in tissue samples from breast cancer patients, and two microarray-based gene expression datasets to different clinicopathological and therapeutic parameters. RESULTS: High cPLA(2)alpha mRNA expression correlated with clinical parameters of poor prognosis, which are characteristic of highly invasive tumours of the HER2-positive and basal-like subtype, including low oestrogen receptor expression and high EGFR expression. High cPLA(2)alpha expression decreased overall survival in patients with luminal cancers, and correlated with a reduced effect of tamoxifen treatment. The cPLA(2)alpha expression was an independent predictive parameter of poor response to endocrine therapy in the first 5 years of follow-up. CONCLUSION: This study shows a role of cPLA(2)alpha in luminal breast cancer progression, in which the enzyme could represent a novel therapeutic target and a predictive marker.

  3. Chorionic gonadotropin regulates the transcript level of VHL, p53, and HIF-2alpha in human granulosa lutein cells.

    Science.gov (United States)

    Herr, D; Keck, C; Tempfer, C; Pietrowski, Detlef

    2004-12-01

    The ovarian corpus luteum plays a critical role in reproduction being the primary source of circulating progesterone. After ovulation the corpus luteum is build by avascular granulosa lutein cells through rapid vascularization regulated by gonadotropic hormones. The present study was performed to investigate whether this process might be influenced by the human chorionic gonadotropin (hCG)-dependent expression of different tumor suppressor genes and hypoxia dependent transcription factors. RNA was isolated from cultured granulosa lutein cells, transcribed into cDNA, and the transcript level of following genes were determined: RB-1, VHL, NF-1, NF-2, Wt-1, p53, APC, and hypoxia inducible factor-1 (HIF-1), -2, and -3alpha. Additionally, the influence of hCG on the expression of VHL, p53, and HIf2alpha were investigated. We demonstrate that in human granulosa lutein cells the tumor suppressor genes RB-1, VHL, NF-1, NF-2, Wt-1, p53, and APC and the hypoxia dependent transcription factors HIF-1alpha, -2alpha, and -3alpha are expressed. In addition, we showed that hCG regulates the expression of p53, VHL, and HIF-2alpha. Our results indicate that hCG may determine the growth and development of the corpus luteum by mediating hypoxic and apoptotic pathways in human granulosa lutein cells. Copyright 2004 Wiley-Liss, Inc.

  4. Tracking cell surface GABAB receptors using an alpha-bungarotoxin tag.

    Science.gov (United States)

    Wilkins, Megan E; Li, Xinyan; Smart, Trevor G

    2008-12-12

    GABA(B) receptors mediate slow synaptic inhibition in the central nervous system and are important for synaptic plasticity as well as being implicated in disease. Located at pre- and postsynaptic sites, GABA(B) receptors will influence cell excitability, but their effectiveness in doing so will be dependent, in part, on their trafficking to, and stability on, the cell surface membrane. To examine the dynamic behavior of GABA(B) receptors in GIRK cells and neurons, we have devised a method that is based on tagging the receptor with the binding site components for the neurotoxin, alpha-bungarotoxin. By using the alpha-bungarotoxin binding site-tagged GABA(B) R1a subunit (R1a(BBS)), co-expressed with the R2 subunit, we can track receptor mobility using the small reporter, alpha-bungarotoxin-conjugated rhodamine. In this way, the rates of internalization and membrane insertion for these receptors could be measured with fixed and live cells. The results indicate that GABA(B) receptors rapidly turnover in the cell membrane, with the rate of internalization affected by the state of receptor activation. The bungarotoxin-based method of receptor-tagging seems ideally suited to follow the dynamic regulation of other G-protein-coupled receptors.

  5. Development of nano-sized {alpha}-Al{sub 2}O{sub 3}:C films for application in digital radiology

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Edna C., E-mail: edca@cdtn.b [Universidade Federal de Minas Gerais (DEN/UFMG), Belo Horizonte (Brazil). Dept. de Engenharia Nuclear; Fontainha, Crissia C. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte (Brazil). Dept. de Propedeutica Complemetar; Oliveira, Vitor H.; Ferraz, Wilmar B.; Faria, Luiz O. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2011-07-01

    Ceramic materials are widely used as sensors for ionizing radiation. In nuclear applications, the alpha-alumina doped with carbon ({alpha}-Al{sub 2}O{sub 3}:C) is the most widely ceramic used because of its excellent optically stimulated luminescence (OSL) and thermoluminescent (TL) properties applied to detection of ionizing radiation. Another application of OSL and TL materials are in Digital Radiography, with ceramic/polymeric film composites. Recently, Computed Radiography (CR) devices based on OSL materials are replacing the old conventional film radiography. In this study we investigate the thermoluminescence of nano-sized {alpha}-Al{sub 2}O{sub 3} samples doped with different percentages of carbon, sintered in reducing atmospheres at temperatures ranging from 1300 to 1750 deg C. The results indicate that the nano-sized {alpha}-Al{sub 2}O{sub 3}:C materials have a luminescent response that could be due to both OSL and RPL properties, but without application to radiation dosimetry. Moreover, the results indicate that micro-sized {alpha}-Al{sub 2}O{sub 3}:C, doped with 0.5% carbon, and nano-sized ones doped with 2% of carbon, present thermoluminescent signal around 30 to 100 times the TL output signal of commercial TLD-100, the most used TL dosimeter in the world. The results indicate that these ceramic nano-particles have great potential for use in Digital Radiography based on thermoluminescent film imaging, being able to provide image resolutions much higher than the micro-sized {alpha}-Al{sub 2}O{sub 3}:C, in view of their improved resolution provided by nano-particulates. (author)

  6. Chemokines, macrophage inflammatory protein-2 and stromal cell-derived factor-1{alpha}, suppress amyloid {beta}-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Raman, Dayanidhi; Milatovic, Snjezana-Zaja [Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States); Milatovic, Dejan [Department of Pediatrics/Pediatric Toxicology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States); Splittgerber, Ryan [Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States); Fan, Guo-Huang [Department of Neurobiology and Neurotoxicology, Meharry Medical College, Nashville, TN 37221 (United States); Richmond, Ann, E-mail: ann.richmond@vanderbilt.edu [VA Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States)

    2011-11-15

    Alzheimer's disease (AD) is characterized by a progressive cognitive decline and accumulation of neurotoxic oligomeric peptides amyloid-{beta} (A{beta}). Although the molecular events are not entirely known, it has become evident that inflammation, environmental and other risk factors may play a causal, disruptive and/or protective role in the development of AD. The present study investigated the ability of the chemokines, macrophage inflammatory protein-2 (MIP-2) and stromal cell-derived factor-1{alpha} (SDF-1{alpha}), the respective ligands for chemokine receptors CXCR2 and CXCR4, to suppress A{beta}-induced neurotoxicity in vitro and in vivo. Pretreatment with MIP-2 or SDF-1{alpha} significantly protected neurons from A{beta}-induced dendritic regression and apoptosis in vitro through activation of Akt, ERK1/2 and maintenance of metalloproteinase ADAM17 especially with SDF-1{alpha}. Intra-cerebroventricular (ICV) injection of A{beta} led to reduction in dendritic length and spine density of pyramidal neurons in the CA1 area of the hippocampus and increased oxidative damage 24 h following the exposure. The A{beta}-induced morphometric changes of neurons and increase in biomarkers of oxidative damage, F{sub 2}-isoprostanes, were significantly inhibited by pretreatment with the chemokines MIP-2 or SDF-1{alpha}. Additionally, MIP-2 or SDF-1{alpha} was able to suppress the aberrant mislocalization of p21-activated kinase (PAK), one of the proteins involved in the maintenance of dendritic spines. Furthermore, MIP-2 also protected neurons against A{beta} neurotoxicity in CXCR2-/- mice, potentially through observed up regulation of CXCR1 mRNA. Understanding the neuroprotective potential of chemokines is crucial in defining the role for their employment during the early stages of neurodegeneration. -- Research highlights: Black-Right-Pointing-Pointer Neuroprotective ability of the chemokines MIP2 and CXCL12 against A{beta} toxicity. Black-Right-Pointing-Pointer MIP

  7. Karyopherin alpha7 (KPNA7), a divergent member of the importin alpha family of nuclear import receptors.

    Science.gov (United States)

    Kelley, Joshua B; Talley, Ashley M; Spencer, Adam; Gioeli, Daniel; Paschal, Bryce M

    2010-08-11

    Classical nuclear localization signal (NLS) dependent nuclear import is carried out by a heterodimer of importin alpha and importin beta. NLS cargo is recognized by importin alpha, which is bound by importin beta. Importin beta mediates translocation of the complex through the central channel of the nuclear pore, and upon reaching the nucleus, RanGTP binding to importin beta triggers disassembly of the complex. To date, six importin alpha family members, encoded by separate genes, have been described in humans. We sequenced and characterized a seventh member of the importin alpha family of transport factors, karyopherin alpha 7 (KPNA7), which is most closely related to KPNA2. The domain of KPNA7 that binds Importin beta (IBB) is divergent, and shows stronger binding to importin beta than the IBB domains from of other importin alpha family members. With regard to NLS recognition, KPNA7 binds to the retinoblastoma (RB) NLS to a similar degree as KPNA2, but it fails to bind the SV40-NLS and the human nucleoplasmin (NPM) NLS. KPNA7 shows a predominantly nuclear distribution under steady state conditions, which contrasts with KPNA2 which is primarily cytoplasmic. KPNA7 is a novel importin alpha family member in humans that belongs to the importin alpha2 subfamily. KPNA7 shows different subcellular localization and NLS binding characteristics compared to other members of the importin alpha family. These properties suggest that KPNA7 could be specialized for interactions with select NLS-containing proteins, potentially impacting developmental regulation.

  8. Platelet factor XIII increases the fibrinolytic resistance of platelet-rich clots by accelerating the crosslinking of alpha 2-antiplasmin to fibrin

    Science.gov (United States)

    Reed, G. L.; Matsueda, G. R.; Haber, E.

    1992-01-01

    Platelet clots resist fibrinolysis by plasminogen activators. We hypothesized that platelet factor XIII may enhance the fibrinolytic resistance of platelet-rich clots by catalyzing the crosslinking of alpha 2-antiplasmin (alpha 2AP) to fibrin. Analysis of plasma clot structure by polyacrylamide gel electrophoresis and immunoblotting revealed accelerated alpha 2AP-fibrin crosslinking in platelet-rich compared with platelet-depleted plasma clots. A similar study of clots formed with purified fibrinogen (depleted of factor XIII activity), isolated platelets, and specific factor XIII inhibitors indicated that this accelerated crosslinking was due to the catalytic activity of platelet factor XIII. Moreover, when washed platelets were aggregated by thrombin, there was evidence of platelet factor XIII-mediated crosslinking between platelet alpha 2AP and platelet fibrin(ogen). Specific inhibition (by a monoclonal antibody) of the alpha 2AP associated with washed platelet aggregates accelerated the fibrinolysis of the platelet aggregate. Thus in platelet-rich plasma clots, and in thrombin-induced platelet aggregates, platelet factor XIII actively formed alpha 2AP-fibrin crosslinks, which appeared to enhance the resistance of platelet-rich clots to fibrinolysis.

  9. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres.

    Science.gov (United States)

    Lin, Jiandie; Wu, Hai; Tarr, Paul T; Zhang, Chen-Yu; Wu, Zhidan; Boss, Olivier; Michael, Laura F; Puigserver, Pere; Isotani, Eiji; Olson, Eric N; Lowell, Bradford B; Bassel-Duby, Rhonda; Spiegelman, Bruce M

    2002-08-15

    The biochemical basis for the regulation of fibre-type determination in skeletal muscle is not well understood. In addition to the expression of particular myofibrillar proteins, type I (slow-twitch) fibres are much higher in mitochondrial content and are more dependent on oxidative metabolism than type II (fast-twitch) fibres. We have previously identified a transcriptional co-activator, peroxisome-proliferator-activated receptor-gamma co-activator-1 (PGC-1 alpha), which is expressed in several tissues including brown fat and skeletal muscle, and that activates mitochondrial biogenesis and oxidative metabolism. We show here that PGC-1 alpha is expressed preferentially in muscle enriched in type I fibres. When PGC-1 alpha is expressed at physiological levels in transgenic mice driven by a muscle creatine kinase (MCK) promoter, a fibre type conversion is observed: muscles normally rich in type II fibres are redder and activate genes of mitochondrial oxidative metabolism. Notably, putative type II muscles from PGC-1 alpha transgenic mice also express proteins characteristic of type I fibres, such as troponin I (slow) and myoglobin, and show a much greater resistance to electrically stimulated fatigue. Using fibre-type-specific promoters, we show in cultured muscle cells that PGC-1 alpha activates transcription in cooperation with Mef2 proteins and serves as a target for calcineurin signalling, which has been implicated in slow fibre gene expression. These data indicate that PGC-1 alpha is a principal factor regulating muscle fibre type determination.

  10. Circulating Apolipoprotein A1, Haptoglobin and Α2 Macroglobulin ...

    African Journals Online (AJOL)

    α2-MG), Apolipoprotein A1 (Apo-1) and Haptoglobin (HP) as non-invasive index of the presence of cirrhosis in chronic hepatitis C patients in relation to the histopathological findings. Subjects and Methods: The study was carried out on 20 ...

  11. Randomized study on hydroxyurea alone versus hydroxyurea combined with low-dose interferon-alpha 2b for chronic myeloid leukemia

    NARCIS (Netherlands)

    Kluin-Nelemans, JC; Delannoy, A; Louwagie, A; Le Cessie, S; Hermans, J; van der Burgh, JF; Hagemeijer, AM; Van den Berghe, H

    1998-01-01

    Interferon-alpha (IFN-alpha) is considered the standard therapy for chronic myeloid leukemia (CML) patients not suitable for allogeneic stem cell transplantation. From 1987 through 1992, 195 patients in the Benelux with recent untreated CML were randomized between low-dose IFN-alpha 2b (3 MIU, 5

  12. Resolution of G(s)alpha and G(q)alpha/G(11)alpha proteins in membrane domains by two-dimensional electrophoresis: the effect of long-term agonist stimulation.

    Science.gov (United States)

    Matousek, P; Novotný, J; Svoboda, P

    2004-01-01

    Low-density membrane-domain fractions were prepared from S49 lymphoma cells and clone e2m11 of HEK293 cells expressing a large number of thyrotropin-releasing hormone receptor (TRH-R) and G(11)alpha by flotation on sucrose density gradients. The intact cell structure was broken by detergent-extraction, alkaline-treatment or drastic homogenization. Three types of low-density membranes were resolved by two-dimensional electrophoresis and analyzed for G(s)alpha (S49) or G(q)alpha/G11) (e2m11) content. Four individual immunoblot signals of Gsalpha protein were identified in S49 lymphoma cells indicating complete resolution of the long G(s)alpha L+/-ser and short G(s)alpha S+/-ser variants of G(s)alpha. All these were diminished by prolonged agonist (isoprenaline) stimulation. In e2m11-HEK cells, five different immunoblot signals were detected indicating post-translational modification of G proteins of G(q)alpha/G(11)alpha family. The two major spots corresponding to exogenously (over)expressed G(11)alpha and endogenous G(q)alpha were reduced; the minor spots diminished by hormonal stimulation. Parallel analysis by silver staining of the total protein content indicated that no major changes in protein composition occurred under these conditions. Our data thus indicate that agonist-stimulation of target cells results in down-regulation of all different members of G(s) and G(q)/G(11) families. This agonist-specific effect may be demonstrated in crude membrane as well as domain/raft preparations and it is not accompanied by changes in overall protein composition.

  13. Studies of alpha-helicity and intersegmental interactions in voltage-gated Na+ channels: S2D4.

    Directory of Open Access Journals (Sweden)

    Zhongming Ma

    2009-11-01

    Full Text Available Much data, including crystallographic, support structural models of sodium and potassium channels consisting of S1-S4 transmembrane segments (the "voltage-sensing domain" clustered around a central pore-forming region (S5-S6 segments and the intervening loop. Voltage gated sodium channels have four non-identical domains which differentiates them from the homotetrameric potassium channels that form the basis for current structural models. Since potassium and sodium channels also exhibit many different functional characteristics and the fourth domain (D4 of sodium channels differs in function from other domains (D1-D3, we have explored its structure in order to determine whether segments in D4 of sodium channels differ significantly from that determined for potassium channels. We have probed the secondary and tertiary structure and the role of the individual amino acid residues of the S2D4 of Na(v1.4 by employing cysteine-scanning mutagenesis (with tryptophan and glutamine substituted for native cysteine. A Fourier transform power spectrum of perturbations in free energy of steady-state inactivation gating (using midpoint potentials and slopes of Boltzmann equation fits of channel availability, h(infinity-V plots indicates a substantial amount of alpha-helical structure in S2D4 (peak at 106 degrees, alpha-Periodicity Index (alpha-PI of 3.10, This conclusion is supported by alpha-PI values of 3.28 and 2.84 for the perturbations in rate constants of entry into (beta and exit from (alpha fast inactivation at 0 mV for mutant channels relative to WT channels assuming a simple two-state model for transition from the open to inactivated state. The results of cysteine substitution at the two most sensitive sites of the S2D4 alpha-helix (N1382 and E1392C support the existence of electrostatic network interactions between S2 and other transmembrane segments within Na(v1.4D4 similar to but not identical to those proposed for K+ channels.

  14. Point mutations in the post-M2 region of human alpha-ENaC regulate cation selectivity.

    Science.gov (United States)

    Ji, H L; Parker, S; Langloh, A L; Fuller, C M; Benos, D J

    2001-07-01

    We tested the hypothesis that an arginine-rich region immediately following the second transmembrane domain may constitute part of the inner mouth of the epithelial Na+ channel (ENaC) pore and, hence, influence conduction and/or selectivity properties of the channel by expressing double point mutants in Xenopus oocytes. Double point mutations of arginines in this post-M2 region of the human alpha-ENaC (alpha-hENaC) led to a decrease and increase in the macroscopic conductance of alphaR586E,R587Ebetagamma- and alphaR589E,R591Ebetagamma-hENaC, respectively, but had no effect on the single-channel conductance of either double point mutant. However, the apparent equilibrium dissociation constant for Na+ was decreased for both alphaR586E,R587Ebetagamma- and alphaR589E,R591Ebetagamma-hENaC, and the maximum amiloride-sensitive Na+ current was decreased for alphaR586E,R587Ebetagamma-hENaC and increased for alphaR589E,R591Ebetagamma-hENaC. The relative permeabilities of Li+ and K+ vs. Na+ were increased 11.25- to 27.57-fold for alphaR586E,R587Ebetagamma-hENaC compared with wild type. The relative ion permeability of these double mutants and wild-type ENaC was inversely related to the crystal diameter of the permeant ions. Thus the region of positive charge is important for the ion permeation properties of the channel and may form part of the pore itself.

  15. Main metabolites of 1-(2-chloroethyl)-3-[1'-(5'-p-nitrobenzoyl-2',3'-isopropylidene)-alpha, beta-D-ribofuranosyl]-1-nitrosourea and 1-(2-chloroethyl)-3-(2',3', 4'-tri-O-acetyl-alpha, beta-D-ribopyranosyl)-1-nitrosourea in rats

    International Nuclear Information System (INIS)

    Madelmont, J.C.; Moreau, M.F.; Godeneche, D.; Duprat, J.; Plagne, R.; Meyniel, G.

    1982-01-01

    The metabolism of two glycosylnitrosoureas, 1-(2-chloroethyl)-3-[1'-(5'-p-nitrobenzoyl-2',3'-isopropylidene)-alpha, beta-D-ribofuranosyl]-1-nitrosourea (RFCNU) and 1-(2-chloroethyl)-3-(2',3',4'-tri-O-acetyl-alpha, beta-D-ribopyranosyl)-1-nitrosourea (RPCNU), has been investigated in the rat. With the label on the carboxyl moiety of RFCNU, we have shown that hydrolysis of the 4-nitrobenzoyl ester occurred to a large extent in vivo; 4-nitrobenzoic acid and its glucuronide were the major urinary metabolites. Two other minor metabolites and their glucuronides were identified as 4-aminobenzoic acid and 4-acetamidobenzoic acid. With the label on the chloroethyl moieties of RFCNU and RPCNU, we have shown that chloroethanol was a major degradation product of this alkylating part of the molecule. The concentration of chloroethanol in plasma vs. time has been determined. In urine, four metabolites derived from alkylated glutathione, namely thiodiacetic acid and its sulfoxide, N-acetylcarboxymethylcysteine, and N-acetylhydroxyethylcysteine, have been identified

  16. Genetic evidence that HNF-1alpha-dependent transcriptional control of HNF-4alpha is essential for human pancreatic beta cell function

    DEFF Research Database (Denmark)

    Hansen, Sara K; Párrizas, Marcelina; Jensen, Maria L

    2002-01-01

    Mutations in the genes encoding hepatocyte nuclear factor 4alpha (HNF-4alpha) and HNF-1alpha impair insulin secretion and cause maturity onset diabetes of the young (MODY). HNF-4alpha is known to be an essential positive regulator of HNF-1alpha. More recent data demonstrates that HNF-4alpha...... in human islets and exocrine cells is primarily mediated by the P2 promoter. Furthermore, we describe a G --> A mutation in a conserved nucleotide position of the HNF-1alpha binding site of the P2 promoter, which cosegregates with MODY. The mutation results in decreased affinity for HNF-1alpha...

  17. Raman spectrum, quantum mechanical calculations and vibrational assignments of (95% alpha-TeO2/5% Sm2O3) glass.

    Science.gov (United States)

    Shaltout, I; Mohamed, Tarek A

    2007-06-01

    Chozen system of tellurite glasses doped with rare earth oxides (95% alpha-TeO(2)+5% Sm2O3) was prepared by melt quenching. Consequently, the Raman spectrum (150-1250 cm(-1)) of the modified tellurite have been recorded. As a continuation to our normal coordinate analysis, force constants and quantum mechanical (QM) calculations for tbp TeO4(4-) (triagonal bipyramid, C(2v)) and TeO(3+1); Te2O7(6-) (bridged tetrahedral), we have carried out ab initio frequency calculations for tpy TeO3(2-) (triagonal pyramidal, C(3v) and C(s)) and tp TeO3(2-) (triagonal planar, D(3h)) ions. The quantum mechanical calculations at the levels of RHF, B3LYP and MP2 allow confident vibrational assignments and structural identification in the binary oxide glass (95% alpha-TeO2 +5% Sm2O3). The dominant three-dimensional network structures in the modified glass are triagonal pyramidal TeO3 with minor features of short range distorted tbp TeO4 and bridged tetrahedral unit of TeO(3+1), leading to a structure of infinite chain. Therefore, alpha-TeO2/Sm2O3 (95/5%) glass experience structural changes from TeO4 (tbp); Te2O7 (TeO(3+1))-->TeO3 (tpy).

  18. Biased mutagenesis in the N-terminal region by degenerate oligonucleotide gene shuffling enhances secretory expression of barley alpha-amylase 2 in yeast

    DEFF Research Database (Denmark)

    Fukuda, Kenji; Jensen, Malene Hillerup; Aghajari, Nushin

    2005-01-01

    Recombinant barley alpha-amylase 1 (rAMY1) and 2 (rAMY2), despite 80% sequence identity, are produced in very different amounts of 1.1 and alpha loop 2 that interacts with domain B (beta-->alpha loop 3) protruding from the catalytic (beta/alpha)(8)-barrel. Most remarkably Pichia pastoris strain G...... residue. Moreover, the G to C substitution for the A42P mutation might have a positive impact on protein translation....

  19. Distribution of alpha3, alpha5 and alpha(v) integrin subunits in mature and immature human oocytes.

    Science.gov (United States)

    Capmany, G; Mart, M; Santaló, J; Bolton, V N

    1998-10-01

    The distribution of three integrin subunits, alpha3, alpha5 and alpha(v), in immature and mature human oocytes has been examined using immunofluorescence and confocal microscopy. The results demonstrate that both alpha5 and alpha(v) are present at the germinal vesicle stage, while alpha3 was only detected in oocytes after germinal vesicle breakdown, in metaphase I and II stage oocytes. The cortical concentration of integrin subunits alpha3 and alpha5 is consistent with their localization in the oolemma. In contrast, the homogeneous distribution of alpha(v) throughout the oocyte suggests the existence of cytoplasmic reservoirs of this protein in the oocyte.

  20. Dissolution rate of alpha-doped UO2 in natural groundwater

    International Nuclear Information System (INIS)

    Ollila, Kaija; Myllykylä, Emmi; Tanhua-Tyrkkö, Merja; Lavonen, Tiina

    2013-01-01

    The objective of this work is to determine whether the presence of trace elements in natural groundwaters affects the dissolution rate of uranium dioxide in the presence of alpha radiation that causes radiolysis of water. The study is a part of the project Reducing Uncertainty in Performance Prediction (REDUPP) under the Seventh Framework Programme of the European Atomic Energy Community (EURATOM). The project aims to reduce uncertainties related to the extrapolation of the results of laboratory experiments to the conditions expected under geologic disposal. Thus far, synthetic groundwater has been normally used in the experiments. The synthetic groundwaters used do not contain all of the chemical elements that occur in natural groundwaters. Three natural groundwaters were chosen for the dissolution experiments with 0%, 5%, and 10% 233 U-doped UO 2 samples. These include a brackish groundwater, a saline groundwater and a low ionic strength groundwater. At the time of writing this paper, the dissolution experiments have been finished in the first groundwater, which was a moderately saline, brackish groundwater. The groundwater samples for the experiments were taken from a borehole in the Olkiluoto site in Finland. The measurements for dissolution rates were conducted under reducing conditions established using metallic iron in solution and an argon atmosphere in the glove box. The isotope dilution method was used to decrease uncertainties due to precipitation and sorption effects. The resulting dissolution rates in OL-KR6 natural groundwater were generally somewhat higher than the rates measured previously in synthetic groundwaters under similar redox conditions. No clear effect of alpha radiolysis could be seen for tests with lower SA/V, while those for higher SA/V indicated that the dissolution rate was higher for the 10% 233 U-doped UO 2 , suggesting the effect of alpha radiolysis under these conditions

  1. Fasting induces basolateral uptake transporters of the SLC family in the liver via HNF4alpha and PGC1alpha.

    Science.gov (United States)

    Dietrich, Christoph G; Martin, Ina V; Porn, Anne C; Voigt, Sebastian; Gartung, Carsten; Trautwein, Christian; Geier, Andreas

    2007-09-01

    Fasting induces numerous adaptive changes in metabolism by several central signaling pathways, the most important represented by the HNF4alpha/PGC-1alpha-pathway. Because HNF4alpha has been identified as central regulator of basolateral bile acid transporters and a previous study reports increased basolateral bile acid uptake into the liver during fasting, we hypothesized that HNF4alpha is involved in fasting-induced bile acid uptake via upregulation of basolateral bile acid transporters. In rats, mRNA of Ntcp, Oatp1, and Oatp2 were significantly increased after 48 h of fasting. Protein expression as determined by Western blot showed significant increases for all three transporters 72 h after the onset of fasting. Whereas binding activity of HNF1alpha in electrophoretic mobility shift assays remained unchanged, HNF4alpha binding activity to the Ntcp promoter was increased significantly. In line with this result, we found significantly increased mRNA expression of HNF4alpha and PGC-1alpha. Functional studies in HepG2 cells revealed an increased endogenous NTCP mRNA expression upon cotransfection with either HNF4alpha, PGC-1alpha, or a combination of both. We conclude that upregulation of the basolateral bile acid transporters Ntcp, Oatp1, and Oatp2 in fasted rats is mediated via the HNF4alpha/PGC-1alpha pathway.

  2. Surface structure of alpha-Fe sub 2 O sub 3 nanocrystal observed by O K-edge X-ray absorption spectroscopy

    CERN Document Server

    Zhang, J; Ibrahim, K; Abbas, M I; Ju, X

    2003-01-01

    X-ray absorption near edge structure (XANES) spectra is used as a probe of surface structure of alpha-Fe sub 2 O sub 3 nanocrystal, prepared by sol-gel method. We present O K-edge XANES of alpha-Fe sub 2 O sub 3 in nanocrystal and bulk by total electron yield at the photoemission station of Beijing Synchrotron Radiation Facility. The spectrum of alpha-Fe sub 2 O sub 3 shows a splitting of the pre-edge structure, which is interpreted as two subsets of Fe 3d t sub 2 sub g and e sub g orbitals in oxygen octahedral (O sub h) crystal field, and is also sensitive to long-range order effects. However, no distinguishable splitting of the pre-edge peak of nanocrystal alpha-Fe sub 2 O sub 3 is observed. This suggests that there exists the distorted octahedral coordination around Fe sites and also the long-range disorder due to the surface as compared with bulk alpha-Fe sub 2 O sub 3.

  3. The alpha-cell as target for type 2 diabetes therapy

    DEFF Research Database (Denmark)

    Christensen, Mikkel; Bagger, Jonatan I; Vilsboll, Tina

    2011-01-01

    -coupled receptors in the hepatocytes. Type 2 diabetic patients are characterized by elevated glucagon levels contributing decisively to hyperglycemia in these patients. Accumulating evidence demonstrates that targeting the pancreatic alpha-cell and its main secretory product glucagon is a possible treatment....... Furthermore, potential advantages and limitations of antagonizing the glucagon receptor or suppressing glucagon secretion in the treatment of type 2 diabetes are discussed with a focus on already marketed drugs and drugs in clinical development. It is concluded that the development of novel glucagon receptor...

  4. arXiv Proceedings, High-Precision $\\alpha_s$ Measurements from LHC to FCC-ee Geneva, Switzerland, October 2-13, 2015

    CERN Document Server

    d'Enterria, David; Alekhin, S.; Banfi, A.; Bethke, S.; Blümlein, J.; Chetyrkin, K.G.; Dissertori, G.; Garcia i Tormo, X.; Hoang, A.H.; Klasen, M.; Klijnsma, T.; Kluth, S.; Kneur, J.-L.; Kniehl, B.A.; Kolodrubetz, D.W.; Kühn, J.; Mackenzie, P.; Malaescu, B.; Mateu, V.; Mihaila, L.; Moch, S.; Mönig, K.; Pérez-Ramos, R.; Pich, A.; Pires, J.; Rabbertz, K.; Salam, G.P.; Sannino, F.; Soto i Riera, J.; Srebre, M.; Stewart, I.W.

    2015-01-01

    This document provides a writeup of all contributions to the workshop on "High precision measurements of $\\alpha_s$: From LHC to FCC-ee" held at CERN, Oct. 12--13, 2015. The workshop explored in depth the latest developments on the determination of the QCD coupling $\\alpha_s$ from 15 methods where high precision measurements are (or will be) available. Those include low-energy observables: (i) lattice QCD, (ii) pion decay factor, (iii) quarkonia and (iv) $\\tau$ decays, (v) soft parton-to-hadron fragmentation functions, as well as high-energy observables: (vi) global fits of parton distribution functions, (vii) hard parton-to-hadron fragmentation functions, (viii) jets in $e^\\pm$p DIS and $\\gamma$-p photoproduction, (ix) photon structure function in $\\gamma$-$\\gamma$, (x) event shapes and (xi) jet cross sections in $e^+e^-$ collisions, (xii) W boson and (xiii) Z boson decays, and (xiv) jets and (xv) top-quark cross sections in proton-(anti)proton collisions. The current status of the theoretical and experiment...

  5. Clinical differences between patients with MODY-3, MODY-2 and type 2 diabetes mellitus with I27L polymorphism in the HNF1alpha gene.

    Science.gov (United States)

    Pinés Corrales, Pedro José; López Garrido, María P; Aznar Rodríguez, Silvia; Louhibi Rubio, Lynda; López Jiménez, Luz M; Lamas Oliveira, Cristina; Alfaro Martínez, Jose J; Lozano García, Jose J; Hernández López, Antonio; Requejo Castillo, Ramón; Escribano Martínez, Julio; Botella Romero, Francisco

    2010-01-01

    The aim of our study was to describe and evaluate the clinical and metabolic characteristics of patients with MODY-3, MODY-2 or type 2 diabetes who presented I27L polymorphism in the HNF1alpha gene. The study included 31 previously diagnosed subjects under follow-up for MODY-3 (10 subjects from 5 families), MODY-2 (15 subjects from 9 families), or type 2 diabetes (6 subjects) with I27L polymorphism in the HNF1alpha gene. The demographic, clinical, metabolic, and genetic characteristics of all patients were analyzed. No differences were observed in distribution according to sex, age of onset, or form of diagnosis. All patients with MODY-2 or MODY-3 had a family history of diabetes. In contrast, 33.3% of patients with type 2 diabetes mellitus and I27L polymorphism in the HNF1alpha gene had no family history of diabetes (p MODY-3 patients, but not required by 100% of MODY-2 patients or 16.7% of patients with type 2 diabetes mellitus and I27L polymorphism in the HNF1alpha gene (p MODY-2, MODY-3 or type 2 diabetes of atypical characteristics, in this case patients who present I27L polymorphism in the HNF1alpha gene. Copyright 2010 Sociedad Española de Endocrinología y Nutrición. Published by Elsevier Espana. All rights reserved.

  6. Estrogen receptor alpha and risk for cognitive impairment in postmenopausal women

    DEFF Research Database (Denmark)

    Olsen, Line; Rasmussen, Henrik B; Hansen, Thomas

    2006-01-01

    The estrogen receptor alpha (ESR1) gene has been implicated in the process of cognitive impairment in elderly women. In a paired case-control study, we tested whether two ESR1 gene polymorphisms (the XbaI and PvuII sites) are risk factors for cognitive impairment as measured by the six-item Orien......The estrogen receptor alpha (ESR1) gene has been implicated in the process of cognitive impairment in elderly women. In a paired case-control study, we tested whether two ESR1 gene polymorphisms (the XbaI and PvuII sites) are risk factors for cognitive impairment as measured by the six......-item Orientation-Memory-Concentration test in postmenopausal Danish women. Hormone replacement therapy, age and executive cognitive ability were examined as covariates for ESR1 gene effects on cognitive impairment. The XbaI polymorphism showed a marginal effect on cognitive abilities (P=0.054) when adjusted...... cognitive ability. These data support that the ESR1 gene variants affect cognitive functioning in postmenopausal women....

  7. Alpha-Driven MHD and MHD-Induced Alpha Loss in TFTR DT Experiments

    Science.gov (United States)

    Chang, Zuoyang

    1996-11-01

    Theoretical calculation and numerical simulation indicate that there can be interesting interactions between alpha particles and MHD activity which can adversely affect the performance of a tokamak reactor (e.g., ITER). These interactions include alpha-driven MHD, like the toroidicity-induced-Alfven-eigenmode (TAE) and MHD induced alpha particle losses or redistribution. Both phenomena have been observed in recent TFTR DT experiments. Weak alpha-driven TAE activity was observed in a NBI-heated DT experiment characterized by high q0 ( >= 2) and low core magnetic shear. The TAE mode appears at ~30-100 ms after the neutral beam turning off approximately as predicted by theory. The mode has an amplitude measured by magnetic coils at the edge tildeB_p ~1 mG, frequency ~150-190 kHz and toroidal mode number ~2-3. It lasts only ~ 30-70 ms and has been seen only in DT discharges with fusion power level about 1.5-2.0 MW. Numerical calculation using NOVA-K code shows that this type of plasma has a big TAE gap. The calculated TAE frequency and mode number are close to the observation. (2) KBM-induced alpha particle loss^1. In some high-β, high fusion power DT experiments, enhanced alpha particle losses were observed to be correlated to the high frequency MHD modes with f ~100-200 kHz (the TAE frequency would be two-times higher) and n ~5-10. These modes are localized around the peak plasma pressure gradient and have ballooning characteristics. Alpha loss increases by 30-100% during the modes. Particle orbit simulations show the added loss results from wave-particle resonance. Linear instability analysis indicates that the plasma is unstable to the kinetic MHD ballooning modes (KBM) driven primarily by strong local pressure gradients. ----------------- ^1Z. Chang, et al, Phys. Rev. Lett. 76 (1996) 1071. In collaberation with R. Nazikian, G.-Y. Fu, S. Batha, R. Budny, L. Chen, D. Darrow, E. Fredrickson, R. Majeski, D. Mansfield, K. McGuire, G. Rewoldt, G. Taylor, R. White, K

  8. Glycosylation of alpha(2)delta(1) subunit: a sweet talk with Ca(v)1.2 channels

    Czech Academy of Sciences Publication Activity Database

    Lazniewska, Joanna; Weiss, Norbert

    2016-01-01

    Roč. 35, č. 3 (2016), s. 239-242 ISSN 0231-5882 R&D Projects: GA ČR GA15-13556S; GA MŠk 7AMB15FR015 Institutional support: RVO:61388963 Keywords : calcium channel * Ca(v)1.2 channel * ancillary subunit * alpha(2)delta(1) subunit * glycosylation * trafficking Subject RIV: CE - Biochemistry Impact factor: 1.170, year: 2016

  9. Disruption of an AP-2alpha binding site in an IRF6 enhancer is associated with cleft lip

    DEFF Research Database (Denmark)

    Rahimov, Fedik; Marazita, Mary L; Visel, Axel

    2008-01-01

    demonstrate that the risk allele disrupts the binding site of transcription factor AP-2alpha and expression analysis in the mouse localizes the enhancer activity to craniofacial and limb structures. Our findings place IRF6 and AP-2alpha in the same developmental pathway and identify a high-frequency variant...

  10. Selective alpha autoradiography for monitoring thorium distribution in UO[sub 2]-ThO[sub 2] fuel pellets

    Energy Technology Data Exchange (ETDEWEB)

    Shriwastwa, B.B.; Raghunath, B.; Ghosh, J.K. (Bhabha Atomic Research Centre, Bombay (India))

    1992-10-01

    Although natural uranium and thorium decay with similar alpha energies (4.20 and 3.98 MeV), their daughter products have different alpha characteristics. This has been exploited for selective alpha autoradiography for thoria in urania-thoria mixed nuclear fuel pellets. Difficulties in getting sufficient track density in alpha sensitive films due to the very low specific activity of natural uranium and thorium material were overcome by using a special film with annealing and pre-etching treatment. (orig./HP).

  11. Alpha amylase assisted synthesis of TiO2 nanoparticles: Structural characterization and application as antibacterial agents

    International Nuclear Information System (INIS)

    Ahmad, Razi; Mohsin, Mohd; Ahmad, Tokeer; Sardar, Meryam

    2015-01-01

    Graphical abstract: - Highlights: • Green synthesis of TiO 2 nanoparticles using an enzyme alpha amylase has been described. • The morphology and shape depends upon the concentration of the alpha amylase enzyme. • The biosynthesized nanoparticles show good bactericidal effect against both gram positive and gram negative bacteria. • The bactericidal effect was further confirmed by Confocal microscopy and TEM. - Abstract: The enzyme alpha amylase was used as the sole reducing and capping agent for the synthesis of TiO 2 nanoparticles. The biosynthesized nanoparticles were characterized by X-ray diffraction (XRD) and transmission electron microscopic (TEM) methods. The XRD data confirms the monophasic crystalline nature of the nanoparticles formed. TEM data shows that the morphology of nanoparticles depends upon the enzyme concentration used at the time of synthesis. The presence of alpha amylase on TiO 2 nanoparticles was confirmed by FTIR. The nanoparticles were investigated for their antibacterial effect on Staphylococcus aureus and Escherichia coli. The minimum inhibitory concentration value of the TiO 2 nanoparticles was found to be 62.50 μg/ml for both the bacterial strains. The inhibition was further confirmed using disc diffusion assay. It is evident from the zone of inhibition that TiO 2 nanoparticles possess potent bactericidal activity. Further, growth curve study shows effect of inhibitory concentration of TiO 2 nanoparticles against S. aureus and E. coli. Confocal microscopy and TEM investigation confirm that nanoparticles were disrupting the bacterial cell wall

  12. Reduction in high blood tumor necrosis factor-alpha levels after manipulative therapy in 2 cervicogenic headache patients.

    Science.gov (United States)

    Ormos, Gábor; Mehrishi, J N; Bakács, Tibor

    2009-09-01

    This case report discusses the treatment of 2 patients with cervicogenic headache (CHA) attending the Outpatient Clinic of the Hungarian National Institute for Rheumatology and Physiotherapy (Budapest, Hungary) and reviews the pathophysiology, therapeutic strategy, and problems associated with the treatment of CHA. Patient 1 was a 27-year-old female who sustained a whiplash injury. A sharp, shooting headache developed, readily induced, and aggravated by just bending the neck backward or by turning her head. Magnetic resonance imaging revealed a disk protrusion at C4-C5 pressing the anterior cerebrospinal space. Patient 2 was a 62-year-old female who sustained a whiplash injury; her cervical movements became restricted, which precipitated headaches. Magnetic resonance imaging revealed a paramedian disk hernia between the C4 and C5 vertebrae that intruded into the right ventral cerebrospinal space. After 4 weeks of manipulative therapy for patient 1, both active and passive range of motion returned to normal, and the high tumor necrosis factor-alpha (TNF-alpha) level (63 pg/mL) was substantially reduced (28 pg/mL). Patient 2 was started on manipulative therapy twice a week for 4 weeks; after 2 months, the patient became symptom-free, and high TNF-alpha level (72 pg/mL) was reduced greatly (35 pg/mL). Two patients with whiplash injury and disk herniation developed CHA associated with very high TNF-alpha levels. After manipulative therapy, these patients became symptom-free, and their TNF-alpha levels decreased substantially.

  13. A cog in cognition: how the alpha 7 nicotinic acetylcholine receptor is geared towards improving cognitive deficits.

    Science.gov (United States)

    Leiser, Steven C; Bowlby, Mark R; Comery, Thomas A; Dunlop, John

    2009-06-01

    Cognition, memory, and attention and arousal have been linked to nicotinic acetylcholine receptors (nAChRs). Thus it is not surprising that nAChRs have been strongly implicated as therapeutic targets for treating cognitive deficits in disorders such as schizophrenia and Alzheimer's disease (AD). In particular the alpha7 (alpha7) nAChR has been closely linked with normalization of P50 auditory evoked potential (AEP) gating deficits, and to a lesser extent improvements in pre-pulse inhibition (PPI) of the acoustic startle response. These two brain phenomena can be considered as pre-attentive, occurring while sensory information is being processed, and are important endophenotypes in schizophrenia with deficits likely contributing to the cognitive fragmentation associated with the disease. In addition alpha7 nAChRs have been implicated in attention, in particular under high attentional demand, and in more demanding working memory tasks such as long delays in delayed matching tasks. Efficacy of alpha7 nAChR agonists across a range of cognitive processes ranging from pre-attentive to attentive states and working and recognition memory provides a solid basis for their pro-cognitive effects. This review will focus on the recent work highlighting the role of alpha7 in cognition and cognitive processes.

  14. Development of technology for biological dosimetry

    International Nuclear Information System (INIS)

    Kim, In Gyu; Kim, Kug Chan; Lee, Kang Sik; Kim, Jin Kyu; Chun, Ki Jung; Shim, Hye Won; Park, Seon Young.

    1997-07-01

    Adult male rats were treated a single, whole body exposure to a dose of 0.1, 0.5, 1, 2, 3, 5, 7 and 9 Gy. The animal were sacrificed 6, 24, 48, 72, 96 and 212 hours following exposure. Enzyme activity changes such as alkaline phosphatase, GOT, creating kinase, MDH and LDH in rat serum as biochemical indicators useful for evaluating radiation exposure were measured. An competitive enzyme linked immunosorbent assay (ELISA) has been developed to measure acute phase reactants (APRs) in rat serum after gamma-irradiation. Rat alpha-2 macroglobulin, alpha-1 acid glycoprotein, haptoglobin, ceruloplasmin, C-reactive protein and alpha-1 antitrypsin were purified from the plasma of turpentine treated rats. In vitro somatic mutation induced by gamma-irradiation and pentachlorophenol (PCP) which is representative of chemical pollutant was measured at the hypoxanthine-guanine phosphorybosyl transferase (HPRT) locus in human T-lymphocytes by a cell cloning assay. Mutant cells were selected by their ability to form a clone in the presence of purine analogue 6-thioguanine. Reverse transcriptase/polymerase chain reaction technique was needed for the mutation spectrum to discriminate combined exposure to radiation and chemicals. (author). 98 refs., 7 tabs., 47 figs

  15. Development of technology for biological dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Kim, In Gyu; Kim, Kug Chan; Lee, Kang Sik; Kim, Jin Kyu; Chun, Ki Jung; Shim, Hye Won; Park, Seon Young

    1997-07-01

    Adult male rats were treated a single, whole body exposure to a dose of 0.1, 0.5, 1, 2, 3, 5, 7 and 9 Gy. The animal were sacrificed 6, 24, 48, 72, 96 and 212 hours following exposure. Enzyme activity changes such as alkaline phosphatase, GOT, creating kinase, MDH and LDH in rat serum as biochemical indicators useful for evaluating radiation exposure were measured. An competitive enzyme linked immunosorbent assay (ELISA) has been developed to measure acute phase reactants (APRs) in rat serum after gamma-irradiation. Rat alpha-2 macroglobulin, alpha-1 acid glycoprotein, haptoglobin, ceruloplasmin, C-reactive protein and alpha-1 antitrypsin were purified from the plasma of turpentine treated rats. In vitro somatic mutation induced by gamma-irradiation and pentachlorophenol (PCP) which is representative of chemical pollutant was measured at the hypoxanthine-guanine phosphorybosyl transferase (HPRT) locus in human T-lymphocytes by a cell cloning assay. Mutant cells were selected by their ability to form a clone in the presence of purine analogue 6-thioguanine. Reverse transcriptase/polymerase chain reaction technique was needed for the mutation spectrum to discriminate combined exposure to radiation and chemicals. (author). 98 refs., 7 tabs., 47 figs.

  16. alpha2 adrenoceptors are involved in the regulation of the gripping-induced immobility episodes in taiep rats.

    Science.gov (United States)

    Eguibar, José R; Cortés, Ma Del Carmen; Valencia, Jaime; Arias-Montaño, José A

    2006-10-01

    In 1989 Holmgren et al. (Holmgren et al. 1989 Lab Anim Sci 39:226-228) described a new mutant rat that developed a progressive motor disturbance during its lifespan. The syndrome is characterized by a tremor in the hind limbs followed by ataxia, episodes of tonic immobility, epilepsy, and paralysis. The acronym of these symptoms (taiep) became the name of this autosomic, recessive mutant rat. The taiep rats are neurological mutant animals with a hypomyelination, followed by a progressive demyelination process. At 7-8 months of age, taiep rats develop immobility episodes (IEs) characterized by a cortical desynchronization, associated with the theta rhythm in the hippocampus and changes of the nucal electromyogram (EMG), whose pattern is like rapid-eye-movement (REM) sleep. These rats also show an altered sleep pattern with an equal REM sleep distribution. This study analyzed therole of alpha(2) adrenoceptors in the expression of gripping-induced IEs in 8-month-old male taiep rats. The alpha(2) adrenoceptor agonists clonidine and xylacine increased the frequency of gripping-induced IEs whereas the alpha(2) antagonists yohimbine and idazoxandecreased or prevented such episodes. These findings correlate with the pharmacological observations in narcoleptic dogs and humans in which alpha(2) adrenergic mechanisms are involved in the modulation of cataplexy. Unexpectedly, the repetitive administration of clonidine resulted in jumping behavior, indicative of phasic activation of extensor musculature. Taken together, our results show that alpha(2) adrenoceptors are involved in the modulation in gripping-induced IEs and after the administration of several doses of clonidine produced phasic motor activation.

  17. Enantioselective conjugate radical addition to alpha'-hydroxy enones.

    Science.gov (United States)

    Lee, Sunggi; Lim, Chae Jo; Kim, Sunggak; Subramaniam, Rajesh; Zimmerman, Jake; Sibi, Mukund P

    2006-09-14

    Enantioselective conjugate radical addition to alpha'-hydroxy alpha,beta-unsaturated ketones, compounds containing bidentate donors, has been investigated. It has been found that radical additions to alpha'-hydroxy alpha,beta-unsaturated ketones in the presence of Mg(NTf2)2 and bisoxazoline ligand 5a proceeded cleanly, yielding the addition products in high chemical yields and good enantiomeric excesses.

  18. alpha7 Nicotinic acetylcholine receptor knockout selectively enhances ethanol-, but not beta-amyloid-induced neurotoxicity.

    Science.gov (United States)

    de Fiebre, Nancyellen C; de Fiebre, Christopher M

    2005-01-03

    The alpha7 subtype of nicotinic acetylcholine receptor (nAChR) has been implicated as a potential site of action for two neurotoxins, ethanol and the Alzheimer's disease related peptide, beta-amyloid. Here, we utilized primary neuronal cultures of cerebral cortex from alpha7 nAChR null mutant mice to examine the role of this receptor in modulating the neurotoxic properties of subchronic, "binge" ethanol and beta-amyloid. Knockout of the alpha7 nAChR gene selectively enhanced ethanol-induced neurotoxicity in a gene dosage-related fashion. Susceptibility of cultures to beta-amyloid induced toxicity, however, was unaffected by alpha7 nAChR gene null mutation. Further, beta-amyloid did not inhibit the binding of the highly alpha7-selective radioligand, [(125)I]alpha-bungarotoxin. On the other hand, in studies in Xenopus oocytes ethanol efficaciously inhibited alpha7 nAChR function. These data suggest that alpha7 nAChRs modulate the neurotoxic effects of binge ethanol, but not the neurotoxicity produced by beta-amyloid. It is hypothesized that inhibition of alpha7 nAChRs by ethanol provides partial protection against the neurotoxic properties of subchronic ethanol.

  19. Alpha and beta detection and spectrometry

    International Nuclear Information System (INIS)

    Saro, S.

    1984-01-01

    The theory of alpha and beta radioactive decay, the interaction of alpha and beta particles with matter, and their detection and spectrometry are dealt with in seven chapters: 1. Alpha transformation of atomic nuclei; 2. Basic properties of detectors and statistics of detection; 3. Alpha detectors and spectrometers; 4. Applications of alpha detection and spectrometry; 5. Beta transformation of atomic nuclei; 6. Beta particle detectors and spectrometers; 7. Detection of low energy beta particles. Chapter 8 is devoted to sampling and preparation of samples for radiometry. (E.F.)

  20. Comparative first-principle analysis of un-doped and V{sup 3+}-doped {alpha}-ZnAl{sub 2}S{sub 4} spinel

    Energy Technology Data Exchange (ETDEWEB)

    Brik, M.G. [Institute of Physics, University of Tartu, Riia 142, Tartu 51014 (Estonia); Nazarov, M., E-mail: mvnazarov@mail.ru [School of Materials and Mineral Resources Engineering, Universiti Sains Malaysia, 14300 Nibong Tebal, Penang (Malaysia); Institute of Applied Physics, Academiei Street 5, Chisinau MD-2028, Republic of Moldova (Moldova, Republic of); Ahmad-Fauzi, M.N. [School of Materials and Mineral Resources Engineering, Universiti Sains Malaysia, 14300 Nibong Tebal, Penang (Malaysia); Kulyuk, L.; Anghel, S. [Institute of Applied Physics, Academiei Street 5, Chisinau MD-2028, Republic of Moldova (Moldova, Republic of); Sushkevich, K. [Moldova State University, Mateevici Street 60, Chisinau, MD-2009, Republic of Moldova (Moldova, Republic of); Boulon, G. [Physical Chemistry of Luminescent Materials, Claude Bernard Lyon 1 University, UMR 5620 CNRS, La Doua, 69622 Villeurbanne (France)

    2012-09-15

    The experimental and theoretical studies of the optical properties of pure {alpha}-ZnAl{sub 2}S{sub 4} and {alpha}-ZnAl{sub 2}S{sub 4}:V{sup 3+} crystals were carried out. The ab initio and crystal field calculations of the structural and optical properties of {alpha}-ZnAl{sub 2}S{sub 4}:V{sup 3+} were compared with the corresponding experimental data. It was shown that the lowest vanadium 3d states are located at about 1.36 eV above the valence band's top. The complete energy level scheme of the {alpha}-ZnAl{sub 2}S{sub 4}:V{sup 3+} system, which includes the host's electronic band structure and impurity ion's energy levels, was suggested on the basis of the performed calculations. - Highlights: Black-Right-Pointing-Pointer Experimental and theoretical studies of {alpha}-ZnAl{sub 2}S{sub 4} and {alpha}-ZnAl{sub 2}S{sub 4}:V{sup 3+} crystals were carried out. Black-Right-Pointing-Pointer Ab inito and crystal field calculations were used in structural and spectroscopic analyses. Black-Right-Pointing-Pointer The complete energy level scheme of the {alpha}-ZnAl{sub 2}S{sub 4}:V{sup 3+} system was suggested. Black-Right-Pointing-Pointer The lowest vanadium 3d states are located at about 1.36 eV above the valence band's top.

  1. The involvement of peripheral alpha 2-adrenoceptors in the antihyperalgesic effect of oxcarbazepine in a rat model of inflammatory pain.

    Science.gov (United States)

    Tomić, Maja A; Vucković, Sonja M; Stepanović-Petrović, Radica M; Ugresić, Nenad D; Paranos, Sonja Lj; Prostran, Milica S; Bosković, Bogdan

    2007-11-01

    We studied whether peripheral alpha2-adrenergic receptors are involved in the antihyperalgesic effects of oxcarbazepine by examining the effects of yohimbine (selective alpha2-adrenoceptor antagonist), BRL 44408 (selective alpha(2A)-adrenoceptor antagonist), MK-912 (selective alpha2C-adrenoceptor antagonist), and clonidine (alpha2-adrenoceptor agonist) on the antihyperalgesic effect of oxcarbazepine in the rat model of inflammatory pain. Rats were intraplantarly (i.pl.) injected with the proinflammatory compound concanavalin A (Con A). A paw-pressure test was used to determine: 1) the development of hyperalgesia induced by Con A; 2) the effects of oxcarbazepine (i.pl.) on Con A-induced hyperalgesia; and 3) the effects of i.pl. yohimbine, BRL 44408, MK-912 and clonidine on the oxcarbazepine antihyperalgesia. Both oxcarbazepine (1000-3000 nmol/paw; i.pl.) and clonidine (1.9-7.5 nmol/paw; i.pl.) produced a significant dose-dependent reduction of the paw inflammatory hyperalgesia induced by Con A. Yohimbine (260 and 520 nmol/paw; i.pl.), BRL 44408 (100 and 200 nmol/paw; i.pl.) and MK-912 (10 and 20 nmol/paw; i.pl.) significantly depressed the antihyperalgesic effects of oxcarbazepine (2000 nmol/paw; i.pl.) in a dose-dependent manner. The effects of antagonists were due to local effects since they were not observed after administration into the contralateral hindpaw. Oxcarbazepine and clonidine administered jointly in fixed-dose fractions of the ED(50) (1/4, 1/2, and 3/4) caused significant and dose-dependent reduction of hyperalgesia induced by Con A. Isobolographic analysis revealed an additive antihyperalgesic effect. Our results indicate that the peripheral alpha2A and alpha2C adrenoceptors could be involved in the antihyperalgesic effects of oxcarbazepine in a rat model of inflammatory hyperalgesia.

  2. Extended no-scale structure and {alpha}'{sup 2} corrections to the type IIB action

    Energy Technology Data Exchange (ETDEWEB)

    Pedro, F.G. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Rummel, M. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik; Hong Kong Univ. of Science and Technology (China). Inst. for Advanced Study; Westphal, A. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany); Kavali Institute for Theoretical Physics, Santa Barbara, CA (United States)

    2013-06-15

    We analyse a new N=1 string tree level correction at O({alpha}'{sup 2}) to the Kaehler potential of the volume moduli of type IIB Calabi-Yau flux compactification found recently by T. W. Grimm, R. Savelli and M. Weissenbacher (arXiv:1303.3317 [hep-th]) and its impact on the moduli potential. We find that it imposes a strong lower bound the Calabi-Yau volume in the Large Volume Scenario of moduli stabilisation. For KKLT-like scenarios we find that consistency of the action imposes an upper bound on the flux superpotential vertical stroke W{sub 0} vertical stroke or similar 10{sup 3}. We discuss the phenomenological implication of these bounds on V in the various scenarios.

  3. Chemioxyexcitation (delta pO2/ROS)-dependent release of IL-1 beta, IL-6 and TNF-alpha: evidence of cytokines as oxygen-sensitive mediators in the alveolar epithelium.

    Science.gov (United States)

    Haddad, J J; Safieh-Garabedian, B; Saadé, N E; Kanaan, S A; Land, S C

    2001-02-07

    The signalling mechanisms in oxidative stress mediated by cytokines in the perinatal alveolar epithelium are not well known. In an in vitro model of fetal alveolar type II epithelial cells, we investigated the profile of cytokines in response to ascending Deltap O(2)regimen (oxyexcitation). The peak of TNF-alpha (4 h) preceded IL-1beta and IL-6 (6-9 h), indicating a positive feedback autocrine loop confirmed by exogenous rmTNF-alpha. Reactive oxygen species (ROS) induced a dose-dependent release of cytokines, an effect specifically obliterated by selective antioxidants of the hydroxyl radical (*OH) and superoxide anion (O(2)-). Actinomycin and cycloheximide blocked the induced production of cytokines, implicating transcriptional and translational control. Whilst the dismutating enzymes superoxide dismutase (SOD) and catalase were ineffective in reducing ROS-induced cytokines, MnP, a cell-permeating SOD mimetic, abrogated xanthine/xanthine oxidase-dependent cytokine release. Desferrioxamine mesylate, which inhibits the iron-catalysed generation of *OH via the Fenton reaction, exhibited a mild effect on the release of cytokines. Dynamic variation in alveolar p O(2)constitutes a potential signalling mechanism within the perinatal lung allowing upregulation of cytokines in an ROS-dependent manner. Copyright 2001 Academic Press.

  4. Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein

    DEFF Research Database (Denmark)

    Jacobsen, Linda; Madsen, P; Moestrup, S K

    1996-01-01

    the corresponding cDNA. The gene, designated SORL1, maps to chromosome 11q 23/24 and encodes a 2214-residue type 1 receptor containing a furin cleavage site immediately preceding the N terminus determined in the purified protein. The receptor, designated sorLA-1, has a short cytoplasmic tail containing a tyrosine...... density lipoprotein receptor gene family receptors, and 3) six tandemly arranged fibronectin type III repeats also found in certain neural adhesion proteins. sorLA-1 may therefore be classified as a hybrid receptor. Northern blotting revealed specific mRNA transcripts in brain, spinal cord, and testis......The 39-40-kDa receptor-associated protein (RAP) binds to the members of the low density lipoprotein receptor gene family and functions as a specialized endoplasmic reticulum/Golgi chaperone. Using RAP affinity chromatography, we have purified a novel approximately 250-kDa brain protein and isolated...

  5. Measurement and analysis of $\\alpha$ particle induced reactions on yttrium

    CERN Document Server

    Singh, N L; Chintalapudi, S N

    2000-01-01

    Excitation functions for /sup 89/Y[( alpha ,3n); ( alpha ,4n); ( alpha , p3n); ( alpha , alpha n); ( alpha , alpha 2n)] reactions were measured up to 50 MeV using stacked foil activation technique and HPGe gamma ray spectroscopy method. The experimental data were compared with calculations considering equilibrium as well as preequilibrium reactions according to the hybrid model of Blann (ALICE/90). For ( alpha , xnyp) type of reactions, the precompound contributions are described by the model. There seems to be indications of direct inelastic scattering effects in ( alpha , alpha xn) type of reactions. To the best of our knowledge, the excitation functions for ( alpha ,4n), ( alpha , p3n), ( alpha , alpha n) and ( alpha , alpha 2n) reactions were measured for the first time. (23 refs).

  6. Measurement and analysis of alpha particle induced reactions on yttrium

    Energy Technology Data Exchange (ETDEWEB)

    Singh, N.L.; Gadkari, M.S. [Baroda Univ. (India). Dept. of Physics; Chintalapudi, S.N. [IUC-DAEF Calcutta Centre, Calcutta (India)

    2000-05-01

    Excitation functions for {sup 89}Y[({alpha},3n);({alpha},4n);({alpha},p3n);({alpha},{alpha}n);({alpha},{alpha}2n)] reactions were measured up to 50 MeV using stacked foil activation technique and HPGe gamma ray spectroscopy method. The experimental data were compared with calculations considering equilibrium as well as preequilibrium reactions according to the hybrid model of Blann (ALICE/90). For ({alpha},xnyp) type of reactions, the precompound contributions are described by the model. There seems to be indications of direct inelastic scattering effects in ({alpha},{alpha}xn) type of reactions. To the best of our knowledge, the excitation functions for ({alpha},4n), ({alpha},p3n), ({alpha},{alpha}n) and ({alpha},{alpha}2n) reactions were measured for the first time. (orig.)

  7. Test of the Flavour Independence of $\\alpha_{s}$ using Next-to-Leading Order Calculations for Heavy Quarks

    CERN Document Server

    Abbiendi, G.; Alexander, G.; Allison, John; Altekamp, N.; Anderson, K.J.; Anderson, S.; Arcelli, S.; Asai, S.; Ashby, S.F.; Axen, D.; Azuelos, G.; Ball, A.H.; Barberio, E.; Barlow, Roger J.; Batley, J.R.; Baumann, S.; Bechtluft, J.; Behnke, T.; Bell, Kenneth Watson; Bella, G.; Bellerive, A.; Bentvelsen, S.; Bethke, S.; Betts, S.; Biebel, O.; Biguzzi, A.; Bloodworth, I.J.; Bock, P.; Bohme, J.; Bonacorsi, D.; Boutemeur, M.; Braibant, S.; Bright-Thomas, P.; Brigliadori, L.; Brown, Robert M.; Burckhart, H.J.; Capiluppi, P.; Carnegie, R.K.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, David G.; Chrisman, D.; Ciocca, C.; Clarke, P.E.L.; Clay, E.; Cohen, I.; Conboy, J.E.; Cooke, O.C.; Couchman, J.; Couyoumtzelis, C.; Coxe, R.L.; Cuffiani, M.; Dado, S.; Dallavalle, G.Marco; Davis, R.; De Jong, S.; de Roeck, A.; Dervan, P.; Desch, K.; Dienes, B.; Dixit, M.S.; Dubbert, J.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Estabrooks, P.G.; Etzion, E.; Fabbri, F.; Fanfani, A.; Fanti, M.; Faust, A.A.; Fiedler, F.; Fierro, M.; Fleck, I.; Frey, A.; Furtjes, A.; Futyan, D.I.; Gagnon, P.; Gary, J.W.; Gascon-Shotkin, S.M.; Gaycken, G.; Geich-Gimbel, C.; Giacomelli, G.; Giacomelli, P.; Gibson, V.; Gibson, W.R.; Gingrich, D.M.; Glenzinski, D.; Goldberg, J.; Gorn, W.; Grandi, C.; Graham, K.; Gross, E.; Grunhaus, J.; Gruwe, M.; Hajdu, C.; Hanson, G.G.; Hansroul, M.; Hapke, M.; Harder, K.; Harel, A.; Hargrove, C.K.; Harin-Dirac, M.; Hauschild, M.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Herndon, M.; Herten, G.; Heuer, R.D.; Hildreth, M.D.; Hill, J.C.; Hobson, P.R.; Hocker, James Andrew; Hoffman, Kara Dion; Homer, R.J.; Honma, A.K.; Horvath, D.; Hossain, K.R.; Howard, R.; Huntemeyer, P.; Igo-Kemenes, P.; Imrie, D.C.; Ishii, K.; Jacob, F.R.; Jawahery, A.; Jeremie, H.; Jimack, M.; Jones, C.R.; Jovanovic, P.; Junk, T.R.; Kanaya, N.; Kanzaki, J.; Karlen, D.; Kartvelishvili, V.; Kawagoe, K.; Kawamoto, T.; Kayal, P.I.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Kim, D.H.; Klier, A.; Kobayashi, T.; Kobel, M.; Kokott, T.P.; Kolrep, M.; Komamiya, S.; Kowalewski, Robert V.; Kress, T.; Krieger, P.; von Krogh, J.; Kuhl, T.; Kyberd, P.; Lafferty, G.D.; Landsman, H.; Lanske, D.; Lauber, J.; Lawson, I.; Layter, J.G.; Lellouch, D.; Letts, J.; Levinson, L.; Liebisch, R.; List, B.; Littlewood, C.; Lloyd, A.W.; Lloyd, S.L.; Loebinger, F.K.; Long, G.D.; Losty, M.J.; Lu, J.; Ludwig, J.; Lui, D.; Macchiolo, A.; Macpherson, A.; Mader, W.; Mannelli, M.; Marcellini, S.; Martin, A.J.; Martin, J.P.; Martinez, G.; Mashimo, T.; Mattig, Peter; McDonald, W.John; McKenna, J.; Mckigney, E.A.; McMahon, T.J.; McPherson, R.A.; Meijers, F.; Mendez-Lorenzo, P.; Merritt, F.S.; Mes, H.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Mohr, W.; Montanari, A.; Mori, T.; Nagai, K.; Nakamura, I.; Neal, H.A.; Nisius, R.; O'Neale, S.W.; Oakham, F.G.; Odorici, F.; Ogren, H.O.; Okpara, A.; Oreglia, M.J.; Orito, S.; Pasztor, G.; Pater, J.R.; Patrick, G.N.; Patt, J.; Perez-Ochoa, R.; Petzold, S.; Pfeifenschneider, P.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Poffenberger, P.; Poli, B.; Polok, J.; Przybycien, M.; Quadt, A.; Rembser, C.; Rick, H.; Robertson, S.; Robins, S.A.; Rodning, N.; Roney, J.M.; Rosati, S.; Roscoe, K.; Rossi, A.M.; Rozen, Y.; Runge, K.; Runolfsson, O.; Rust, D.R.; Sachs, K.; Saeki, T.; Sahr, O.; Sang, W.M.; Sarkisian, E.K.G.; Sbarra, C.; Schaile, A.D.; Schaile, O.; Scharff-Hansen, P.; Schieck, J.; Schmitt, S.; Schoning, A.; Schroder, Matthias; Schumacher, M.; Schwick, C.; Scott, W.G.; Seuster, R.; Shears, T.G.; Shen, B.C.; Shepherd-Themistocleous, C.H.; Sherwood, P.; Siroli, G.P.; Sittler, A.; Skuja, A.; Smith, A.M.; Snow, G.A.; Sobie, R.; Soldner-Rembold, S.; Spagnolo, S.; Sproston, M.; Stahl, A.; Stephens, K.; Steuerer, J.; Stoll, K.; Strom, David M.; Strohmer, R.; Surrow, B.; Talbot, S.D.; Taras, P.; Tarem, S.; Teuscher, R.; Thiergen, M.; Thomas, J.; Thomson, M.A.; Torrence, E.; Towers, S.; Trigger, I.; Trocsanyi, Z.; Tsur, E.; Turner-Watson, M.F.; Ueda, I.; Van Kooten, Rick J.; Vannerem, P.; Verzocchi, M.; Voss, H.; Wackerle, F.; Wagner, A.; Ward, C.P.; Ward, D.R.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wermes, N.; Wetterling, D.; White, J.S.; Wilson, G.W.; Wilson, J.A.; Wyatt, T.R.; Yamashita, S.; Zacek, V.; Zer-Zion, D.

    1999-01-01

    We present a test of the flavour independence of the strong coupling constant for charm and bottom quarks with respect to light (uds) quarks, based on a hadronic event sample obtained with the OPAL detector at LEP. Five observables related to global event shapes were used to measure alpha_s in three flavour tagged samples (uds, c and b). The event shape distributions were fitted by Order(alpha_s**2) calculations of jet production taking into account mass effects for the c and b quarks. We find: = 0.997 +- 0.038(stat.) +- 0.030(syst.) +- 0.012(theory) and = 0.993 +- 0.008(stat.) +- 0.006(syst.) +- 0.011(theory) for the ratios alpha_s(charm)/alpha_s(uds) and alpha_s(b)/alpha_s(uds) respectively.

  8. Evidence that two stereochemically different alpha-2 adrenoceptors modulate norepinephrine release in rat cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Harsing, L.G. Jr.; Vizi, E.S. (Institute of Experimental Medicine, Budapest (Hungary))

    1991-01-01

    Cerebral cortex slices from the rat were loaded with (3H)norepinephrine ((3H)NE) and superfused in order to measure the release of radioactivity at rest and in response to electrical stimulation. The (-)-isomer and the (+)-isomer of CH-38083 (7,8-(methylenedioxy)-14- alpha-hydroxyalloberbane HCl), a selective alpha-2-adrenoceptor antagonist with an alloberbane skeleton, increased the electrically induced release of (3H)NE in a concentration-dependent manner, and a similar effect was observed with racemic CH-38083 and idazoxan. The stereoisomers of CH-38083 applied in a concentration range of 10(-8) to 10(-6) mol/l were equipotent in facilitating stimulation-evoked (3H)NE release: concentrations needed to enhance tritium outflow by 50% were 1.3 X 10(-7) mol/l for (-)-CH-38083 and 1.4 X 10(-7) mol/l for (+)-CH-38083. Exogenous NE decreased the electrically stimulated release of (3H)NE, and the stereoisomers of CH-38083 antagonized this inhibition with different potencies: the dissociation constant (KB) values for (-)-isomer and for (+)-isomer of CH-38083 were 14.29 and 97.18 nmol/l. These data indicate that presynaptic alpha-2 adrenoceptors that are available for NE released from axon terminals do not show stereospecificity toward enantiomers of CH-38083, whereas those that are occupied by exogenous NE are much more sensitive toward (-)-CH-38083. The alpha-1 adrenoceptor antagonist prazosin also differentiated between the alpha-2 adrenoceptor subtypes: prazosin (10(-6) mol/l) did not alter the increase of electrically induced (3H)NE release evoked by (-)- and (+)-CH-38083; however, in its presence, the stereoisomers of CH-38083 failed to antagonize the inhibitory effect of exogenous NE on its own release.

  9. The interaction of CK2alpha and CK2beta, the subunits of protein kinase CK2, requires CK2beta in a preformed conformation and is enthalpically driven

    DEFF Research Database (Denmark)

    Raaf, Jennifer; Brunstein, Elena; Issinger, Olaf-Georg

    2008-01-01

    . In contrast to the cyclins in the case of the cyclin-dependent kinases CK2beta is no on-switch of CK2alpha; rather the formation of the CK2 holoenzyme is accompanied with an overall change of the enzyme's profile including a modulation of the substrate specificity, an increase of the thermostability......, and an allocation of docking sites for membranes and other proteins. In this study we used C-terminal deletion variants of human CK2alpha and CK2beta that were enzymologically fully competent and in particular able to form a heterotetrameric holoenzyme. With differential scanning calorimetry (DSC) we confirmed...

  10. SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate binding to growth factor receptors.

    Science.gov (United States)

    McGlade, C J; Ellis, C; Reedijk, M; Anderson, D; Mbamalu, G; Reith, A D; Panayotou, G; End, P; Bernstein, A; Kazlauskas, A

    1992-01-01

    The binding of cytoplasmic signaling proteins such as phospholipase C-gamma 1 and Ras GTPase-activating protein to autophosphorylated growth factor receptors is directed by their noncatalytic Src homology region 2 (SH2) domains. The p85 alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase, which associates with several receptor protein-tyrosine kinases, also contains two SH2 domains. Both p85 alpha SH2 domains, when expressed individually as fusion proteins in bacteria, bound stably to the activated beta receptor for platelet-derived growth factor (PDGF). Complex formation required PDGF stimulation and was dependent on receptor tyrosine kinase activity. The bacterial p85 alpha SH2 domains recognized activated beta PDGF receptor which had been immobilized on a filter, indicating that SH2 domains contact autophosphorylated receptors directly. Several receptor tyrosine kinases within the PDGF receptor subfamily, including the colony-stimulating factor 1 receptor and the Steel factor receptor (Kit), also associate with PI 3-kinase in vivo. Bacterially expressed SH2 domains derived from the p85 alpha subunit of PI 3-kinase bound in vitro to the activated colony-stimulating factor 1 receptor and to Kit. We infer that the SH2 domains of p85 alpha bind to high-affinity sites on these receptors, whose creation is dependent on receptor autophosphorylation. The SH2 domains of p85 are therefore primarily responsible for the binding of PI 3-kinase to activated growth factor receptors. Images PMID:1372092

  11. Involvement of activated leukocytes in the regulation of plasma levels of acute phase proteins in microgravity simulation experiments

    Science.gov (United States)

    Larina, Olga; Bekker, Anna; Turin-Kuzmin, Alexey

    2016-07-01

    Earth-based studies of microgravity effects showed the induction of the mechanisms of acute phase reaction (APR). APR comprises the transition of stress-sensitive protein kinases of macrophages and other responsive cells into the active state and the phosphorylation of transcription factors which in turn stimulate the production of acute-phase reaction cytokines. Leukocyte activation is accompanied by the acceleration of the formation of oxygen radicals which can serve a functional indice of leukocyte cell state. The series of events at acute phase response result in selective changes in the synthesis of a number of secretory blood proteins (acute phase proteins, APPs) in liver cells thus contributing the recovery of homeostasis state in the organism. Earlier experiment with head-down tilt showed the increase in plasma concentrations of two cytokine mediators of acute phase response, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) being the outcome of the activation of producer cells, foremost, leukocytes. In experiment with 4-day dry immersion chemiluminescent (ChL) reply of the whole blood samples to a test stimulus were studied along with the measurements of plasma levels of APPs, namely, alpha1-antitrypsin (alpha1-AT), alpha1-acid glycoprotein (alpha1-AGP), alpha2-macroglobulin (alpha2-M), ceruloplasmin (Cer), haptoglobin (Hp), C3-complement component (C3), C-reactive protein (CRP). Eight individuals aged 21.2 ± 3.2 years were the test subjects in the investigation. Protein studies showed a noticeable increase in the mean plasma levels of all APPs measured in experiment thus producing the evidence of the activation of acute phase response mechanisms while individual patterns revealed variability during the immersion period. The overall trends were similar to these in the previous immersion series. The augment in the strength of signal in stimulated light emission tests was higher after 1- and 2-day of immersion exposure than before the

  12. Identification of metabolites in urine and feces from rats dosed with the heterocyclic amine, 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C)

    DEFF Research Database (Denmark)

    Frederiksen, H; Frandsen, H

    2004-01-01

    2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeA alpha C can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study, the in ......2-Amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeA alpha C can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study...

  13. Evaluation of radioiodinated (2S,{alpha}S)-2-({alpha}-(2-iodophenoxy)benzyl)morpholine as a radioligand for imaging of norepinephrine transporter in the heart

    Energy Technology Data Exchange (ETDEWEB)

    Kiyono, Yasushi [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan)], E-mail: ykiyono@u-fukui.ac.jp; Sugita, Taku [Department of Pathofunctional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Ueda, Masashi [Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Kawashima, Hidekazu [Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Kanegawa, Naoki; Kuge, Yuji [Department of Pathofunctional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Saji, Hideo [Department of Pathofunctional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)

    2008-02-15

    Introduction: The norepinephrine transporter (NET) is located presynaptically on noradrenergic nerve terminals and plays a critical role in the regulation of the synaptic norepinephrine (NE) concentration via the reuptake of NE. Changes in NET have been recently reported in several cardiac failures. Therefore, a NET-specific radioligand is useful for in vivo assessment of changes in NET density in various cardiac disorders. Recently, we developed a radioiodinated reboxetine analogue, (2S,{alpha}S)-2-({alpha}-(2-iodophenoxy)benzyl)morpholine ((S,S)-IPBM), for NET imaging. In the current study, we assessed the applicability of radioiodinated (S,S)-IPBM to NET imaging in the heart. Methods: The NET affinity and selectivity were measured from the ability to displace specific [{sup 3}H]nisoxetine and (S,S)-[{sup 125}I]IPBM binding to rat heart membrane, respectively. To evaluate the distribution of (S,S)-[{sup 125}I]IPBM in vivo, biodistribution experiment was performed in rats. With the use of several monoamine transporter binding agents, pharmacological blocking experiments were performed in rats. Results: In vitro binding assays showed that the affinity of (S,S)-IPBM to NET was similar to those of the well-known NET-specific binding agents, nisoxetine and desipramine. Furthermore, (S,S)-[{sup 125}I]IPBM binding was inhibited by nisoxetine and desipramine, but not by dopamine or serotonin transporter binding agents. These data indicated that (S,S)-IPBM had high affinity and selectivity for NET in vitro. Biodistribution studies in rats showed rapid and high uptake of (S,S)-[{sup 125}I]IPBM by the heart and rapid clearance from the blood. The heart-to-blood ratio was 31.9 at 180 min after the injection. The administration of nisoxetine and desipramine decreased (S,S)-[{sup 125}I]IPBM accumulation in the heart, but injection of fluoxetine and GBR12909 had little influence. Conclusions: Radioiodinated (S,S)-IPBM is a potential radioligand for NET imaging in the heart.

  14. Reverse-phase HPLC analysis of human alpha crystallin.

    Science.gov (United States)

    Swamy, M S; Abraham, E C

    1991-03-01

    A rapid and highly sensitive reverse-phase HPLC (RP-HPLC) method was used to separate crystallin subunits from human alpha crystallin. Three distinct peaks were separated; by electrophoretic and immunological analyses the first and second peaks were identified as alpha B and alpha A respectively. On the other hand, peak 3 appeared to be a modified form of alpha crystallin. The ratio of alpha A and alpha B proteins was 3:1 in 1 day old lenses which gradually changed to 2:1 in 17 year old lenses and to 1:1 in the 50 and 82 year old whole lenses and 82 year old lens cortex, with a concomitant increase in the modified alpha, suggesting that alpha A subunits are relatively more involved in aggregation. Analysis of the 82 year old lens nucleus also supported this conclusion. The RP-HPLC analysis of the HMW aggregate fraction showed substantial enrichment of the modified alpha. The alpha A and alpha B subunits independently reassociated to form polymeric alpha crystallin whereas the modified alpha reassociated to form HMW aggregates as shown by molecular sieve HPLC. Hence it appears that the HMW aggregate peak was constituted by modified alpha crystallin. Only in the peak 3 material the 280 nm absorbance was about 2-fold higher than what was expected from the actual protein content. The data suggest that the changes induced by post-translational modifications may have some role in the formation of modified alpha. The present RP-HPLC method is useful in separating these modified alpha from the unmodified alpha A and alpha B subunits.

  15. Far-Infrared and Millimeter Continuum Studies of K-Giants: Alpha Boo and Alpha Tau

    Science.gov (United States)

    Cohen, Martin; Carbon, Duane F.; Welch, William J.; Lim, Tanya; Forster, James R.; Goorvitch, David; Thigpen, William (Technical Monitor)

    2002-01-01

    We have imaged two normal, non-coronal, infrared-bright K-giants, alpha Boo and alpha Tau, in the 1.4-millimeter and 2.8-millimeter continuum using BIMA. These stars have been used as important absolute calibrators for several infrared satellites. Our goals are: (1) to probe the structure of their upper photospheres; (2) to establish whether these stars radiate as simple photospheres or possess long-wavelength chromospheres; and (3) to make a connection between millimeter-wave and far-infrared absolute flux calibrations. To accomplish these goals we also present ISO Long Wavelength Spectrometer (LWS) measurements of both these K-giants. The far-infrared and millimeter continuum radiation is produced in the vicinity of the temperature minimum in a Boo and a Tau, offering a direct test of the model photospheres and chromospheres for these two cool giants. We find that current photospheric models predict fluxes in reasonable agreement with those observed for those wavelengths which sample the upper photosphere, namely less than or equal to 170 micrometers in alpha Tau and less than or equal to 125 micrometers in alpha Boo. It is possible that alpha Tau is still radiative as far as 0.9 - 1.4 millimeters. We detect chromospheric radiation from both stars by 2.8 millimeters (by 1.4 millimeters in alpha Boo), and are able to establish useful bounds on the location of the temperature minimum. An attempt to interpret the chromospheric fluxes using the two-component "bifurcation model" proposed by Wiedemann et al. (1994) appears to lead to a significant contradiction.

  16. Determination of $\\alpha_{s}$ using Jet Rates at LEP with the OPAL detector

    CERN Document Server

    Abbiendi, G.; Akesson, P.F.; Alexander, G.; Anagnostou, G.; Anderson, K.J.; Asai, S.; Axen, D.; Bailey, I.; Barberio, E.; Barillari, T.; Barlow, R.J.; Batley, R.J.; Bechtle, P.; Behnke, T.; Bell, Kenneth Watson; Bell, P.J.; Bella, G.; Bellerive, A.; Benelli, G.; Bethke, S.; Biebel, O.; Boeriu, O.; Bock, P.; Boutemeur, M.; Braibant, S.; Brown, Robert M.; Burckhart, H.J.; Campana, S.; Capiluppi, P.; Carnegie, R.K.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, D.G.; Ciocca, C.; Csilling, A.; Cuffiani, M.; Dado, S.; De Roeck, A.; De Wolf, E.A.; Desch, K.; Dienes, B.; Donkers, M.; Dubbert, J.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Etzion, E.; Fabbri, F.; Ferrari, P.; Fiedler, F.; Fleck, I.; Ford, M.; Frey, A.; Gagnon, P.; Gary, John William; Geich-Gimbel, C.; Giacomelli, G.; Giacomelli, P.; Giunta, Marina; Goldberg, J.; Gross, E.; Grunhaus, J.; Gruwe, M.; Gunther, P.O.; Gupta, A.; Hajdu, C.; Hamann, M.; Hanson, G.G.; Harel, A.; Hauschild, M.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Herten, G.; Heuer, R.D.; Hill, J.C.; Horvath, D.; Igo-Kemenes, P.; Ishii, K.; Jeremie, H.; Jovanovic, P.; Junk, T.R.; Kanzaki, J.; Karlen, D.; Kawagoe, K.; Kawamoto, T.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Kluth, S.; Kobayashi, T.; Kobel, M.; Komamiya, S.; Kramer, T.; Krasznahorkay, A.; Krieger, P.; von Krogh, J.; Kuhl, T.; Kupper, M.; Lafferty, G.D.; Landsman, H.; Lanske, D.; Lellouch, D.; Lettso, J.; Levinson, L.; Lillich, J.; Lloyd, S.L.; Loebinger, F.K.; Lu, J.; Ludwig, A.; Ludwig, J.; Mader, W.; Marcellini, S.; Martin, A.J.; Mashimo, T.; Mattig, Peter; McKenna, J.; McPherson, R.A.; Meijers, F.; Menges, W.; Merritt, F.S.; Mes, H.; Meyer, Niels T.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Mohr, W.; Mori, T.; Mutter, A.; Nagai, K.; Nakamura, I.; Nanjo, H.; Neal, H.A.; Nisius, R.; O'Neale, S.W.; Oh, A.; Oreglia, M.J.; Orito, S.; Pahl, C.; Pasztor, G.; Pater, J.R.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Pooth, O.; Przybycien, M.; Quadt, A.; Rabbertz, K.; Rembser, C.; Renkel, P.; Roney, J.M.; Rossi, A.M.; Rozen, Y.; Runge, K.; Sachs, K.; Saeki, T.; Sarkisyan, E.K.G.; Schaile, A.D.; Schaile, O.; Scharff-Hansen, P.; Schieck, J.; Schorner-Sadenius, T.; Schroder, Matthias; Schumacher, M.; Seuster, R.; Shears, T.G.; Shen, B.C.; Sherwood, P.; Skuja, A.; Smith, A.M.; Sobie, R.; Soldner-Rembold, S.; Spano, F.; Stahl, A.; Strom, David M.; Strohmer, R.; Tarem, S.; Tasevsky, M.; Teuscher, R.; Thomson, M.A.; Torrence, E.; Toya, D.; Tran, P.; Trigger, I.; Trocsanyi, Z.; Tsur, E.; Turner-Watson, M.F.; Ueda, I.; Ujvari, B.; Vollmer, C.F.; Vannerem, P.; Vertesi, R.; Verzocchi, M.; Voss, H.; Vossebeld, J.; Ward, C.P.; Ward, D.R.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wengler, T.; Wermes, N.; Wilson, G.W.; Wilson, J.A.; Wolf, G.; Wyatt, T.R.; Yamashita, S.; Zer-Zion, D.; Zivkovic, Lidija

    2006-01-01

    Hadronic events produced in e+e- collisions by the LEP collider and recorded by the OPAL detector were used to form distributions based on the number of reconstructed jets. The data were collected between 1995 and 2000 and correspond to energies of 91 GeV, 130-136 GeV and 161-209 GeV. The jet rates were determined using four different jet-finding algorithms (Cone, JADE, Durham and Cambridge). The differential two-jet rate and the average jet rate with the Durham and Cambridge algorithms were used to measure alpha(s) in the LEP energy range by fitting an expression in which order alpah_2s calculations were matched to a NLLA prediction and fitted to the data. Combining the measurements at different centre-of-mass energies, the value of alpha_s (Mz) was determined to be alpha(s)(Mz)=0.1177+-0.0006(stat.)+-0.0012$(expt.)+-0.0010(had.)+-0.0032

  17. Analysis of Maxi-K alpha subunit splice variants in human myometrium

    Directory of Open Access Journals (Sweden)

    Morrison John J

    2004-09-01

    Full Text Available Abstract Background Large-conductance, calcium-activated potassium (Maxi-K channels are implicated in the modulation of human uterine contractions and myometrial Ca2+ homeostasis. However, the regulatory mechanism(s governing the expression of Maxi-K channels with decreased calcium sensitivity at parturition are unclear. The objectives of this study were to investigate mRNA expression of the Maxi-K alpha subunit, and that of its splice variants, in human non-pregnant and pregnant myometrium, prior to and after labour onset, to determine whether altered expression of these splice variants is associated with decreased calcium sensitivity observed at labour onset. Methods Myometrial biopsies were obtained at hysterectomy (non-pregnant, NP, and at Caesarean section, at elective (pregnant not-in-labour, PNL and intrapartum (pregnant in-labour, PL procedures. RNA was extracted from all biopsies and quantitative real-time RT-PCR was used to investigate for possible differential expression of the Maxi-K alpha subunit, and that of its splice variants, between these functionally-distinct myometrial tissue sets. Results RT-PCR analysis identified the presence of a 132 bp and an 87 bp spliced exon of the Maxi-K alpha subunit in all three myometrial tissue sets. Quantitative real-time PCR indicated a decrease in the expression of the Maxi-K alpha subunit with labour onset. While there was no change in the proportion of Maxi-K alpha subunits expressing the 87 bp spliced exon, the proportion of alpha subunits expressing the 132 bp spliced exon was significantly increased with labour onset, compared to both non-pregnant and pregnant not-in-labour tissues. An increased proportion of 132 bp exon-containing alpha subunit variants with labour onset is of interest, as channels expressing this spliced exon have decreased calcium and voltage sensitivities. Conclusions Our findings suggest that decreased Maxi-K alpha subunit mRNA expression in human myometrium at

  18. Activation of peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) suppresses postprandial lipidemia through fatty acid oxidation in enterocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Rino [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Takahashi, Nobuyuki, E-mail: nobu@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Murota, Kaeko [Department of Life Science, School of Science and Engineering, Kinki University, Osaka 770-8503 (Japan); Yamada, Yuko [Laboratory of Physiological Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Niiya, Saori; Kanzaki, Noriyuki; Murakami, Yoko [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Moriyama, Tatsuya [Department of Applied Cell Biology, Graduate School of Agriculture, Kinki University, Nara 631-8505 (Japan); Goto, Tsuyoshi; Kawada, Teruo [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)

    2011-06-24

    Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of fatty acid oxidation-related genes in human intestinal epithelial Caco-2 cells. {yields} PPAR{alpha} activation also increased oxygen consumption rate and CO{sub 2} production and decreased secretion of triglyceride and ApoB from Caco-2 cells. {yields} Orally administration of bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and CO{sub 2} production in small intestinal epithelial cells. {yields} Treatment with bezafibrate decreased postprandial serum concentration of triglyceride after oral injection of olive oil in mice. {yields} It suggested that intestinal lipid metabolism regulated by PPAR{alpha} activation suppresses postprandial lipidemia. -- Abstract: Activation of peroxisome proliferator-activated receptor (PPAR)-{alpha} which regulates lipid metabolism in peripheral tissues such as the liver and skeletal muscle, decreases circulating lipid levels, thus improving hyperlipidemia under fasting conditions. Recently, postprandial serum lipid levels have been found to correlate more closely to cardiovascular diseases than fasting levels, although fasting hyperlipidemia is considered an important risk of cardiovascular diseases. However, the effect of PPAR{alpha} activation on postprandial lipidemia has not been clarified. In this study, we examined the effects of PPAR{alpha} activation in enterocytes on lipid secretion and postprandial lipidemia. In Caco-2 enterocytes, bezafibrate, a potent PPAR{alpha} agonist, increased mRNA expression levels of fatty acid oxidation-related genes, such as acyl-CoA oxidase, carnitine palmitoyl transferase, and acyl-CoA synthase, and oxygen consumption rate (OCR) and suppressed secretion levels of both triglycerides and apolipoprotein B into the basolateral side. In vivo experiments revealed that feeding high-fat-diet containing bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and

  19. Exhaustive Weakly Wandering Sequences and Alpha-type Transformations

    Directory of Open Access Journals (Sweden)

    Stanley Eigen

    2015-12-01

    Full Text Available An increasing sequence of integers, $\\mathbb{B}$, is given for which there exists a family of ergodic, infinite measure preserving transformations $T_\\alpha$, $0 \\leq \\alpha \\leq 1$ so that (1 $T_\\alpha$ is of $\\alpha$-type and (2 $\\mathbb{B}$ is an exhaustive weakly wandering sequence for each $T_\\alpha$.

  20. Effects of cigarette smoke exposure on nicotinic acetylcholine receptor subunits {alpha}7 and {beta}2 in the sudden infant death syndrome (SIDS) brainstem

    Energy Technology Data Exchange (ETDEWEB)

    Machaalani, Rita, E-mail: rita.machaalani@sydney.edu.au [Department of Medicine, The University of Sydney, NSW 2006 (Australia); Bosch Institute, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia); Say, Meichien [Department of Medicine, The University of Sydney, NSW 2006 (Australia); Bosch Institute, The University of Sydney, NSW 2006 (Australia); Waters, Karen A. [Department of Medicine, The University of Sydney, NSW 2006 (Australia); Bosch Institute, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia)

    2011-12-15

    It is postulated that nicotine, as the main neurotoxic constituent of cigarette smoke, influences SIDS risk through effects on nicotinic acetylcholine receptors (nAChRs) in brainstem nuclei that control respiration and arousal. This study compared {alpha}7 and {beta}2 nAChR subunit expression in eight nuclei of the caudal and rostral medulla and seven nuclei of the pons between SIDS (n = 46) and non-SIDS infants (n = 14). Evaluation for associations with known SIDS risk factors included comparison according to whether infants had a history of exposure to cigarette smoke in the home, and stratification for sleep position and gender. Compared to non-SIDS infants, SIDS infants had significantly decreased {alpha}7 in the caudal nucleus of the solitary tract (cNTS), gracile and cuneate nuclei, with decreased {beta}2 in the cNTS and increased {beta}2 in the facial. When considering only the SIDS cohort: 1-cigarette smoke exposure was associated with increased {alpha}7 in the vestibular nucleus and increased {beta}2 in the rostral dorsal motor nucleus of the vagus, rNTS and Cuneate, 2-there was a gender interaction for {alpha}7 in the gracile and cuneate, and {beta}2 in the cNTS and rostral arcuate nucleus, and 3-there was no effect of sleep position on {alpha}7, but prone sleep was associated with decreased {beta}2 in three nuclei of the pons. In conclusion, SIDS infants demonstrate differences in expression of {alpha}7 and {beta}2 nAChRs within brainstem nuclei that control respiration and arousal, which is independent on prior history of cigarette smoke exposure, especially for the NTS, with additional differences for smoke exposure ({beta}2), gender ({alpha}7 and {beta}2) and sleep position ({beta}2) evident. -- Highlights: Black-Right-Pointing-Pointer The 'normal' response to smoke exposure is decreased {alpha}7 and {beta}2 in certain nuclei. Black-Right-Pointing-Pointer SIDS infants have decreased {alpha}7 in cNTS, Grac and Cun. Black

  1. 3-[2,4-Dimethoxybenzylidene]anabaseine (DMXB) selectively activates rat alpha7 receptors and improves memory-related behaviors in a mecamylamine-sensitive manner.

    Science.gov (United States)

    Meyer, E M; Tay, E T; Papke, R L; Meyers, C; Huang, G L; de Fiebre, C M

    1997-09-12

    The alpha7 nicotinic receptor agonist 3-[2,4-dimethoxybenzylidene]anabaseine (DMXB; GTS-21) was investigated for its ability to: (1) activate a variety of nicotinic receptor subtypes in Xenopus oocytes; (2) improve passive avoidance and spatial Morris water task performances in mecamylamine-sensitive manners in bilaterally nucleus basalis lesioned rats; and (3) elevate high-affinity [3H]acetylcholine (ACh) and high-affinity alpha-[125I]bungarotoxin binding in rat neocortex following 2 weeks of daily injections. DMXB (100 microM) activated alpha7 homo-oligomeric receptors, without significant activity at alpha2-, alpha3- and alpha4-containing subtypes. Mecamylamine blocked rat alpha7 receptors weakly if co-administered with agonist, but much more potently when pre-applied. Bilateral ibotenic acid lesions of the nucleus basalis interfered with passive avoidance and spatial memory-related behaviors. DMXB (0.5 mg/kg, i.p.) improved passive avoidance behavior in lesioned animals in a mecamylamine-sensitive manner. DMXB (0.5 mg/kg 15 min before each session) also improved performance in the training and probe components of the Morris water task. DMXB-induced improvement in the probe component but not the training phase was mecamylamine-sensitive. [3H]ACh binding was elevated after 14 days of daily i.p. injections with 0.2 mg/kg nicotine but not after 1 mg/kg DMXB. Neither drug elevated high-affinity alpha-[125I]bungarorotoxin binding over this interval.

  2. Serum concentrations of interleukin-1 alpha, interleukin-6 and tumor necrosis factor-alpha in neonatal sepsis and meningitis

    International Nuclear Information System (INIS)

    Fida, Nadia M.; Fadelallah, Mohamed F.; Al-Mughales, Jamil A.

    2006-01-01

    To investigate whether serum levels of interleukin-1alpha (IL-1alpha), IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP) are useful in the diagnosis of neonatal sepsis and meningitis and differentiate them. Blood samples were collected from 35 full term neonates with suspected infection who admitted to the Neonatology Unit, Pediatric Department, King Abdul-Aziz University Hospital, Jeddah, Saudi Arabia during January 2002 - June 2003. On the basis of laboratory and bacteriological results, newborns were classified into: sepsis (n=28), meningitis (n=7), and healthy controls (n=16). Sepsis groups were further subdivided according to culture results into: group 1 = proven sepsis (n=6), group 2 = clinical sepsis (n=14), and group 3 = possible-infected (n=8). Serum levels of IL-1alpha, IL-6, TNF-alpha were measured using Enzyme-Linked Immunosorbent Assay while CRP by nephelometer: In sepsis and meningitis patients, serum levels of CRP (p<0.01, p<0.05,) and IL-1alpha (p<0.001, p<0.05) were elevated than controls. C-reactive protein levels elevated in proven sepsis (p<0.001) and IL-1alpha elevated in all subgroups of sepsis (groups 1, 2, 3) compared with (p<0.05, p<0.001, p<0.01) controls. Interleukin-6, TNF-alpha showed no significant differences between studied groups. In sepsis and meningitis, IL-1alpha had a highest sensitivity (89%, 86%), and negative predictive values (89% and 93%). Interleukin-1alpha and CRP increased in neonatal sepsis and meningitis, but cannot differentiate between them. Interleukin-1alpha had a highest sensitivity in prediction of neonatal infection and its assessment may improve accuracy of diagnosis. (author)

  3. Inhibition of [11C]mirtazapine binding by alpha2-adrenoceptor antagonists studied by positron emission tomography in living porcine brain

    DEFF Research Database (Denmark)

    Smith, Donald F; Dyve, Suzan; Minuzzi, Luciano

    2006-01-01

    Inhibition of [11C]mirtazapine binding by alpha2-adrenoceptor antagonists studied by positron emission tomography in living porcine brain......Inhibition of [11C]mirtazapine binding by alpha2-adrenoceptor antagonists studied by positron emission tomography in living porcine brain...

  4. VNTR alleles associated with the {alpha}-globin locus are haplotype and population related

    Energy Technology Data Exchange (ETDEWEB)

    Martinson, J.J.; Clegg, J.B.; Boyce, A.J. [Univ. of Oxford (United Kingdom)

    1994-09-01

    The human {alpha}-globin complex contains several polymorphic restriction-enzyme sites (i.e., RFLPs) linked to form haplotypes and is flanked by two hypervariable VNTR loci, the 5{prime} hypervariable region (HVR) and the more highly polymorphic 3{prime}HVR. Using a combination of RFLP analysis and PCR, the authors have characterized the 5{prime}HVR and 3{prime}HVR alleles associated with the {alpha}-globin haplotypes of 133 chromosomes, and they here show that specific {alpha}-globin haplotypes are each associated with discrete subsets of the alleles observed at these two VNTR loci. This statistically highly significant association is observed over a region spanning {approximately} 100 kb. With the exception of closely related haplotypes, different haplotypes do not share identically sized 3{prime}HVR alleles. Earlier studies have shown that {alpha}-globin haplotype distributions differ between populations; the current findings also reveal extensive population substructure in the repertoire of {alpha}-globin VNTRs. If similar features are characteristic of other VNTR loci, this will have important implications for forensic and anthropological studies. 42 refs., 5 figs., 5 tabs.

  5. ALPHA-BETA SEPARATION PORTFOLIO STRATEGIES FOR ISLAMIC FINANCE

    Directory of Open Access Journals (Sweden)

    Valentyn Khokhlov

    2016-11-01

    Full Text Available The purpose of this paper is to develop a mathematical alpha-beta separation model that can be used to create a core-satellite portfolio management strategy that complies with the principles of Islamic finance. Methodology. Core-satellite portfolio construction methodology is used to implement the alpha-beta separation approach, where the core part of the portfolio is managed using the tracking error minimization strategy, and the satellite part of the portfolio is managed using the mean-variance optimization strategy. Results of the portfolio dynamics clearly show that a significant amount of value was created by alpha-beta separation. The typical alpha ranges from 4% to 5.7%. The most aggressive portfolio strategies that allow short positions in the satellite portfolio work best with frequent rebalancing and benefit from the active bets. Smoothing technique that was introduced to decrease the portfolio turnover and stabilize its composition works better when active bets are less efficient, particularly with less frequent rebalancing. The best risk-return combinations are achieved with modest (3% to 10% allocation of the total portfolio to the satellite, and the remaining part (90% to 97% being managed in order to minimize the tracking error. Practical implications. The alpha-beta separation framework suggested in this paper can be used to enhance the portfolio management techniques for the hedge funds that operate under tight restrictions, particularly under the Islamic finance principles. The mathematical models developed in this paper allow practical implementation of the alphabeta separation concept. Originality/value. While the idea of alpha-beta separation existed in hedge fund management before, there was no comprehensive mathematical model under it, so its implementation was based on the ad hoc approach. This paper introduces such a mathematical model and demonstrates how portfolio managers can create value for their clients using it.

  6. Mild prenatal protein malnutrition increases alpha 2C-adrenoceptor expression in the rat cerebral cortex during postnatal life.

    Science.gov (United States)

    Sierralta, Walter; Hernández, Alejandro; Valladares, Luis; Pérez, Hernán; Mondaca, Mauricio; Soto-Moyano, Rubén

    2006-05-15

    Mild reduction in the protein content in the diet of pregnant rats from 25 to 8% casein, calorically compensated by carbohydrates, does not alter body and brain weights of rat pups at birth, but results in significant changes of the concentration and release of cortical noradrenaline during postnatal life, together with impaired long-term potentiation and memory formation. Since some central noradrenergic receptors are critically involved in neuroplasticity, the present study evaluated, by utilizing immunohistochemical methods, the effect of mild prenatal protein malnutrition on the alpha 2C-adrenoceptor expression in the frontal and occipital cortices of 8- and 60-day-old rats. At day 8 of postnatal age, prenatally malnourished rats exhibited a three-fold increase of alpha 2C-adrenoceptor expression in both the frontal and the occipital cortices, as compared to well-nourished controls. At 60 days of age, prenatally malnourished rats showed normal expression levels scores of alpha 2C-adrenoceptor in the neocortex. Results suggest that overexpression of neocortical alpha 2C-adrenoceptors during early postnatal life, subsequent to mild prenatal protein malnutrition, could in part be responsible for neural and behavioral disturbances showing prenatally malnourished animals during the postnatal life.

  7. Concentration levels of alpha emitting radionuclides in natural waters. Implications in the use of various radionuclides of reference for the determination of total alpha activity index; Niveles de concentracion de radionucleidos emisores alfa en aguas de origen natural. Implicaciones en el uso de los distintos radionucleidos de referencia para la determinacion del indice de actividad total alfa

    Energy Technology Data Exchange (ETDEWEB)

    Corbacho, J. A.; Baeza, A.; Guillen, J.; Valles, I.; Serrano, I.; Camacho, A.; Montana, M.

    2013-07-01

    The present study was carried out a statistical evaluation of the natural radioactive contents of a large number of water samples collected at different points of the Spanish geography, in order to meet its controlling radioactive composition and assessing the implications of total alpha activity index can have in this type of samples. (Author)

  8. Gene Therapy for Fracture Repair

    Science.gov (United States)

    2007-05-01

    modulator-1; c-myc binding protein [ Homo sapiens ]. regulation of transcription, DNA dependent NM_012488 1.55 2.53 Rattus norvegicus α-2-macroglobulin...myc binding protein [ Homo sapiens ] Regulation of transcription, DNA dependent NM_012488 1.55 2.53 Rattus norvegicus α-2-macroglobulin (A2m) Protease...1-HIV LTR-MLV Promoter EG FP -C el l N um be r (M ea n) 10 ul Vector 50 ul Vector 7 Periosteal/Endosteal Cell Transduction 0 200 400 600 800

  9. Diverse functional consequences of mutations in the Na+/K+-ATPase alpha2-subunit causing familial hemiplegic migraine type 2.

    NARCIS (Netherlands)

    Tavraz, N.N.; Friedrich, T.; Durr, K.L.; Koenderink, J.B.; Bamberg, E.; Freilinger, T.; Dichgans, M.

    2008-01-01

    Mutations in ATP1A2, the gene coding for the Na(+)/K(+)-ATPase alpha(2)-subunit, are associated with both familial hemiplegic migraine and sporadic cases of hemiplegic migraine. In this study, we examined the functional properties of 11 ATP1A2 mutations associated with familial or sporadic

  10. Induction of VEGF expression by alpha-tocopherol and alpha-tocopheryl phosphate via PI3Kgamma/PKB and hTAP1/SEC14L2-mediated lipid exchange

    Science.gov (United States)

    In several studies, vitamin E has been observed to influence angiogenesis and vasculogenesis. We recently showed that the phosphorylated form of alpha-tocopherol (alphaT), alpha-tocopheryl phosphate (alphaTP), increases the expression of the vascular endothelial growth factor (VEGF). Thus, alphaTP m...

  11. Mapping of the mouse actin capping protein {alpha} subunit genes and pseudogenes

    Energy Technology Data Exchange (ETDEWEB)

    Hart, M.C.; Korshunova, Y.O.; Cooper, J.A. [Washington Univ. School of Medicine, St. Louis, MO (United States)

    1997-02-01

    Capping protein (CP), a heterodimer of {alpha} and {beta} subunits, is found in all eukaryotes. CP binds to the barbed ends of actin filaments in vitro and controls actin assembly and cell motility in vivo. Vertebrates have three {alpha} isoforms ({alpha}1, {alpha}2, {alpha}3) produced from different genes, whereas lower organisms have only one gene and one isoform. We isolated genomic clones corresponding to the a subunits of mouse CP and found three {alpha}1 genes, two of which are pseudogenes, and a single gene for both {alpha}2 and {alpha}3. Their chromosomal locations were identified by interspecies backcross mapping. The {alpha}1 gene (Cappa1) mapped to Chromosome 3 between D3Mit11 and D3Mit13. The {alpha}1 pseudogenes (Cappa1-ps1 and Cappa1-ps2) mapped to Chromosomes 1 and 9, respectively. The {alpha}2 gene (Cappa2) mapped to Chromosome 6 near Ptn. The {alpha}3 gene (Cappa3) also mapped to Chromosome 6, approximately 68 cM distal from Cappa2 near Kras2. One mouse mutation, de, maps in the vicinity of the {alpha}1 gene. No known mouse mutations map to regions near the {alpha}2 or {alpha}3 genes. 29 refs., 3 figs., 1 tab.

  12. Interstitial positions of tin ions in alpha-(FerichSn)(2)O-3 solid solutions prepared by mechanical alloying

    DEFF Research Database (Denmark)

    Jiang, Jianzhong; Lin, Rong; Nielsen, Kurt

    1997-01-01

    The microstructure of samples of 91, 85, and 71 mol % alpha-Fe-2-O-3-SnO2. prepared by mechanical alloying, has been studied by x-ray diffraction with Rietveld structure refinements, On the basis of the structure refinements to the whole x-ray diffraction patterns for the four as-milled samples, ......, it is found that tin ions do not substitute iron ions in the solid solution, although this model is generally assumed in the literature. The Sn4+ ions occupy the empty octahedral holes in the lattice of the alpha-Fe2O3 phase.......The microstructure of samples of 91, 85, and 71 mol % alpha-Fe-2-O-3-SnO2. prepared by mechanical alloying, has been studied by x-ray diffraction with Rietveld structure refinements, On the basis of the structure refinements to the whole x-ray diffraction patterns for the four as-milled samples...

  13. Development of a high-throughput screening-compatible assay to identify inhibitors of the CK2alpha/CK2beta interaction

    DEFF Research Database (Denmark)

    Hochscherf, Jennifer; Lindenblatt, Dirk; Steinkrueger, Michaela

    2015-01-01

    Increased activity of protein kinase CK2 is associated with various types of cancer, neurodegenerative diseases, and chronic inflammation. In the search for CK2 inhibitors, attention has expanded toward compounds disturbing the interaction between CK2alpha and CK2beta in addition to established a...

  14. Synthesis and properties of iridium-doped hematite ({alpha}-Fe{sub 2}O{sub 3})

    Energy Technology Data Exchange (ETDEWEB)

    Krehula, Stjepko, E-mail: krehul@irb.hr [Division of Materials Chemistry, Ruder Boskovic Institute, P.O. Box 180, HR-10002 Zagreb (Croatia); Stefanic, Goran [Division of Materials Chemistry, Ruder Boskovic Institute, P.O. Box 180, HR-10002 Zagreb (Croatia); Zadro, Kreso [Department of Physics, Faculty of Science, University of Zagreb, Bijenicka 32, 10000 Zagreb (Croatia); Kratofil Krehula, Ljerka [Faculty of Chemical Engineering and Technology, University of Zagreb, Marulicev trg 19, 10000 Zagreb (Croatia); Marcius, Marijan; Music, Svetozar [Division of Materials Chemistry, Ruder Boskovic Institute, P.O. Box 180, HR-10002 Zagreb (Croatia)

    2012-12-25

    Highlights: Black-Right-Pointing-Pointer Ir-doped hematites were prepared by heating Ir-doped goethites. Black-Right-Pointing-Pointer Ir-doping in hematite led to an increase in unit cell and a decrease in crystallite size. Black-Right-Pointing-Pointer Ir-doping significantly affected magnetic, infrared and UV-Vis properties of hematite. Black-Right-Pointing-Pointer The Morin transition temperature increased with an increase in Ir-doping. Black-Right-Pointing-Pointer Ir ions brought about changes in the size and shape of the formed hematite particles. - Abstract: The effect of the incorporation of Ir{sup 3+} ions on the properties of {alpha}-Fe{sub 2}O{sub 3} formed by dehydroxylation of {alpha}-FeOOH was investigated using X-ray powder diffraction (XRD), thermogravimetric analysis (TGA), {sup 57}Fe Moessbauer, UV-Vis-NIR and FT-IR spectroscopies, SQUID magnetometer, field emission scanning electron microscopy (FE-SEM) and energy dispersive X-ray spectroscopy (EDS). Pure and Ir-doped hematite samples were obtained by heating of pure and Ir-doped goethites ({alpha}-FeOOH) formed by precipitation from mixed Fe(III)-Ir(III) chloride solutions in a highly alkaline medium. The incorporation of Ir{sup 3+} ions into the {alpha}-Fe{sub 2}O{sub 3} structure led to changes in unit-cell dimensions, crystallinity, particle size and shape, as well as changes in the magnetic, infrared and UV-Vis properties. An increase in the temperature of the Morin transition with an increase in Ir-doping was observed by Moessbauer spectroscopy and magnetic measurements.

  15. Effects of tumor necrosis factor-alpha and interferon-gamma on expressions of matrix metalloproteinase-2 and -9 in human bladder cancer cells.

    Science.gov (United States)

    Shin, K Y; Moon, H S; Park, H Y; Lee, T Y; Woo, Y N; Kim, H J; Lee, S J; Kong, G

    2000-10-31

    We have investigated the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon (INF-gamma), the potent Bacillus Calmette-Guerin (BCG)-induced cytokines on the production of MMP-2, MMP-9, TIMP-1, TIMP-2 and MT1-MMP in high grade human bladder cancer cell lines, T-24, J-82 and HT-1376 cell lines. MMP-2 expression and activity were decreased in T-24 cells treated with both cytokines in a dose dependent manner. However, J-82 cells treated with TNF-alpha and INF-gamma revealed dose dependent increases of MMP-9 expression and activity with similar baseline expression and activity of MMP-2. HT-1376 cells after exposure to TNF-alpha only enhanced the expression and activity of MMP-9. These results indicate that TNF-alpha and INF-gamma could regulate the production of MMP-2 or MMP-9 on bladder cancer cells and their patterns of regulation are cell specific. Furthermore, this diverse response of bladder cancer cells to TNF-alpha and INF-gamma suggests that BCG immunotherapy may enhance the invasiveness of bladder cancer in certain conditions with induction of MMPs.

  16. Identification of 4,5-didemethyl-4-O-alpha-D-glucopyranosylsimmondsin and pinitol alpha-D-galactosides in jojoba seed meal (Simmondsia chinensis).

    Science.gov (United States)

    Van Boven, M; Leyssen, T; Busson, R; Holser, R; Cokelaere, M; Flo, G; Decuypere, E

    2001-09-01

    The isolation and identification of two pinitol alpha-D-galactosides from jojoba meal are described. The products were isolated by a combination of preparative HPLC on silica gel and TLC on amino silica gel and were identified by MS, NMR spectroscopy, and chemical derivatization as 5-O-(alpha-D-galactopyranosyl)-3-O-methyl-D-chiro-inositol or 5-alpha-D-galactopyranosyl-D-pinitol and 2-O-(alpha-D-galactopyranosyl)-3-O-methyl-D-chiro-inositol or 2-alpha-D-galactopyranosyl-D-pinitol. The same preparative HPLC method on silica gel allowed a new simmondsin derivative to be isolated and identified as 4,5-didemethyl-4-O-alpha-D-glucopyranosylsimmondsin mainly by NMR spectroscopy and high-resolution mass spectrometry.

  17. Resting alpha activity predicts learning ability in alpha neurofeedback

    Directory of Open Access Journals (Sweden)

    Wenya eNan

    2014-07-01

    Full Text Available Individuals differ in their ability to learn how to regulate the alpha activity by neurofeedback. This study aimed to investigate whether the resting alpha activity is related to the learning ability of alpha enhancement in neurofeedback and could be used as a predictor. A total of 25 subjects performed 20 sessions of individualized alpha neurofeedback in order to learn how to enhance activity in the alpha frequency band. The learning ability was assessed by three indices respectively: the training parameter changes between two periods, within a short period and across the whole training time. It was found that the resting alpha amplitude measured before training had significant positive correlations with all learning indices and could be used as a predictor for the learning ability prediction. This finding would help the researchers in not only predicting the training efficacy in individuals but also gaining further insight into the mechanisms of alpha neurofeedback.

  18. QCD analyses and determinations of $\\alpha_{s}$ in $e^{+}e^{-}$ annihilation at energies between 35 and 189 GeV

    CERN Document Server

    Pfeifenschneider, P.; Movilla Fernandez, P.A.; Abbiendi, G.; Ackerstaff, K.; Akesson, P.F.; Alexander, G.; Allison, John; Anderson, K.J.; Arcelli, S.; Asai, S.; Ashby, S.F.; Axen, D.; Azuelos, G.; Bailey, I.; Ball, A.H.; Barberio, E.; Barlow, Roger J.; Batley, J.R.; Baumann, S.; Behnke, T.; Bell, Kenneth Watson; Bella, G.; Bellerive, A.; Bentvelsen, S.; Bethke, S.; Biguzzi, A.; Bloodworth, I.J.; Bock, P.; Bohme, J.; Boeriu, O.; Bonacorsi, D.; Boutemeur, M.; Braibant, S.; Bright-Thomas, P.; Brigliadori, L.; Brown, Robert M.; Burckhart, H.J.; Cammin, J.; Capiluppi, P.; Carnegie, R.K.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, David G.; Chrisman, D.; Ciocca, C.; Clarke, P.E.L.; Clay, E.; Cohen, I.; Cooke, O.C.; Couchman, J.; Couyoumtzelis, C.; Coxe, R.L.; Cuffiani, M.; Dado, S.; Dallavalle, G.Marco; Dallison, S.; Davis, R.; de Roeck, A.; Dervan, P.; Desch, K.; Dienes, B.; Dixit, M.S.; Donkers, M.; Dubbert, J.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Estabrooks, P.G.; Etzion, E.; Fabbri, F.; Fanfani, A.; Fanti, M.; Faust, A.A.; Feld, L.; Ferrari, P.; Fiedler, F.; Fierro, M.; Fleck, I.; Frey, A.; Furtjes, A.; Futyan, D.I.; Gagnon, P.; Gary, J.W.; Gaycken, G.; Geich-Gimbel, C.; Giacomelli, G.; Giacomelli, P.; Gingrich, D.M.; Glenzinski, D.; Goldberg, J.; Gorn, W.; Grandi, C.; Graham, K.; Gross, E.; Grunhaus, J.; Gruwe, M.; Gunther, P.O.; Hajdu, C.; Hanson, G.G.; Hansroul, M.; Hapke, M.; Harder, K.; Harel, A.; Hargrove, C.K.; Harin-Dirac, M.; Hauke, A.; Hauschild, M.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Hensel, C.; Herten, G.; Heuer, R.D.; Hildreth, M.D.; Hill, J.C.; Hobson, P.R.; Hocker, James Andrew; Hoffman, Kara Dion; Homer, R.J.; Honma, A.K.; Horvath, D.; Hossain, K.R.; Howard, R.; Huntemeyer, P.; Igo-Kemenes, P.; Imrie, D.C.; Ishii, K.; Jacob, F.R.; Jawahery, A.; Jeremie, H.; Jimack, M.; Jones, C.R.; Jovanovic, P.; Junk, T.R.; Kanaya, N.; Kanzaki, J.; Karapetian, G.; Karlen, D.; Kartvelishvili, V.; Kawagoe, K.; Kawamoto, T.; Kayal, P.I.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Kim, D.H.; Klier, A.; Kobayashi, T.; Kobel, M.; Kokott, T.P.; Kolrep, M.; Komamiya, S.; Kowalewski, Robert V.; Kress, T.; Krieger, P.; von Krogh, J.; Kuhl, T.; Kupper, M.; Kyberd, P.; Lafferty, G.D.; Landsman, H.; Lanske, D.; Lawson, I.; Layter, J.G.; Leins, A.; Lellouch, D.; Letts, J.; Levinson, L.; Liebisch, R.; Lillich, J.; List, B.; Littlewood, C.; Lloyd, A.W.; Lloyd, S.L.; Loebinger, F.K.; Long, G.D.; Losty, M.J.; Lu, J.; Ludwig, J.; Macchiolo, A.; Macpherson, A.; Mader, W.; Mannelli, M.; Marcellini, S.; Marchant, T.E.; Martin, A.J.; Martin, J.P.; Martinez, G.; Mashimo, T.; Mattig, Peter; McDonald, W.John; McKenna, J.; McMahon, T.J.; McPherson, R.A.; Meijers, F.; Mendez-Lorenzo, P.; Merritt, F.S.; Mes, H.; Meyer, I.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Mohr, W.; Montanari, A.; Mori, T.; Nagai, K.; Nakamura, I.; Neal, H.A.; Nisius, R.; O'Neale, S.W.; Oakham, F.G.; Odorici, F.; Ogren, H.O.; Okpara, A.; Oreglia, M.J.; Orito, S.; Pasztor, G.; Pater, J.R.; Patrick, G.N.; Patt, J.; Perez-Ochoa, R.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Poli, B.; Polok, J.; Przybycien, M.; Quadt, A.; Rembser, C.; Rick, H.; Robins, S.A.; Rodning, N.; Roney, J.M.; Rosati, S.; Roscoe, K.; Rossi, A.M.; Rozen, Y.; Runge, K.; Runolfsson, O.; Rust, D.R.; Sachs, K.; Saeki, T.; Sahr, O.; Sang, W.M.; Sarkisian, E.K.G.; Sbarra, C.; Schaile, A.D.; Schaile, O.; Scharff-Hansen, P.; Schieck, J.; Schmitt, S.; Schoning, A.; Schroder, Matthias; Schumacher, M.; Schwick, C.; Scott, W.G.; Seuster, R.; Shears, T.G.; Shen, B.C.; Shepherd-Themistocleous, C.H.; Sherwood, P.; Siroli, G.P.; Skuja, A.; Smith, A.M.; Snow, G.A.; Sobie, R.; Soldner-Rembold, S.; Spagnolo, S.; Sproston, M.; Stahl, A.; Stephens, K.; Stoll, K.; Strom, David M.; Strohmer, R.; Surrow, B.; Talbot, S.D.; Tarem, S.; Taylor, R.J.; Teuscher, R.; Thiergen, M.; Thomas, J.; Thomson, M.A.; Torrence, E.; Towers, S.; Trefzger, T.; Trigger, I.; Trocsanyi, Z.; Tsur, E.; Turner-Watson, M.F.; Ueda, I.; Van Kooten, Rick J.; Vannerem, P.; Verzocchi, M.; Voss, H.; Waller, D.; Ward, C.P.; Ward, D.R.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wengler, T.; Wermes, N.; Wetterling, D.; White, J.S.; Wilson, G.W.; Wilson, J.A.; Wyatt, T.R.; Yamashita, S.; Zacek, V.; Zer-Zion, D.; Jade, The

    2000-01-01

    We employ data taken by the JADE and OPAL experiments for an integrated QCD study in hadronic e+e- annihilations at c.m.s. energies ranging from 35 GeV through 189 GeV. The study is based on jet-multiplicity related observables. The observables are obtained to high jet resolution scales with the JADE, Durham, Cambridge and cone jet finders, and compared with the predictions of various QCD and Monte Carlo models. The strong coupling strength, alpha_s, is determined at each energy by fits of O(alpha_s^2) calculations, as well as matched O(alpha_s^2) and NLLA predictions, to the data. Matching schemes are compared, and the dependence of the results on the choice of the renormalization scale is investigated. The combination of the results using matched predictions gives alpha_s(MZ)=0.1187+{0.0034}-{0.0019}. The strong coupling is also obtained, at lower precision, from O(alpha_s^2) fits of the c.m.s. energy evolution of some of the observables. A qualitative comparison is made between the data and a recent MLLA p...

  19. Application of four anti-human interferon-alpha monoclonal antibodies for immunoassay and comparative analysis of natural interferon-alpha mixtures

    International Nuclear Information System (INIS)

    Andersson, G.; Lundgren, E.; Ekre, H.P.

    1991-01-01

    Four different mouse monoclonal antibodies to human interferon-alpha (IFN-alpha) were evaluated for application in quantitative and comparative analysis of natural IFN-alpha mixtures. Binding to IFN-alpha subtypes in solution revealed individual reactivity patterns. These patterns changed if the IFN-alpha molecules were immobilized either passively to a surface or bound by another antibody. Also, substitution of a single amino acid in IFN-alpha 2 affected the binding, apparently by altering the conformation. Isoelectric focusing of three natural IFN-alpha preparations from different sources, followed by immunoblotting, resulted in individual patterns with each of the four mAbs and also demonstrated variation in the composition of the IFN-alpha preparations. None of the mAbs was subtype specific, but by combining the different mAbs, and also applying polyclonal anti-human IFN-alpha antibodies, it was possible to design sensitive sandwich ELISAs with broad or more limited IFN-alpha subtype specificity

  20. Measurement of $\\alpha_{s}$ and the non-strange spectral functions in hadronic $\\tau$ decays with OPAL

    CERN Document Server

    Menke, S

    1999-01-01

    The spectral functions of the vector current and the axial-vector current have been measured in hadronic tau decays using the OPAL detector at LEP. Within the framework of the Operator Product Expansion a simultaneous determination of the strong coupling constant alpha /sub s/, the non-perturbative operators of dimension 6 and 8 and of the gluon condensate has been performed. Different perturbative descriptions have been compared to the data. The Contour Improved Fixed Order Perturbation Theory gives alpha /sub s/(m/sub tau //sup 2/)=0.348+or-0.009/sub exp/+or-0.019/sub theo/ at the tau - mass scale and alpha /sub s/(m/sub Z//sup 2/)=0.1219+or-0.0010/sub exp/+or-0.0017/sub theo/ at the Z/sup 0/-mass scale. The values obtained for alpha /sub s/(m/sub Z//sup 2/) using Fixed Order Perturbation Theory or Renormalon Chain Resummation are 2.3and 4.1 smaller, respectively. The `running' of the strong coupling between s /sub 0/ approximately=1.3 GeV/sup 2/ and s/sub 0/=m/sub tau //sup 2/ has been tested from direct f...

  1. Caffeine-mediated release of alpha-radiation-induced G2 arrest increases the yield of chromosome aberrations

    International Nuclear Information System (INIS)

    Luecke-Huhle, C.; Hieber, L.; Wegner, R.D.

    1983-01-01

    Severe and partly irreversible G2 arrest caused by americium-241 alpha-particles in Chinese hamster V79 cells acted as a competing process to the yield of detectable aberrant mitoses at metaphase. With increasing dose of alpha-radiation an increasing fraction of cells was irreversibly arrested in G2 with the consequence of interphase death before the first post-irradiation mitosis. This irreversible G2 arrest (demonstrated by flow cytofluorometry and mitotic indices) could be overcome by adding caffeine 8 hours after irradiation, the time point of maximum G2 arrest (80-90 per cent of all cells). Within 3.5 hours the number of aberrant mitoses increased by this treatment from 54 to 96 per cent and from 65 to 99.9 per cent for doses of 1.75 and 4.38 Gy of alpha-particles, respectively. The aberration frequency per mitotic cell, scored as chromatid and isochromatid breaks, rings, interchanges and dicentrics increased by a factor of about 3 after releasing G2 arrested cells. The frequency distribution of aberrations per cell revealed that, after 4.38 Gy, 58 per cent of the formerly G2-arrested cells had more than five aberrations per cell compared to only 8 per cent without the interaction of caffeine. (author)

  2. Alpha-particle emission probabilities of ²³⁶U obtained by alpha spectrometry.

    Science.gov (United States)

    Marouli, M; Pommé, S; Jobbágy, V; Van Ammel, R; Paepen, J; Stroh, H; Benedik, L

    2014-05-01

    High-resolution alpha-particle spectrometry was performed with an ion-implanted silicon detector in vacuum on a homogeneously electrodeposited (236)U source. The source was measured at different solid angles subtended by the detector, varying between 0.8% and 2.4% of 4π sr, to assess the influence of coincidental detection of alpha-particles and conversion electrons on the measured alpha-particle emission probabilities. Additional measurements were performed using a bending magnet to eliminate conversion electrons, the results of which coincide with normal measurements extrapolated to an infinitely small solid angle. The measured alpha emission probabilities for the three main peaks - 74.20 (5)%, 25.68 (5)% and 0.123 (5)%, respectively - are consistent with literature data, but their precision has been improved by at least one order of magnitude in this work. © 2013 Published by Elsevier Ltd.

  3. Behavior of a cloned murine interferon alpha/beta receptor expressed in homospecific or heterospecific background.

    Science.gov (United States)

    Uzé, G; Lutfalla, G; Bandu, M T; Proudhon, D; Mogensen, K E

    1992-05-15

    A murine interferon (IFN) alpha/beta receptor was cloned from the IFN-sensitive L1210 cell line on the basis of its homology with the human receptor. A combination of methods that includes the screening of random-primed and oligo(dT)-primed cDNA libraries and polymerase chain reactions with a single-side specificity was used. At the amino acid level, the murine IFN-alpha/beta shows 46% identity with its human counterpart. Both human WISH cells presenting a low sensitivity to mouse IFN and a murine L1210 mutant subline that does not express the receptor have been stably transfected with the murine IFN-alpha/beta receptor. Whereas transfected human cells became sensitive to a limited number of mouse IFN-alpha/beta subtypes, the transfected murine L1210 mutant was found to be fully complemented and became sensitive to all mouse IFN-alpha/beta subtypes tested, including those that were not active on transfected human cells. These results strongly suggest that the receptor described here is implicated in the mediation of the activities of all murine IFN-alpha/beta subtypes.

  4. The host-dependent interaction of alpha-importins with influenza PB2 polymerase subunit is required for virus RNA replication.

    Directory of Open Access Journals (Sweden)

    Patricia Resa-Infante

    Full Text Available The influenza virus polymerase is formed by the PB1, PB2 and PA subunits and is required for virus transcription and replication in the nucleus of infected cells. As PB2 is a relevant host-range determinant we expressed a TAP-tagged PB2 in human cells and isolated intracellular complexes. Alpha-importin was identified as a PB2-associated factor by proteomic analyses. To study the relevance of this interaction for virus replication we mutated the PB2 NLS and analysed the phenotype of mutant subunits, polymerase complexes and RNPs. While mutant PB2 proteins showed reduced nuclear accumulation, they formed polymerase complexes normally when co expressed with PB1 and PA. However, mutant RNPs generated with a viral CAT replicon showed up to hundred-fold reduced CAT accumulation. Rescue of nuclear localisation of mutant PB2 by insertion of an additional SV40 TAg-derived NLS did not revert the mutant phenotype of RNPs. Furthermore, determination of recombinant RNP accumulation in vivo indicated that PB2 NLS mutations drastically reduced virus RNA replication. These results indicate that, above and beyond its role in nuclear accumulation, PB2 interaction with alpha-importins is required for virus RNA replication. To ascertain whether PB2-alpha-importin binding could contribute to the adaptation of H5N1 avian viruses to man, their association in vivo was determined. Human alpha importin isoforms associated efficiently to PB2 protein of an H3N2 human virus but bound to diminished and variable extents to PB2 from H5N1 avian or human strains, suggesting that the function of alpha importin during RNA replication is important for the adaptation of avian viruses to the human host.

  5. Alpha 1-blockers vs 5 alpha-reductase inhibitors in benign prostatic hyperplasia. A comparative review

    DEFF Research Database (Denmark)

    Andersen, J T

    1995-01-01

    During recent years, pharmacological treatment of symptomatic benign prostatic hyperplasia (BPH) has become the primary treatment choice for an increasing number of patients. The 2 principal drug classes employed are alpha 1-blockers and 5 alpha-reductase inhibitors. Current information from...... of patients who will respond well to alpha 1-blockers have yet to be identified, and data concerning the long term effects of these drugs are not yet available. 5 alpha-Reductase inhibitors have a slow onset of effect, but treatment leads to improvement in symptoms, reduction of the size of the prostate gland...... and improvement in objective parameters for bladder outflow obstruction. Approximately 30 to 50% of patients will respond to treatment with 5 alpha-reductase inhibitors. The definitive role of pharmacological treatment in symptomatic BPH remains to be established, although it seems that patients unfit...

  6. Regulation of bovine kidney alpha-ketoglutarate dehydrogenase complex by calcium ion and adenine nucleotides. Effects on S0.5 for alpha-ketoglutarate.

    Science.gov (United States)

    Lawlis, V B; Roche, T E

    1981-04-28

    Regulation of bovine kidney alpha-ketoglutarate dehydrogenase complex by energy-linked metabolites was investigated. Ca2+, ADP, or inorganic phosphate markedly enhanced the activity of the complex, and ATP or, to a lesser extent, GTP decreased the activity of the complex. Initial velocity studies with alpha-ketoglutarate as the varied substrate demonstrated that these modulators induced large changes in S0.5 for alpha-ketoglutarate (based on analysis in Hill plots) with no change in the maximum velocity (as determined by double-reciprocal plots). For all conditions studied, the Hill coefficients were significantly less than 1.0 with slopes that were linear over wide ranges of alpha-ketoglutarate concentrations, indicating negative cooperativity that probably resulted from multiple site-site interactions. Ca2+ (maintained at 10 muM by a Ca2+ buffer) decreased the S0.5 for alpha-ketoglutarate 63-fold (from 25 to 0.40 mM); even in the presence of a positive effector, ADP or phosphate, Ca2+ decreased the S0.5 for alpha-ketoglutarate 7.8- or 28-fold, respectively. Consistent with a mechanism of action dependent of Ca2+, ADP (1.60 mM) or phosphate (20 mM) reduced the S0.5 for alpha-ketoglutarate in the presence of Ca2+ (i.e., 4.5- or 1.67-fold, respectively); however, these effectors elicited larger decreases in S0.5 in the absence of Ca2+ (i.e., 37- or 3.7-fold, respectively). ATP (1.6 mM) increased the S0.5 for alpha-ketoglutarate, and Ca2+ appreciably reduced the effect, lowering the S0.5 98-fold from 66 to 0.67 mM. Thus the activity of the kidney alpha-ketoglutarate dehydrogenase complex is poised to increase as the energy potential in mitochondria declines, and Ca2+ has a pronounced modulatory effect. Comparative studies on bovine heart alpha-ketoglutarate dehydrogenase complex and the effects of varying the ADP/ATP ratio in the presence or absence of Ca2+ or phosphate are also described.

  7. First-principles characterization of a heteroceramic interface: ZrO2(001) deposited on an alpha-Al2O3(1(1)over-bar02) substrate

    DEFF Research Database (Denmark)

    Christensen, Asbjørn; Carter, Emily A.

    2000-01-01

    We have studied an alumina/zirconia interface using the all-electron projector augmented wave formalism within density functional theory. We present the electronic, structural, and energetic properties of the ZrO2(001)/(alpha -Al2O3(1 (1) over bar 02) interface as well as of the free alpha -Al2O3......(1 (1) over bar 02) and ZrO2(001) surfaces. We find that the generalized gradient correction significantly lowers the oxide surface energies, compared to values obtained by the local density approximation. The monoclinic-tetragonal transition in ZrO2(001) thin films is discussed as well as strain...... effects involved in the interface formation. The stoichiometric alumina/zirconia interface is found to be weakly bonded, regardless of the film thickness, and the ZrO2(001)/alpha -Al2O3(1 (1) over bar 02) interface has a rather epitaxial character, due to a low lattice mismatch of similar to4%. The impact...

  8. [Effect of melatonin instillations on the clinical course of experimental uveitis and biochemical processes in tears and aqueous humor].

    Science.gov (United States)

    Chesnokova, N B; Beznos, O V; Lozinskaya, N A; Beyshenova, G A; Nesterova, T V

    2016-01-01

    Acute immunogenic uveitis was modeled in rabbits via the subcutaneous and intravitreal injections of normal horse serum. We studied the effect of instillations of 0.1% melatonin solution on the clinical course of uveitis and biochemical parameters of tear fluid and aqueous humor: antioxi-dant activity, protein concentration and α(2)-macroglobulin level. Melatonin instillations decreased clinical manifestations of uveitis. We found that the antioxidant activity in tears of the rabbits treated with melatonin was substantially higher and the α(2)-macroglobulin level lower than in untreated animals. Antioxidant activity in aqueous humor taken on day 10 of uveitis was also twice higher while protein and α(2)-macroglobulin levels were 1.5-2 times lower than in untreated animals. These data indicate that instillations of melatonin increase the local antioxidant activity and decrease the acuity of inflammation and permeability of hematoophthalmic barrier in uveitis.

  9. Severe IgE-mediated anaphylaxis following consumption of fried frog legs: definition of alpha-parvalbumin as the allergen in cause.

    Science.gov (United States)

    Hilger, C; Grigioni, F; Thill, L; Mertens, L; Hentges, F

    2002-11-01

    IgE-mediated allergic reactions to bullfrog and edible frog have been reported. The implicated allergens have not been defined so far. The frog material and the patient's serum from a case of severe food-induced anaphylaxis were used to define the implicated allergen at the protein and DNA level. Immunoblotting techniques and N-terminal protein microsequencing were used to define the allergen recognized by the patient's serum. Back translation from the identified protein sequence was used to design degenerated primers to amplify the allergen's cDNA by polymerase chain reaction (PCR). We defined the nucleotide sequence of the allergen from the frog of Indonesian origin that was consumed by the patient, and the homologous cDNA from Rana esculenta. Protein microsequencing revealed that the implicated frog allergen belonged to the parvalbumin family. cDNAs coding for alpha- and beta-parvalbumin of R. esculenta and Rana species were cloned. Recombinant proteins were expressed in Escherichia coli. The patient's serum IgE antibodies recognized parvalbumin prepared from frog muscle and recombinant alpha-parvalbumin from R. species but not from R. esculenta. Recombinant beta-parvalbumin was not recognized by the IgE antibodies. This work defines at the protein and DNA levels alpha-parvalbumin as the allergen implicated in a case of IgE-mediated anaphylaxis to frog muscle. It also shows that a protein belonging to the parvalbumin family is implicated in type I allergies outside the fish species.

  10. Expression and secretion of Bacillus amyloliquefaciens alpha-amylase by using the yeast pheromone alpha-factor promoter and leader sequence in Saccharomyces cerevisiae.

    OpenAIRE

    Southgate, V J; Steyn, A J; Pretorius, I S; Van Vuuren, H J

    1993-01-01

    Replacement of the regulatory and secretory signals of the alpha-amylase gene (AMY) from Bacillus amylolique-faciens with the complete yeast pheromone alpha-factor prepro region (MF alpha 1p) resulted in increased levels of extracellular alpha-amylase production in Saccharomyces cerevisiae. However, the removal of the (Glu-Ala)2 peptide from the MF alpha 1 spacer region (Lys-Arg-Glu-Ala-Glu-Ala) yielded decreased levels of extracellular alpha-amylase.

  11. Measurement of the Strong Coupling Constant $\\alpha_s$ and the Vector and Axial-Vector Spectral Functions in Hadronic Tau Decays

    CERN Document Server

    Ackerstaff, K; Allison, J; Altekamp, N; Anderson, K J; Anderson, S; Arcelli, S; Asai, S; Ashby, S F; Axen, D A; Azuelos, Georges; Ball, A H; Barberio, E; Barlow, R J; Bartoldus, R; Batley, J Richard; Baumann, S; Bechtluft, J; Behnke, T; Bell, K W; Bella, G; Bentvelsen, Stanislaus Cornelius Maria; Bethke, Siegfried; Betts, S; Biebel, O; Biguzzi, A; Bird, S D; Blobel, Volker; Bloodworth, Ian J; Bobinski, M; Bock, P; Böhme, J; Boutemeur, M; Braibant, S; Bright-Thomas, P G; Brown, R M; Burckhart, Helfried J; Burgard, C; Bürgin, R; Capiluppi, P; Carnegie, R K; Carter, A A; Carter, J R; Chang, C Y; Charlton, D G; Chrisman, D; Ciocca, C; Clarke, P E L; Clay, E; Cohen, I; Conboy, J E; Cooke, O C; Couyoumtzelis, C; Coxe, R L; Cuffiani, M; Dado, S; Dallavalle, G M; Davis, R; De Jong, S; del Pozo, L A; de Roeck, A; Desch, Klaus; Dienes, B; Dixit, M S; Doucet, M; Dubbert, J; Duchovni, E; Duckeck, G; Duerdoth, I P; Eatough, D; Estabrooks, P G; Etzion, E; Evans, H G; Fabbri, Franco Luigi; Fanfani, A; Fanti, M; Faust, A A; Fiedler, F; Fierro, M; Fischer, H M; Fleck, I; Folman, R; Fürtjes, A; Futyan, D I; Gagnon, P; Gary, J W; Gascon, J; Gascon-Shotkin, S M; Geich-Gimbel, C; Geralis, T; Giacomelli, G; Giacomelli, P; Gibson, V; Gibson, W R; Gingrich, D M; Glenzinski, D A; Goldberg, J; Gorn, W; Grandi, C; Gross, E; Grunhaus, Jacob; Gruwé, M; Hanson, G G; Hansroul, M; Hapke, M; Hargrove, C K; Hartmann, C; Hauschild, M; Hawkes, C M; Hawkings, R; Hemingway, Richard J; Herndon, M; Herten, G; Heuer, R D; Hildreth, M D; Hill, J C; Hillier, S J; Hobson, P R; Höcker, Andreas; Homer, R James; Honma, A K; Horváth, D; Hossain, K R; Howard, R; Hüntemeyer, P; Igo-Kemenes, P; Imrie, D C; Ishii, K; Jacob, F R; Jawahery, A; Jeremie, H; Jimack, Martin Paul; Joly, A; Jones, C R; Jovanovic, P; Junk, T R; Karlen, D A; Kartvelishvili, V G; Kawagoe, K; Kawamoto, T; Kayal, P I; Keeler, Richard K; Kellogg, R G; Kennedy, B W; Klier, A; Kluth, S; Kobayashi, T; Kobel, M; Koetke, D S; Kokott, T P; Kolrep, M; Komamiya, S; Kowalewski, R V; Kress, T; Krieger, P; Von Krogh, J; Kyberd, P; Lafferty, G D; Lanske, D; Lauber, J; Lautenschlager, S R; Lawson, I; Layter, J G; Lazic, D; Lee, A M; Lefebvre, E; Lellouch, Daniel; Letts, J; Levinson, L; Liebisch, R; List, B; Littlewood, C; Lloyd, A W; Lloyd, S L; Loebinger, F K; Long, G D; Losty, Michael J; Ludwig, J; Liu, D; Macchiolo, A; MacPherson, A L; Mannelli, M; Marcellini, S; Markopoulos, C; Martin, A J; Martin, J P; Martínez, G; Mashimo, T; Mättig, P; McDonald, W J; McKenna, J A; McKigney, E A; McMahon, T J; McPherson, R A; Meijers, F; Menke, S; Merritt, F S; Mes, H; Meyer, J; Michelini, Aldo; Mihara, S; Mikenberg, G; Miller, D J; Mir, R; Mohr, W; Montanari, A; Mori, T; Nagai, K; Nakamura, I; Neal, H A; Nellen, B; Nisius, R; O'Neale, S W; Oakham, F G; Odorici, F; Ögren, H O; Oreglia, M J; Orito, S; Pálinkás, J; Pásztor, G; Pater, J R; Patrick, G N; Patt, J; Pérez-Ochoa, R; Petzold, S; Pfeifenschneider, P; Pilcher, J E; Pinfold, James L; Plane, D E; Poffenberger, P R; Poli, B; Polok, J; Przybycien, M B; Rembser, C; Rick, Hartmut; Robertson, S; Robins, S A; Rodning, N L; Roney, J M; Roscoe, K; Rossi, A M; Rozen, Y; Runge, K; Runólfsson, O; Rust, D R; Sachs, K; Saeki, T; Sahr, O; Sang, W M; Sarkisyan-Grinbaum, E; Sbarra, C; Schaile, A D; Schaile, O; Scharf, F; Scharff-Hansen, P; Schieck, J; Schmitt, B; Schmitt, S; Schöning, A; Schörner-Sadenius, T; Schröder, M; Schumacher, M; Schwick, C; Scott, W G; Seuster, R; Shears, T G; Shen, B C; Shepherd-Themistocleous, C H; Sherwood, P; Siroli, G P; Sittler, A; Skuja, A; Smith, A M; Snow, G A; Sobie, Randall J; Söldner-Rembold, S; Sproston, M; Stahl, A; Stephens, K; Steuerer, J; Stoll, K; Strom, D; Ströhmer, R; Tafirout, R; Talbot, S D; Tanaka, S; Taras, P; Tarem, S; Teuscher, R; Thiergen, M; Thomson, M A; Von Törne, E; Torrence, E; Towers, S; Trigger, I; Trócsányi, Z L; Tsur, E; Turcot, A S; Turner-Watson, M F; Van Kooten, R; Vannerem, P; Verzocchi, M; Vikas, P; Voss, H; Wäckerle, F; Wagner, A; Ward, C P; Ward, D R; Watkins, P M; Watson, A T; Watson, N K; Wells, P S; Wermes, N; White, J S; Wilson, G W; Wilson, J A; Wyatt, T R; Yamashita, S; Yekutieli, G; Zacek, V; Zer-Zion, D

    1999-01-01

    The spectral functions of the vector current and the axial-vector current have been measured in hadronic tau decays using the OPAL detector at LEP. Within the framework of the Operator Product Expansion a simultaneous determination of the strong coupling constant alpha_s, the non-perturbative operators of dimension 6 and 8 and of the gluon condensate has been performed. Different perturbative descriptions have been compared to the data. The Contour Improved Fixed Order Perturbation Theory gives alpha_s(mtau**2) = 0.348 +- 0.009 +- 0.019 at the tau-mass scale and alpha_s(mz**2) = 0.1219 +- 0.0010 +- 0.0017 at the Z-mass scale. The values obtained for alpha_s(mz**2) using Fixed Order Perturbation Theory or Renormalon Chain Resummation are 2.3% and 4.1% smaller, respectively. The running of the strong coupling between s_0 ~1.3 GeV**2 and s_0 = mtau**2 has been tested from direct fits to the integrated differential hadronic decay rate R_tau. A test of the saturation of QCD sum rules at the tau-mass scale has been...

  12. The loss of alpha2beta1 integrin suppresses joint inflammation and cartilage destruction in mouse models of rheumatoid arthritis.

    NARCIS (Netherlands)

    Peters, M.E.W.J.; Wendholt, D.; Strietholt, S.; Frank, S.; Pundt, N.; Korb-Pap, A.; Joosten, L.A.B.; Berg, W.B. van den; Kollias, G.; Eckes, B.; Pap, T.

    2012-01-01

    OBJECTIVE: Integrin alpha2beta1 functions as a major receptor for type I collagen on different cell types, including fibroblasts and inflammatory cells. Although in vitro data suggest a role for alpha2beta1 integrin in regulating both cell attachment and expression of matrix-degrading enzymes such

  13. Role of Peripheral Alpha2 Adrenergic Receptors in Tonic Pain During Different Stages of Estrous Cycle in Rats

    Directory of Open Access Journals (Sweden)

    AR Abyazi Shelmani

    2007-12-01

    Full Text Available Introduction: Estrogen and progesterone are supposed to modify pain sensitivity. However, the actual role of each of these steroid hormones in this respect is not well known. Plasma concentrations of these hormones show variation during estrous cycle. The role of alpha2 receptors in tonic pain has been pointed out. The aim of the present study was to investigate the agonist and antagonist effect of alpha2 adrenergic receptors on tonic pain sensitivity during all stages of estrous cycle in female rats. Methods: Xylasine as alpha2 agonist and yohimbin as alpha2 antagonist were used via intraperitoneal route (IP. Adult rats weighing 180-200 grams were used. Animals were maintained on 12h reverse light/dark cycle for 7 days prior to the experiment. Water and food was available ad libitum. Formalin test was performed by subcutaneous injection of 50 l formalin (2.5% solution into the hind paw. Formalin test was performed in all stages of estrous cycle for 60 minutes. Animals were divided into four groups; 1- control group (intact animal, 2- Sham group (animals received 0.2 ml normal saline by IP route, 3- Agonist groups (animals received 0.2 ml xylasine 1, 3 mg/kg body weight by IP route and 4- Antagonist group (animals received 0.2 ml yohimbine 1, 3 mg/kg body weight by IP route. Data were statistically analyzed using 2 way ANOVA test followed by Tukey's test as post-hoc test. P<0.05 was considered significant. Results: Results showed that xylasine significantly (p<0.05 decreases pain sensitivity in all stages of estrous cycle. Analgesic effect of xylasine was maximum in estrus stage of estrous cycle and minimum in metestrus stage of estrous cycle. Yohimbine significantly (p<0.05 increases pain sensitivity in all stages of estrous cycle. Hyperalgesic effect of yohimbine was maximum in metestrus stage of estrous cycle and minimum in estrus stage of estrous cycle. Conclusion: These results indicate that alpha2 adrenergic system and endogenous

  14. Prostaglandin E and F2 alpha receptors in human myometrium during the menstrual cycle and in pregnancy and labor

    International Nuclear Information System (INIS)

    Giannopoulos, G.; Jackson, K.; Kredentser, J.; Tulchinsky, D.

    1985-01-01

    The binding of prostaglandins E1 and F2 alpha has been studied in the human myometrium and cervix during the menstrual cycle and in the myometrium of pregnant patients at term before and during labor. Tritium-labeled prostaglandin E1 and F2 alpha binding was saturable and reversible. Scatchard analysis of tritium-labeled prostaglandin E1 binding was linear, which suggests a single class of high-affinity binding sites with an estimated apparent equilibrium dissociation constant of 2.5 to 5.4 nmol/L and inhibitor affinities of 0.9, 273, 273, and 217 nmol/L for prostaglandins E2, A1, B1, and F2 alpha, respectively. Scatchard analysis of tritium-labeled prostaglandin F2 alpha, binding was also linear, but the affinity of these binding sites was much lower, with an average dissociation constant of 50 nmol/L and inhibitor affinities of 1.6, 2.2, and 11.2 nmol/L for prostaglandins E1, E2, and A1, respectively. In nonpregnant patients, the concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were similar in the myometrium during the proliferative and secretory phases of the menstrual cycle, but the concentration of these sites was much lower in the cervix. The concentration of the tritium-labeled prostaglandin E1 binding sites was significantly lower in the myometrium of pregnant patients at term than in the myometrium of nonpregnant patients. The concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were not significantly different in the upper and lower myometrium of pregnant patients at term or in the myometrium of such patients before and during labor. The concentrations of the tritium-labeled prostaglandin F2 alpha binding sites during the menstrual cycle and in pregnancy at term were similar to those of tritium-labeled prostaglandin E1 binding sites

  15. Prostaglandin E and F2 alpha receptors in human myometrium during the menstrual cycle and in pregnancy and labor

    Energy Technology Data Exchange (ETDEWEB)

    Giannopoulos, G.; Jackson, K.; Kredentser, J.; Tulchinsky, D.

    1985-12-15

    The binding of prostaglandins E1 and F2 alpha has been studied in the human myometrium and cervix during the menstrual cycle and in the myometrium of pregnant patients at term before and during labor. Tritium-labeled prostaglandin E1 and F2 alpha binding was saturable and reversible. Scatchard analysis of tritium-labeled prostaglandin E1 binding was linear, which suggests a single class of high-affinity binding sites with an estimated apparent equilibrium dissociation constant of 2.5 to 5.4 nmol/L and inhibitor affinities of 0.9, 273, 273, and 217 nmol/L for prostaglandins E2, A1, B1, and F2 alpha, respectively. Scatchard analysis of tritium-labeled prostaglandin F2 alpha, binding was also linear, but the affinity of these binding sites was much lower, with an average dissociation constant of 50 nmol/L and inhibitor affinities of 1.6, 2.2, and 11.2 nmol/L for prostaglandins E1, E2, and A1, respectively. In nonpregnant patients, the concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were similar in the myometrium during the proliferative and secretory phases of the menstrual cycle, but the concentration of these sites was much lower in the cervix. The concentration of the tritium-labeled prostaglandin E1 binding sites was significantly lower in the myometrium of pregnant patients at term than in the myometrium of nonpregnant patients. The concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were not significantly different in the upper and lower myometrium of pregnant patients at term or in the myometrium of such patients before and during labor. The concentrations of the tritium-labeled prostaglandin F2 alpha binding sites during the menstrual cycle and in pregnancy at term were similar to those of tritium-labeled prostaglandin E1 binding sites.

  16. Acquisition of T regulatory function in cathepsin L-inhibited T cells by eye-derived CTLA-2alpha during inflammatory conditions.

    Science.gov (United States)

    Sugita, Sunao; Horie, Shintaro; Nakamura, Orie; Maruyama, Kazuichi; Takase, Hiroshi; Usui, Yoshihiko; Takeuchi, Masaru; Ishidoh, Kazumi; Koike, Masato; Uchiyama, Yasuo; Peters, Christoph; Yamamoto, Yoshimi; Mochizuki, Manabu

    2009-10-15

    Pigment epithelium isolated from the eye possesses immunosuppressive properties such as regulatory T (Treg) cell induction; e.g., cultured retinal pigment epithelium (RPE) converts CD4(+) T cells into Treg cells in vitro. RPE constitutively expresses a novel immunosuppressive factor, CTLA-2alpha, which is a cathepsin L (CathL) inhibitor, and this molecule acts via RPE to induce Treg cells. To clarify CTLA-2alpha's role in the T cell response to RPE in ocular inflammation, we used the experimental autoimmune uveitis (EAU) animal model to examine this new immunosuppressive property of RPE. In EAU models, TGF-beta, but not IFN-gamma inflammatory cytokines, promotes the up-regulation of the expression of CTLA-2alpha in RPE. Similarly, CTLA-2alpha via RPE was able to promote TGF-beta production by the CD4(+) T cells. The RPE-exposed T cells (RPE-induced Treg cells) greatly produced TGF-beta and suppressed bystander effector T cells. There was less expression of CathL by the RPE-exposed T cells, and CathL-inhibited T cells were able to acquire the Treg phenotype. Moreover, CathL-deficient mice spontaneously produced Treg cells, with the increase in T cells potentially providing protection against ocular inflammation. More importantly, CD4(+) T cells from EAU in CathL knockout mice or rCTLA-2alpha from EAU animals were found to contain a high population of forkhead box p3(+) T cells. In both EAU models, there was significant suppression of the ocular inflammation. These results indicate that RPE secretes CTLA-2alpha, thereby enabling the bystander T cells to be converted into Treg cells via TGF-beta promotion.

  17. Alpha amylase assisted synthesis of TiO{sub 2} nanoparticles: Structural characterization and application as antibacterial agents

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Razi; Mohsin, Mohd [Department of Biosciences, Jamia Millia Islamia, New Delhi 110025 (India); Ahmad, Tokeer [Department of Chemistry, Jamia Millia Islamia, New Delhi 110025 (India); Sardar, Meryam, E-mail: msardar@jmi.ac.in [Department of Biosciences, Jamia Millia Islamia, New Delhi 110025 (India)

    2015-02-11

    Graphical abstract: - Highlights: • Green synthesis of TiO{sub 2} nanoparticles using an enzyme alpha amylase has been described. • The morphology and shape depends upon the concentration of the alpha amylase enzyme. • The biosynthesized nanoparticles show good bactericidal effect against both gram positive and gram negative bacteria. • The bactericidal effect was further confirmed by Confocal microscopy and TEM. - Abstract: The enzyme alpha amylase was used as the sole reducing and capping agent for the synthesis of TiO{sub 2} nanoparticles. The biosynthesized nanoparticles were characterized by X-ray diffraction (XRD) and transmission electron microscopic (TEM) methods. The XRD data confirms the monophasic crystalline nature of the nanoparticles formed. TEM data shows that the morphology of nanoparticles depends upon the enzyme concentration used at the time of synthesis. The presence of alpha amylase on TiO{sub 2} nanoparticles was confirmed by FTIR. The nanoparticles were investigated for their antibacterial effect on Staphylococcus aureus and Escherichia coli. The minimum inhibitory concentration value of the TiO{sub 2} nanoparticles was found to be 62.50 μg/ml for both the bacterial strains. The inhibition was further confirmed using disc diffusion assay. It is evident from the zone of inhibition that TiO{sub 2} nanoparticles possess potent bactericidal activity. Further, growth curve study shows effect of inhibitory concentration of TiO{sub 2} nanoparticles against S. aureus and E. coli. Confocal microscopy and TEM investigation confirm that nanoparticles were disrupting the bacterial cell wall.

  18. Transition-state structure in the yeast alcohol dehydrogenase reaction: the magnitude of solvent and alpha-secondary hydrogen isotope effects

    International Nuclear Information System (INIS)

    Welsh, K.M.; Creighton, D.J.; Klinman, J.P.

    1980-01-01

    Solvent and alpha-secondary isotope effects have been measured in the yeast alcohol dehydrogenase reaction, under conditions of a rate-limiting transfer of hydrogen between coenzyme and substrate. Determination of catalytic constants in H20 and D20 as a function of pH(D) has allowed the separation of solvent effects on pKa from kcat. The small effect of D20 on pKa is tentatively assigned to ionization of an active-site ZnOH 2 . The near absence of an isotope effect on kcat in the direction of alcohol oxidation rules out a mechanism involving concerted catalysis by an active-site base of hydride transfer. The near identity of kinetic and equilibrium alpha-secondary isotope effects in the direction of alcohol oxidation implicates a transition-state structure which resembles aldehyde with regard to bond hybridization properties. The result contrasts sharply with previously reported structure - reactivity correlations, which implicate a transition-state structure resembling alcohol with regard to charge properties. The significance of these findings to the mechanism of NAD(P)H-dependent redox reactions is discussed

  19. Effects of thyroid status on presynaptic. cap alpha. 2-adrenoceptor and. beta. -adrenoceptor binding in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Atterwill, C.K.; Bunn, S.J.; Atkinson, D.J. (Development Neurobiology Unit, London (UK). Inst. of Neurology); Smith, S.L.; Heal, D.J. (Radcliffe Infirmary, Oxford (UK))

    1984-01-01

    The effect of thyroid status on noradrenergic synaptic function in the mature brain was examined by measuring presynaptic ..cap alpha..2- and postsynaptic ..beta..-adrenoceptors. Repeated triiodothyronine (T/sub 3/) administration to rats (100..mu..g/kg x 14 days hyperthyroid) caused an 18% increase in striatal ..beta..-adrenoceptors as shown by (/sup 3/H)-dihydroalprenolol binding with no change in membranes from cerebral cortex or hypothalamus. In contrast, hypothyroidism (propylthiouracil, PTU x 14 days) produced significant 12% and 30% reductions in striatal and hypothalamic ..beta..-adrenoceptors respectively with no change in the cerebral cortex. Presynaptic ..cap alpha..2-adrenoceptor function was measured in the two dysthyroid states using the clonidine-induced hypoactivity model. Experimental hyperthyroidism increased the degree of clonidine-induced hypoactivity, and suggests increased presynaptic ..cap alpha..2-adrenoceptor function compared with control rats, whereas hypothyroidism suppressed presynaptic ..cap alpha..2-adrenoceptor function. These results show firstly that changes of thyroid status in the mature rat may produce homeostatic alterations at central noradrenergic synapses as reflected by changes in pre- and postsynaptic adrenoceptor function. Secondly, there appear to be T/sub 3/-induced changes in ..beta..-adrenoceptors in the striatum where changes in dopaminergic neuronal activity have previously been demonstrated.

  20. Diving behaviour and haemoglobin function: the primary structure of the alpha- and beta-chains of the sea turtle (Caretta caretta) and its functional implications.

    Science.gov (United States)

    Petruzzelli, R; Aureli, G; Lania, A; Galtieri, A; Desideri, A; Giardina, B

    1996-06-15

    The amino acid sequence of the alpha- and beta-chains of haemoglobin (Hb) from the loggerhead sea turtle (Caretta caretta) has been determined. Comparison with that of human Hb shows differences in several residues involved in both alpha 1 beta 1 and alpha 1 beta 2 packing contacts. On the whole, in spite of the mutations, the essential characteristics of both interfaces seem to be maintained. The functional properties of the sea turtle Hb have been investigated at different temperatures and as a function of proton, chloride and organic phosphate concentrations. In addition to overall similarities shared with most of the vertebrate Hbs previously described, this molecule shows significant differences which could be related to the life behaviour of the turtle. In fact, while the shape of the Bohr-effect curve is well adapted for gas exchange during prolonged dives, the very small enthalpy change for O2 binding ensures that O2 delivery becomes essentially insensitive to the temperature changes of the environment. Moreover, and similarly to the case of emperor penguin Hb, the small alkaline Bohr effect appears to be only choride-linked, since the pH dependence of the O2 affinity is abolished in the absence of this ion. These functional characteristics are discussed on the basis of the primary structure of alpha- and beta-chains.

  1. Synergistic effect of interleukin 1 alpha on nontypeable Haemophilus influenzae-induced up-regulation of human beta-defensin 2 in middle ear epithelial cells

    Directory of Open Access Journals (Sweden)

    Park Raekil

    2006-01-01

    Full Text Available Abstract Background We recently showed that beta-defensins have antimicrobial activity against nontypeable Haemophilus influenzae (NTHi and that interleukin 1 alpha (IL-1 alpha up-regulates the transcription of beta-defensin 2 (DEFB4 according to new nomenclature of the Human Genome Organization in human middle ear epithelial cells via a Src-dependent Raf-MEK1/2-ERK signaling pathway. Based on these observations, we investigated if human middle ear epithelial cells could release IL-1 alpha upon exposure to a lysate of NTHi and if this cytokine could have a synergistic effect on beta-defensin 2 up-regulation by the bacterial components. Methods The studies described herein were carried out using epithelial cell lines as well as a murine model of acute otitis media (OM. Human cytokine macroarray analysis was performed to detect the released cytokines in response to NTHi exposure. Real time quantitative PCR was done to compare the induction of IL-1 alpha or beta-defensin 2 mRNAs and to identify the signaling pathways involved. Direct activation of the beta-defensin 2 promoter was monitored using a beta-defensin 2 promoter-Luciferase construct. An IL-1 alpha blocking antibody was used to demonstrate the direct involvement of this cytokine on DEFB4 induction. Results Middle ear epithelial cells released IL-1 alpha when stimulated by NTHi components and this cytokine acted in an autocrine/paracrine synergistic manner with NTHi to up-regulate beta-defensin 2. This synergistic effect of IL-1 alpha on NTHi-induced beta-defensin 2 up-regulation appeared to be mediated by the p38 MAP kinase pathway. Conclusion We demonstrate that IL-1 alpha is secreted by middle ear epithelial cells upon exposure to NTHi components and that it can synergistically act with certain of these molecules to up-regulate beta-defensin 2 via the p38 MAP kinase pathway.

  2. Insights into the electrochemical activity of nanosized {alpha}-LiFeO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Morales, J.; Santos-Pena, J.; Trocoli, R. [Departamento de Quimica Inorganica e Ingenieria Quimica, Edificio Marie Curie, Campus de Rabanales, Universidad de Cordoba, Cordoba 14071 (Spain); Franger, S. [Laboratoire de Physico-Chimie de l' Etat Solide, ICMMO, Universite Paris XI, Orsay 91405 (France); Rodriguez-Castellon, E. [Departamento de Quimica Inorganica, Cristalografia y Mineralogia, Campus de Teatinos, Universidad de Malaga, Malaga 29071 (Spain)

    2008-09-20

    In recent work [J. Morales, J. Santos-Pena, Electrochem. Commun. 9 (2007) 2116], we prepared nanosized {alpha}-LiFeO{sub 2} with increased electrochemical activity in lithium cells relative to various lithium ferrite polymorphs. In this work, we studied the previous electrodes in different charge states in order to obtain a more accurate picture of the phenomena occurring during cycling. Exsitu X-ray photoelectron spectroscopy (XPS) measurements confirmed the oxidation/reduction of iron atoms during the charge/discharge process. The electrochemical impedance spectroscopy results suggested that the electrolyte is not oxidised during the first charge, but rather than a solid electrolyte interface is formed after one cycle. Also, thermal tests revealed that Fe(IV) present in the electrodes reacted with the electrolyte to form oxidised carbon species. Finally, {alpha}-LiFeO{sub 2} was tested as a positive electrode material in a lithium battery under different regimes. Stabilised capacities up to 150 mAh g{sup -1} were obtained under a C/4 regime. This lithium ferrite is therefore an attractive alternative to LiCoO{sub 2}. (author)

  3. Comparative therapeutic response to pegylated interferon plus ribavirin versus interferon alpha-2b in chronic hepatitis C patients

    International Nuclear Information System (INIS)

    Ali, S.; Nazir, G.; Khan, S.A.; Fatima, F.; Iram, S.

    2010-01-01

    Background: Hepatitis C is an epidemic worldwide since discovery in 1989. Conventional interferon alpha-2b plus Ribavirin therapy was started in 1998 but over all sustained viral response (SVR) rates are much below the desired rates to eradicate the diseases and stopping its epidemic. This study was conducted to access the therapeutic and cost-effectiveness of long acting pegylated interferon alpha-2b plus Ribavirin therapy verses conventional interferon alpha-2b plus Ribavirin. Methods: This comparative study was done at PAF Hospital Shorkot Cantt from July 2005 to July 2008. One hundred anti-HCV positive patients were selected randomly for the study according to willingness due to cost afford ability of the patients for conventional interferon. Group-A was labelled as pegylated interferon alpha-2b plus Ribavirin group, and Group-B interferon alpha-2b plus Ribavirin group. Both groups were given treatment for 24 weeks. Early virological response (EVR) was accessed at 12 weeks of the treatment. Sustained virological response (SVR) in both the groups was done at 24 week during the treatment and 6 monthly after treatment for 2 years. Initially non-responders and relapsed patients within 2 years of treatment were re-treated for 24 weeks with the same treatment. In both groups non-responders and relapsed patients were labelled as resistant patients. Both groups were followed with same protocol for 2 years. Results: Out of 100 patients included in the study, 34% were females and 66% were males. Group-A patients over all showed 94% SVR as compare to 80% in Group-B in 2 year follow-up. Group-A showed 6% resistant patients as compare to Group-B (20%). Conventional interferons were better tolerated. Higher incidence of side-effects was seen in Group-A. Conclusion: Pegylated interferon plus Ribavirin showed 94% SVR in 2 years. Pegylated interferon plus Ribavirin is the treatment of choice.

  4. Seven-Disk Manifold, alpha-attractors and B-modes

    CERN Document Server

    Ferrara, Sergio

    2016-01-01

    Cosmological alpha-attractor models in \\cN=1 supergravity are based on hyperbolic geometry of a Poincar\\'e disk with the radius square {\\cal R}^2=3\\alpha. The predictions for the B-modes, r\\approx 3\\alpha {4\\over N^2}, depend on moduli space geometry and are robust for a rather general class of potentials. Here we notice that starting with M-theory compactified on a 7-manifold with G_2 holonomy, with a special choice of Betti numbers, one can obtain d=4 \\cN=1 supergravity with rank 7 scalar coset \\Big[{SL(2)\\over SO(2)}\\Big]^7. In a model where these 7 unit size Poincar\\'e disks have identified moduli one finds that 3 alpha =7. Assuming that the moduli space geometry of the phenomenological models is inherited from this version of M-theory, one would predict r \\approx 10^{-2} for 53 e-foldings. We also describe the related maximal supergravity and M/string theory models leading to preferred values 3 alpha =1,2,3,4,5,6,7.

  5. Synthesis and evaluation of [{sup 125}I]I-TSA as a brain nicotinic acetylcholine receptor {alpha}{sub 7} subtype imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Mikako [Laboratory of Genome Bio-Photonics, Photon Medical Research Center, Hamamatsu Medical University, Hamamatsu 431-3192 (Japan); Tatsumi, Ryo [Pharmaceuticals Research Unit, Research and Development Division, Mitsubishi Pharma Corporation, Yokohama 227-0033 (Japan); Fujio, Masakazu [Pharmaceuticals Research Unit, Research and Development Division, Mitsubishi Pharma Corporation, Yokohama 227-0033 (Japan); Katayama, Jiro [Pharmaceuticals Research Unit, Research and Development Division, Mitsubishi Pharma Corporation, Yokohama 227-0033 (Japan); Magata, Yasuhiro [Laboratory of Genome Bio-Photonics, Photon Medical Research Center, Hamamatsu Medical University, Hamamatsu 431-3192 (Japan)]. E-mail: magata@hama-med.ac.jp

    2006-04-15

    Introduction: Some in vitro investigations have suggested that the nicotinic acetylcholine receptor (nAChR) {alpha}{sub 7} subtype is implicated in Alzheimer's disease, schizophrenia and others. Recently, we developed (R)-3'-(5-bromothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'-[1',3'] oxazolidin]-2'-one (Br-TSA), which has a high affinity and selectivity for {alpha}{sub 7} nAChRs. Therefore we synthesized (R)-3'-(5-[{sup 125}I]iodothiophen-2-yl)spiro[1-azabicyclo[2.2.2]octane-3,5'- [1',3']oxazolidin]-2'-one ([{sup 125}I]I-TSA) and evaluated its potential for the in vivo detection of {alpha}{sub 7} nAChR in brain. Methods: In vitro binding affinity of I-TSA was measured in rat brain homogenates. Radioiodination was accomplished by a Br-I exchange reaction. Biodistribution studies were undertaken in mice by tail vein injection of [{sup 125}I]I-TSA. In vivo receptor blocking studies were carried out by treating mice with methyllycaconitine (MLA; 5 nmol/5 {mu}l, i.c.v.) or nonradioactive I-TSA (50 {mu}mol/kg, i.v.). Results: I-TSA exhibited a high affinity and selectivity for the {alpha}{sub 7} nAChR (K {sub i} for {alpha}{sub 7} nAChR=0.54 nM). Initial uptake in the brain was high (4.42 %dose/g at 5 min), and the clearance of radioactivity was relatively slow in the hippocampus ({alpha}{sub 7} nAChR-rich region) and was rather rapid in the cerebellum ({alpha}{sub 7} nAChR poor region). The hippocampus to cerebellum uptake ratio was 0.9 at 5 min postinjection, but it was increased to 1.8 at 60 min postinjection. Although the effect was not statistically significant, administration of I-TSA and MLA decreased the accumulation of radioactivity in hippocampus. Conclusion: Despite its high affinity and selectivity, [{sup 125}I]I-TSA does not appear to be a suitable tracer for in vivo {alpha}{sub 7} nAChR receptor imaging studies due to its high nonspecific binding. Further structural optimization is needed.

  6. [Examination of acute phase proteins concentrations in children with allergic rhinitis].

    Science.gov (United States)

    Steiner, Iwona; Sobieska, Magdalena; Pucher, Beata; Grzegorowski, Michał; Samborski, Włodzimierz

    2006-01-01

    Allergic rhinitis is an inflammatory disorder of upper respiratory tract (about 15 per cent of the population in industrialized countries suffer from this condition), characterized by frequent sneezing and a runny or stuffy nose sometimes accompanied by watery eyes. As the most common allergic condition, allergic rhinitis affects people of all ages. Boys are twice as likely to get allergic rhinitis than girls. The median age of onset of the condition is 10 years old, meaning that equal numbers of children develop the condition before and after age 10. Symptoms usually appear in childhood first and then lessen by the age of 30 or 40. Seasonal allergic rhinitis usually results from tree, grass or weed pollen. With this type of rhinitis, symptoms will decrease with the arrival of cold weather. Perennial allergic rhinitis can cause year-round symptoms. This allergic reaction is the result of indoor irritants such as feathers, mold spores, animal dander (hair and skin shed by pets) or dust mites. It is often aggravated by a food allergy, the most common being an allergy to milk. Acute phase proteins (APP) belong to the most ancient part of the unspecific immunity and contribute markedly to the keeping of homeostasis. As much as 30 various proteins are for the moment regarded as APP. Being multifunctional regulators and effectors APP stay in multiple relations to practically all types of cells and molecules. Among APP following functional groups may be described: transport proteins (transferrin, ceruloplasmin and haptoglobin), clotting factors (fibrinogen), antiproteases (alpha1-antitrypsin, alpha1-antichymotrypsin, alpha2-macroglobulin), complement components (C3, C4) and several proteins of hardly known function, like C-reactive protein (CRP), serum amyloid A, acid alpha1-glycoprotein (AGP) and others. From a group of 32 children, aged from 5 to 14 years, with symptoms of seasonal allergic rhinitis, and from a control group of 10 healthy children sex and age matched

  7. Differential Recognition of CD1d-[alpha]-Galactosyl Ceramide by the V[beta]8.2 and V[beta]7 Semi-invariant NKT T Cell Receptors

    Energy Technology Data Exchange (ETDEWEB)

    Pellicci, Daniel G.; Patel, Onisha; Kjer-Nielsen, Lars; Pang, Siew Siew; Sullivan, Lucy C.; Kyparissoudis, Konstantinos; Brooks, Andrew G.; Reid, Hugh H.; Gras, Stephanie; Lucet, Isabelle S.; Koh, Ruide; Smyth, Mark J.; Mallevaey, Thierry; Matsuda, Jennifer L.; Gapin, Laurent; McCluskey, James; Godfrey, Dale I.; Rossjohn, Jamie; PMCI-A; Monash; UCHSC; Melbourne

    2009-09-02

    The semi-invariant natural killer T cell receptor (NKT TCR) recognizes CD1d-lipid antigens. Although the TCR{alpha} chain is typically invariant, the {beta} chain expression is more diverse, where three V{beta} chains are commonly expressed in mice. We report the structures of V{alpha}14-V{beta}8.2 and V{alpha}14-V{beta}7 NKT TCRs in complex with CD1d-{alpha}-galactosylceramide ({alpha}-GalCer) and the 2.5 {angstrom} structure of the human NKT TCR-CD1d-{alpha}-GalCer complex. Both V{beta}8.2 and V{beta}7 NKT TCRs and the human NKT TCR ligated CD1d-{alpha}-GalCer in a similar manner, highlighting the evolutionarily conserved interaction. However, differences within the V{beta} domains of the V{beta}8.2 and V{beta}7 NKT TCR-CD1d complexes resulted in altered TCR{beta}-CD1d-mediated contacts and modulated recognition mediated by the invariant {alpha} chain. Mutagenesis studies revealed the differing contributions of V{beta}8.2 and V{beta}7 residues within the CDR2{beta} loop in mediating contacts with CD1d. Collectively we provide a structural basis for the differential NKT TCR V{beta} usage in NKT cells.

  8. The MAPKERK-1,2 pathway integrates distinct and antagonistic signals from TGF alpha and FGF7 in morphogenesis of mouse mammary epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Fata, Jimmie E; Mori, Hidetoshi; Ewald, Andrew J; Zhang, Hui; Yao, Evelyn; Werb, Zena; Bissell, Mina J

    2006-10-03

    Transforming growth factor-{alpha} (TGF{alpha}) and fibroblast growth factor-7 (FGF7) exhibit distinct expression patterns in the mammary gland. Both factors signal through mitogen-activated kinase/extracellular regulated kinase-1,2 (MAPK{sup ERK1,2}); however, their unique and/or combined contributions to mammary morphogenesis have not been examined. In ex vivo mammary explants, we show that a sustained activation of MAPK{sup ERK1,2} for 1 h, induced by TGF{alpha}, was necessary and sufficient to initiate branching morphogenesis, whereas a transient activation (15 min) of MAPK{sup ERK1,2}, induced by FGF7, led to growth without branching. Unlike TGF{alpha}, FGF7 promoted sustained proliferation as well as ectopic localization of, and increase in, keratin-6 expressing cells. The response of the explants to FGF10 was similar to that to FGF7. Simultaneous stimulation by FGF7 and TGF{alpha} indicated that the FGF7-induced MAPK{sup ERK1,2} signaling and associated phenotypes were dominant: FGF7 may prevent branching by suppression of two necessary TGF{alpha}-induced morphogenetic effectors, matrix metalloproteinase-3 (MMP-3/stromelysin-1), and fibronectin. Our findings indicate that expression of morphogenetic effectors, proliferation, and cell-type decisions during mammary organoid morphogenesis are intimately dependent on the duration of activation of MAPK{sup ERK1,2} activation.

  9. Pulse radiolytic study of alpha-tocopherol radical mechanisms in ethanolic solution

    International Nuclear Information System (INIS)

    Jore, D.; Patterson, L.K.; Ferradini, C.

    1986-01-01

    Pulse radiolytic studies of alpha-tocopherol (alpha TH) oxidation-reduction processes were carried out with low doses (5 Gy) of high-energy electrons in O 2 -, N 2 -, and air-saturated ethanolic solutions. Depending on the concentration of oxygen in solution, two different radicals, A . and B ., were observed. The first, A ., was obtained under N 2 and results from alpha TH reaction with solvated electron (k alpha TH + e-solv = 3.4 X 10(8) mol-1 liter s-1) and with H 3 C-CH-OH, (R.) (k alpha TH + R. = 5 X 10(5) mol-1 liter s-1). B., observed under O 2 , is produced by alpha TH reaction with RO 2 . peroxyl radicals (k alpha TH + RO 2 . = 9.5 X 10(4) mol-1 liter s-1)

  10. Differences in genotoxic activity of alpha-Ni3S2 on human lymphocytes from nickel-hypersensitized and nickel-unsensitized donors.

    Science.gov (United States)

    Arrouijal, F Z; Marzin, D; Hildebrand, H F; Pestel, J; Haguenoer, J M

    1992-05-01

    The genotoxic activity of alpha-Ni3S2 was assessed on human lymphocytes from nickel-hypersensitized (SSL) and nickel-unsensitized (USL) subjects. Three genotoxicity tests were performed: the sister chromatid exchange (SCE) test, the metaphase analysis test and the micronucleus test. (i) The SCE test (3-100 micrograms/ml) showed a weak but statistically significant increase in the number of SCE in both lymphocyte types with respect to controls, USL presenting a slightly higher SCE incidence but only at one concentration. (ii) The metaphase analysis test demonstrated a high dose-dependent clastogenic activity of alpha-Ni3S2 in both lymphocyte types. The frequency of chromosomal anomalies was significantly higher in USL than in SSL for all concentrations applied. (iii) The micronucleus test confirmed the dose-dependent clastogenic activity of alpha-Ni3S2 and the differences already observed between USL and SSL, i.e. the number of cells with micronuclei was statistically higher in USL. Finally, the incorporation study with alpha-63Ni3S2 showed a higher uptake of its solubilized fraction by USL. This allows an explanation of the different genotoxic action of nickel on the two cell types. In this study we demonstrated that hypersensitivity has an influence on the incorporation of alpha-Ni3S2 and subsequently on the different induction of chromosomal aberrations in human lymphocytes.

  11. Orientation of the calcium channel beta relative to the alpha(12.2 subunit is critical for its regulation of channel activity.

    Directory of Open Access Journals (Sweden)

    Iuliia Vitko

    Full Text Available BACKGROUND: The Ca(vbeta subunits of high voltage-activated Ca(2+ channels control the trafficking and biophysical properties of the alpha(1 subunit. The Ca(vbeta-alpha(1 interaction site has been mapped by crystallographic studies. Nevertheless, how this interaction leads to channel regulation has not been determined. One hypothesis is that betas regulate channel gating by modulating movements of IS6. A key requirement for this direct-coupling model is that the linker connecting IS6 to the alpha-interaction domain (AID be a rigid structure. METHODOLOGY/PRINCIPAL FINDINGS: The present study tests this hypothesis by altering the flexibility and orientation of this region in alpha(12.2, then testing for Ca(vbeta regulation using whole cell patch clamp electrophysiology. Flexibility was induced by replacement of the middle six amino acids of the IS6-AID linker with glycine (PG6. This mutation abolished beta2a and beta3 subunits ability to shift the voltage dependence of activation and inactivation, and the ability of beta2a to produce non-inactivating currents. Orientation of Ca(vbeta with respect to alpha(12.2 was altered by deletion of 1, 2, or 3 amino acids from the IS6-AID linker (Bdel1, Bdel2, Bdel3, respectively. Again, the ability of Ca(vbeta subunits to regulate these biophysical properties were totally abolished in the Bdel1 and Bdel3 mutants. Functional regulation by Ca(vbeta subunits was rescued in the Bdel2 mutant, indicating that this part of the linker forms beta-sheet. The orientation of beta with respect to alpha was confirmed by the bimolecular fluorescence complementation assay. CONCLUSIONS/SIGNIFICANCE: These results show that the orientation of the Ca(vbeta subunit relative to the alpha(12.2 subunit is critical, and suggests additional points of contact between these subunits are required for Ca(vbeta to regulate channel activity.

  12. d-Limonene-induced male rat-specific nephrotoxicity: Evaluation of the association between d-limonene and alpha 2u-globulin

    International Nuclear Information System (INIS)

    Lehman-McKeeman, L.D.; Rodriguez, P.A.; Takigiku, R.; Caudill, D.; Fey, M.L.

    1989-01-01

    d-Limonene is a naturally occurring monoterpene, which when dosed orally, causes a male rat-specific nephrotoxicity manifested acutely as the exacerbation of protein droplets in proximal tubule cells. Experiments were conducted to examine the retention of [ 14 C]d-limonene in male and female rat kidney, to determine whether d-limonene or one or more of its metabolites associates with the male rat-specific protein, alpha 2u-globulin, and if so, to identify the bound material. The results indicated that, 24 hr after oral administration of 3 mmol d-limonene/kg, the renal concentration of d-limonene equivalents was approximately 2.5 times higher in male rats than in female rats. Equilibrium dialysis in the presence or absence of sodium dodecyl sulfate indicated that approximately 40% of the d-limonene equivalents in male rat kidney associated with proteins in a reversible manner, whereas no significant association was observed between d-limonene equivalents and female rat kidney proteins. Association between d-limonene and male rat kidney proteins was characterized by high-performance gel filtration and reverse-phase chromatography. Gel filtration HPLC indicated that d-limonene in male rat kidney is associated with a protein fraction having a molecular weight of approximately 20,000. Separation of alpha 2u-globulin from other kidney proteins by reverse-phase HPLC indicated that d-limonene associated with a protein present only in male rat kidney which was definitively identified as alpha 2u-globulin by amino acid sequencing. The major metabolite associated with alpha 2u-globulin was d-limonene-1,2-oxide. Parent d-limonene was also identified as a minor component in the alpha 2u-globulin fraction

  13. Anti-pp,. cap alpha cap alpha. and p. cap alpha. elastic scattering at high energies and Chou-Yang conjecture

    Energy Technology Data Exchange (ETDEWEB)

    Saleem, M.; Fazal-e-Aleem; Rifique, M.

    1987-03-01

    The recent experimental measurements for anti-pp and ..cap alpha cap alpha.. elastic scattering at high energies have shown that the Chou-Yang conjecture regarding the relationship between the electromagnetic and the hadronic form factor of a particle is only an approximation. A new ansatz has been proposed to obtain hadronic form factors of proton and the ..cap alpha..-particle. These form factors have been used to explain the various characteristics of anti-pp, ..cap alpha cap alpha.. and p..cap alpha.. elastic scattering at high energies.

  14. Inferring uncertainty from interval estimates: Effects of alpha level and numeracy

    Directory of Open Access Journals (Sweden)

    Luke F. Rinne

    2013-05-01

    Full Text Available Interval estimates are commonly used to descriptively communicate the degree of uncertainty in numerical values. Conventionally, low alpha levels (e.g., .05 ensure a high probability of capturing the target value between interval endpoints. Here, we test whether alpha levels and individual differences in numeracy influence distributional inferences. In the reported experiment, participants received prediction intervals for fictitious towns' annual rainfall totals (assuming approximately normal distributions. Then, participants estimated probabilities that future totals would be captured within varying margins about the mean, indicating the approximate shapes of their inferred probability distributions. Results showed that low alpha levels (vs. moderate levels; e.g., .25 more frequently led to inferences of over-dispersed approximately normal distributions or approximately uniform distributions, reducing estimate accuracy. Highly numerate participants made more accurate estimates overall, but were more prone to inferring approximately uniform distributions. These findings have important implications for presenting interval estimates to various audiences.

  15. Adsorption of {alpha}-amylase onto poly(N-vinyl 2-pyrrolidone/itaconic acid) hydrogels

    Energy Technology Data Exchange (ETDEWEB)

    Tuemtuerk, Hayrettin; Caykara, Tuncer; Kantoglu, Oemer; Gueven, Olgun

    1999-05-02

    {alpha}-Amylase enzyme was adsorbed on poly(N-vinyl 2-pyrrolidone/itaconic acid) (P(VP/IA)) hydrogels prepared by irradiating the ternary mixtures of VP/IA/water by {gamma}-rays at ambient temperature. The adsorption capacity of the hydrogels was determined to increase from 2.30 to 3.40 mg {alpha}-amylase/g dry gel with increasing amount of IA in gel system. Kinetic parameters were calculated as 2.51 g/dm{sup 3} for K{sub m} and 1.67x10{sup -3} g/dm{sup 3} min for V{sub max} for free enzyme and in the range of 3.88-5.02 g/dm{sup 3} for K{sub m} and 1.62x10{sup -3}-2.27 x 10{sup -3} g/dm{sup 3} min for V{sub max} depending on the amount of IA in the hydrogel. Enzyme activities were found to increase from 49.9% to 77.4% with increasing amount of IA in the gel system and retained their activities for one month storage. On the other hand, the free enzyme loses its activity completely after 20 days.

  16. Epitaxial growth of branched {alpha}-Fe{sub 2}O{sub 3}/SnO{sub 2} nano-heterostructures with improved lithium-ion battery performance

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Weiwei; Cheng, Chuanwei; Jia, Xingtao; Yu, Ting; Fan, Hong Jin [Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, 637371 (Singapore); Liu, Jinping; Jiang, Jian [Institute of Nanoscience and Nanotechnology, Department of Physics, Huazhong Normal University, Wuhan 430079 (China); Tay, Yee Yan; Hng, Huey Hoon [School of Materials Science and Engineering, Nanyang Technological University, 639798 (Singapore); Zhang, Jixuan; Gong, Hao [Department of Materials Science and Engineering, National University of Singapore, 117576 (Singapore)

    2011-07-08

    We report the synthesis of a novel branched nano-heterostructure composed of SnO{sub 2} nanowire stem and {alpha}-Fe{sub 2}O{sub 3} nanorod branches by combining a vapour transport deposition and a facile hydrothermal method. The epitaxial relationship between the branch and stem is investigated by high resolution transmission electron microscopy (HRTEM). The SnO{sub 2} nanowire is determined to grow along the [101] direction, enclosed by four side surfaces. The results indicate that distinct crystallographic planes of SnO{sub 2} stem can induce different preferential growth directions of secondary nanorod branches, leading to six-fold symmetry rather than four-fold symmetry. Moreover, as a proof-of-concept demonstration of the function, such {alpha}-Fe{sub 2}O{sub 3}/SnO{sub 2} composite material is used as a lithium-ion batteries (LIBs) anode material. Low initial irreversible loss and high reversible capacity are demonstrated, in comparison to both single components. The synergetic effect exerted by SnO{sub 2} and {alpha}-Fe{sub 2}O{sub 3} as well as the unique branched structure are probably responsible for the enhanced performance. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  17. Transcriptional Response of Human Cells to Microbeam Irradiation with 2.1 MeV Alpha Particles

    Science.gov (United States)

    Hellweg, C. E.; Bogner, S.; Spitta, L.; Arenz, A.; Baumstark-Khan, C.; Greif, K. D.; Giesen, U.

    Within the next decades an increasing number of human beings in space will be simultaneously exposed to different stimuli especially microgravity and radiation To assess the risks for humans during long-duration space missions the complex interplay of these parameters at the cellular level must be understood Cellular stress protection responses lead to increased transcription of several genes via modulation of transcription factors Activation of the Nuclear Factor kappa B NF- kappa B pathway as a possible anti-apoptotic route represents such an important cellular stress response A screening assay for detection of NF- kappa B-dependent gene activation using the destabilized variant of Enhanced Green Fluorescent Protein d2EGFP as reporter protein had been developed It consists of Human Embryonic Kidney HEK 293 Cells stably transfected with a receptor-reporter-construct carrying d2EGFP under the control of a NF- kappa B response element Clones positive for Tumor Necrosis Factor alpha TNF- alpha inducible d2EGFP expression were selected as cellular reporters Irradiation was performed either with X-rays 150 kV 19 mA at DLR Cologne or with 2 1 MeV alpha particles LET sim 160 keV mu m at PTB Braunschweig After irradiation the following biological endpoints were determined i cell survival via the colony forming ability test ii time-dependent activation of NF- kappa B dependent d2EGFP gene expression using flow cytometry iii quantitative RT-PCR

  18. Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes

    DEFF Research Database (Denmark)

    Plomgaard, P; Nielsen, A R; Fischer, C P

    2007-01-01

    AIMS/HYPOTHESIS: Clear evidence exists that TNF-alpha inhibits insulin signalling and thereby glucose uptake in myocytes and adipocytes. However, conflicting results exist with regard to the role of TNF-alpha in type 2 diabetes. METHODS: We obtained blood and biopsy samples from skeletal muscle...... and subcutaneous adipose tissue in patients with type 2 diabetes (n = 96) and healthy controls matched for age, sex and BMI (n = 103). RESULTS: Patients with type 2 diabetes had higher plasma levels of fasting insulin (p ...) uptake (VO2/kg) in the diabetes group (p type 2 diabetic patients. Immunohistochemistry revealed more TNF-alpha protein...

  19. Coincidence study of alpha particle fragmentation at E/sub alpha/ = 140 MeV

    International Nuclear Information System (INIS)

    Koontz, R.W.

    1980-01-01

    Results of an experimental study of the interaction of 140 MeV alpha particles with 90 Zr nuclei resulting in fragmentation of the alpha particle are reported. The experimental observations of the study are analyzed and are found to show that alpha particle breakup reactions leading to at least 4-body final states, composed of two charged alpha particle fragments, contribute significantly to the singles yield of charged fragments observed at a fixed forward angle. The conclusions are based on coincidence measurements where one charged fragment is detected at a small forward angle which remains fixed, while the second charged fragment is detected at a series of coplanar secondary angles. The largest coincidence charged particle yield for the multiparticle final state events results from 90 Zr(α,pp)X reactions, where both of the measured protons have energy distributions similar to the proton singles energy distributions. The second largest observed coincidence yield involving two charged fragments arises from 90 Zr(α,pd)X reactions, where the p and d fragments, as in the 90 Zr(α,pp)X reactions also have energy distribution similar to the singles energy distributions. Analysis of additional measurements, where alpha particle fragments at the fixed angle are detected in coincidence with evaporation and nonequilibrium particles at many coplanar angles, show that the alpha particle fragmentation reactions are also generally associated with large energy transfer to the target nucleus. A multiple scattering model of the fragmentation reaction is employed, in conjunction with the experimental observations, to estimate the cross sections for alpha particle fragmentation into multi-particle final states resulting in n, 2n, p, pp, d, dn, dp, t and 3 He fragments. The estimated total cross section for all fragmentation reactions is 755 mb or approximately 38% of the total reaction cross section for 140 MeV alpha particle interactions with 90 Zr

  20. Reversal of behavioral depression by infusion of an alpha-2 adrenergic agonist into the locus coeruleus.

    Science.gov (United States)

    Simson, P G; Weiss, J M; Hoffman, L J; Ambrose, M J

    1986-04-01

    This experiment demonstrated that behavioral depression produced by exposure of rats to strong uncontrollable shocks could be reversed by infusion of the alpha-2 adrenergic agonist clonidine into the region of the locus coeruleus (LC). A 20-min infusion, through bilateral cannulae, into the locus coeruleus of clonidine, piperoxane (alpha-2 antagonist) or inactive vehicle (0.85% saline), was given beginning 70 min after the animals were removed from the stress situation. The dose and volume of drug given in the infusion (0.16 microgram/microliter, 0.1 microliter/min) had been previously shown to produce effects specific to the locus coeruleus (Weiss, Simson, Hoffman, Ambrose, Cooper and Webster, 1986; Neuropharmacology 25: 367-384). At the conclusion of the infusion, active behavior of animals was measured in a 15-min swim test. Results showed that stressed animals infused with vehicle exhibited significantly less active behavior in the swim test than did non-stressed animals infused with vehicle, thereby showing the usual behavioral depression seen after exposure to an uncontrollable stress. Stressed animals infused with clonidine showed no difference in active behavior in comparison to non-stressed animals infused with vehicle and showed significantly more activity than did the stressed animals infused with vehicle. Stressed animals infused with piperoxane showed no significant difference in activity in comparison to the stressed animals infused with vehicle and were significantly less active than either the non-stressed animals infused with vehicle or the stressed animals infused with clonidine. Thus, infusion into the locus coeruleus of the alpha-2 agonist clonidine, but not the alpha-2 antagonist piperoxane, eliminated behavioral depression.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Determination of $\\alpha_s$ from Hadronic Event Shapes in $e^+ e^-$ Annihilation at $192 \\le \\sqrt{s} \\le 208$ GeV

    CERN Document Server

    Achard, P.; Aguilar-Benitez, M.; Alcaraz, J.; Alemanni, G.; Allaby, J.; Aloisio, A.; Alviggi, M.G.; Anderhub, H.; Andreev, Valery P.; Anselmo, F.; Arefev, A.; Azemoon, T.; Aziz, T.; Bagnaia, P.; Bajo, A.; Baksay, G.; Baksay, L.; Baldew, S.V.; Banerjee, S.; Banerjee, Sw.; Barczyk, A.; Barillere, R.; Bartalini, P.; Basile, M.; Batalova, N.; Battiston, R.; Bay, A.; Becattini, F.; Becker, U.; Behner, F.; Bellucci, L.; Berbeco, R.; Berdugo, J.; Berges, P.; Bertucci, B.; Betev, B.L.; Biasini, M.; Biglietti, M.; Biland, A.; Blaising, J.J.; Blyth, S.C.; Bobbink, G.J.; Bohm, A.; Boldizsar, L.; Borgia, B.; Bottai, S.; Bourilkov, D.; Bourquin, M.; Braccini, S.; Branson, J.G.; Brochu, F.; Burger, J.D.; Burger, W.J.; Cai, X.D.; Capell, M.; Cara Romeo, G.; Carlino, G.; Cartacci, A.; Casaus, J.; Cavallari, F.; Cavallo, N.; Cecchi, C.; Cerrada, M.; Chamizo, M.; Chang, Y.H.; Chemarin, M.; Chen, A.; Chen, G.; Chen, G.M.; Chen, H.F.; Chen, H.S.; Chiefari, G.; Cifarelli, L.; Cindolo, F.; Clare, I.; Clare, R.; Coignet, G.; Colino, N.; Costantini, S.; de la Cruz, B.; Cucciarelli, S.; van Dalen, J.A.; de Asmundis, R.; Deglon, P.; Debreczeni, J.; Degre, A.; Deiters, K.; Della Volpe, D.; Delmeire, E.; Denes, P.; De Notaristefani, F.; De Salvo, A.; Diemoz, M.; Dierckxsens, M.; Dionisi, C.; Dittmar, M.; Doria, A.; Dova, M.T.; Duchesneau, D.; Echenard, B.; Eline, A.; El Mamouni, H.; Engler, A.; Eppling, F.J.; Ewers, A.; Extermann, P.; Falagan, M.A.; Falciano, S.; Favara, A.; Fay, J.; Fedin, O.; Felcini, M.; Ferguson, T.; Fesefeldt, H.; Fiandrini, E.; Field, J.H.; Filthaut, F.; Fisher, P.H.; Fisher, W.; Fisk, I.; Forconi, G.; Freudenreich, K.; Furetta, C.; Galaktionov, Iouri; Ganguli, S.N.; Garcia-Abia, Pablo; Gataullin, M.; Gentile, S.; Giagu, S.; Gong, Z.F.; Grenier, Gerald Jean; Grimm, O.; Gruenewald, M.W.; Guida, M.; van Gulik, R.; Gupta, V.K.; Gurtu, A.; Gutay, L.J.; Haas, D.; Hakobian, R.Sh.; Hatzifotiadou, D.; Hebbeker, T.; Herve, Alain; Hirschfelder, J.; Hofer, H.; Hohlmann, M.; Holzner, G.; Hou, S.R.; Hu, Y.; Jin, B.N.; Jones, Lawrence W.; de Jong, P.; Josa-Mutuberria, I.; Kafer, D.; Kaur, M.; Kienzle-Focacci, M.N.; Kim, J.K.; Kirkby, Jasper; Kittel, W.; Klimentov, A.; Konig, A.C.; Kopal, M.; Koutsenko, V.; Kraber, M.; Kraemer, R.W.; Krenz, W.; Kruger, A.; Kunin, A.; Ladron de Guevara, P.; Laktineh, I.; Landi, G.; Lebeau, M.; Lebedev, A.; Lebrun, P.; Lecomte, P.; Lecoq, P.; Le Coultre, P.; Le Goff, J.M.; Leiste, R.; Levtchenko, M.; Levchenko, P.; Li, C.; Likhoded, S.; Lin, C.H.; Lin, W.T.; Linde, F.L.; Lista, L.; Liu, Z.A.; Lohmann, W.; Longo, E.; Lu, Y.S.; Lubelsmeyer, K.; Luci, C.; Luminari, L.; Lustermann, W.; Ma, W.G.; Malgeri, L.; Malinin, A.; Mana, C.; Mangeol, D.; Mans, J.; Martin, J.P.; Marzano, F.; Mazumdar, K.; McNeil, R.R.; Mele, S.; Merola, L.; Meschini, M.; Metzger, W.J.; Mihul, A.; Milcent, H.; Mirabelli, G.; Mnich, J.; Mohanty, G.B.; Muanza, G.S.; Muijs, A.J.M.; Musicar, B.; Musy, M.; Nagy, S.; Natale, S.; Napolitano, M.; Nessi-Tedaldi, F.; Newman, H.; Niessen, T.; Nisati, A.; Kluge, Hannelies; Ofierzynski, R.; Organtini, G.; Palomares, C.; Pandoulas, D.; Paolucci, P.; Paramatti, R.; Passaleva, G.; Patricelli, S.; Paul, Thomas Cantzon; Pauluzzi, M.; Paus, C.; Pauss, F.; Pedace, M.; Pensotti, S.; Perret-Gallix, D.; Petersen, B.; Piccolo, D.; Pierella, F.; Pioppi, M.; Piroue, P.A.; Pistolesi, E.; Plyaskin, V.; Pohl, M.; Pozhidaev, V.; Pothier, J.; Prokofev, D.O.; Prokofev, D.; Quartieri, J.; Rahal-Callot, G.; Rahaman, M.A.; Raics, P.; Raja, N.; Ramelli, R.; Rancoita, P.G.; Ranieri, R.; Raspereza, A.; Razis, P.; Ren, D.; Rescigno, M.; Reucroft, S.; Riemann, S.; Riles, Keith; Roe, B.P.; Romero, L.; Rosca, A.; Rosier-Lees, S.; Roth, Stefan; Rosenbleck, C.; Roux, B.; Rubio, J.A.; Ruggiero, G.; Rykaczewski, H.; Sakharov, A.; Saremi, S.; Sarkar, S.; Salicio, J.; Sanchez, E.; Sanders, M.P.; Schafer, C.; Shchegelsky, V.; Schmidt-Kaerst, S.; Schmitz, D.; Schopper, H.; Schotanus, D.J.; Schwering, G.; Sciacca, C.; Servoli, L.; Shevchenko, S.; Shivarov, N.; Shoutko, V.; Shumilov, E.; Shvorob, A.; Siedenburg, T.; Son, D.; Spillantini, P.; Steuer, M.; Stickland, D.P.; Stoyanov, B.; Straessner, A.; Sudhakar, K.; Sultanov, G.; Sun, L.Z.; Sushkov, S.; Suter, H.; Swain, J.D.; Szillasi, Z.; Tang, X.W.; Tarjan, P.; Tauscher, L.; Taylor, L.; Tellili, B.; Teyssier, D.; Timmermans, Charles; Ting, S.C.C.; Ting, S.M.; Tonwar, S.C.; Toth, J.; Tully, C.; Tung, K.L.; Ulbricht, J.; Valente, E.; Van de Walle, R.T.; Veszpremi, V.; Vesztergombi, G.; Vetlitsky, I.; Vicinanza, D.; Viertel, G.; Villa, S.; Vivargent, M.; Vlachos, S.; Vodopyanov, I.; Vogel, H.; Vogt, H.; Vorobev, I.; Vorobov, A.A.; Wadhwa, M.; Wallraff, W.; Wang, X.L.; Wang, Z.M.; Weber, M.; Wienemann, P.; Wilkens, H.; Wynhoff, S.; Xia, L.; Xu, Z.Z.; Yamamoto, J.; Yang, B.Z.; Yang, C.G.; Yang, H.J.; Yang, M.; Yeh, S.C.; Zalite, A.; Zalite, Yu.; Zhang, Z.P.; Zhao, J.; Zhu, G.Y.; Zhu, R.Y.; Zhuang, H.L.; Zichichi, A.; Zilizi, G.; Zimmermann, B.; Zoller, M.

    2002-01-01

    Results are presented from a study of the structure of high energy hadronic events recorded by the L3 detector at sqrt(s)>192 GeV. The distributions of several event shape variables are compared to resummed O(alphaS^2) QCD calculations. We determine the strong coupling constant at three average centre-of-mass energies: 194.4, 200.2 and 206.2 GeV. These measurements, combined with previous L3 measurements at lower energies demonstrate the running of alphaS as expected in QCD and yield alphaS(mZ) = 0.1227 +- 0.0012 +- 0.0058, where the first uncertainty is experimental and the second is theoretical.

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

    Science.gov (United States)

    Lee, Dae-Hee; Lee, Yong J

    2008-10-01

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

  3. Synthesis and evaluation of alpha-[[(2-haloethyl)amino]methyl]-2- nitro-1H-imidazole-1-ethanols as prodrugs of alpha-[(1-aziridinyl)methyl]-2- nitro-1H-imidazole-1-ethanol (RSU-1069) and its analogues which are radiosensitizers and bioreductively activated cytotoxins

    International Nuclear Information System (INIS)

    Jenkins, T.C.; Naylor, M.A.; O'Neill, P.; Threadgill, M.D.; Cole, S.; Stratford, I.J.; Adams, G.E.; Fielden, E.M.; Suto, M.J.; Stier, M.A.

    1990-01-01

    alpha-[(1-Aziridinyl)methyl]-2-nitro-1H-imidazole-1-ethanols, of general formula ImCH2CH(OH)CH2NCR1R2CR3R4, where Im = 2-nitroimidazole and R1, R2, R3, R4 = H, Me, are radiosensitizers and selective bioreductively activated cytotoxins toward hypoxic tumor cells in vitro and in vivo. Treatment of the aziridines with hydrogen halide in acetone or aqueous acetone gave the corresponding 2-haloethylamines of general formula ImCH2CH(OH)CH2(+)-NH2CR1R2CR3R4X X-, where R1, R2, R3, R4 = H, Me, and X = F, Cl, Br, I. These 2-haloethylamines were evaluated as prodrugs of the parent aziridines. The rates of ring closure in aqueous solution at pH approximately 6 were found to increase with increasing methyl substitution and to depend on the nature of the leaving group (I approximately Br greater than Cl much greater than F). A competing reaction of ImCH2CH(OH)CH2+NH2CH2CH2X X- (X = Cl, Br) with aqueous HCO3- ions gives 3-[2-hyroxy-3-(2-nitro-1H-imidazol-1-yl)propyl]-2-oxazolidinone. The activities of these prodrugs as radiosensitizers or as bioreductively activated cytotoxins were consistent with the proportion converted to the parent aziridine during the course of the experiment. alpha-[[(2-Bromoethyl)amino]methyl]-2-nitro-1H-imidazole-1- ethanol (RB 6145, 10), the prodrug of alpha-[(1-aziridinyl)methyl]-2-nitro-1H-imidazole-1-ethanol (RSU-1069, 3), is identified as the most useful compound in terms of biological activity and rate of ring closure under physiological conditions

  4. Feasibility of alpha particle measurement in a magnetically confined plasma by CO2 laser Thomson scattering

    International Nuclear Information System (INIS)

    Richards, R.K.; Vander Sluis, K.L.; Hutchinson, D.P.

    1987-08-01

    Fusion-product alpha particles will dominate the behavior of the next generation of ignited D-T fusion reactors. Advanced diagnostics will be required to characterize the energy deposition of these fast alpha particles in the magnetically confined plasma. For small-angle coherent Thomson scattering of a CO 2 laser beam from such a plasma, a resonance in the scattered power occurs near 90 0 with respect to the magnetic field direction. This spatial concentration permits a simplified detection of the scattered laser power from the plasma using a heterodyne system. The signal produced by the presence of fusion-product alpha particles in an ignited plasma is calculated to be well above the noise level, which results from statistical variations of the background signal produced by scattering from free electrons. 7 refs

  5. Investigation of the Pygmy Dipole Resonance in (alpha, alpha 'gamma) coincidence experiments

    NARCIS (Netherlands)

    Savran, D.; Babilon, M.; van den Berg, A. M.; Harakeh, M. N.; Hasper, J.; Wortche, H. J.; Zilges, A.

    2007-01-01

    We report on first results from experiments using the (alpha, alpha'gamma) reaction at E alpha = 136 MeV to investigate bound electric dipole (El) excitations building the so-called Pygmy Dipole Resonance (PDR) in the semi-magic nucleus Ce-140. The method of (alpha, alpha'gamma) allows the

  6. Alpha and beta-adrenoceptors in hypertension. I. Cardiac and renal alpha 1-, beta 1-, and beta 2-adrenoceptors in rat models of acquired hypertension

    NARCIS (Netherlands)

    Michel, M. C.; Kanczik, R.; Khamssi, M.; Knorr, A.; Siegl, H.; Beckeringh, J. J.; Brodde, O. E.

    1989-01-01

    To determine whether adrenoceptor changes in genetic hypertension occur primary or secondary to blood pressure elevation, we measured cardiac and renal alpha 1- (by [125I]Be 2254 binding) and beta 1- and beta 2-adrenoceptors (by (-)-[125I]iodocyanopindolol binding) densities in various rat models of

  7. Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

    DEFF Research Database (Denmark)

    Larsen, T.S.; Pallisgaard, N.; Andersen, M.T.

    2008-01-01

    with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response Udgivelsesdato: 2008/10...

  8. Potential antisecretory antidiarrheals. 1. Alpha 2-adrenergic aromatic aminoguanidine hydrazones.

    Science.gov (United States)

    Pitzele, B S; Moormann, A E; Gullikson, G W; Albin, D; Bianchi, R G; Palicharla, P; Sanguinetti, E L; Walters, D E

    1988-01-01

    Guanabenz, a centrally acting antihypertensive agent, has been shown to have intestinal antisecretory properties. A series of aromatic aminoguanidine hydrazones was made in an effort to separate the antisecretory and cardiovascular activities. Benzaldehyde, naphthaldehyde, and tetralone derivatives were synthesized. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and in the Ussing chamber using a rabbit ileum preparation. A number of compounds, including members of each structural class, were active upon subcutaneous administration in the rat. Active compounds were determined to be alpha 2-adrenergic agonists by yohimbine reversals of their Ussing chamber activities. The compound displaying the best separation of activities was the aminoguanidine hydrazone of 2,6-dimethyl-4-hydroxybenzaldehyde (20).

  9. Optical properties, electronic structure and magnetism of alpha '-NaxV2O5

    NARCIS (Netherlands)

    Konstantinovic, MI; Popovic, ZV; Presura, C; Gajic, R; Isobe, M; Ueda, Y; Moshchalkov, VV

    2002-01-01

    The optical properties of sodium-deficient alpha'-NaxV2O5 (0.85 less than or equal to x less than or equal to 1.00) single crystals are analyzed using ellipsometry, and infrared reflectivity techniques. In sodium deficient samples, the optical absorption peak associated to the fundamental electronic

  10. Cr/alpha-Cr2O3 monodispersed spherical core-shell particles based solar absorbers

    CSIR Research Space (South Africa)

    Khamlich, S

    2011-07-01

    Full Text Available as reported. The coated Cr/alpha-Cr2O3 spherical particles on rough copper substrates by a simple self-assembly-like method were characterized by scanning electron microscopy, energy dispersive spectrometry, Raman spectroscopy, and diffuse reflectance UV...

  11. Phytanic acid alpha-oxidation: decarboxylation of 2-hydroxyphytanoyl-CoA to pristanic acid in human liver

    NARCIS (Netherlands)

    Verhoeven, N. M.; Wanders, R. J.; Schor, D. S.; Jansen, G. A.; Jakobs, C.

    1997-01-01

    The degradation of the first intermediate in the alpha-oxidation of phytanic acid, 2-hydroxyphytanoyl-CoA, was investigated. Human liver homogenates were incubated with 2-hydroxyphytanoyl-CoA or 2-hydroxyphytanic acid, after which formation of 2-ketophytanic acid and pristanic acid were studied.

  12. Espectroscopia Mössbauer e refinamento estrutural no sistema cerâmico isomórfico (alfa-Fe2O3-(alfa-Al2O 3 Mössbauer spectroscopy and structural refinement in the isomorphic (alpha-Fe2O3-( alpha-Al2O3 ceramic system

    Directory of Open Access Journals (Sweden)

    J. A. Moreto

    2007-06-01

    Full Text Available Os multiferróicos são materiais em que duas ou três propriedades tais como ferroeletricidade, ferromagnetismo e ferroelasticidade são observadas em uma mesma fase. Em particular, os multiferróicos magnetoelétricos representam os materiais que são simultaneamente (antiferromagnéticos e ferroelétricos, com ou sem ferroelasticidade. Especificamente, o sistema hematita (alfa-Fe2O3-alumina (alfa-Al2O3 tem sido estudado, principalmente devido às suas potencialidades para aplicações em metalurgia e como catalisador na síntese de amônia. Contudo, compostos deste sistema também podem apresentar efeitos magnetoelétricos. Neste trabalho um estudo estrutural do composto (alfa-Fe2O30,25(alfa-Al2O 30,75 submetido à moagem em altas energias e tratamento térmico pós-moagem é apresentado. As amostras foram caracterizadas por difração de raios X, refinamento estrutural Rietveld e espectroscopia Mössbauer. A determinação e identificação das fases cristalográficas, parâmetros de rede e volume de celas unitárias nas amostras moída e tratada termicamente permitiu verificar as mudanças dos parâmetros, a formação de espinélios e possíveis deformações relativas advindas do processo de moagem em altas energias.Multiferroics are materials in which two or all three of the properties, ferroelectricity, ferromagnetism, and ferroelasticity occur in the same phase. In particular, multiferroic magnetoelectrics represent the materials that are simultaneously ferromagnetic and ferroelectric, with or without ferroelasticity. Specifically, the hematite (alpha-Fe2O3-alumina (alpha-Al2O3 system has been studied, mainly due to its potential applications in metallurgy and as catalyst of ammonia synthesis. However, compounds of this system also may present magnetoelectric effects. In this work, a structural study of the high-energy ball milled and annealed (alpha-Fe2O3 0.25(alpha-Al2O30.75 compound was carefully conducted. The samples were

  13. Effect of size of alpha phases on cyclic deformation and fatigue crack initiation during fatigue of an alpha-beta titanium alloy

    Directory of Open Access Journals (Sweden)

    Sun Qiaoyan

    2018-01-01

    Full Text Available Alpha phase exhibits equiaxed or lamellar morphologies with size from submicron to microns in an alpha-beta titanium alloy. Cyclic deformation, slip characteristics and crack nucleation during fatigue in different microstructures of TC21 alloy (Ti-6Al-2Sn-2Zr-3Mo-1Cr-2Nb-0.1Si were systematically investigated and analyzed. During low-cycle fatigue, equiaxed microstructure (EM in TC21 alloy exhibits higher strength, ductility and longer low-cycle fatigue life than those of the lamellar microstructure (LM. There are more voids in the single lamellar alpha than the equiaxed alpha grains. As a result, voids more easily link up to form crack in the lamellar alpha phase than the equiaxed alpha phase. However, during high-cycle fatigue, the fine lamellar microstructure (FLM shows higher fatigue limit than bimodal microstructure (BM. The localized plastic deformation can be induced during high-cycle fatigue. The slip bands or twins are observed in the equiaxed and lamellar alpha phases(>1micron, which tends to form strain concentration and initiate fatigue crack. The localized slip within nanoscale alpha plates is seldom observed and extrusion/intrusion dispersedly distributed on the sample surface in FLM. This indicates that FLM show super resistance to fatigue crack which bring about higher fatigue limit than BM.

  14. Low Cost silicon photodiodes for alpha spectrometry

    International Nuclear Information System (INIS)

    Khoury, H.; Lopes, A.; Hazin, C.; Lira, C.B.; Silva, E. da

    1998-01-01

    This study was carried out to evaluate the suitability of using commercially available photodiodes for alpha spectrometry, since the principle on which both operate are similar. Photodiodes are low priced compared to the commonly used semiconductor detectors making them potentially useful for research and teaching purposes. Very thin calibrated alpha sources of 2 41 A m, 2 44 C m and 2 35 U , produced at the Metrology Laboratory of IRD/CNEN, were used to test the performance of three photodiodes. The results showed that the responses of the photodiodes were linear with the alpha particle energy and that the energy resolution varied between 0,79% and 0,45%, with an efficiency of 8%. The resolution and efficiency presented by the photodiodes tested are similar to those obtained with other semiconductor detectors, evidencing that they can be used successfully as alpha detectors

  15. Discovery of an Oxybenzylglycine Based Peroxisome Proliferator Activated Receptor [alpha] Selective Agonist 2-((3-((2-(4-Chlorophenyl)-5-methyloxazol-4-yl)methoxy)benzyl)(methoxycarbonyl)amino)acetic Acid (BMS-687453)

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jun; Kennedy, Lawrence J.; Shi, Yan; Tao, Shiwei; Ye, Xiang-Yang; Chen, Stephanie Y.; Wang, Ying; Hernndez, Andrs S.; Wang, Wei; Devasthale, Pratik V.; Chen, Sean; Lai, Zhi; Zhang, Hao; Wu, Shung; Smirk, Rebecca A.; Bolton, Scott A.; Ryono, Denis E.; Zhang, Huiping; Lim, Ngiap-Kie; Chen, Bang-Chi; Locke, Kenneth T.; O’Malley, Kevin M.; Zhang, Litao; Srivastava, Rai Ajit; Miao, Bowman; Meyers, Daniel S.; Monshizadegan, Hossain; Search, Debra; Grimm, Denise; Zhang, Rongan; Harrity, Thomas; Kunselman, Lori K.; Cap, Michael; Kadiyala, Pathanjali; Hosagrahara, Vinayak; Zhang, Lisa; Xu, Carrie; Li, Yi-Xin; Muckelbauer, Jodi K.; Chang, Chiehying; An, Yongmi; Krystek, Stanley R.; Blanar, Michael A.; Zahler, Robert; Mukherjee, Ranjan; Cheng, Peter T.W.; Tino, Joseph A. (BMS)

    2010-04-12

    An 1,3-oxybenzylglycine based compound 2 (BMS-687453) was discovered to be a potent and selective peroxisome proliferator activated receptor (PPAR) {alpha} agonist, with an EC{sub 50} of 10 nM for human PPAR{alpha} and 410-fold selectivity vs human PPAR{gamma} in PPAR-GAL4 transactivation assays. Similar potencies and selectivity were also observed in the full length receptor co-transfection assays. Compound 2 has negligible cross-reactivity against a panel of human nuclear hormone receptors including PPAR{delta}. Compound 2 demonstrated an excellent pharmacological and safety profile in preclinical studies and thus was chosen as a development candidate for the treatment of atherosclerosis and dyslipidemia. The X-ray cocrystal structures of the early lead compound 12 and compound 2 in complex with PPAR{alpha} ligand binding domain (LBD) were determined. The role of the crystal structure of compound 12 with PPAR{alpha} in the development of the SAR that ultimately resulted in the discovery of compound 2