Sample records for 12cgamma 3alpha ehnergeticheskoe

  1. Simultaneous quantification of GABAergic 3alpha,5alpha/3alpha,5beta neuroactive steroids in human and rat serum. (United States)

    Porcu, Patrizia; O'Buckley, Todd K; Alward, Sarah E; Marx, Christine E; Shampine, Lawrence J; Girdler, Susan S; Morrow, A Leslie


    The 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone enhance GABAergic neurotransmission and produce inhibitory neurobehavioral and anti-inflammatory effects. Despite substantial information on the progesterone derivative (3alpha,5alpha)-3-hydroxypregnan-20-one (3alpha,5alpha-THP, allopregnanolone), the physiological significance of the other endogenous GABAergic neuroactive steroids has remained elusive. Here, we describe the validation of a method using gas chromatography-mass spectrometry to simultaneously identify serum levels of the eight 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone. The method shows specificity, sensitivity and enhanced throughput compared to other methods already available for neuroactive steroid quantification. Administration of pregnenolone to rats and progesterone to women produced selective effects on the 3alpha,5alpha- and 3alpha,5beta-reduced neuroactive steroids, indicating differential regulation of their biosynthetic pathways. Pregnenolone administration increased serum levels of 3alpha,5alpha-THP (+1488%, psteroid was detected only in 3/16 control subjects. Levels of 3alpha,5alpha-A, 3alpha,5beta-A and pregnenolone were not altered. This method can be used to investigate the physiological and pathological role of neuroactive steroids and to develop biomarkers and new therapeutics for neurological and psychiatric disorders.

  2. Activating STAT3 Alpha for Promoting Healing of Neurons (United States)

    Conway, Greg


    A method of promoting healing of injured or diseased neurons involves pharmacological activation of the STAT3 alpha protein. Usually, injured or diseased neurons heal incompletely or not at all for two reasons: (1) they are susceptible to apoptosis (cell death); and (2) they fail to engage in axogenesis that is, they fail to re-extend their axons to their original targets (e.g., muscles or other neurons) because of insufficiency of compounds, denoted neurotrophic factors, needed to stimulate such extension. The present method (see figure) of treatment takes advantage of prior research findings to the effect that the STAT3 alpha protein has anti-apoptotic and pro-axogenic properties.

  3. 3$\\alpha$-cluster structure and monopole transition in $^{12}$C and $^{14}$C

    CERN Document Server

    Yoshida, Yuta


    3$\\alpha$-cluster structures and monopole transitions of $0^+$ states in $^{12}$C and $^{14}$C were investigated with $3\\alpha$- and $^{10}$Be+$\\alpha$-cluster models. A gas-like $3\\alpha$ state and a bending-chain $3\\alpha$ state were obtained in the $0^+_2$ and $0^+_3$ states of $^{12}$C, respectively. In $^{14}$C, a linear-chain 3$\\alpha$ structure is found in the $0^+_4$ state near the $^{10}$Be+$\\alpha$ threshold, but a cluster gas-like state does not appear because valence neutrons attract $\\alpha$ clusters and suppress spatial development of 3$\\alpha$ clustering. It was found that the linear-chain state in $^{14}$C is stabilized against the bending and $\\alpha$ escaping modes by valence neutrons. The monopole transition strengths in $^{12}$C are enhanced by $3\\alpha$-cluster developing, whereas, those in $^{14}$C are not enhanced so much because of the tight binding of $\\alpha$ clusters by valence neutrons.

  4. Infusions of 3alpha,5alpha-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3alpha,5alpha-THP in midbrain, hippocampus, diencephalon, and cortex of female rats. (United States)

    Frye, Cheryl A; Rhodes, Madeline E


    17beta-Estradiol (E2) and progesterone (P4) influence the onset and duration of sexual behavior and are also associated with changes in behaviors that may contribute to mating, such as exploration, anxiety, and social behaviors (socio-sexual behaviors). In the midbrain ventral tegmental area (VTA), the P4 metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), modulates lordosis of E2-primed rodents; 3alpha,5alpha-THP can also influence anxiety and social behaviors. To examine if 3alpha,5alpha-THP in the VTA mediates socio-sexual behaviors, we infused 3alpha,5alpha-THP to the VTA of diestrous and proestrous rats. As expected, proestrous, compared to diestrous, rats showed more exploratory (open field), anxiolytic (elevated plus maze), pro-social (partner preference, social interaction), and sexual (paced mating) behavior and had increased E2, P4, dihydroprogesterone (DHP), and 3alpha,5alpha-THP in serum, midbrain, hippocampus, diencephalon, and cortex. Infusions of 3alpha,5alpha-THP to the VTA, but not control sites, such as the substantia nigra (SN) or central grey (CG), of diestrous rats produced behavioral and endocrine effects akin to that of proestrous rats and increased DHP and 3alpha,5alpha-THP levels in midbrain, hippocampus, and diencephalon. Levels of DHP and 3alpha,5alpha-THP, but neither E2 nor P4 concentrations, in midbrain, hippocampus, diencephalon, and/or cortex were positively correlated with socio-sexual behaviors. Thus, 3alpha,5alpha-THP infusions to the VTA, but not SN or CG, can enhance socio-sexual behaviors and increase levels in midbrain, hippocampus, and diencephalon.

  5. Interleukin 2 and 15 activate Stat3alpha in human T lymphocytes

    DEFF Research Database (Denmark)

    Nielsen, M; Nordahl, M; Svejgaard, A


    in response to interleukin (IL)-2 and IL-15. Here, cytokine-induced activation of Stat3 in previously activated CD4(+) human T cells was examined using Stat3 antibodies directed against different regions of Stat3. As determined by tyrosine phosphorylation, nuclear translocation and binding to an h......SIE-oligonucleotide probe, IL-2 and IL-15 activated the slowly migrating isoform, Stat3alpha. In contrast, minimal or no activation of Stat3beta was observed, suggesting that IL-2 and IL-15 predominantly activate Stat3alpha in human CD4(+) T cells. In this way, diversity in the expression and activation of Stat3 proteins...... may provide additional means of regulating cytokine-induced T cell responses....

  6. Almost Redundant Components in the 3 alpha Faddeev Equation for the Buck, Friedlich and Wheatly alpha alpha Potential

    CERN Document Server

    Fujiwara, Y; Kohno, M


    The 3 alpha orthogonality condition model using the Pauli-forbidden bound states of the Buck, Friedlich and Wheatly alpha alpha potential can yield a compact 3 alpha ground state with a large binding energy, in which a small admixture of the redundant components can never be eliminated.

  7. 4 Birds 1 Stone to Inhibit 5androstane-3alpha,17beta-diol Conversion to DHT (United States)


    Award Number: W81XWH-15-1-0409 TITLE: 4 Birds 1 Stone to Inhibit 5androstane-3alpha,17beta-diol Conversion to DHT PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-04094 Birds 1 Stone to Inhibit 5androstane-3alpha,17beta-diol Conversion to DHT 5c...testicular androgens, testosterone or dihydrotestosterone ( DHT ). Men diagnosed with advanced prostate cancer or failure potentially curative therapy are

  8. TOPO3alpha influences antigenic variation by monitoring expression-site-associated VSG switching in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Hee-Sook Kim

    Full Text Available Homologous recombination (HR mediates one of the major mechanisms of trypanosome antigenic variation by placing a different variant surface glycoprotein (VSG gene under the control of the active expression site (ES. It is believed that the majority of VSG switching events occur by duplicative gene conversion, but only a few DNA repair genes that are central to HR have been assigned a role in this process. Gene conversion events that are associated with crossover are rarely seen in VSG switching, similar to mitotic HR. In other organisms, TOPO3alpha (Top3 in yeasts, a type IA topoisomerase, is part of a complex that is involved in the suppression of crossovers. We therefore asked whether a related mechanism might suppress VSG recombination. Using a set of reliable recombination and switching assays that could score individual switching mechanisms, we discovered that TOPO3alpha function is conserved in Trypanosoma brucei and that TOPO3alpha plays a critical role in antigenic switching. Switching frequency increased 10-40-fold in the absence of TOPO3alpha and this hyper-switching phenotype required RAD51. Moreover, the preference of 70-bp repeats for VSG recombination was mitigated, while homology regions elsewhere in ES were highly favored, in the absence of TOPO3alpha. Our data suggest that TOPO3alpha may remove undesirable recombination intermediates constantly arising between active and silent ESs, thereby balancing ES integrity against VSG recombination.

  9. Detection and localization of Mip-3alpha/LARC/Exodus, a macrophage proinflammatory chemokine, and its CCR6 receptor in human pancreatic cancer. (United States)

    Kleeff, J; Kusama, T; Rossi, D L; Ishiwata, T; Maruyama, H; Friess, H; Büchler, M W; Zlotnik, A; Korc, M


    Macrophage Proinflammatory Human Chemokine-3alpha (Mip-3alpha/LARC/Exodus) belongs to a large family of chemotactic cytokines, which participate in directing inflammatory cell migration and in modulating angiogenesis. Mip-3alpha signals through a recently identified G-protein linked 7-transmembrane receptor, CCR6. In this study, we have characterized the expression of Mip-3alpha and CCR6 in 12 normal and 16 cancerous human pancreatic tissues and in 4 cultured pancreatic cancer cell lines, and assessed the effects of Mip-3alpha on growth and invasion of these cell lines. Pancreatic cancer tissues markedly overexpressed Mip-3alpha in comparison with normal pancreatic samples. By in situ hybridization Mip-3alpha and CCR6 mRNA moieties were present in cancer cells within the tumors. In addition, Mip-3alpha was abundant in the macrophages infiltrating the tumor mass. Mip-3alpha and its receptor CCR6 were expressed in all 4 tested pancreatic cancer cell lines. Mip-3alpha stimulated the growth of one cell line, enhanced the migration of another cell line, and was without effect in the other 2 cell lines. Together, our findings suggest that Mip-3alpha has the potential to act via autocrine and paracrine mechanisms to contribute to the pathobiology of human pancreatic cancer.

  10. Genomic organization of the CC chemokine mip-3alpha/CCL20/larc/exodus/SCYA20, showing gene structure, splice variants, and chromosome localization. (United States)

    Nelson, R T; Boyd, J; Gladue, R P; Paradis, T; Thomas, R; Cunningham, A C; Lira, P; Brissette, W H; Hayes, L; Hames, L M; Neote, K S; McColl, S R


    We describe the genomic organization of a recently identified CC chemokine, MIP3alpha/CCL20 (HGMW-approved symbol SCYA20). The MIP-3alpha/CCL20 gene was cloned and sequenced, revealing a four exon, three intron structure, and was localized by FISH analysis to 2q35-q36. Two distinct cDNAs were identified, encoding two forms of MIP-3alpha/CCL20, Ala MIP-3alpha/CCL20 and Ser MIP-3alpha/CCL20, that differ by one amino acid at the predicted signal peptide cleavage site. Examination of the sequence around the boundary of intron 1 and exon 2 showed that use of alternative splice acceptor sites could give rise to Ala MIP-3alpha/CCL20 or Ser MIP-3alpha/CCL20. Both forms of MIP-3alpha/CCL20 were chemically synthesized and tested for biological activity. Both flu antigen plus IL-2-activated CD4(+) and CD8(+) T lymphoblasts and cord blood-derived dendritic cells responded to Ser and Ala MIP-3alpha/CCL20. T lymphocytes exposed only to IL-2 responded inconsistently, while no response was detected in naive T lymphocytes, monocytes, or neutrophils. The biological activity of Ser MIP-3alpha/CCL20 and Ala MIP-3alpha/CCL20 and the tissue-specific preference of different splice acceptor sites are not yet known.

  11. Research on the reactions {sup 9}Be ({sup 3}He, 3 {alpha}) and {sup 10}B (d, 3 {alpha}); Contribution a l'etude experimentale des reactions {sup 9}Be ({sup 3}He, 3 {alpha}) et {sup 10}B (d, 3 {alpha})

    Energy Technology Data Exchange (ETDEWEB)

    Thouvenin, P. [Commissariat a l' Energie Atomique, Bruyeres-le-Chatel (France). Centre d' Etudes


    For studying these reactions, the detection of the final particles emitted in coincidence in the directions {theta}{sub 1} and {theta}{sub 2}, together with the bi-parametric analysis of the corresponding pulses are used. This method enables us to obtain the orthogonal Dalitz diagrams (E{sub 1}, E{sub 2}). An examination of the spectra obtained shows that the sequential mechanism appears to predominate. The contribution of the purely statistical process is less than 15 per cent of the total spectrum. In the case of {sup 10}B (d, 3 {alpha}), for E{sub d} = 1.5 MeV, 2,66 MeV and 3 MeV, the width of the peak of the first particles emitted, with respect to {sup 8}Be excitations close to 11 MeV, is found to be equal to 2.6 {+-} 0.6 MeV, much less than the width of the 2. excited state observed by {alpha} - {alpha} scattering. The coincidence spectra and the free spectra give an excitation energy of E{sub x} = 2.68 {+-} 0.07 MeV for the first excited state of {sup 8}Be. Some remarks are made concerning the anomalies observed for E{sub d} = 5 MeV and 9 MeV. The excited levels of {sup 8}Be at 13.91 MeV and 7.56 MeV which have been described in the past are not observed. (author) [French] La detection de deux des particules finales emises en cofncidence dans les directions {theta}{sub 1} et {theta}{sub 2}, et l'analyse biparametrique des impulsions correspondantes sont utilisees pour etudier ces reactions. Cette methode nous permet d'obtenir des diagrammes de Dalitz orthogonaux (E{sub 1}, E{sub 2}). L'examen des spectres obtenus montre que le mecanisme sequentiel semble predominant. La contribution du processus purement statistique est inferieure a 15 pour cent du spectre total. Dans le cas de {sup 10}B (d, 3 {alpha}), pour E{sub d} = 1,5 MeV, 2,66 MeV et 3 MeV, la largeur du pic des premieres particules emises relatives a des excitations de {sup 8}Be voisines de 11 MeV, est trouvee egale a 2,6 {+-} 0,6 MeV, tres inferieure a la largeur du 2. etat excite

  12. Cloning, sequencing, and functional analysis of the 5'-flanking region of the rat 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase gene. (United States)

    Lin, H K; Penning, T M


    Rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase (3 alpha-HSD/DD) is a member of the aldo-keto reductase gene superfamily. It displays high constitutive expression and inactivates circulating steroid hormones and suppresses the formation of polycyclic aromatic hydrocarbon anti- and syn-diol-epoxides (ultimate carcinogens). To elucidate mechanisms responsible for constitutive expression of the 3 alpha-HSD/DD gene a rat genomic library obtained from adult Sprague-Dawley female liver (HaeIII partial digest) was screened, using a probe corresponding to the 5'-end of the cDNA (-15 to +250), and a 15.8-kb genomic clone was isolated. Sequencing revealed that 6.3 kb contained exon 1 (+16 to +138 bp) plus additional introns and exons. The transcription start site (+1) was located by primer extension analysis, and the initiation codon, ATG, was located at +55 bp. The remaining 9.5 kb represented the 5'-flanking region of the rat 3 alpha-HSD/DD gene. A 1.6-kb fragment of this region was sequenced. A TATTTAA sequence (TATA box) was found at 33 bp upstream from the major transcription start site. cis-acting elements responsible for the constitutive expression of the rat 3 alpha-HSD/DD gene were located on the 5'-flanking region by transient transfection of reporter-gene (chloramphenicol acetyl transferase, CAT) constructs into human hepatoma cells (HepG2). CAT assays identified the basal promoter between (-199 and +55 bp), the presence of a proximal enhancer (-498 to -199 bp) which stimulated CAT activity 6-fold, the existence of a powerful silencer (-755 to -498 bp), and a strong distal enhancer (-4.0 to -2.0 kb) which increased CAT activity by 20-40-fold. A computer search of available consensus sequences for trans-acting factors revealed that a cluster of Oct-sites were uniquely located in the silencer region. Using the negative response element (-797 to -498 bp) as a probe and nuclear extracts from HepG2 cells, three bands were identified by gel mobility shift

  13. Topoisomerase 3alpha and RMI1 suppress somatic crossovers and are essential for resolution of meiotic recombination intermediates in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Frank Hartung


    Full Text Available Topoisomerases are enzymes with crucial functions in DNA metabolism. They are ubiquitously present in prokaryotes and eukaryotes and modify the steady-state level of DNA supercoiling. Biochemical analyses indicate that Topoisomerase 3alpha (TOP3alpha functions together with a RecQ DNA helicase and a third partner, RMI1/BLAP75, in the resolution step of homologous recombination in a process called Holliday Junction dissolution in eukaryotes. Apart from that, little is known about the role of TOP3alpha in higher eukaryotes, as knockout mutants show early lethality or strong developmental defects. Using a hypomorphic insertion mutant of Arabidopsis thaliana (top3alpha-2, which is viable but completely sterile, we were able to define three different functions of the protein in mitosis and meiosis. The top3alpha-2 line exhibits fragmented chromosomes during mitosis and sensitivity to camptothecin, suggesting an important role in chromosome segregation partly overlapping with that of type IB topoisomerases. Furthermore, AtTOP3alpha, together with AtRECQ4A and AtRMI1, is involved in the suppression of crossover recombination in somatic cells as well as DNA repair in both mammals and A. thaliana. Surprisingly, AtTOP3alpha is also essential for meiosis. The phenotype of chromosome fragmentation, bridges, and telophase I arrest can be suppressed by AtSPO11 and AtRAD51 mutations, indicating that the protein is required for the resolution of recombination intermediates. As Atrmi1 mutants have a similar meiotic phenotype to Attop3alpha mutants, both proteins seem to be involved in a mechanism safeguarding the entangling of homologous chromosomes during meiosis. The requirement of AtTOP3alpha and AtRMI1 in a late step of meiotic recombination strongly hints at the possibility that the dissolution of double Holliday Junctions via a hemicatenane intermediate is indeed an indispensable step of meiotic recombination.

  14. Faddeev calculation of 3 alpha and alpha alpha Lambda systems using alpha alpha resonating-group method kernel

    CERN Document Server

    Fujiwara, Y; Kohno, M; Suzuki, Y; Baye, D; Sparenberg, J M


    We carry out Faddeev calculations of three-alpha (3 alpha) and two-alpha plus Lambda (alpha alpha Lambda) systems, using two-cluster resonating-group method kernels. The input includes an effective two-nucleon force for the alpha alpha resonating-group method and a new effective Lambda N force for the Lambda alpha interaction. The latter force is a simple two-range Gaussian potential for each spin-singlet and triplet state, generated from the phase-shift behavior of the quark-model hyperon-nucleon interaction, fss2, by using an inversion method based on supersymmetric quantum mechanics. Owing to the exact treatment of the Pauli-forbidden states between the clusters, the present three-cluster Faddeev formalism can describe the mutually related, alpha alpha, 3 alpha and alpha alpha Lambda systems, in terms of a unique set of the baryon-baryon interactions. For the three-range Minnesota force which describes the alpha alpha phase shifts quite accurately, the ground-state and excitation energies of 9Be Lambda are...

  15. Isolation, structure determination and biological activity of 25-epi, 3{alpha}-carboxyacetylquercinic acid in daedalea dickinsii

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Kang Gyu; Min, Tae Jin [Dongguk Univ., Seoul (Korea, Republic of)


    In order to develope bioactive substances, dried fruit body of Daedalea dickinsii collected from Taeback mountain was extracted with ethanol. The compounds 1 and 2 were purified by solvent extraction, silica gel column chromatography and recrystallization from the ethanol extracts. Melting point, molecular weight and molar extinction coefficient of the compound 1 were estimated to be 167{approx}168 .deg. C, 572 and 5,040 at 208 nm. The structure of this compound 1 has been elucidated to be 24S, 25S, 3{alpha}-carboxyacetylquercinic acid using spectroscopic properties. This compound showed antibiotic activities against fungi, yeasts and bacteria and it also showed anticancer activity(IC{sub 50}=64.5 {mu}M/ml) against Korean stomach cancer cell. Melting point, molecular weight and molar extinction coefficient of the compound 2 were estimated to be 233{approx}235 .deg. C, 572 and 5,080 at 208 nm. The structure of this compound was elucidated to be 24S, 25R, 3{alpha}-carboxyacetylquercinic acid. The compound 2 showed different antibiotic activities with the compound 1.

  16. Collagen IV alpha 3, alpha 4, and alpha 5 chains in rodent basal laminae: sequence, distribution, association with laminins, and developmental switches



    Collagen IV is a major component of vertebrate basal laminae (BLs). Studies in humans have revealed a family of genes encoding alpha 1- alpha 6 collagen IV chains and implicated alpha 3-alpha 6 in disease processes (Goodpasture and Alport syndromes and diffuse leiomyomatosis). To extend studies of these components to an experimentally accessible animal, we cloned cDNAs encoding partial collagen alpha 3, alpha 4, and alpha 5(IV) chains from the mouse. Ribonuclease protection assays showed that...

  17. Characterization of 3alpha-acetyl-11-keto-alpha-boswellic acid, a pentacyclic triterpenoid inducing apoptosis in vitro and in vivo. (United States)

    Büchele, Berthold; Zugmaier, Waltraud; Estrada, Aidee; Genze, Felicitas; Syrovets, Tatiana; Paetz, Christian; Schneider, Bernd; Simmet, Thomas


    3Alpha-acetyl-11-keto-alpha-boswellic acid (3alpha-acetoxy-11-oxo-olean-12-en-24-oic acid, 1) was synthesized by a radical-type reaction using bromine and 3alpha-acetyl-alpha-boswellic acid isolated from the oleo-gum-resin of Boswellia carterii. 1D and 2D NMR (COSY, HMBC, ROESY) at 500 MHz were used for shift assignments and structure verification. The compound investigated is present in a herbal preparation extracted from Boswellia serrata oleo-gum-resin, it inhibits the growth of chemotherapy-resistant human PC-3 prostate cancer cells in vitro and induces apoptosis as shown by activation of caspase 3 and the induction of DNA fragmentation. In addition, compound 1 is active IN VIVO as shown by inhibition of proliferation and induction of apoptosis in PC-3 prostate cancer cells xenotransplanted onto the chick chorioallantoic membrane.

  18. Association of protein kinase FA/GSK-3alpha (a proline-directed kinase and a regulator of protooncogenes) with human cervical carcinoma dedifferentiation/progression. (United States)

    Yang, S D; Yu, J S; Lee, T T; Ni, M H; Yang, C C; Ho, Y S; Tsen, T Z


    Computer analysis of protein phosphorylation-sites sequence revealed that most transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of protein kinase FA/glycogen synthase kinase-3alpha (kinase FA/GSK-3alpha) (a particular member of PDPK family) has been optimized for human cervical tissue and used to demonstrate for the first time significantly increased (P < 0.001) activity in poorly differentiated cervical carcinoma (82.8 +/- 6.6 U/mg of protein), moderately differentiated carcinoma (36.2 +/- 3.4 U/mg of protein), and well-differentiated carcinoma (18.3 +/- 2.4 U/mg of protein) from 36 human cervical carcinoma samples when compared to 12 normal controls (4.9 +/- 0.6 U/mg of protein). Immunoblotting analysis further revealed that increased activity of kinase FA/GSK-3alpha in cervical carcinoma is due to overexpression of protein synthesis of the kinase. Taken together, the results provide initial evidence that overexpression of protein synthesis and cellular activity of kinase FA/GSK-3alpha may be involved in human cervical carcinoma dedifferentiation/progression, supporting an association of proline-directed protein kinase with neoplastic transformation and tumorigenesis. Since protein kinase FA/GSK-3alpha may function as a possible regulator of transcription factors/proto-oncogenes, the results further suggest that kinase FA/GSK-3alpha may play a potential role in human cervical carcinogenesis, especially in its dedifferentiation and progression.

  19. Increasing 3alpha,5alpha-THP following inhibition of neurosteroid biosynthesis in the ventral tegmental area reinstates anti-anxiety, social, and sexual behavior of naturally receptive rats. (United States)

    Frye, Cheryl A; Paris, Jason J; Rhodes, Madeline E


    The progesterone metabolite and neurosteroid, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), has actions in the midbrain ventral tegmental area (VTA) to modulate lordosis, but its effects on other reproductively relevant behaviors are not well understood. Effects on exploration, anxiety, and social behavior resulting from inhibition of 3alpha,5alpha-THP formation, as well as 3alpha,5alpha-THP enhancement, were investigated in the midbrain VTA. Naturally sexually receptive, female rats (n=8-10/group) received infusions aimed at the midbrain VTA of vehicle, PK11195 (an inhibitor of neurosteroidogenesis), and/or indomethacin (an inhibitor of 3alpha,5alpha-THP formation from prohormones), and were subsequently infused with vehicle or FGIN 1-27 (a neurosteroidogenesis enhancer). The rats were then assessed in a behavioral battery that examined exploration (open field), anxiety (elevated plus maze), social (social interaction), and sexual (paced mating) behavior. Inhibition of 3alpha,5alpha-THP formation decreased exploratory, anti-anxiety, social, and sexual behavior, as well as midbrain 3alpha,5alpha-THP levels. Infusions of FGIN 1-27 following 3alpha,5alpha-THP inhibition restored these behaviors and midbrain 3alpha,5alpha-THP levels to those commensurate with control rats that had not been administered inhibitors. These findings suggest that 3alpha,5alpha-THP formation in the midbrain VTA may influence appetitive, as well as consummatory, aspects of mating behavior.

  20. Dissection of the physiological interconversion of 5alpha-DHT and 3alpha-diol by rat 3alpha-HSD via transient kinetics shows that the chemical step is rate-determining: effect of mutating cofactor and substrate-binding pocket residues on catalysis. (United States)

    Heredia, Vladi V; Penning, Trevor M


    3Alpha-hydroxysteroid dehydrogenases (3alpha-HSDs) catalyze the interconversion between 5alpha-dihydrotestosterone (5alpha-DHT), the most potent androgen, and 3alpha-androstanediol (3alpha-diol), a weak androgen metabolite. To identify the rate-determining step in this physiologically important reaction, rat liver 3alpha-HSD (AKR1C9) was used as the protein model for the human homologues in fluorescence stopped-flow transient kinetic and kinetic isotope effect studies. Using single and multiple turnover experiments to monitor the NADPH-dependent reduction of 5alpha-DHT, it was found that k(lim) and k(max) values were identical to k(cat), indicating that chemistry is rate-limiting overall. Kinetic isotope effect measurements, which gave (D)k(cat) = 2.4 and (D)2(O)k(cat) = 3.0 at pL 6.0, suggest that the slow chemical transformation is significantly rate-limiting. When the NADP(+)-dependent oxidation of 3alpha-diol was monitored, single and multiple turnover experiments showed a k(lim) and burst kinetics consistent with product release as being rate-limiting overall. When NAD(+) was substituted for NADP(+), burst phase kinetics was eliminated, and k(max) was identical to k(cat). Thus with the physiologically relevant substrates 5alpha-DHT plus NADPH and 3alpha-diol plus NAD(+), the slowest event is chemistry. R276 forms a salt-linkage with the phosphate of 2'-AMP, and when it is mutated, tight binding of NAD(P)H is no longer observed [Ratnam, K., et al. (1999) Biochemistry 38, 7856-7864]. The R276M mutant also eliminated the burst phase kinetics observed for the NADP(+)-dependent oxidation of 3alpha-diol. The data with the R276M mutant confirms that the release of the NADPH product is the slow event; and in its absence, chemistry becomes rate-limiting. W227 is a critical hydrophobic residue at the steroid binding site, and when it is mutated to alanine, k(cat)/K(m) for oxidation is significantly depressed. Burst phase kinetics for the NADP(+)-dependent turnover of 3

  1. Neutron decay of deep hole states and isobaric analog states in Sn-115 populated by the (He-3,alpha) reaction at 102 MeV

    NARCIS (Netherlands)

    Soderman, PO; Ringbom, A; Blomgren, J; Olsson, N; Nilsson, L; Bordewijk, JA; van't Hof, G; Hofstee, MA; van der Ploeg, H; van der Werf, SY; Krasznahorkay, A; Balanda, A; Chmielewska, D; Laurent, H


    Neutron decay of excited hole states and isobaric analog states (IAS) populated by the Sn-116(He-3,alpha) reaction at an energy of 102 MeV has been investigated. The alpha -particles were analysed in a magnetic spectrograph positioned at 1.4 degrees and detected with a multiwire drift chamber. Excit

  2. Interaction between obesity and the Hypoxia Inducible Factor 3 Alpha Subunit rs3826795 polymorphism in relation with plasma alanine aminotransferase. (United States)

    Wang, Shuo; Song, Jieyun; Yang, Yide; Zhang, Yining; Chawla, Nitesh V; Ma, Jun; Wang, Haijun


    Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) DNA has been demonstrated to be associated with obesity in the methylation level, and it also has a Body Mass Index (BMI)-independent association with plasma alanine aminotransferase (ALT). However, the relation among obesity, plasma ALT, HIF3A polymorphism and methylation remains unclear. This study aims to identify the association between HIF3A polymorphism and plasma ALT, and further to determine whether the effect of HIF3A polymorphism on ALT could be modified by obesity or mediated by DNA methylation. The HIF3A rs3826795 polymorphism was genotyped in a case-control study including 2030 Chinese children aged 7-18 years (705 obese cases and 1325 non-obese controls). Furthermore, the HIF3A DNA methylation of the peripheral blood was measured in 110 severely obese children and 110 age- and gender- matched normal-weight controls. There was no overall association between the HIF3A rs3826795 polymorphism and ALT. A significant interaction between obesity and rs3826795 in relation with ALT was found (P inter = 0.042), with rs3826795 G-allele number elevating ALT significantly only in obese children (β' = 0.075, P = 0.037), but not in non-obese children (β' = -0.009, P = 0.741). Additionally, a mediation effect of HIF3A methylation was found in the association between the HIF3A rs3826795 polymorphism and ALT among obese children (β' = 0.242, P = 0.014). This is the first study to report the interaction between obesity and HIF3A gene in relation with ALT, and also to reveal a mediation effect among the HIF3A polymorphism, methylation and ALT. This study provides new evidence to the function of HIF3A gene, which would be helpful for future risk assessment and personalized treatment of liver diseases.

  3. Enzymic synthesis of di- and tri-saccharide glycosides, using glycosidases and beta-D-galactoside 3-alpha-sialyl-transferase. (United States)

    Nilsson, K G


    The following disaccharide glycosides were obtained in yields of 10-35% from the appropriate donor and acceptor glycosides by employing glycosidases as catalysts: alpha-D-Galp-(1----3)-alpha-D-GalpNAc-OEt (alpha-D-galactosidase), beta-D-Galp-(1----3)-alpha-D-GalpNAc-OEt and beta-D-Galp-(1----3)-beta-D-GalpNAc-OEtBr (beta-D-galactosidase), beta-D-GlcpNAc-(1----6)-beta-D-Galp-OMe and beta-D-GlcpNAc-(1----6)-alpha-D-Manp-OMe (beta-N-acetylglucosaminidase). With beta-D-GlcpNAc-OEtSiMe3 as the acceptor, beta-D-galactosidase gave beta-D-Galp-(1----3)-beta-D-GlcpNAc-OEtSiMe3 almost exclusively, whereas, with beta-D-GlcpNAc-OMe as the acceptor, beta-D-Galp-(1----3)-beta-D-GlcpNAc-OMe was formed in only slightly excess over teh analogous beta-(1----4)-linked glycoside. The use of beta-D-galactosidase and beta-D-galactoside 3-alpha-sialyltransferase in sequence provided a convenient route to the trisaccharide glycosides alpha-D-Neup5Ac-(2----3)-beta-D-Galp-(1----3)-alpha-D-GalpNAc-OEt, alpha-D-Neup5Ac-(2----3)-beta-D-Galp-(1----3)-beta-D-GalpNAc-OE tBr, and alpha-D-Neup5Ac-(2----3)-beta-D-Galp-(1----3)-beta-D-GlcpNAc-OMe.

  4. Purification and properties of a 3 alpha-hydroxysteroid dehydrogenase of rat liver cytosol and its inhibition by anti-inflammatory drugs. (United States)

    Penning, T M; Mukharji, I; Barrows, S; Talalay, P


    An NAD(P)-dependent 3 alpha-hydroxysteroid dehydrogenase (EC was purified to homogeneity from rat liver cytosol, where it is responsible for most if not all of the capacity for the oxidation of androsterone, 1-acenaphthenol and benzenedihydrodiol (trans-1,2-dihydroxycyclohexa-3,5-diene). The dehydrogenase has many properties (substrate specificity, pI, Mr, amino acid composition) in common with the dihydrodiol dehydrogenase (EC purified from the same source [Vogel, Bentley, Platt & Oesch (1980) J. Biol. Chem. 255, 9621-9625]. Since 3 alpha-hydroxysteroids are by far the most efficient substrates, the enzyme is more appropriately designated a 3 alpha-hydroxysteroid dehydrogenase. It also promotes the NAD(P)H-dependent reductions of quinones (e.g. 9,10-phenanthrenequinone, 1,4-benzoquinone), aromatic aldehydes (4-nitrobenzaldehyde) and aromatic ketones (4-nitroacetophenone). The dehydrogenase is not inhibited by dicoumarol, disulfiram, hexobarbital or pyrazole. The mechanism of the powerful inhibition of this enzyme by both non-steroidal and steroidal anti-inflammatory drugs [Penning & Talalay (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 4504-4508] was examined with several substrates. Most non-steroidal anti-inflammatory drugs are competitive inhibitors (e.g. Ki for indomethacin, 0.20 microM for 9,10-phenanthrenequinone reduction at pH 6.0, and 0.835 microM for androsterone oxidation at pH 7.0), except for salicylates, which act non-competitively (e.g. Ki for aspirin, 650 microM for androsterone oxidation). The inhibitory potency of these agents falls sharply as the pH is increased from 6 to 9. Most anti-inflammatory steroids are likewise competitive inhibitors, except for the most potent (betamethasone and dexamethasone), which act non-competitively. The enzyme is inhibited competitively by arachidonic acid and various prostaglandins. PMID:6435601

  5. Potential anti-tumor-promoting activity of 3alpha-hydroxy-D:A-friedooleanan-2-one from the stem bark of Mallotus philippensis. (United States)

    Tanaka, Reiko; Nakata, Tomoko; Yamaguchi, Chiharu; Wada, Shun-Ichi; Yamada, Takeshi; Tokuda, Harukuni


    Four known friedelane-type triterpenoids, friedelin ( 1), 3-hydroxy-D:A-friedoolean-3-en-2-one ( 2), 2beta-hydroxy-D:A-friedooleanan-3-one ( 3), and 3alpha-hydroxy-D:A-friedooleanan-2-one ( 4), and two known lupane-type triterpenoids, lupeol ( 5) and betulin ( 6), were isolated from the stem bark of Mallotus philippensis. Isolates 1 - 4 and their synthetic analogues, 3-acetoxy-D:A-friedoolean-3-en-2-one ( 2A) and 3alpha-acetoxy-D:A-friedooleanan-2-one ( 4A), were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12- O-tetradecanoylphorbol 13-acetate (TPA). The inhibitory effect of compounds 2 (IC (50) = 292 mol ratio/32 pmol/TPA) and 4 (IC (50) = 288) was stronger than those of the other compounds tested and the positive control, curcumin (IC (50) = 343). Compound 4 strongly inhibited mouse skin tumor promotion in an IN VIVO two-stage carcinogenesis model. Studies have been conducted to identify the biologically active compounds extracted from the leaves, bark, and cones of trees that currently have no specific commercial use and are therefore treated as waste in the forestry industry.

  6. The Expression of Interleukin-17, Interferon-gamma, and Macrophage Inflammatory Protein-3 Alpha mRNA in Patients with Psoriasis Vulgaris

    Institute of Scientific and Technical Information of China (English)

    李家文; 李东升; 谭志建


    Summary: To investigate the role of Interleukin-17 (IL-17), Interferon-gamma (IFN-γ), and macrophage inflammatory protein-3 alpha (MIP-3α) in the pathogenesis of psoriasis, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to semi-quantitatively analyze the mRNA expression of IL 17, IFN-γ, and MIP-3α in 31 psoriatic lesions and 16 normal skin tissues. The results showed that the mRNA of the three cytokines was present in all specimens. And the expression level of IL-17 mRNA in skin lesions was 1. 1416±0. 0591, which was significantly higher than that in normal controls (0. 8788±0. 0344, P<0. 001). The expression levels of IFN-γ mRNA were 1.1142±0. 0561 and 0. 9050±0. 0263, respectively, with significant difference(P<0. 001). And the expression levels of MIP-3α mRNA in psoriatic lesions was 1. 1397 ± 0. 0521, which was markedly higher than that in normal controls (0. 8681±0. 0308, P<0. 001). These findings indicate that up regulated expression of IL-17, IFN-γ, and MIP-3α might be involved in the pathogenesis of psoriasis.

  7. Complex-Scaling Calculation of Three-Body Resonances Using Complex-Range Gaussian Basis Functions --- Application to 3\\alpha resonances in 12C ---

    CERN Document Server

    Ohtsubo, Shin-Ichi; Kamimura, Masayasu; Hiyama, Emiko


    We propose to use the complex-range Gaussian basis functions, {r^l e^{-(1 \\pm i\\omega)(r/r_n)^2}Y_{lm}(\\hat{r}); r_n in a geometric progression}, in the calculation of three-body resonances with the complex-scaling method (CSM) in which use is often made of the real-range Gaussian basis functions, {r^l e^{-(r/r_n)^2}Y_{lm}(\\hat{r})}, that are suitable for describing the short-distance structure and the asymptotic decaying behavior of few-body systems. The former basis set is more powerful than the latter when describing the resonant and nonresonant continuum states with highly oscillating amplitude at large scaling angles \\theta. We applied the new basis functions to the CSM calculation of the 3\\alpha resonances with J=0^+, 2^+ and 4^+ in 12C. The eigenvalue distribution of the complex scaled Hamiltonian becomes more precise and the maximum scaling angle becomes drastically larger (\\theta_{max}=16 deg. \\arrow 36 deg.) than those given by the use of the real-range Gaussians. Owing to these advantages, we were ...

  8. 4-(3'alpha15'beta-dihydroxy-5'beta-estran-17'beta-yl)furan-2-methyl alcohol: an anti-digoxin agent with a novel mechanism of action. (United States)

    Deutsch, Joseph; Jang, Huang G; Mansur, Nura; Ilovich, Ohad; Shpolansky, Uri; Galili, Dana; Feldman, Tomer; Rosen, Haim; Lichtstein, David


    The synthesis and some pharmacological properties of 4-(3'alpha-15'beta-dihydroxy-5beta-estran-17'beta-yl)furan-2-methyl alcohol (16) have been described. The compound was synthesized by reacting a synthetic 3alpha- benzyloxy-5beta-estr-15-en-17-one with the ethylene acetal of 4-bromo-2-furancarboxyaldehyde, followed by hydrolysis of the ethylene acetal and reduction of the aldehyde. Despite its resemblance to the structure of cardiac steroids (CS), 16 does not bind to the CS receptor on Na(+),K(+)-ATPase and does not increase the force of contraction of heart muscle. However, 16 inhibited the digoxin-induced increase in the force of contraction and arrhythmias in guinea pig papillary muscle and human atrial appendages. The steroid also inhibited digoxin-induced alteration in endocytosed membrane traffic, indicating a novel mechanism of action.

  9. Polysaccharides in fungi. XXXVII. Immunomodulating activities of carboxymethylated derivatives of linear (1-->3)-alpha-D-glucans extracted from the fruiting bodies of Agrocybe cylindracea and Amanita muscaria. (United States)

    Yoshida, I; Kiho, T; Usui, S; Sakushima, M; Ukai, S


    Immunomodulating activities of three carboxymethylated derivatives (AG-AL-CMS, AG-AL-CMI, and AM-APP-CM) of linear (1-->3)-alpha-D-glucans from Agrocybe cylindracea and Amanita muscaria were evaluated with murine peritoneal macrophages playing an important role in tumor immunity. The ratio of macrophages in peritoneal exudate cells increased more than 50% after the administration of three carboxymethylated (1-->3)-alpha-D-glucans. These carboxymethylated (1-->3)-alpha-D-glucans exhibited higher potentiating activities for macrophages than carboxymethylated linear (1-->3)-beta-D-glucan (CMPS) in the potency of reduction of nitro blue tetrazolium, products of nitric oxide and the soluble cytotoxic factor, the amount of glucose consumption, and the activation of acid phosphatase. AG-AL-CMS, AG-AL-CMI, and AM-APP-CM were found to induce the tumor regressing factor in mouse serum, although the ability of the induction of this factor was weaker than that of CMPS. The reticuloendothelial system-potentiating activation of three carboxymethylated alpha-D-glucans was similar to that of the carboxymethylated beta-D-glucan. AG-AL-CMS and AG-AL-CMI, but not AM-APP-CM, were suggested to possess a higher-order structure, resulting from the formation of a fluorescent complex with aniline blue.

  10. 3-(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-alkyl-N-arylbenzamides: potent, non-peptidic agonists of both the micro and delta opioid receptors. (United States)

    Bishop, Michael J; Garrido, Dulce M; Boswell, G Evan; Collins, Mark A; Harris, Philip A; McNutt, Robert W; O'Neill, Scott J; Wei, Ke; Chang, Kwen-Jen


    Opioid analgesics with both micro and delta opioid receptor activation represent a new approach to the treatment of severe pain with an improved safety profile. Compounds with this profile may exhibit strong analgesic properties due to micro agonism, with a reduced side effect profile resulting from delta agonism. Replacing the p-diethylamide of the known potent delta opioid receptor selective agonist BW373U86 with a m-diethylamide resulted in a compound with agonist activity at both the micro and delta opioid receptors. Modifying the amide to an N-methyl-N-phenylamide increased agonist potency at both receptors. A series of 3-(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-alkyl-N-arylbenzamides have been made to explore the structure-activity relationship (SAR) around the N-methyl-N-phenylamide. Several potent agonists of both the micro and delta opioid receptors have been identified, including (+)-3-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-(4-fluorophenyl)-N-methylbenzamide (23), which has EC50 values of 0.67 and 1.1 nM at the micro (guinea pig ileum assay) and delta (mouse vas deferens assay) opioid receptors, respectively.

  11. Determination of 5alpha-androst-16-en-3alpha-ol in truffle fermentation broth by solid-phase extraction coupled with gas chromatography-flame ionization detector/electron impact mass spectrometry. (United States)

    Wang, Guan; Li, Yuan-Yuan; Li, Dong-Sheng; Tang, Ya-Jie


    A novel method using solid-phase extraction coupled with gas chromatography and flame ionization detector (FID)/electron impact mass spectrometry (EIMS) was developed for the determination of 5alpha-androst-16-en-3alpha-ol (androstenol), a steroidal compound belonging to the group of musk odorous 16-androstenes, in truffle fermentation broth. Comparison studies between FID and EIMS indicated two detectors gave similar quantitative results. The highest androstenol concentration of 123.5 ng/mL was detected in Tuber indicum fermentation broth, while no androstenol was found in Tuber aestivum fermentation broth. For the first time, this work confirmed the existence of androstenol in the truffle fermentation broth, which suggested truffle fermentation is a promising alternative for androstenol production on a large scale.

  12. Human macrophage inflammatory protein-3alpha/CCL20/LARC/Exodus/SCYA20 is transcriptionally upregulated by tumor necrosis factor-alpha via a non-standard NF-kappaB site. (United States)

    Harant, H; Eldershaw, S A; Lindley, I J


    The 5'-flanking sequences of the human macrophage inflammatory protein-3alpha/CCL20 gene were cloned and transfected into G-361 human melanoma cells in a luciferase reporter construct. Tumor necrosis factor-alpha (TNF-alpha) treatment stimulated luciferase expression, and promoter truncations demonstrated that TNF-alpha inducibility is conferred by a region between nt -111 and -77, which contains a non-standard nuclear factor-kappaB (NF-kappaB) binding site. The requirement for NF-kappaB was demonstrated as follows: (i) mutations in this NF-kappaB site abrogated TNF-alpha responsiveness; (ii) TNF-alpha activated a construct containing two copies of the CCL20 NF-kappaB binding site; (iii) overexpression of NF-kappaB p65 activated the CCL20 promoter; (iv) NF-kappaB from nuclear extracts of TNF-alpha-stimulated cells bound specifically to this NF-kappaB site.

  13. Phenotypic consequences of deletion of the {gamma}{sub 3}, {alpha}{sub 5}, or {beta}{sub 3} subunit of the type A {gamma}-aminobutyric acid receptor in mice

    Energy Technology Data Exchange (ETDEWEB)

    Culia, C.T.; Stubbs, L.J.; Montgomery, C.S.; Russell, L.B.; Rinchik, E.M. [Oak Ridge National Lab., TN (United States)


    Three genes (Gabrg3, Gabra5, and Gabrb3) encoding the {gamma}{sub 3}, {alpha}{sub 5}, and {beta}{sub 3} subunits of the type A {gamma}-aminobutyric acid receptor, respectively, are known to map near the pink-eyed dilution (p) locus in mouse chromosome 7. This region shares homology with a segment of human chromosome 15 that is implicated in Angelman syndrome, an inherited neurobehavioral disorder. By mapping Gabrg3-Gabra5-Gabrb3-telomere. Like Gabrb3, neither the Gabra5 nor Gabrg3 gene is functionally imprinted in adult mouse brain. Mice deleted for all three subunits die at birth with a cleft palate, although there are rare survivors ({approximately} 5%) that do not have a cleft palate but do exhibit a neurological abnormality characterized by tremor, jerky gait, and runtiness. The authors have previously suggested that deficiency of the {beta}{sub 3} subunit may be responsible for the clefting defect. Most notably, however, in this report they describe mice carrying two overlapping, complementing p deletions that fail to express the {gamma}{sub 3} transcript, as well as mice from another line that express neither the {gamma}{sub 3} nor {alpha}{sub 5} transcripts. Surprisingly, mice from both of these lines are phenotypically normal and do not exhibit any of the neurological symptoms characteristic of the rare survivors that are deleted for all three ({gamma}{sub 3}, {alpha}{sub 5}, and {beta}{sub 3}) subunits. These mice therefore provide a whole-organism type A {gamma}-aminobutyric-acid receptor background that is devoid of any receptor subtypes that normally contain the {gamma}{sub 3} and/or {alpha}{sub 5} subunits. The absence of an overt neurological phenotype in mice lacking the {gamma}{sub 3} and/or {alpha}{sub 5} subunits also suggests that mutations in these genes are unlikely to provide useful animal models for Angelman syndrome in humans.

  14. CE -3有效载荷 APXS 可靠性预计及评估%The Reliability Prediction and Assessment of Chang'E-3 Alpha Particle X-ray Spectrometer

    Institute of Scientific and Technical Information of China (English)

    高旻; 王焕玉; 张承模; 崔兴柱; 梁晓华; 彭文溪


    This paper introduces the reliability prediction of Chang'E-3 Alpha Particle X-ray Spectrometer. The payload is aimed to identify elements of lunar surface, and it is capable to determine the abundances of the elements.Weakness in the design could be found by calculating the reliability of the APXS reliability prediction reliability of a given comparison.APXS electronics systems carry out aging tests.The life factor of operating temperature could be obtained by Arrhenius reaction model.And then the reliability prediction of the results could be assessed through Bayesian point estimation and Bayesian internal estimation method.The main factors affecting the results were discussed.The reliability requirements of APXS under the development phase are pro-posed.%粒子激发X射线谱仪( APXS)是以元素成分鉴别和定量分析为目标的CE-3巡视器有效载荷。该工作针对APXS电子学系统建立了可靠性模型,并进行了可靠性预计。通过对APXS可靠性预计计算的可靠度与给定的可靠度进行对比,发现设计中的薄弱环节。对APXS电子学系统进行老化试验,用阿伦尼乌斯( ARRHENISUS)反应模型获得了工作温度下的寿命因子,利用贝叶斯法点估计和区间估计对试验的结果进行了可靠性评估,并对影响结果的主要因素进行讨论,提出APXS研制阶段的各项可靠性要求。

  15. A cobalt-free perovskite-type La{sub 0.6}Sr{sub 0.4}Fe{sub 0.9}Cr{sub 0.1}O{sub 3-{alpha}} cathode for proton-conducting intermediate temperature solid oxide fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Zuolong; Yang, Zhijie; Zhao, Dongmei; Deng, Xuli [Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123 (China); Ma, Guilin, E-mail: [Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123 (China)


    Highlights: Black-Right-Pointing-Pointer A cobalt-free cathode material LSFC10 for IT-SOFCs was prepared and studied in detail. Black-Right-Pointing-Pointer The conductivity of LSFC10 reached 138 S cm{sup -1} under oxygen at 550 Degree-Sign C. Black-Right-Pointing-Pointer An anode-supported BZCY electrolyte membrane was successfully fabricated by a simple spin coating process. Black-Right-Pointing-Pointer Power density of the ceramic membrane fuel cell using LSFC10 as cathode reached 412 mW cm{sup -2} at 700 Degree-Sign C. - Abstract: A cobalt-free perovskite-type cathode material La{sub 0.6}Sr{sub 0.4}Fe{sub 0.9}Cr{sub 0.1}O{sub 3-{alpha}} (LSFC10) was prepared by a citric acid-nitrate process and investigated as a potential cathode material for proton-conducting intermediate-temperature solid oxide fuel cells (IT-SOFCs). The maximum conductivity of LSFC10 reached 138 S cm{sup -1} under oxygen at 550 Degree-Sign C. A Ni-BZCY composite anode-supported proton-conducting BaZr{sub 0.1}Ce{sub 0.7}Y{sub 0.2}O{sub 3-{alpha}} (BZCY) electrolyte membrane was successfully fabricated by a simple, cost-effective spin coating process. The peak power densities of the H{sub 2}/O{sub 2} fuel cell using BZCY electrolyte membrane, Ni-BZCY composite anode and LSFC10 cathode reached 412 mW cm{sup -2}, and the interfacial polarization resistance for the fuel cell was as low as 0.19 {Omega} cm{sup 2} under open circuit conditions, at 700 Degree-Sign C. These results reveal LSFC10 is a suitable cathode material for proton-conducting IT-SOFCs.

  16. {sup 12}C spectroscopy above the 3{alpha} threshold

    Energy Technology Data Exchange (ETDEWEB)

    Descouvemont, Pierre, E-mail: [Physique Nucleaire Theorique et Physique Mathematique, CP229 Universite Libre de Bruxelles (ULB), B1050 Brussels (Belgium)


    We investigate three-a continuum states in the hyperspherical formalism for J = 0{sup +} and J = 2{sup +}. We use the shallow Ali-Bodmer potential and the deep potential of Buck et al. We determine the 3a phase shifts up to E = 6 MeV, in parallel with an analysis of resonances in the framework of the Complex Scaling method. We show that shallow potentials provide additional narrow resonances, in contrast with experimental data. Deep potentials, however, only give rise to broad resonances, and are more consistent with the data.

  17. Genetic diversity of plasmodium vivax merozoite surface protein-3alpha (Pvmsp-3alpha) gene in Jhapa District of Nepal

    DEFF Research Database (Denmark)

    Adhikari, Madhav; Ranjitkar, Samir; Schousboe, Mette Leth


    In Nepal, Plasmodium vivax accounts for approximately 80-90% of the malaria cases, but limited studies have been conducted on the genetic diversity of this parasite population. This study was carried out to determine the genetic diversity of P. vivax population sampled from subjects living...

  18. Measurements of $L_{31}, L_{3}\\alpha, L_{3}\\beta, L_{2}\\beta, L_{2} \\gamma, L_{1}\\beta, L_{1}\\gamma, L_{\\beta}, L_{\\gamma}, L_{1x}, L_{2x}$ and $L_{3x}$ X-ray production cross sections and L subshell fluorescence

    CERN Document Server

    Ertugrul, M


    The L/sub 3l/, L/sub 3 alpha /, L/sub 3 beta /, L/sub 2 beta /, L/sub 2 gamma /, L/sub 1 beta /, L/sub 1 gamma /, L/sub beta /, L/sub gamma /, L/sub 1x/, L/sub 2x/ and L/sub 3x/ X-ray production cross sections in Re, W and Ta have been measured using the 59.5 keV incident photon energy. The measurements were performed using an Am-241 radioisotope as the photon source and a Si(Li) detector. The L X-rays are resolved with a new analytical method. The obtained L/sub l/, L/sub alpha /, L /sub 3 beta /, L/sub 2 beta /, L/sub 2 gamma /, L/sub 1 beta /, L/sub 1 gamma /, L/sub beta /, L/sub gamma /, L/sub 1x/, L/sub 2x/ and L /sub 3x/ X-rays are compared with the theoretical calculations using the most reliable theoretical values of L/sub i/ (i=1, 2, 3) subshell photoionization cross sections, fluorescence yields, X-ray emission rates and Coster-Kronig transition probabilities. The results in the present paper are found to be in good agreement with the calculated values. (23 refs).

  19. Five different profiles of dihydropyridines in blocking T-type Ca(2+) channel subtypes (Ca(v)3.1 (alpha(1G)), Ca(v)3.2 (alpha(1H)), and Ca(v)3.3 (alpha(1I))) expressed in Xenopus oocytes. (United States)

    Furukawa, Taiji; Nukada, Toshihide; Namiki, Yoshiko; Miyashita, Yoriko; Hatsuno, Kento; Ueno, Yasunari; Yamakawa, Takeshi; Isshiki, Takaaki


    1,4-dihydropyridine (DHP) Ca(2+) antagonists have recently been shown to block T-type Ca(2+) channels, which may render favorable actions on cardiovascular systems. However, this evaluation remains to be done systematically for each T-type Ca(2+) channel subtype except for the Ca(v)3.1 (alpha(1G)) subtype. To address this issue at the molecular level, blocking effects of 14 kinds of DHPs (amlodipine, aranidipine, azelnidipine, barnidipine, benidipine, cilnidipine, efonidipine, felodipine, manidipine, nicardipine, nifedipine, nilvadipine, nimodipine, nitrendipine), which are clinically used for treatments of hypertension, on 3 subtypes of T-type Ca(2+) channels [Ca(v)3.2 (alpha(1H)), Ca(v)3.3 (alpha(1I)), and Ca(v)3.1 (alpha(1G))] were investigated in the Xenopus oocyte expression system using the two-microelectrode voltage-clamp technique. These 3 kinds (alpha(1H), alpha(1I) and alpha(1G)) of T-type channels were blocked by amlodipine, manidipine and nicardipine. On the other hand, azelnidipine, barnidipine, benidipine and efonidipine significantly blocked alpha(1H) and alpha(1G), but not alpha(1I) channels, while nilvadipine and nimodipine apparently blocked alpha(1H) and alpha(1I), but not alpha(1G) channels. Moreover, aranidipine blocked only alpha(1H) channels. By contrast, cilnidipine, felodipine, nifedipine and nitrendipine had little effects on these subtypes of T-type channels. The result indicates that the blockade of T-type Ca(2+) channels by derivatives of DHP Ca(2+) antagonist was selective for the channel subtype. Therefore, these selectivities of DHPs in blocking T-type Ca(2+) channel subtypes would provide useful pharmacological and clinical information on the mode of action of the drugs including side-effects and adverse effects.

  20. Table of radionuclides (Vol.3 - {alpha} = 3 to 244); Table de radionucleides

    Energy Technology Data Exchange (ETDEWEB)

    Be, M.M.; Chiste, V.; Dulieu, Ch. [Laboratoire National Henri Becquerel - Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France); Browne, E.; Baglin, C. [Lawrence Berkeley National Lab., CA (United States); Chechev, V.; Kuzmenko [Khlopin Radium Institute (KRI) (Russian Federation); Helmer, R. [Idaho National Engineering and Environmental Lab., Idaho Falls, ID (United States); Kondev, F. [Argonne National Lab., IL (United States); MacMahon, T.D. [National Physical Lab., Teddington (United Kingdom); Lee, K.B. [Korea Research Inst. of Standards and Science (Korea, Republic of)


    This monograph is one of several published in a series by the Bureau International des Poids et Mesures (BIPM) on behalf of the Comite Consultatif des Rayonnements Ionisants (CCRI), previously known as the Comite Consultatif pour les Etalons de Mesure des Rayonnements Ionisants (CCEMRI). The aim of this series of publications is to review topics that are of importance for the measurement of ionizing radiation and especially of radioactivity, in particular those techniques normally used by participants in international comparisons. It is hoped that these publications will prove to be useful reference volumes both for those who are already engaged in this field and for those who are approaching such measurements for the first time. The purpose of this monograph, number 5 in the series, is to present the recommended values of nuclear and decay data for a wide range of radionuclides. Activity measurements for more than forty of these radionuclides have already been the subject of comparisons under the auspices of Section II of the CCRI. The material for this monograph is now covered in three volumes. The first two volumes contain the primary recommended data relating to half-lives, decay modes, x-rays, gamma-rays, electron emissions; alpha- and beta-particle transitions and emissions, and their uncertainties for a set of sixty-eight radionuclides, Volume 1 for those radionuclides with mass number up to and including 150 and Volume 2 for those radionuclides with mass number over 150. Volume 3 contains the equivalent data for twenty-six additional radionuclides as listed and re-evaluation for {sup 125}Sb and {sup 153}Sm. The data have been collated and evaluated by an international working group (Decay Data Evaluation Project) led by the LNE-LNHB. The evaluators have agreed on the methodologies to be used and the CD-ROM included with this monograph contains the evaluators' comments for each radionuclide in addition to the data tables included in the monograph. The work involved in evaluating nuclear data is on-going and the recommended values are updated on the LNHB web site at WG/DDEPdata.htm. The publication of further volumes of Monographie 5 is envisaged as and when necessary to add new radionuclide data or re-evaluations in a more permanent format that can be referenced easily. Although other data sets may still be used when evaluating radionuclide activity, use of this common, recommended data set should help to reduce the uncertainties in activity evaluations and lead to more coherent results for comparisons. This volume includes the evaluation of the following radionuclides: {sup 3}H, {sup 55}Fe, {sup 56}Co, {sup 60}Co, {sup 63}Ni, {sup 65}Zn, {sup 79}Se, {sup 90}Sr, {sup 90}Y, {sup 90}Y{sup m}, {sup 108}Ag, {sup 108}Ag{sup mn} {sup 111}In, {sup 125}Sb, {sup 137}Cs, {sup 153}Sm, {sup 159}Gd, {sup 203}Pb, {sup 233}Pa, {sup 233}Th, {sup 234}U, {sup 236}Np, {sup 236}Np{sup m}, {sup 237}U, {sup 238}U, {sup 242}Cm, {sup 243}Am, {sup 244}Cm. Primary recommended data comprise half-lives, decay modes, X-rays, gamma-rays, electron emissions, alpha- and beta-particle transitions and emissions, and their uncertainties. (authors)

  1. ENEA extremity dosemeter based on LiF(Mg,Cu,P) to evaluate Hp(3,alpha). (United States)

    Mariotti, F; Fantuzzi, E; Morelli, B; Gualdrini, G; Botta, M C; Uleri, G; Bordy, J M; Denoziere, M


    Recent epidemiological studies suggest a rather low-dose threshold (ORAMED) Project, whose WP2 is aimed at the quantity H(p)(3) and eye lens dosimetry in practice, are taken into account. The paper summarises the main aspects of the study carried out at ENEA-Radiation Protection Institute (Bologna, Italy) to provide practical solutions (in the use and the design) to evaluate the response of the ENEA TL extremity dosemeter in terms of H(p)(3).

  2. Functional bread with n-3 alpha linolenic acid from whole chia (Salvia hispanica L.) flour. (United States)

    Luna Pizarro, Patricia; Almeida, Eveline Lopes; Coelho, Alessandra Silva; Sammán, Norma Cristina; Hubinger, Miriam Dupas; Chang, Yoon Kil


    This work proposed to study the effects of the addition of whole chia flour (WCF) on the technological, nutritional and sensory qualities of bread. Different WCF contents (0 and 20 %) and vital gluten (VG) (0 and 4 %) were added to bread according to a 2(2) central composite rotational design. WCF decreased the specific volume, lightness and hue angle of the bread loaves, but did not affect the chroma values. WCF and VG contributed to maintenance of the moisture content of the loaves during the storage period. The increased firmness found with the addition of high levels of WCF (more than 10 %) was countered by larger amounts of VG (more than 2 %). The optimum loaf (10 % WCF and 2 % VG) showed 26 % more lipids, 19 % more protein and 11 % more ash than the standard loaf (0 % WCF and 0 % VG). A better lipid profile was also found (higher omega-3 fatty acid content and a better omega-6/omega-3 ratio). Both breads were positively rated in the sensory profile analysis.

  3. Chromosomal mapping and mutational analysis of the coding region of the glycogen synthase kinase-3alpha and beta isoforms in patients with NIDDM

    DEFF Research Database (Denmark)

    Hansen, L; Arden, K C; Rasmussen, S B


    Activation of glycogen synthesis in skeletal muscle in response to insulin results from the combined inactivation of glycogen synthase kinase-3 (GSK-3) and activation of the protein phosphatase-1, changing the ratio between the inactive phosphorylated state of the glycogen synthase to the active ...

  4. Arabidopsis thaliana RGXT1 and RGXT2 encode Golgi-localized (1,3)-alpha-D-xylosyltransferases involved in the synthesis of pectic rhamnogalacturonan-II

    DEFF Research Database (Denmark)

    Madsen, Jack Egelund; Petersen, Bent Larsen; Motawia, Mohammed Saddik


    of a type II membrane protein structure. Soluble secreted forms of the corresponding proteins expressed in insect cells showed xylosyltransferase activity, transferring d-xylose from UDP-alpha-d-xylose to l-fucose. The disaccharide product was hydrolyzed by alpha-xylosidase, whereas no reaction...


    NARCIS (Netherlands)



    In the sera of patients with Wegener's granulomatosis (WG), C-ANCA can be detected that are directed against proteinase 3 (PR3). We have previously observed that C-ANCA interfere with PR3 proteolytic activity and with complexation of PR3 with its major physiologic inhibitor, alpha1-antitrypsin (alph

  6. GM3 alpha2,8-sialyltransferase (GD3 synthase): protein characterization and sub-golgi location in CHO-K1 cells. (United States)

    Daniotti, J L; Martina, J A; Giraudo, C G; Zurita, A R; Maccioni, H J


    GD3 synthase (Sial-T2) is a key enzyme of ganglioside synthesis that, in concert with GM2 synthase (GalNAc-T), regulates the ratio of a- and b-pathway gangliosides. In this work, we study the sub-Golgi location of an epitope-tagged version of chicken Sial-T2 transfected to CHO-K1 cells. The expressed protein was enzymatically active both in vitro and in vivo and showed a molecular mass of approximately 47 or approximately 95 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence or absence of, respectively, beta-mercaptoethanol. The 95-kDa form of Sial-T2 was also detected if the protein was retained in the endoplasmic reticulum (ER) due to impaired glycosylation, indicating that it was formed in the ER. Confocal immunofluorescence microscopy showed Sial-T2 localized to the Golgi complex and, within the organelle, partially co-localizing with the mannose-6-phosphate receptor, a marker of the trans-Golgi network (TGN). In cells treated with brefeldin A, a major fraction of Sial-T2 redistributed to the ER, even under controlled expression to control for mislocalization due to protein overloading. In experiments of incorporation of sugars into endogenous acceptors of Golgi membranes in vitro, GD3 molecules formed by incubation with CMP-NeuAc were converted to GD2 upon incubation with UDP-GalNAc. These results indicate that Sial-T2 localizes mainly to the proximal Golgi, although a fraction is located in the TGN functionally coupled to GalNAc-T. Consistent with this, most of the enzyme was in an endoglycosidase H (Endo-H)-sensitive, neuraminidase (NANase)-insensitive form. A minor secreted form lacking approximately 40 amino acids was Endo-H-resistant and NANase-sensitive, indicating that the cells were able to process N-glycans to Endo-H-resistant forms. Taken together, the results of these biochemical and immunocytochemical experiments indicate that in CHO-K1 cells, most Sial-T2 localizes in the proximal Golgi and that a functional fraction is also present in the TGN.

  7. Crystallographic Analysis of Murine Constitutive Androstane Receptor Ligand-Binding Domain Complexed with 5[alpha]-androst-16-en-3[alpha]-ol

    Energy Technology Data Exchange (ETDEWEB)

    Vincent, J.; Shan, L.; Fan, M.; Brunzelle, J.S.; Forman, B.M.; Fernandez, E.J. (Tennessee-K); (NWU); (CHNMC)


    The constitutive androstane receptor (CAR) is a member of the nuclear receptor superfamily. In contrast to classical nuclear receptors, which possess small-molecule ligand-inducible activity, CAR exhibits constitutive transcriptional activity in the apparent absence of ligand. CAR is among the most important transcription factors; it coordinately regulates the expression of microsomal cytochrome P450 genes and other drug-metabolizing enzymes. The murine CAR ligand-binding domain (LBD) was coexpressed with the steroid receptor coactivator protein (SRC-1) receptor-interacting domain (RID) in Escherichia coli. The mCAR LBD subunit was purified away from SRC-1 by affinity, anion-exchange and size-exclusion chromatography, crystallized with androstenol and the structure of the complex determined by molecular replacement.

  8. Crystallization and preliminary X-ray diffraction analysis of the interleukin-3 alpha receptor bound to the Fab fragment of antibody CSL362. (United States)

    Broughton, Sophie E; Hercus, Timothy R; Nero, Tracy L; Dhagat, Urmi; Owczarek, Catherine M; Hardy, Matthew P; Fabri, Louis J; Scotney, Pierre D; Nash, Andrew D; Wilson, Nicholas J; Lopez, Angel F; Parker, Michael W


    Interleukin-3 (IL-3) is a member of the beta common family of cytokines that regulate multiple functions of myeloid cells. The IL-3 receptor-specific alpha subunit (IL3Rα) is overexpressed on stem cells/progenitor cells of patients with acute myeloid leukaemia, where elevated receptor expression correlates clinically with a reduced patient survival rate. The monoclonal antibody (MAb) CSL362 is a humanized MAb derived from the murine MAb 7G3, originally identified for its ability to specifically recognize the human IL-3 receptor and for blocking the signalling of IL-3 in myeloid and endothelial cells. In order to elucidate the molecular mechanism of CSL362 antagonism, a preliminary structure of human IL3Rα in complex with the MAb CSL362 has been determined.

  9. Direct capture in nuclear astrophysics: The cases of Oxygen-17(p,gamma)Fluorine-18 and Helium-3(alpha,gamma)Beryllium-7 (United States)

    Kontos, Antonios

    Direct radiative capture is a non-resonant one-step nuclear reaction mechanism that in principle does not involve the formation of a compound nucleus. In the absence of strong resonance inside the Gamow window, direct capture can be the dominant contribution to astrophysically important reaction rates. The present thesis studies two such reactions, 17O(p,gamma) 18F and 3He(alpha,gamma)7Be. 17O(p,gamma)18F influences hydrogen-burning nucleosynthesis in several stellar sites, such as red giants, asymptotic giant branch (AGB) stars, massive stars and classical novae. In the relevant temperature range for these environments (T9 = 0.01- 0.4), the main contributions to the rate of this reaction are the direct capture process, two low lying narrow resonances (ElabR = 70 and 193 keV) and the low energy tails of two broad resonances (ElabR = 587 and 714 keV). Previous measurements and calculations give contradictory results for the direct capture contribution which in turn increases the uncertainty of the reaction rate. In addition, very few published cross section data exist for the high energy region that might affect the interpretation of the direct capture and the broad resonances contributions in the lower energy range. In this work we present a measurement of the reaction at a wide proton energy range (Elab = 360 - 1625 keV) and at several angles (θ lab = 0°, 45°, 90°, 135°). 3He(alpha,gamma)7Be is important for the neutrino production in the sun's core and the production of 7Li during the big bang nucleosynthesis. Due to the low level density of 7Be, the reaction mechanism is almost entirely non-resonant at the relevant energies. Recent experiments have improved the uncertainty of the reaction but some discrepancies still exist. In the present work, a relatively wide energy window was measured, ECM = 0.300 -- 1.450 MeV, by detecting the prompt gamma-rays from the reaction. The use of a compact helium jet gas target ensured high gamma-ray detection efficiency. The results are compared with literature.

  10. Association of whirlin with Cav1.3 (alpha1D) channels in photoreceptors, defining a novel member of the usher protein network.

    NARCIS (Netherlands)

    Kersten, F.F.J.; Wijk, E. van; Reeuwijk, J. van; Zwaag, B. van der; Marker, T.; Peters, T.A.; Katsanis, N.; Wolfrum, U.; Keunen, J.E.E.; Roepman, R.; Kremer, J.M.J.


    PURPOSE: Usher syndrome is the most common form of hereditary deaf-blindness. It is both clinically and genetically heterogeneous. The USH2D protein whirlin interacts via its PDZ domains with other Usher-associated proteins containing a C-terminal type I PDZ-binding motif. These proteins co-localize

  11. Comparing prothrombin induced by vitamin K absence-II (PIVKA-II) with the oncofetal proteins glypican-3, Alpha feto protein and carcinoembryonic antigen in diagnosing hepatocellular carcinoma among Egyptian patients. (United States)

    Abd El Gawad, Iman A; Mossallam, Ghada I; Radwan, Noha H; Elzawahry, Heba M; Elhifnawy, Niveen M


    Hepatocellular carcinoma (HCC) is usually asymptomatic in the early stage and does not show elevated alpha-feto protein (AFP). AFP shows 60-80% sensitivity in diagnosing HCC. Glypican3 (GPC-3) is an oncofetal protein that is only detected in HCC cells but not in benign liver tissues, while Carcinoembryonic antigen (CEA) is expressed in various neoplasms including HCC. Although, it is not specific for HCC. Prothrombin induced by vitamin K absence-II (PIVKA-II) is an abnormal prothrombin protein that is increased in the serum of HCC patients. It has higher sensitivity and specificity compared to AFP. The aim of this study is to compare the clinical utility of PIVKA-II with GPC-3, AFP and CEA in diagnosing HCC. This study included 40 patients with HCC, 10 patients with cirrhosis as a benign control group, and 10 apparently healthy volunteers as normal controls. Serum samples were subjected to routine laboratory investigations, measurement of CEA, AFP using MEIA technique (Axsym), glypican3, and PIVKA-II using ELISA technique in the sera of all patients and controls. All markers showed the highest results in the HCC group. Higher concentrations of PIVKA-II were detected in patients with splenomegaly, and in tumors with size (>3cm). Combination of Glypican-3 and PIVKA-II showed the highest sensitivity, while GPC-3 alone and combination of GPC-3 and AFP showed the highest specificity to differentiate HCC from liver cirrhosis and normal controls. GPC-3, PIVKAII, and combination of both showed the highest sensitivity, while GPC-3 alone showed the highest specificity to differentiate HCC from liver cirrhosis. Glypican-3 is the only oncofetal antigen that showed comparable high diagnostic accuracy as PIVKA-II in diagnosing HCC among Egyptian patients. Copyright © 2014. Production and hosting by Elsevier B.V.

  12. Temperature Effect Correction for Chang'E-3 Alpha Particle X-Ray Spectrometer%嫦娥三号粒子激发X射线谱仪能谱温度影响的修正方法

    Institute of Scientific and Technical Information of China (English)

    吴明烨; 樊瑞睿; 刘雅清; 董亦凡; 吴峰; 赵小芸; 王焕玉; 彭文溪; 张承模; 张家字; 崔兴柱; 梁晓华; 汪锦州; 杨家卫


    Alpha particle X-ray spectrometer ( APXS) is one of the payloads of Chang'E-3 lunar rover of China's Lunar Exploration Project The present paper introduces briefly the components of APXS, how it works and its working environment on the lunar surface. The environmental temperature effect has been studied with simulations and experiments, and the results show that the temperature of the APXS sensor will be varying during the measuring on the lunar surface. And another experiment reveals that the energy resolution becomes worse if the sensor's temperature is varying. In this paper, a correction method based on Pearson's chi-squared test is presented. The method can improve the energy resolution when the sensor's temperature is varying. We have tested the method with the spectra acquired by APXS in the temperature varying period of Temperature Cycling Test, and the results show that the method is efficient and reliable.%粒子激发X射线谱仪(APXS)是中国探月工程二期嫦娥三号月球巡视器的有效载荷之一.简要介绍APXS的工作原理、组成部分,以及它在月面的工作环境,通过模拟及实验研究了月面热环境对APXS的影响,结果显示,APXS将工作在显著的变温过程中.相对恒温过程,APXS在变温过程中的能量分辨率明显变差.为了消除该温度效应的影响,提出了一种基于皮尔逊卡方检验(Pearson's chi-squared test)的修正方法,能够有效提高变温过程中的能量分辨率.通过温度循环试验中变温阶段的数据对该方法进行了测试,结果表明,该方法具有很好的修正效果和较高的可靠性.

  13. 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


    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 characterized through X-ray diffraction, Rietveld structural refinement and Mössbauer spectroscopy. The determination and identification of crystallographic phases, lattice parameters and unit cell volume in as-milled and annealed samples allowed verifying structural parameters change, the spinel phase formation and possible relative deformations due to the high-energy ball milling process.

  14. The Value of Combined Serum Alpha-fetoprotein Heteroplasmon-L3 Concentration and AFP-L3/Alpha-fetoprotein Ratio Detection in the Early Diagnosis of Primary Liver Cancer%联合检测血清甲胎蛋白异质体浓度与甲胎蛋白异质体百分含量在原发性肝癌诊断中的价值

    Institute of Scientific and Technical Information of China (English)

    黄彩云; 韩素桂; 贾红莲


    Objective To explore the value of combined serum alpha-fetoprotein inform (AFP-L3) and AFP-L3/AFP as biomarkers in the early diagnosis of hepatocellular carcinoma (HCC).Methods A total of 137 patients from the People's Hospital of Tangshan of Hebei Union University were included in our study.They were treated in hospital from March to November 201 1.All the patients were at the age of 28 to 77 years old,and 98 of them were men,and 39 were women.According to the pathological diagnosis,patients were divided into two groups.HCC group had 92 patients,and benign liver disease group had 45 patients including 37 with liver cirrhosis and 8 with chronic hepatitis.ELISA method was used to test the serum AFP-L3 level.At the same time,microcentrifugal column method was adopted to separate AFP-L3 from the patients' serum,and electrochemical luminescence method was used to detect the separated AFP-L3 and total AFP levels.Then,we calculated the ratio of AFP-L3/AFP.We also calculated the statistical indexes of AFP-L3 level and AFP-L3/AFP ratio in the diagnosis of HCC,such as sensitivity,specificity and Youden index.The above indexes of combined AFP-L3 level and AFP-L3/AFP ratio were also detected to evaluated its diagnostic value.Results HCC group AFP-L3 level (109.04 ± 62.51) ng/mL was significantly higher than that of the benign liver disease group [(25.96 ± 49.43) ng/mL; t=8.28,P < 0.001].HCC group serum AFP-L3/AFP ratio (17.35% ± 14.48%) was significantly higher than that of the benign liver disease group (5.62% ± 6.38%,t=6.545,P < 0.000 1).With serum AFP-L3 level > 38.0 ng/mL as a critical value of primary liver cancer diagnosis,the sensitivity was 83.69%,and the specificity was 88.88%.For AFP-L3/AFP ratio > 10% as a critical value in primary liver cancer diagnosis,the sensitivity was 83.69%,and the specificity was 95.55%.When serum AFP-L3 level > 38.0 ng/mL and AFP-L3/AFP ratio > 7.5% were combined in primary liver cancer diagnosis,the sensitivity was 97.83%,and the specificity was 84.44%.Conclusion Compared with application of single indicators,combined use of AFP-L3 level and the ratio of AFP-L3/AFP in the diagnosis of HCC significantly improves the diagnostic sensitivity,and is more conducive to the early diagnosis of HCC,although its diagnostic specificity is slightly lower.%目的 通过检测肝病患者血清甲胎蛋白异质体(AFP-L3)浓度和AFP-L3/血清甲胎蛋白(AFP)比值,分析探讨并联运用两指标在肝细胞癌(HCC)诊断中的价值.方法 选取2011年3月-11月137例的住院患者血清标本,AFP检测均为阳性.依据病理学诊断,将137例患者分为两组,HCC组92例,良性肝病组45例,后者包括肝硬化结节37例、慢性活动性肝炎8例.采用酶联免疫吸附试验(ELISA)检测所有患者血清AFP-L3浓度;同时运用微量吸附柱法分离血清中的AFP-L3,采用电化学发光法检测分离后的AFP-L3和血清中总AFP浓度,计算AFP-L3/AFP比值.计算采用AFP-L3浓度与AFP-L3/AFP比值以及AFP-L3浓度与AFP-L3/AFP比值两指标并联诊断HCC的灵敏度、特异度、Youden指数等统计学指标,探讨其在原发性肝癌诊断中的价值.结果 ①HCC 组AFP-L3浓度(109.04±62.51)ng/mL,明显高于良性肝病组(25.96±49.43)ng/mL,差异有统计学意义(t=8.28,P< 0.001).HCC组血清AFP-L3/AFP比值(17.35±14.48%)高于良性肝病组(5.617±6.38%),差异有统计学意义(t=6.545,P<0.0001).②以血清AFP-L3浓度>38.0 ng/mL作为临界值诊断原发性肝癌的灵敏度为83.69%,特异度为88.88%,以AFP-L3/AFP比值>10%作为临界值诊断原发性肝癌的灵敏度为83.69%,特异度为95.55%.③并联应用血清AFP-L3浓度>38.0 ng/mL、AFP-L3/AFP>比值7.5%诊断HCC的灵敏度为97.83%,特异度为84.44%.结论 并联应运AFP-L3浓度与AFP-L3/AFP比值诊断HCC较应用单一指标诊断特异度稍有下降,但明显提高了诊断的灵敏度,更有利于HCC的早期诊断.

  15. Regulation of neurosteroid allopregnanolone biosynthesis in the rat spinal cord by glycine and the alkaloidal analogs strychnine and gelsemine. (United States)

    Venard, C; Boujedaini, N; Belon, P; Mensah-Nyagan, A G; Patte-Mensah, C


    The neurosteroid allopregnanolone (3alpha,5alpha-THP) is well characterized as a potentially therapeutic molecule which exerts important neurobiological actions including neuroprotective, antidepressant, anxiolytic, anesthetic and analgesic effects. We have recently observed that neurons and glial cells of the rat spinal cord (SC) contain various key steroidogenic enzymes such as 5alpha-reductase and 3alpha-hydroxysteroid oxido-reductase which are crucial for 3alpha,5alpha-THP biosynthesis. Furthermore, we demonstrated that the rat SC actively produces 3alpha,5alpha-THP. As the key factors regulating neurosteroid production by nerve cells are unknown and because glycine is one of the pivotal inhibitory neurotransmitters in the SC, we investigated glycine effects on 3alpha,5alpha-THP biosynthesis in the rat SC. Glycine markedly stimulated [(3)H]-progesterone conversion into [(3)H]3alpha,5alpha-THP by SC slices. The alkaloid strychnine, well-known as a glycine receptor (Gly-R) antagonist, blocked glycine stimulatory effect on 3alpha,5alpha-THP formation. Gelsemine, another alkaloid containing the same functional groups as strychnine, increased 3alpha,5alpha-THP synthesis. The stimulatory effects of glycine and gelsemine on 3alpha,5alpha-THP production were additive when the two drugs were combined. These results demonstrate that glycine and gelsemine, acting via Gly-R, upregulate 3alpha,5alpha-THP biosynthesis in the SC. The data also revealed a structure-activity relationship of the analogs strychnine and gelsemine on neurosteroidogenesis. Possibilities are opened for glycinergic agents and gelsemine utilization to stimulate selectively 3alpha,5alpha-THP biosynthetic pathways in diseases evoked by a decreased neurosteroidogenic activity of nerve cells.

  16. Functional capacity of XRCC1 protein variants identified in DNA repair-deficient Chinese hamster ovary cell lines and the human population

    DEFF Research Database (Denmark)

    Berquist, Brian R; Singh, Dharmendra Kumar; Fan, Jinshui


    ) and two frequent (R194W and R399Q) amino acid population variants had little or no effect on XRCC1 protein stability or the interactions with POLbeta, PARP-1, LIG3alpha, PCNA or DNA. One common population variant (R280H) had no pronounced effect on the interactions with POLbeta, PARP-1, LIG3alpha and PCNA...

  17. Neurosteroids in depression: a review.

    NARCIS (Netherlands)

    Broekhoven, F. van; Verkes, R.J.


    RATIONALE: A deregulation in concentrations of the neurosteroids (allo)pregnanolone and 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-TH DOC) has been found in depressed patients. These levels normalize following treatment with selective serotonin reuptake inhibitors (SSRIs).

  18. Differential induction of HNF-3 transcription factors during neuronal differentiation. (United States)

    Jacob, A; Budhiraja, S; Reichel, R R


    We have investigated the regulation of transcription factors HNF-3alpha and HNF-3beta during the retinoic acid-mediated differentiation of mouse P19 cells. Retinoic acid treatment converts P19 stem cells into neurons and astrocytes and we have clearly shown that gene expression of both HNF-3alpha and HNF-3beta is activated during this process. HNF-3alpha transcription was detected 2 h after addition of retinoic acid and took place in the absence of de novo protein synthesis. This suggests that HNF-3alpha is a primary target for retinoic acid action. HNF-3alpha induction displays a biphasic profile and HNF-3alpha mRNA reaches maximal levels at 2 and 6 days postdifferentiation. Additional experiments strongly suggest that the second peak is due to HNF-3alpha induction in postmitotic neurons. P19 stem cells, on the other hand, do not contain any detectable HNF-3alpha mRNA. According to our studies, the retinoic acid-mediated induction of HNF-3alpha occurs at the level of transcriptional initiation and is conferred by distal promoter sequences. In comparison to HNF-3alpha, HNF-3beta induction is a subsequent event and detectable levels of HNF-3beta mRNA materialize approximately 1 day after addition of retinoic acid to P19 stem cells. Time course studies firmly demonstrate that HNF-3beta mRNA peaks at about 2 days postdifferentiation and then declines to virtually unreadable levels. This temporal pattern is consistent with HNF-3beta being a secondary target for retinoic acid. In analogy to HNF-3alpha, HNF-3beta activation also takes place at the level of transcriptional initiation. Recent studies implicate HNF-3alpha and HNF-3beta in early mammalian neurogenesis. The detection of HNF-3alpha/beta activation during P19 cell differentiation provides us with a convenient cell culture system to elucidate the induction mechanism and the precise role of both transcriptional regulators in the formation of neuronal cells.


    Directory of Open Access Journals (Sweden)

    Davide v Moretti


    Full Text Available Background: several biomarkers have been proposed for detecting Alzheimer's disease (AD in its earliest stages, that is, in the predementia stage. In an attempt to find noninvasive biomarkers, researchers have investigated the feasibility of neuroimaging tools, such as MRI, SPECT as well as neurophysiological measurements using EEG. Moreover, the increase of EEG alpha3/alpha2 frequency power ratio has been associated with AD-converters subjects with mild cognitive impairment (MCI.Objective: to study the association of alpha3/alpha2 frequency power ratio with regional cerebral blood flow (rCBF changes in subjects with MCI .Methods: 27 adult subjects with MCI underwent EEG recording and perfusion single-photon emission computed tomography (SPECT evaluation. The alpha3/alpha2 frequency power ratio was computed for each subject. Two groups were obtained according to the median values of alpha3/alpha2, at a cut-off of 1.17. Correlation between brain perfusion and EEG markers were detected.Results: subjects with higher alpha3/alpha2 frequency power ratio showed a constant trend to a lower perfusion than low alpha3/alpha2 group. The two groups were significantly different as about the hippocampal volume and correlation with the theta frequency activity.Conclusion: there is a complex interplay between cerebral blood flow, theta frequency activity and hippocampal volume in MCI patients with prodromal Alzheimer's disease, characterized by higher EEG alpha3 /alpha2 frequency power ratio.

  20. Relationships of circulating pregnanolone isomers and their polar conjugates to the status of sex, menstrual cycle, and pregnancy. (United States)

    Kancheva, Radmila; Hill, Martin; Cibula, David; Vceláková, Helena; Kancheva, Lyudmila; Vrbíková, Jana; Fait, Tomás; Parízek, Antonín; Stárka, Luboslav


    Pregnanolone isomers (PIs) and their polar conjugates (PICs) modulate ionotropic receptors such as gamma-aminobutyric acid or pregnane X receptors. Besides, brain synthesis, PI penetrates the blood-brain barrier. We evaluated the physiological importance of PI respecting the status of sex, menstrual cycle, and pregnancy. Accordingly, circulating levels of allopregnanolone (P3alpha 5alpha ), isopregnanolone (P3beta 5alpha ), pregnanolone (P3alpha 5beta ), epipregnanolone (P3beta 5beta ), their polar conjugates, and related steroids were measured in 15 men (M), 15 women in the follicular phase (F), 16 women in the luteal phase (L), and 30 women in the 36th week of gestation (P) using GC-MS. The steroid levels were similar in M and F, increased about thrice in L and escalated in P (38-410 times compared with F). The PICs were prevalent over the PIs (16-150 times). Higher ratios of 5alpha-PIC to 5alpha-PI found in P indicate the more intensive conjugation of 5alpha-PI during pregnancy. This mechanism probably provides for the elimination of neuroinhibitory P3alpha 5alpha in the maternal compartment. Additionally, our result points to a limited sulfation capacity for neuroinhibitory P3alpha 5beta in P. In contrast to the situation in M, F, and L where the P3alpha 5beta C is the most abundant PIC, and P3alpha 5beta is present in minor quantities compared with the P3alpha 5alpha, P3alpha 5beta may acquire physiological importance during pregnancy, contributing to the sustaining thereof. On the other hand, the declining formation of P3alpha 5beta may participate in the initiation of parturition, given the relative abundance of the steroid, its potency to suppress the activity of oxytocin-producing cells and its effectiveness in uterine relaxation.

  1. Flavonoids from Aconitum napellus subsp. neomontanum. (United States)

    Fico, G; Braca, A; De Tommasi, N; Tomè, F; Morelli, I


    Three flavonol glycosides quercetin 7-O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->3)-alpha-rhamnopyranoside-3-O-beta-glucopyranoside (1), kaempferol 7-O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->3)-alpha-rhamnopyranoside-3-O-beta-glucopyranoside (2), and kaempferol 7-O-(6-trans-p-coumaroyl)-beta-glucopyranosyl-(1-->3)-alpha-rhamnopyranoside-3-O-beta-glucopyranoside (3), together with the known beta-3,4-dihydroxyphenethyl beta-glucopyranoside, were isolated from the flowers of Aconitum napellus subsp. neomontanum. Their structures were elucidated by spectroscopic methods, including 2D NMR spectral techniques.

  2. Modification of behavioral effects of drugs in mice by neuroactive steroids

    NARCIS (Netherlands)

    Ungard, JT; Beekman, M; Gasior, M; Carter, RB; Dijkstra, D; Witkin, JM

    Rationale: Neuroactive steroids represent a novel class of potential therapeutic agents (epilepsy, anxiety, migraine, drug dependence) thought to act through positive allosteric modulation of the GABA(A) receptor A synthetically derived neuroactive steroid, ganaxolone (3 alpha-hydroxy-3

  3. GPCR Interaction: 37 [GRIPDB[Archive

    Lifescience Database Archive (English)

    Full Text Available ot show any detectable binding activity for the muscarinic ligand N-[3H]methylscopolamine or the adrenergic ...ligand [3H]rauwolscine. However, cotransfection with alpha 2/m3 and m3/alpha 2 re

  4. Isolation of lignans glycosides from Alibertia sessilis (Vell.) K. Schum. (Rubiaceae) by preparative high-performance liquid chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Silva, V.C. da; Bolzani, V. da S.; Lopes, M.N. [UNESP, Araraquara, SP (Brazil). Inst. de Quimica. Dept. de Quimica Organica; Silva, G.H. [Universidade Federal de Sergipe, Aracaju, SE (Brazil). Dept. de Quimica]. E-mail:


    Enantiomeric aglycone lignans contained in a mixture were separated from a fraction of the extract of the stems of Alibertia sessilis (Vell.) K. Schum. (Rubiaceae) by preparative high-performance liquid chromatography. An efficient and fast separation can be achieved with methanol-water (30:70, v/v). Their structures were identified as (+)-lyoniresinol 3{alpha}-O-{beta}-glucopyranoside and (-)-lyoniresinol 3{alpha}-O-{beta}-glucopyranoside, being reported for the first time in Rubiaceae. (author)

  5. 3-Epiabruslactone A, a New Triterpene Lactone Isolated from Austroplenckia populnea

    Directory of Open Access Journals (Sweden)

    Silva Grácia Divina de Fátima


    Full Text Available A new lactonic triterpene isolated from the heartwood of Austroplenckia populnea (Celastraceae was characterized as 3alpha-hydroxyolean-12-en-29,22alpha-olide (the gamma-lactone of the 3alpha,22alpha-dihydroxyolean-12-en-29alpha-oic acid, the 3-epimer of the abruslactone A, on the basis of its spectral data, chemical transformations, and single crystal X-ray analysis.

  6. Two new ent-kaurane diterpenoids from Albizia mollis (Wall.) Boiv

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Zhong-Quan; Yang, Dan; Liu, Yu-Qing; Hu, Jiang-Miao; Jiang, He-Zhong; Wang, Peng-Cheng; Zhoua, Jun; Zhao, You-Xing, E-mail: [Chinese Academy of Sciences, Kunming (China). Kunming Institute of Botany. State Key Lab. of Phytochemistry and Plant Resources in West China; Li, Ning [Anhui University, Hefei (China). School of Life Sciences


    Two new kaurane diterpenoid, 3{alpha}, 16{beta}, 17-trihydroxy-ent-kaurane 3-O-{beta}-D-glucopyranoside and 2{beta},3{alpha}-dihydroxy-ent-kaur-15-en-17-oic acid 3-O-{beta}-D-glucopyranoside, were isolated from the bark of Albizia mollis (Wall.) Boiv. The structures of two new compounds were elucidated by extensive 1D- and 2D-NMR spectroscopic methods in combination with MS experiments. (author)

  7. 21beta-Hydroxy-oleanane-type triterpenes from Hippocratea excelsa. (United States)

    Cáceres-Castillo, David; Mena-Rejón, Gonzalo J; Cedillo-Rivera, Roberto; Quijano, Leovigildo


    Stem bark of Hippocratea excelsa afforded six pentacyclic triterpenes, five oleanane and one ursane types. They were identified as 11beta,21beta-dihydroxy-olean-12-ene-3-one (2), 3alpha,11alpha,21beta-trihydroxy-olean-12-ene (3), 3alpha,21beta-dihydroxy-11alpha-methoxy-olean-12-ene (4), 3alpha,21beta-dihydroxy-olean-9(11),12-diene (5), 3alpha,21beta-dihydroxy-olean-12-ene (6) and 3alpha,21beta-dihydroxy-11alpha-methoxy-urs-12-ene, isolated as its diacetate derivative (7), as well as 3alpha,21beta-dihydroxy-olean-12-ene (1) previously isolated from the root bark. The known alpha- and beta-amyrin, oleanoic and ursolic acids, trans-polyisoprene, and the ubiquitous beta-sitosterol were also isolated. Structures were elucidated on the basis of spectroscopic analyses, including homo- and heteronuclear correlation NMR experiments (COSY, ROESY, HSQC and HMBC) and comparison with literature data. The antigiardial activity of compounds 2-5 was not significant.


    Directory of Open Access Journals (Sweden)

    Davide Vito Moretti


    Full Text Available Background: reduction of regional cerebral perfusion in hippocampus as well as temporo-parietal and medial temporal cortex atrophy are associated to mild cognitive impairment (MCI due to Alzheimer disease (AD. Methods: 74 adult subjects with MCI underwent clinical and neuropsychological evaluation, electroencephalogram (EEG recording and high resolution 3D magnetic resonance imaging (MRI. Among the patients, a subset of 27 subjects underwent also perfusion single-photon emission computed tomography (SPECT and hippocampal atrophy evaluation. Alpha3/alpha2 power ratio as well as cortical thickness was computed for each subject. Three MCI groups were detected according to increasing tertile values of alpha3/alpha2 power ratio and difference of cortical thickness among the groups estimated. Results: higher alpha3/alpha2 power ratio group had wider cortical thinning than other groups, mapped to the Supramarginal and Precuneus bilaterally. Subjects with higher alpha3/alpha2 frequency power ratio showed a constant trend to a lower perfusion than lower alpha3/alpha2 group. Moreover, this group correlates with both a bigger hippocampal atrophy and an increase of theta frequency power.Conclusion: Higher EEG alpha3/alpha2 power ratio was associated with temporo-parietal cortical thinning, hippocampal atrophy and reduction of regional cerebral perfusion in medial temporal cortex. In this group an increase of theta frequency power was detected inMCI subjects. The combination of higher EEG alpha3/alpha2 power ratio, cortical thickness measure and regional cerebral perfusion reveals a complex interplay between EEG cerebral rhythms, structural and functional brain modifications.

  9. The dark and the bright side of Stat3: proto-oncogene and tumor-suppressor. (United States)

    Ecker, Andrea; Simma, Olivia; Hoelbl, Andrea; Kenner, Lukas; Beug, Hartmut; Moriggl, Richard; Sexl, Veronika


    Stat transcription factors have been implicated in tumorigenesis in mice and men. Stat3 and Stat5 are considered powerful proto-oncogenes, whereas Stat1 has been demonstrated to suppress tumor formation. We demonstrate here for the first time that a constitutive active version of Stat3alpha (Stat3alphaC) may also suppress transformation. Mouse embryonic fibroblasts (MEFs) deficient for p53 can be transformed with either c-myc or with rasV12 alone. Interestingly, transformation by c-myc is efficiently suppressed by co-expression of Stat3alphaC, but Stat3alphaC does not interfere with transformation by the rasV12-oncogene. In contrast, transplantation of bone marrow cells expressing Stat3alphaC induces the formation of a highly aggressive T cell leukemia in mice. The leukemic cells invaded multiple organs including lung, heart, salivary glands, liver and kidney. Interestingly, transplanted mice developed a similar leukemia when the bone marrow cells were transduced with Stat3beta, which is also constitutively active when expressed at significant levels. Our experiments demonstrate that Stat3 has both - tumor suppressing and tumor promoting properties.

  10. Infusions of bicuculline to the ventral tegmental area attenuates sexual, exploratory, and anti-anxiety behavior of proestrous rats. (United States)

    Frye, Cheryl A; Paris, Jason J


    Actions of 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), in the midbrain ventral tegmental area (VTA) modulate sexual receptivity of female rats. Actions of 3alpha,5alpha-THP at GABAergic substrates in the VTA are known to modulate consummatory aspects of sexual behavior among rodents, such as lordosis. However, the extent to which GABA(A) receptors in the VTA are important for appetitive (exploratory, anti-anxiety, social) aspects of sexual receptivity is not well-understood. Proestrous rats were bilaterally-infused with saline or bicuculline (100 ng), a GABA(A) receptor antagonist, to the VTA or missed control sites. Rats were assessed for exploratory/anti-anxiety (open field/elevated plus maze), social (social interaction), and sexual (paced-mating) behavior. Compared to saline or missed site controls, intra-VTA bicuculline significantly reduced the number of central entries in an open field, time spent on the open arms of an elevated plus maze, frequency and intensity of lordosis, anti-aggression towards a male, pacing of sexual contacts, and 3alpha,5alpha-THP concentrations in midbrain and hippocampus. Bicuculline-infused rats also displayed less affiliation with a novel conspecific, fewer sexual solicitations, and had lower 3alpha,5alpha-THP concentrations in diencephalon and cortex, albeit these were not significant differences. Thus, actions at GABA(A) receptors in the midbrain VTA are essential for appetitive and consummatory aspects of sexual receptivity among rats.

  11. Enzymic synthesis of oligosaccharides terminating in the tumor-associated sialyl-Lewis-a determinant. (United States)

    Palcic, M M; Venot, A P; Ratcliffe, R M; Hindsgaul, O


    The isomeric sialyl-Lea-terminating pentasaccharide derivatives, alpha-Neup5Ac-(2----3)-beta-D-Galp-(1----3)-[alpha-L-Fucp-(1 ----4)]-beta- D-GlcpNAc-(1----3)-beta-D-Galp-O(CH2)8COOMe and alpha-Neup5Ac-(2----3)-beta-D-Galp-(1----3)-[alpha-L-Fucp-(1 ----4)]- beta-D-GlcpNAc-(1----6)-beta-D-Galp-O(CH2)8COOMe, have been prepared by the action in sequence of a porcine submaxillary (2----3)-alpha-sialyltransferase and a human-milk (1----3/4)-alpha-fucosyltransferase on the chemically synthesized trisaccharides beta-D-Galp-(1----3)-beta-D-GlcpNAc-(1----3)- and -(1----6)-beta-D-Galp- O(CH2)8COOMe, respectively.

  12. Differential inhibition of aflatoxin B1 oxidation by gestodene action on human liver microsomes. (United States)

    Kim, B R; Oh, H S; Kim, D H


    Human cytochrome P450 (P450) 3A is known to be involved in the formation of both aflatoxin B1-exo-8,9-epoxide (exo-epoxidation) and aflatoxin Q1 (3 alpha-hydroxylation). Gestodene, a known inactivator of P450 3A4, inhibited the formation of AFB1 metabolites in a variety of ways depending on the incubation condition. Preincubation of gestodene with human liver microsomes prior to the addition of AFB1 inhibited both exo-epoxidation and 3 alpha-hydroxylation whereas simultaneous incubation of gestodene with AFB1 only inhibited 3 alpha-hydroxylation. These results suggest that two independent substrate binding sites exist in P450 3A4, and AFB1 binds to both of the binding sites. Gestodene selectively binds to one of the binding sites leading to the formation of AFQ1, whereas it does not affect the formation of exo-epoxide via the other binding site.

  13. Two new sesquiterpene lactones from Montanoa tomentosa ssp. microcephala. (United States)

    Braca, A; Cioffi, G; Morelli, I; Venturella, F; Pizza, C; De Tommasi, N


    Two new sesquiterpene lactones: 8alpha-(4'-acetoxymethacryloyloxy)-3alpha,9beta-dihydroxy-1(10)E,4Z,11(13)-germacratrien-12,6alpha-olide (1) and 8alpha-(2'E)-(2'-acetoxymethyl-2'-butenoyloxy)-3alpha,9beta-dihydroxy-1(10)E,4Z,11(13)-germacratrien-12,6alphaolide (2), together with the known zoapatanolide A were isolated from the aerial parts of Montanoa tomentosa Cerv. in La Llave et Lex ssp. microcephala (Sch. Bip. In K. Koch) V.A. Funk (Asteraceae). The structures of all compounds were established on the basis of 1D, 2D NMR, and EIMS analysis.

  14. Triterpenos da resina de Protium heptaphyllum March (B0urseraceae: caracterização em misturas binárias

    Directory of Open Access Journals (Sweden)

    Maia Robinson Magalhães


    Full Text Available Eight triterpenes, maniladiol, breine, ursa-9(11:12-dien-3beta-ol, oleana-9(11:12-dien-3beta-ol, 3alpha-hydroxy-tirucalla-8,24-dien-21-oic acid, 3alpha-hydroxy-tirucalla-7,24-dien-21-oic, alpha and beta amyrines were isolated as binary mixtures obtained from the chloroform extract of the oil-resin of Protium heptaphyllum March. The identification of the compounds was based mainly in 13C NMR data and mass spectra. The diene and the tetracyclic acid triterpenes were not reported before in the literature as constituents of the studied resin.

  15. Triterpenos isolados de Eschweilera longipes miers (Lecythidaceae

    Directory of Open Access Journals (Sweden)

    Carvalho Mario Geraldo de


    Full Text Available The phytochemical studies of Eschweilera longipes have led to the identification of ten triterpenoids: fridelin, fridelinol, alpha-amirin, beta-amirin, 3beta-O-cinamoyl-alpha-amirin, 3beta-O-cinamoyl-beta-amirin, alpha-amirenone, beta-amirenone, 3-alpha-hidroxi-lupeol, 3-alpha-hidroxi-taraxasterol, along with b-sitosterol, stigmasterol, alpha -tocopherol and tocotrienol. The structures of these compounds were identified by analysis of IR, ¹H and 13C NMR data and comparison with values of literature.

  16. Spectroscopy of {sup 12}C within the boundary condition for three-body resonant states

    Energy Technology Data Exchange (ETDEWEB)

    Kurokawa, Chie [Meme Media Laboratory, Hokkaido University, Sapporo 060-8628 (Japan)]. E-mail:; Kato, Kiyoshi [Department of Physics, Faculty of Science, Hokkaido University, Sapporo 060-0810 (Japan)


    The 3{alpha}-cluster structure of excited states in {sup 12}C is investigated by taking into account the correct boundary condition for three-body resonant states. In this study, we adopt the Complex Scaling Method (CSM), which enables us to obtain the resonant states that can be described as square integrable states with the same boundary conditions as those of the bound states, and calculate not only resonance energies but also the total decay widths of the 3{alpha} system. We compare the calculated resonance parameters to the experimental data and also to the previous 3{alpha} model results obtained with a bound state approximation. Our results well explain the many observed levels and give an assurance for the presence of the second 2{sup +} state, which is expected by the 3{alpha} model calculations with the approximations of bound state or two-body scattering. As for the negative-parity states, it is considered that the calculated 4{sup -} state is assigned to the observed E{sub x}=13.4MeV state. Through the calculation of channel amplitudes, the obtained third 0{sup +} state is found to have a s-wave dominant and a more dilute structure compared to the second 0{sup +} state.

  17. A simple relation for the concentration dependence of osmotic pressure and depletion thickness in polymer solutions

    NARCIS (Netherlands)

    Fleer, G.J.; Skvortsov, A.M.; Tuinier, R.


    We propose simple expressions II/IIo = 1 + and (omega/omega(ex))(3 alpha-1) and (delta(0)/delta)(2) = 1 + (omega/omega(ex))(2 alpha) for the osmotic pressure II and the depletion thickness 6 as a function of the polymer concentration omega. Here, IIo and delta 0 correspond to the dilute limit, and o

  18. New sesquiterpenoids from the jordanian medicinal plant inula viscosa (United States)

    Abu Zarga MH; Hamed; Sabri; Voelter; Zeller


    Four new and 14 known compounds have been isolated from Inula viscosa of Jordanian origin. The new isolates are 11(13)-eudesmen-12-oic acids, 3beta-hydroxyilicic acid (1), 3alpha-hydroxy-epi-ilicic acid (2), 2alpha-hydroxyilicic acid (3) and 9beta-hydroxy-2-oxoisocostic acid (4).

  19. Comparative analysis of fibrillar and basement membrane collagen expression in embryos of the sea urchin, Strongylocentrotus purpuratus. (United States)

    Suzuki, H R; Reiter, R S; D'Alessio, M; Di Liberto, M; Ramirez, F; Exposito, J Y; Gambino, R; Solursh, M


    The time of appearance and location of three distinct collagen gene transcripts termed 1 alpha, 2 alpha, and 3 alpha, were monitored in the developing S. purpuratus embryo by in situ hybridization. The 1 alpha and 2 alpha transcripts of fibrillar collagens were detected simultaneously in the primary (PMC) and secondary (SMC) mesenchyme cells of the late gastrula stage and subsequently expressed in the spicules and gut associated cells of the pluteus stage. The 3 alpha transcripts of the basement membrane collagen appeared earlier than 1 alpha and 2 alpha, and were first detected in the presumptive PMC at the vegetal plate of the late blastula stage. The PMC exhibited high expression of 3 alpha at the mesenchyme blastula stage, but during gastrulation the level of expression was reduced differentially among the PMC. In the late gastrula and pluteus stages, both PMC and SMC expressed 3 alpha mRNA, and thus at these stages all three collagen genes displayed an identical expression pattern by coincidence. This study thus provides the first survey of onset and localization of multiple collagen transcripts in a single sea urchin species.

  20. New hopane triterpene from Eleocharis sellowiana (Cyperaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz, Ana Lucia T.G. [Universidade Estadual de Campinas, SP (Brazil). Centro Pluridisciplinar de Pesquisas Quimicas, Biologicas e Agrarias]. E-mail:; Magalhaes, Aderbal F.; Magalhaes, Eva G. [Universidade Estadual de Campinas, SP (Brazil). Inst. de Quimica; Faria, Aparecida D.; Amaral, Maria do Carmo E. [Universidade Estadual de Campinas, SP (Brazil). Inst. de Biologia


    A new triterpene named 3{alpha}-hydroxy-13{alpha},17{alpha},21{beta}-hopan-15,19-dione and E-phytylhexadecanoate were isolated from the hexanic extract of Eleocharis sellowiana. NMR and MS experiments determined the molecular structures. (author)

  1. Functional characterisation of a putative rhamnogalacturonan II specific xylosyltransferase

    DEFF Research Database (Denmark)

    Madsen, Jack Egelund; Damager, Iben; Faber, Kirsten;


    An Arabidopsis thaliana gene, At1g56550, was expressed in Pichia pastoris and the recombinant protein was shown to catalyse transfer of d-xylose from UDP-alpha-d-xylose onto methyl alpha-l-fucoside. The product formed was shown by 1D and 2D (1)H NMR spectroscopy to be Me alpha-d-Xyl-(1,3)-alpha...

  2. Identification of the molecular switch that regulates access of 5alpha-DHT to the androgen receptor. (United States)

    Penning, Trevor M; Bauman, David R; Jin, Yi; Rizner, Tea Lanisik


    Pairs of hydroxysteroid dehydrogenases (HSDs) govern ligand access to steroid receptors in target tissues and act as molecular switches. By acting as reductases or oxidases, HSDs convert potent ligands into their cognate inactive metabolites or vice versa. This pre-receptor regulation of steroid hormone action may have profound effects on hormonal response. We have identified the HSDs responsible for regulating ligand access to the androgen receptor (AR) in human prostate. Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2) acts solely as a reductase to convert 5alpha-dihydrotestosterone (DHT), a potent ligand for the AR (K(d)=10(-11)M for the AR), to the inactive androgen 3alpha-androstanediol (K(d)=10(-6)M for the AR); while RoDH like 3alpha-HSD (a short-chain dehydrogenase/reductase (SDR)) acts solely as an oxidase to convert 3alpha-androstanediol back to 5alpha-DHT. Our studies suggest that aldo-keto reductase (AKRs) and SDRs function as reductases and oxidases, respectively, to control ligand access to nuclear receptors.

  3. Seven-Disk Manifold, alpha-attractors and B-modes

    CERN Document Server

    Ferrara, Sergio


    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.

  4. Environ: E00429 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available E00429 Physalis alkekengi root and rhizoma Physalitis rhizoma et radix Crude drug P...hysalin A, B, C, 3-alpha-tigloyloxytropane Physalis alkekengi [TAX:33120] Solanaceae (nightshade family) Physalis root and rhizoma (dried) Crude drugs [BR:br08305] Dicot plants: asterids Solanaceae (nightshade family) E00429 Physalis alkekengi root and rhizoma ...

  5. Dynamics of solitons and quasisolitons of the cubic third-order nonlinear Schrödinger equation

    DEFF Research Database (Denmark)

    Karpman, V.I.; Juul Rasmussen, J.; Shagalov, A.G.


    The dynamics of soliton and quasisoliton solutions of the cubic third-order nonlinear Schrodinger equation is studied. Regular solitons exist due to a balance between the nonlinear terms and (linear) third-order dispersion; they are not important at small alpha (3) (alpha (3) is the coefficient...

  6. A simple relation for the concentration dependence of osmotic pressure and depletion thickness in polymer solutions

    NARCIS (Netherlands)

    Fleer, G.J.; Skvortsov, A.M.; Tuinier, R.


    We propose simple expressions II/IIo = 1 + and (omega/omega(ex))(3 alpha-1) and (delta(0)/delta)(2) = 1 + (omega/omega(ex))(2 alpha) for the osmotic pressure II and the depletion thickness 6 as a function of the polymer concentration omega. Here, IIo and delta 0 correspond to the dilute limit, and

  7. Alpha macroglobulins and the low-density-lipoprotein-related protein alpha-2-macroglobulin receptor in experimental renal fibrosis

    NARCIS (Netherlands)

    van Goor, H; Diamond, [No Value; Ding, GH; Kaysen, GA


    In this study, we evaluated the location of non-specific proteinase inhibitors and their receptor in experimental glomerular and interstitial fibrosis. The alpha macroglobulins alpha-2-macroglobulin (alpha 2M) and alpha-1-inhibitor 3 (alpha 1I3) are proteinase inhibitors, including metalloproteinase

  8. Modification of behavioral effects of drugs in mice by neuroactive steroids

    NARCIS (Netherlands)

    Ungard, JT; Beekman, M; Gasior, M; Carter, RB; Dijkstra, D; Witkin, JM


    Rationale: Neuroactive steroids represent a novel class of potential therapeutic agents (epilepsy, anxiety, migraine, drug dependence) thought to act through positive allosteric modulation of the GABA(A) receptor A synthetically derived neuroactive steroid, ganaxolone (3 alpha-hydroxy-3 beta-methyl-

  9. Ignition access in a D-{sup 3}He helical reactor

    Energy Technology Data Exchange (ETDEWEB)

    Mitarai, Osamu [Kyushu Tokai Univ., Kumamoto (Japan)


    Ignition access in a D-{sup 3}He helical reactor is studied based on 0-dimensional particle and power balance equations for deuterium, tritium, helium-3, alpha ash, proton ash, electron density and temperature. The calculations are based on the following experimental facts observed in LHD. (author)

  10. Revised structure of a homonojirimycin isomer from Aglaonema treubii: first example of a naturally occurring alpha-homoallonojirimycin. (United States)

    Martin, O R; Compain, P; Kizu, H; Asano, N


    The structure of a homonojirimycin isomer isolated from Aglaonema treublii and originally proposed as alpha-3,4-di-epi-homonojirimycin was revised to alpha-4-epi-homonojirimycin 3 ("alpha-homoallonojirimycin") on the basis of NMR analysis and synthetic studies. Its activity as a glycosidase inhibitor is compared to that of other homonojirimycin isomers.

  11. The Effects of Pooling the Interaction and Within Components on the Alpha and Power for Main Effects Tests. (United States)

    Pohlmann, John T.

    The Monte Carlo method was used, and the factors considered were (1) level of main effects in the population; (2) level of interaction effects in the population; (3) alpha level used in determining whether to pool; and (4) number of degrees of freedom. The results indicated that when the ratio degrees of freedom (axb)/degrees of freedom (within)…

  12. A simple relation for the concentration dependence of osmotic pressure and depletion thickness in polymer solutions

    NARCIS (Netherlands)

    Fleer, G.J.; Skvortsov, A.M.; Tuinier, R.


    We propose simple expressions II/IIo = 1 + and (omega/omega(ex))(3 alpha-1) and (delta(0)/delta)(2) = 1 + (omega/omega(ex))(2 alpha) for the osmotic pressure II and the depletion thickness 6 as a function of the polymer concentration omega. Here, IIo and delta 0 correspond to the dilute limit, and o

  13. Mass-luminosity relation and pulsational properties of Wolf-Rayet stars

    CERN Document Server

    Fadeyev, Yu A


    Evolution of Population I stars with initial masses from 70M_\\odot to 130M_\\odot is considered under various assumptions on the mass loss rate \\dot M. The mass-luminosity relation of W-R stars is shown to be most sensitive to the mass loss rate during the helium burning phase \\dot M_{3\\alpha}. Together with the mass-luminosity relation obtained for all evolutionary sequences several more exact relations are determined for the constant ratio f_{3\\alpha}=\\dot M/\\dot M_{3\\alpha} with 0.5 \\le f_{3\\alpha} \\le 3. Evolutionary models of W-R stars were used as initial conditions in hydrodynamic computations of radial nonlinear stellar oscillations. The oscillation amplitude is larger in W-R stars with smaller initial mass or with lower mass loss rate due to higher surface abundances of carbon and oxygen. In the evolving W-R star the oscillation amplitude decreases with decreasing stellar mass M and for M 10M_\\odot are shown to be also excited by the kappa-mechanism but the instability driving zone is at the bottom o...

  14. Microbial and chemical transformations of some 12,13-epoxytrichothec-9,10-enes. (United States)

    Claridge, C A; Schmitz, H


    Resting cells of Streptomyces griseus, Mucor mucedo, and a growing culture of Acinetobacter calcoaceticus when mixed with compounds related to 12,13-epoxytrichothec-9-ene-4beta,15-diacetoxy-3alpha-ol(anguidine) produced a series of derivatives that were either partially hydrolyzed or selectively acylated. These derivatives showed marked differences in activities as assayed by antifungal and tissue culture cytotoxicity tests.

  15. Tibolone and its metabolites acutely relax rabbit coronary arteries in vitro

    DEFF Research Database (Denmark)

    Lund, Claus Otto; Nilas, Lisbeth; Pedersen, Susan Helene


    under curve (AUC). RESULTS: Tibolone and its metabolites induced a concentration-dependent vasodilatation comparable to that of 17 beta-estradiol with the rank of potency: 3 beta-OH-tibolone approximately = to tibolone>3 alpha-OH-tibolone>Delta 4-isomer (ANOVA). l-NAME partly inhibited the relaxation...

  16. Functional aspects of dexamethasone upregulated nicotinic acetylcholine receptors in C2C12 myotubes

    NARCIS (Netherlands)

    Maestrone, E; Lagostena, L; Henning, RH; DenHertog, A; Nobile, M


    Three days of treatment with the glucocorticoid dexamethasone (1 nM-mu M) induced a concentration-dependent up-regulation of muscle nicotinic acetylcholine receptor (nAChR) in C2C12 mouse myotubes (EC(50)=10+/-7.3 nM), as assessed by [H-3]alpha-BuTx binding. The maximum increase in binding amounted

  17. News on C-12 from beta-decay studies

    NARCIS (Netherlands)

    Fynbo, HOU; Diget, CA; Prezado, Y; Aysto, J; Bergmann, UC; Cederkall, J; Dendooven, P; Fraile, LM; Franchoo, S; Fulton, BR; Huang, W; Huikari, J; Jeppesen, H; Jokinen, A; Jonson, B; Jones, P; Koster, U; Meister, M; Nilsson, T; Nyman, G; Borge, MJG; Riisager, K; Rinta-Antila, S; Vogelius, IS; Tengblad, O; Turrion, M; Wang, Y; Weissman, L; Wilhelmsen, K


    We discuss the importance of the spectroscopic properties of the resonances of C-12 just above the 3alpha-threshold, and review the existing experimental information of this region with emphasis on 0(+) and 2(+) states. A new experimental approach for studying the beta-decays of B-12 and N-12 is pre

  18. A locus on chromosome 15q for a dominantly inherited nemaline myopathy with core-like lesions.

    NARCIS (Netherlands)

    Gommans, I.M.P.; Davis, M.; Saar, K.; Lammens, M.M.Y.; Mastaglia, F.; Lamont, P.; Duijnhoven, G.C.F. van; Laak, H.J. ter; Reis, A.; Vogels, O.J.M.; Laing, N.G.; Engelen, B.G.M. van; Kremer, J.M.J.


    Nemaline myopathy is a congenital neuromuscular disorder characterized by muscle weakness and the presence of nemaline rods. Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1). In

  19. R-matrix analysis of the beta decays of N-12 and B-12

    NARCIS (Netherlands)

    Hyldegaard, S.; Alcorta, M.; Bastin, B.; Borge, M. J. G.; Boutami, R.; Brandenburg, S.; Buscher, J.; Dendooven, P.; Diget, C. Aa; Van Duppen, P.; Eronen, T.; Fox, S. P.; Fraile, L. M.; Fulton, B. R.; Fynbo, H. O. U.; Huikari, J.; Huyse, M.; Jeppesen, H. B.; Jokinen, A. S.; Jonson, B.; Jungmann, K.; Kankainen, A.; Kirsebom, O. S.; Madurga, M.; Moore, I.; Nieminen, A.; Nilsson, T.; Nyman, G.; Onderwater, G. J. G.; Penttila, H.; Perajarvi, K.; Raabe, R.; Riisager, K.; Rinta-Antila, S.; Rogachevskiy, A.; Saastamoinen, A.; Sohani, M.; Tengblad, O.; Traykov, E.; Wang, Y.; Wilhelmsen, K.; Wilschut, H. W.; Aysto, J.

    The beta decays of N-12 and B-12 have been studied at KVI and JYFL to resolve the composition of the broad and interfering 0(+) and 2(+) strengths in the triple-alpha continuum. For the first time a complete treatment of 3 alpha decay is presented including all major breakup channels. A multilevel,

  20. Topography and function of androgen-metabolizing enzymes in the central nervous system. (United States)

    Tsuruo, Yoshihiro


    The present review describes concisely the topography and function of the three androgen-metabolizing enzymes, namely aromatase, 5alpha-reductase and 3alpha-hydroxysteroid dehydrogenase, in the central nervous system (CNS). Aromatase, estrogen synthetase, is the key enzyme for converting androgens to estrogens. Aromatase is indispensable for the sexual differentiation of the brain and the enzyme activity and expression of aromatase are high during the critical period of neural development, which extends from the late embryonal to the early neonatal period in rodents. Aromatase is expressed in neurons within specific hypothalamic and limbic regions. The locations of aromatase-immunoreactive neurons are divided into three groups according to the period of enzyme expression. Steroid 5alpha-reductase converts a number of steroids with a C3 ketone group and a C4-C5 double bond (delta4; androgens, progestins and glucocorticoids) to their 5alpha-reduced metabolites. Two isoforms of 5alpha-reductase are found and type 1 is predominant in neural tissues. The enzyme activity of 5alpha-reductase is found widely in the CNS and is high in white matter regions. The enzyme expression of 5alpha-reductase peaks during the late embryonic period. 3alpha-Hydroxysteroid dehydrogenase is the oxidoreductase that interconverts 3-ketosteroids to 3alpha-hydroxysteroids. Four isozymes have been found in humans and only one type has been found in rats. The enzyme converts 5alpha-reduced steroids (e.g. 5alpha-dihydroprogesterone) to tetrahydrosteroids (e.g. 3alpha,5alpha-tetrahydroprogesterone). The latter steroid is a potent stimulator of the GABA(A) receptor. The activity of 3alpha-hydroxysteroid dehydrogenase is high during the first 1-2 postnatal weeks, decreases with development and this enzyme is highly expressed in astrocytes.

  1. Quaternary organization of the goodpasture autoantigen, the alpha 3(IV) collagen chain. Sequestration of two cryptic autoepitopes by intrapromoter interactions with the alpha4 and alpha5 NC1 domains. (United States)

    Borza, Dorin-Bogdan; Bondar, Olga; Todd, Parvin; Sundaramoorthy, Munirathinam; Sado, Yoshikazu; Ninomiya, Yoshifumi; Hudson, Billy G


    Goodpasture's (GP) disease is caused by autoantibodies that target the alpha3(IV) collagen chain in the glomerular basement membrane (GBM). Goodpasture autoantibodies bind two conformational epitopes (E(A) and E(B)) located within the non-collagenous (NC1) domain of this chain, which are sequestered within the NC1 hexamer of the type IV collagen network containing the alpha3(IV), alpha4(IV), and alpha5(IV) chains. In this study, the quaternary organization of these chains and the molecular basis for the sequestration of the epitopes were investigated. This was accomplished by physicochemical and immunochemical characterization of the NC1 hexamers using chain-specific antibodies. The hexamers were found to have a molecular composition of (alpha3)(2)(alpha4)(2)(alpha5)(2) and to contain cross-linked alpha3-alpha5 heterodimers and alpha4-alpha4 homodimers. Together with association studies of individual NC1 domains, these findings indicate that the alpha3, alpha4, and alpha5 chains occur together in the same triple-helical protomer. In the GBM, this protomer dimerizes through NC1-NC1 domain interactions such that the alpha3, alpha4, and alpha5 chains of one protomer connect with the alpha5, alpha4, and alpha3 chains of the opposite protomer, respectively. The immunodominant Goodpasture autoepitope, located within the E(A) region, is sequestered within the alpha3alpha4alpha5 protomer near the triple-helical junction, at the interface between the alpha3NC1 and alpha5NC1 domains, whereas the E(B) epitope is sequestered at the interface between the alpha3NC1 and alpha4NC1 domains. The results also reveal the network distribution of the six chains of collagen IV in the renal glomerulus and provide a molecular explanation for the absence of the alpha3, alpha4, alpha5, and alpha6 chains in Alport syndrome.

  2. [Chemical constituents of Rhododendron seniavinii]. (United States)

    Wang, Qing-Qing; Zhang, Ying; Ye, Wen-Cai; Zhou, Guang-Xiong


    To study the chemical constituents of Rhododendron seniavinii. Compounds were isolated from the aqueous extract of the leaves of R. seniavinii by using Sephadex LH-20, ODS open column chromatography and other means. Their structures were elucidated according to spectral data and physiochemical properties. Thirteen compounds were isolated from R. seniavinii and identified as 5-methoxydehydroconiferyl alcohol (1), dehydroconiferyl alcohol (2), (-)-syringaresinol (3), (-)-lyoniresinol (4), (+)-lyoniresinol 3alpha-O-beta-D-glucopyranoside (5), (-)-lyoniresinol 3alpha-O-beta-D-glucopyranoside (6), 3,4,5-trimethoxyphenyl-1-O-beta-D-glucopyranoside (7), nikoenoside (8), 3,5,7-trihydroxychromone-3-0-alpha-L-rhamnopyranoside (9), 3,4,5-trimethoxyphenol (10), scopoletin (11), scopolin (12) and quercitrin (13). Compounds 1-12 were obtained from this plant for the first time.

  3. Triterpenes and new saponins from Ilex chamaedryfolia: chemotaxonomic tool to Ilex species differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Lencina, Claiton L.; Cardoso, Mariana C. de; Zancanaro, Ivomar; Gosmann, Grace, E-mail: grace.gosmann@ufrgs.b [Universidade Federal do Rio Grande do Sul (FF/UFRGS), Porto Alegre, RS (Brazil). Faculdade de Farmacia; Pires, Viviane S.; Sonnet, Pascal; Guillaume, Dominique [UMR-CNRS, Universite de Picardie Jules Verne, Amiens (France). Faculte de Pharmacie. Lab. des Glucides; Schenkel, Eloir P. [Universidade Federal de Santa Catarina (CCS/UFSC), Florianopolis, SC (Brazil). Centro de Ciencias da Saude


    Three saponins were isolated from leaves of Ilex chamaedryfolia. Their structures were established by spectroscopic and mass spectrometry data as the new saponin 3beta-O-beta-D-glucopyranosyl-(1-3)-alpha-L-arabinopyranosyl-20(S)-19alpha- hydroxyurs-12-en-28-oic acid 28-O-beta-D-glucopyranosyl-(1-3)-beta-D-glucopyranosyl ester, the new saponin 3beta-O-beta-D-glucopyranosyl-(1-3)-alpha-L-arabinopyranosyl-20(S)-19alpha- hydroxyurs-12-en-28-oic acid 28-O-beta-D-glucopyranosyl ester and the known saponin 3beta-O-beta-D-glucuronopyranosyl-20(R)-19alpha-hydroxyurs-12-en-28-oic acid 28-O-beta-D-glucopyranosyl ester. Ursolic acid and {alpha}-amyrin were also isolated. (author)

  4. 5alpha-Reduced androgens block estradiol-BSA-stimulated release of oxytocin. (United States)

    Caldwell, Jack D; Song, Yan; Englöf, Ila; Höfle, Simone; Key, Mary; Morris, Mariana


    In this study we test the postulate that estradiol conjugated to bovine serum albumin (E-BSA) acts via receptors for the steroid-binding protein sex hormone binding globulin (SHBG) by attempting to block E-BSA-stimulated release of oxytocin with two antagonists of SHBG receptor actions: the 5alpha-reduced androgens dihydrotestosterone (DHT) and 3alpha-diol. Simultaneous superfusion with either DHT or 3alpha-diol significantly blocked E-BSA-stimulated release of oxytocin. We also found that a wide range of free 17beta-estradiol was unable to stimulate oxytocin release, suggesting that E-BSA stimulates receptors other than those for free estradiol to release oxytocin, perhaps SHBG receptors.

  5. Chemical constituents of Solanum buddleifolium Sendtn; Constituintes quimicos de Solanum buddleifolium Sendtn

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, Francisco das Chagas L.; Torres, Maria da conceicao M.; Silveira, Edilberto R.; Pessoa, Otilia Deusdenia L., E-mail: [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Centro de Ciencias. Dept. de Quimica Organica e Inorganica; Braz-Filho, Raimundo [Universidade Estadual do Norte Fluminense, Campos, RJ (Brazil). Dept. de Quimica; Guedes, Maria Lenise da Silva [Universidade Federal da Bahia (UFBA), Ondina, BA (Brazil). Inst. de Biologia. Dept. de Botanica


    The chemical investigation of the stem EtOH extract of S. buddleifolium resulted in the isolation of terpenoids, amides, lignans and a steroidal alkaloid. Based on HRMS, IR and {sup 1}H and {sup 13}C NMR data analysis, the structures of the isolated compounds were identified as: 13-hydroxysolavetivone, betulinic acid, N-trans-caffeoyltyramine, N-trans-feruloyldopamine, N-trans-p-cumaroyltyramine, N-trans-feruloyltyramine, N-trans-feruloyl- 3'-O-methoxydopamine, alangilignoside C, isolariciresinol, polistachiol, (+)-(8R,7'S,8'S)-3{alpha}-O-({beta}-D-glucopiranosyl)-lioniresinol, (-)-(8S,7'R,8'R)-3{alpha}-O-({beta}-D-glucopiranosyl)-lioniresinol and solamargine. The occurrence of terpenoids and amides is common in Solanum, unlike lignans which are rare. The isolated lignans described in this work are reported for the first time in the genus Solanum. (author)

  6. Low birth weight and zygosity status is associated with defective muscle glycogen and glycogen synthase regulation in elderly twins

    DEFF Research Database (Denmark)

    Poulsen, Pernille; Wojtaszewski, Jørgen; Richter, Erik;


    AND METHODS: We measured the activities of glycogen synthase (GS), GS kinase (GSK)3 alpha, GS phosphorylation, and glycogen levels in muscle biopsies obtained from 184 young and elderly twins before and after a euglycemic-hyperinsulinemic clamp. RESULTS: Elderly monozygotic twins had significantly lower...... fractional GS activity amidst higher glycogen and GS protein levels compared with dizygotic twins. In addition, we demonstrated strong nongenetic associations between birth weight and defect muscle glycogen metabolism in elderly--but not in younger--twins. Thus, for every 100 g increase in birth weight...... within pairs, GS fractional activity, GS protein level, and glycogen content was increased by 4.2, 8.7, and 4.5%, respectively, in elderly twins. Similarly, for every 100 g increase in birth weight, GSK3 alpha activity and GS phosphorylation at the sites 2, 2+2a, and 3a+3b were decreased by 3.1, 9.0, 10...

  7. A new antifungal phenolic glycoside derivative, iridoids and lignans from Alibertia sessilis (vell.) K. Schum. (Rubiaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Viviane C. da; Bolzani, Vanderlan da S.; Lopes, Marcia N. [UNESP, Araraquara, SP (Brazil). Inst. de Quimica. Dept. de Quimica Organica]. E-mail:; Young, Maria C.M. [Instituto de Botanica, Sao Paulo, SP (Brazil). Secao de Fisiologia e Bioquimica de Plantas


    A new antifungal phenolic glycoside, 3,4,5-trimethoxyphenyl-1-O-{beta}-D-(5-O-syringoyl)apiofuranosyl-(1 {yields} 6)-{beta}-D-glucopyranoside (1), together with four known iridoids, geniposidic acid (2), geniposide (3), 6{alpha}-hydroxygeniposide (4) and 6{beta}-hydroxygeniposide (5); two lignans, (+)-lyoniresinol-3{alpha}-O-{beta}-D-glucopyranoside (6), (-)-lyoniresinol-3{alpha}-O-{beta}-D-glucopyranoside (7); and two phenolic acids, chlorogenic (8) and salicylic acids (9) and D-manitol (10), were isolated from the ethanolic extract of the stems of Alibertia sessilis. Structures of 1 and of the known compounds were determined by spectroscopic analysis. All compounds isolated were evaluated for their antifungal activities against two phytopathogenic fungi strains Cladosporium cladosporioides and C. sphaerospermum by direct bioautography. (author)

  8. Chemical constituents of Gustavia Augusta L. (Lecythidaceae); Constituintes quimicos de Gustavia Augusta L. (Lecythidaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Afonso Duarte Leao de; Rocha, Arnaldo F. Imbiriba da; Pinheiro, Maria Lucia Belem; Andrade, Carlos Humberto de S.; Galotta, Ana Lucia de A. Queiroz; Santos, Maria do Perpetuo Socorro S. dos [Amazonas Univ., Manaus, AM (Brazil). Dept. de Quimica]. E-mail:


    The Gustavia augusta is used in the folk medicine against leishmaniasis and showed anti-inflammatory action. The phyto chemical studies of the plant stem bark have led to the isolation of (22E)-stigmasta-7,22-dien-3{beta}-ol, 24{alpha}(S)-ethyl-5{alpha}-colesta-7, trans-22-dien-3-one, D-friedoolean-14-en-3{beta}-ol, D-friedoolean-14-en-3-one and D-friedoolean-14-en-3{alpha}-ol along with stigmasterol, {alpha}-amyrin, {beta}-amyrin, lupeol, 3{alpha}-hydroxy-lupeol and betulinic acid. The structures of these compounds were identified by IR, GC/M S, {sup 1} H and {sup 1} {sup 3} C NMR spectral analysis and comparison with literature data. (author)

  9. Logarithms of alpha in QED bound states from the renormalization group (United States)

    Manohar; Stewart


    The velocity renormalization group is used to determine lnalpha contributions to QED bound state energies. The leading-order anomalous dimension for the potential gives the alpha(5)lnalpha Lamb shift. The next-to-leading-order anomalous dimension determines the alpha(6)lnalpha, alpha(7)ln (2)alpha, and alpha(8)ln (3)alpha corrections to the energy. These are used to obtain the alpha(8)ln (3)alpha Lamb shift and alpha(7)ln (2)alpha hyperfine splitting for hydrogen, muonium, and positronium, as well as the alpha(2)lnalpha and alpha(3)ln (2)alpha corrections to the ortho- and parapositronium lifetimes. This shows for the first time that these logarithms can be computed from the renormalization group.

  10. Antiviral sulfated steroids from the ophiuroid Ophioplocus januarii. (United States)

    Roccatagliata, A J; Maier, M S; Seldes, A M; Pujol, C A; Damonte, E B


    One new and three known sulfated steroidal polyols have been isolated from the ophiuroid Ophioplocus januarii, collected at San Antonio Oeste, Río Negro, Argentina. The four compounds possess 4 alpha,11 beta-dihydroxy-3 alpha,21-disulfoxy substituents and the A/B cis ring junction but differ in the side chain. The new compound has been characterized as (22E)-5 beta-24-norcholest-22-ene-3 alpha,4 alpha,11 beta,21-tetrol 3,21-disulfate (4). The structures of the four compounds were determined from spectral data and comparison with those of related steroidal polyols. The four compounds were tested for their inhibitory effect on the replication of one DNA and three RNA viruses. Compounds 2 and 4 were active against respiratory syncytial and polio viruses, and compound 3 inhibited Junin virus, responsible for Argentine hemorrhagic fever.

  11. Chemical constituents from Aspidosperma illustre (Apocynaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Barbosa, Lara F.; Mathias, Leda; Braz-Filho, Raimundo; Vieira, Ivo J. Curcino, E-mail: curcino@uenf.b [Universidade Estadual do Norte Fluminense Darcy Ribeiro (LCQ/UENF), Campos dos Goytacazes, RJ (Brazil). Lab. de Ciencias Quimicas


    A new natural product oleanane-type triterpene, olean-12-ene-11{alpha}-methoxy-3{beta}-acetate (10) was isolated from Aspidosperma illustre, together with {beta}-amyrin (3), lupeol (4), {beta}-amyrin acetate (5), lupeol acetate (6), olean-12-ene-28-hydroxy-3{alpha}-tetradecanoate (7), olean-12-ene-28-carboxy-3{alpha}-hexadecanoate (8), ursolic acid (9) triterpenes, and two monoterpenic indole alkaloids, b-yoimbine (1) and 1,2-dehydroaspidospermidine (2). These compounds were characterized on their spectral data basis, mainly one- ({sup 1}H, {sup 13}C, APT) and two-dimensional ({sup 1}H-{sup 1}H-COSY, {sup 1}H-{sup 1}HNOESY, HMQC and HMBC) NMR, and mass spectra, involving also comparison with data from the literature. (author)

  12. Indolopyridoquinazoline alkaloids from Esenbeckia grandiflora mart. (Rutaceae); Alkaloides {beta}-indolopiridoquinazolinicos de Esenbeckia grandiflora mart. (Rutaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Januario, Ana Helena; Vieira, Paulo Cezar; Silva, Maria Fatima das Gracas Fernandes da; Fernandes, Joao Batista [Universidade Federal de Sao Carlos (UFSCAR), SP (Brazil). Dept. de Quimica], e-mail:; Silva, Jorge Jose de Brito; Conserva, Lucia Maria [Universidade Federal de Alagoas (UFAL), Maceio, AL (Brazil). Inst. de Quimica e Biotecnologia


    The chemical composition of two specimens of Esenbeckia grandiflora, collected in the south and northeast regions of Brazil, was investigated. In this study, three b-indolopyridoquinazoline alkaloids from the leaves (rutaecarpine, 1-hydroxyrutaecarpine) and roots (euxylophoricine D) were isolated for the first time in this genus. In addition, the triterpenes {alpha}-amyrin, {beta}-amyrin, {alpha}-amyrenonol, {beta}-amyrenonol, 3{alpha}-hydroxy-ursan-12-one, and 3{alpha}-hydroxy-12,13-epoxy-oleanane, the coumarins auraptene, umbelliferone, pimpinelin, and xanthotoxin, the furoquinoline alkaloids delbine and kokusaginine, and the phytosteroids sitosterol, stigmasterol, campesterol and 3{beta}-O-{beta}-D-glucopyranosylsitosterol were also isolated from the leaves, twigs, roots and stems of this species. Structures of these compounds were established by spectral analysis. (author)

  13. Triterpene benzoates from the bark of Picramnia teapensis (Simaroubaceae

    Directory of Open Access Journals (Sweden)

    Rodríguez-Gamboa Tatiana


    Full Text Available Two new benzoic acid esters of triterpene alcohols [lup-20(29-en-28-oic acid 3alpha,7beta-dibenzoate and 3alpha-hydroxy-lup-20(29-en-28-oic acid 7beta-benzoate] were isolated from the stem bark of Picramnia teapensis Tul. The structures of these compounds were established on the basis of spectral analyses. Other known compounds, beta-sitosterol, estigmasterol, lupeol and epilupeol, were identified in mixture by GC-MS. The triterpene esters have not shown in-vitro inhibitory effect on the growth of Leucoagaricus gongylophorus (Fisher, referred also as Leucocoprinus gongylophorus (Heim, syn Rozites gongylophora (Möller, the symbiotic fungus cultivated by the leaf-cutting ant Atta sexdens L.

  14. Synthesis of new derivatives from 1,2{alpha},4{alpha},5-tetramethyl-8-oxabicyclo[3.2.1]oct-6-en-3-one; Sintese de novos herbicidas derivados do 1,2{alpha},4{alpha},5-tetrametil-8-oxabiciclo[3.2.1]oct-6-en-3-ona

    Energy Technology Data Exchange (ETDEWEB)

    Barbosa, Luiz Claudio de Almeida; Maltha, Celia Regina Alvares; Demuner, Antonio Jacinto; Filomeno, Claudinei Andrade [Vicosa Univ., MG (Brazil). Dept. de Quimica]. E-mail:; Silva, Antonio Alberto da [Vicosa Univ., MG (Brazil). Dept. de Fitotecnia


    In this paper we report the synthesis of biologically active compounds through a [3+4] cycloaddition reaction to produce the main frame structure, followed by several conventional transformations. The 1,2{alpha},4{alpha},5-tetramethyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (11) obtained from a [3+4] cycloaddition reaction was converted into 1,2{alpha},4{alpha},5-tetramethyl-6,7-exo-isopropylidenedioxi-8 -oxabicyclo[3.2.1]octan-3-one (13) in 46% yield. This was further converted into the alcohols 1,2{alpha},4{alpha},5-tetramethyl-6,7-exo-isopropylidenedioxi-8-oxabicyclo[3.2= .1]octan-3{alpha}-ol (14), 1,2{alpha},4{alpha},5-tetramethyl-6,7-exo-isopropylidenedioxi-8 -oxabicyclo[3.2.1]octan-3{beta}-ol (15), 1,2{alpha},4{alpha},5-tetramethyl-3-butyl-6,7-exo-isopropylidenedioxi-8-oxabic= yclo[3.2.1]octan-3 {alpha}-ol (17), 1,2{alpha},4{alpha},5-tetramethyl-3-hexyl-6,7-exo-isopropylidenedioxi-8-oxabic= yclo[3.2.1]octan-3 {alpha}-ol (18) and 1,2{alpha},4{alpha},5-tetramethyl-3-decyl-6,7-exo-isopropylidenedioxi-8-oxabic= yclo[3.2.1]octan-3 {alpha}-ol (19). Dehydration of 17, 18 and 19 with thionyl chloride in pyridine resulted in the alkenes 20, 21 and 22 in ca. 82% - 89% yields from starting alcohols. The herbicidal activity of the compounds synthesized was evaluated at a concentration of 100 {mu}g g{sup -1}. The most active compound was 21 causing 42,7% inhibition against Cucumis sativus L. (author)

  15. HIF3A DNA Methylation Is Associated with Childhood Obesity and ALT


    Shuo Wang; Jieyun Song; Yide Yang; Yining Zhang; Haijun Wang; Jun Ma


    Gene polymorphisms associated so far with body mass index (BMI) can explain only 1.18-1.45% of observed variation in BMI. Recent studies suggest that epigenetic modifications, especially DNA methylation, could contribute to explain part of the missing heritability, and two epigenetic genome-wide analysis studies (EWAS) have reported that Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) methylation was associated with BMI or BMI change. We therefore assessed whether the HIF3A methylation is as...

  16. The 3'-terminal exon of the family of steroid and phenol sulfotransferase genes is spliced at the N-terminal glycine of the universally conserved GXXGXXK motif that forms the sulfonate donor binding site.


    Chiba, H; Komatsu, K.; Lee, Y.C.; Tomizuka, T; Strott, C A


    The guinea pig estrogen sulfotransferase gene has been cloned and compared to three other cloned steroid and phenol sulfotransferase genes (human estrogen sulfotransferase, human phenol sulfotransferase, and guinea pig 3 alpha-hydroxysteroid sulfotransferase). The four sulfotransferase genes demonstrate a common outstanding feature: the splice sites for their 3'-terminal exons are identically located. That is, the 3'-terminal exon splice sites involve a glycine that constitutes the N-terminal...

  17. Expression of two different sulfated fucans by females of Lytechinus variegatus may regulate the seasonal variation in the fertilization of the sea urchin. (United States)

    Cinelli, Leonardo P; Castro, Michelle O; Santos, Livia L; Garcia, Clarice R; Vilela-Silva, Ana-Cristina E S; Mourão, Paulo A S


    The egg jellies of sea urchins contain sulfated polysaccharides with unusual structures, composed of linear chains of l-fucose or l-galactose with well-defined repetitive units. The specific pattern of sulfation and the position of the glycosidic bond vary among sulfated polysaccharides from different species. These polysaccharides show species specificity in inducing the acrosome reaction, which is a critical event for fertilization. Females of the sea urchin Lytechinus variegatus spawn eggs containing a sulfated fucan with the repetitive sequence [3-alpha-L-Fucp-2(OSO(3))-1 --> 3-alpha-L-Fucp-4(OSO(3))-1 --> 3-alpha-L-Fucp-2,4(OSO(3))-1 --> 3-alpha-L-Fucp-2(OSO(3))-1](n). We now observe that, close to winter, a period of decreased fertility for the sea urchin, the females synthesize a distinct sulfated fucan with a simple structure, composed of 4-sulfated, 3-linked alpha-fucose residues. This sulfated fucan is inactive when tested in vitro for the acrosome reaction using homologous sperm. The amount of egg jellies spawned by females (and their constituent sulfated polysaccharides) varied greatly throughout the year. Apparently, there is a correlation between the temperature of the sea water and the expression of the 4-sulfated, 3-linked sulfated fucan. Overall, we described the occurrence of two isotypes of sulfated fucan in the egg jelly of the sea urchin L. variegatus, which differ in their biological activity and may be involved in the periodicity of the reproductive cycle of the invertebrate.

  18. Selective cleavage and anticoagulant activity of a sulfated fucan: stereospecific removal of a 2-sulfate ester from the polysaccharide by mild acid hydrolysis, preparation of oligosaccharides, and heparin cofactor II-dependent anticoagulant activity. (United States)

    Pomin, Vitor H; Pereira, Mariana S; Valente, Ana-Paula; Tollefsen, Douglas M; Pavão, Mauro S G; Mourão, Paulo A S


    A linear sulfated fucan with a regular repeating sequence of [3)-alpha-L-Fucp-(2SO4)-(1-->3)-alpha-L-Fucp-(4SO4)-(1-->3)-alpha-L-Fucp-(2,4SO4)-(1-->3)-alpha-L-Fucp-(2SO4)-(1-->]n is an anticoagulant polysaccharide mainly due to thrombin inhibition mediated by heparin cofactor II. No specific enzymatic or chemical method is available for the preparation of tailored oligosaccharides from sulfated fucans. We employ an apparently nonspecific approach to cleave this polysaccharide based on mild hydrolysis with acid. Surprisingly, the linear sulfated fucan was cleaved by mild acid hydrolysis on an ordered sequence. Initially a 2-sulfate ester of the first fucose unit is selectively removed. Thereafter the glycosidic linkage between the nonsulfated fucose residue and the subsequent 4-sulfated residue is preferentially cleaved by acid hydrolysis, forming oligosaccharides with well-defined size. The low-molecular-weight derivatives obtained from the sulfated fucan were employed to determine the requirement for interaction of this polysaccharide with heparin cofactor II and to achieve complete thrombin inhibition. The linear sulfated fucan requires significantly longer chains than mammalian glycosaminoglycans to achieve anticoagulant activity. A slight decrease in the molecular size of the sulfated fucan dramatically reduces its effect on thrombin inactivation mediated by heparin cofactor II. Sulfated fucan with approximately 45 tetrasaccharide repeating units binds to heparin cofactor II but is unable to link efficiently the plasma inhibitor and thrombin. This last effect requires chains with approximately 100 or more tetrasaccharide repeating units. We speculate that the template mechanism may predominate over the allosteric effect in the case of the linear sulfated fucan inactivation of thrombin in the presence of heparin cofactor II.

  19. Sulfated fucans from the egg jellies of the closely related sea urchins Strongylocentrotus droebachiensis and Strongylocentrotus pallidus ensure species-specific fertilization. (United States)

    Vilela-Silva, Ana-Cristina E S; Castro, Michelle O; Valente, Ana-Paula; Biermann, Christiane H; Mourao, Paulo A S


    Sulfated polysaccharides from egg jelly are the molecules responsible for inducing the sperm acrosome reaction in sea urchins. This is an obligatory event for sperm binding to, and fusion with, the egg. The sulfated polysaccharides from sea urchins have simple, well defined repeating structures, and each species represents a particular pattern of sulfate substitution. Here, we examined the egg jellies of the sea urchin sibling species Strongylocentrotus droebachiensis and Strongylocentrotus pallidus. Surprisingly, females of S. droebachiensis possess eggs containing one of two possible sulfated fucans, which differ in the extent of their 2-O-sulfation. Sulfated fucan I is mostly composed of a regular sequence of four residues ([4-alpha-l-Fucp-2(OSO3)-1-->4-alpha-l-Fucp-2(OSO3)-1-->4-alpha-l-Fucp-1-->4-alpha-l-Fucp-1]n), whereas sulfated fucan II is a homopolymer of 4-alpha-l-Fucp-2(OSO3)-1 units. Females of S. pallidus contain a single sulfated fucan with the following repeating structure: [3-alpha-l-Fucp-2(OSO3)-1-->3-alpha-l-Fucp-2(OSO3)-1-->3-alpha-l-Fucp-4(OSO3)-1-->3-alpha-l-Fucp-4(OSO3)-1]n. The egg jellies of these two species of sea urchins induce the acrosome reaction in homologous (but not heterologous) sperm. Therefore, the fine structure of the sulfated alpha-fucans from the egg jellies of S. pallidus and S. droebachiensis, which differ in their sulfation patterns and in the position of their glycosidic linkages, ensures species specificity of the sperm acrosome reaction and prevents interspecies crosses. In addition, our observations allow a clear appreciation of the common structural features among the sulfated polysaccharides from sea urchin egg jelly and help to identify structures that confer finer species specificity of recognition in the acrosome reaction.

  20. Exploiting the CNC side chain in heterocyclic rearrangements: synthesis of 4(5)-acylamino-imidazoles. (United States)

    Piccionello, Antonio Palumbo; Buscemi, Silvestre; Vivona, Nicolò; Pace, Andrea


    A new variation on the Boulton-Katritzky reaction is reported, namely, involving use of a CNC side chain. A novel Montmorillonite-K10 catalyzed nonreductive transamination of a 3-benzoyl-1,2,4-oxadiazole afforded a 3-(alpha-aminobenzyl)-1,2,4-oxadiazole, which was condensed with benzaldehydes to afford the corresponding imines. In the presence of strong base, these imines underwent Boulton-Katritzky-type rearrangement to afford novel 4(5)-acylaminoimidazoles.

  1. Selective reduction of AKR1C2 in prostate cancer and its role in DHT metabolism. (United States)

    Ji, Qing; Chang, Lilly; VanDenBerg, David; Stanczyk, Frank Z; Stolz, Andrew


    As androgens play an essential role in prostate cancer, we sought to develop a real-time PCR to characterize mRNA expression profiles of human members of the Aldo-Keto Reductase (AKR) 1C gene family, as well as of 5 alpha-steroid reductase Type II (SRD5A2) in prostate cancer samples. Functional activity and regulation of AKR1C2, a 3 alpha-hydroxysteroid dehydrogenase (HSD) type III, was also assessed in prostate cancer cell lines. Gene specific PCR primers were established and relative gene expression of human AKR1C family members was determined in paired samples of cancerous and surrounding unaffected prostate tissue. AKR1C2 preferentially reduces DHT to the weak metabolite 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol) without conversion of 3 alpha-diol to DHT in the PC-3 cell line, and its expression was increased by DHT treatment in LNCaP cells. Selectively reduced expression of AKR1C2 mRNA, but not AKR1C1 (97% sequence identity), was found in approximately half of the pairs whereas AKR1C3 relative expression was not significantly altered. No aberrant expression of AKR1C4 expression or significant differences in SRD5A2 gene expression were found. AKR1C2 functions as a DHT reductase in prostate-derived cells lines and is regulated by DHT. Additional studies are needed to further define the significance of reduced AKR1C2 expression in prostate cancer and its potential role in modulating local availability of DHT. Copyright 2003 Wiley-Liss, Inc.

  2. Sickle Cell Trait and Fatal Exertional Heat Illness: Implications for Exercise-Related Death of Young Ddults (United States)


    not require identification of Hb AS since current diagnosis and treatment do not differ by hemoglobin type. 4. The effect of our intervention on...athletes who utilize ordinary weather reports? Alpha- Thalassemia Protects Against Exertional Mortality with Sickle Cell Trait • 30% of African...Americans have alpha- thalassemia (2-3 alpha genes instead of 4). In those with sickle cell trait the main effect is to lower the Hb S fraction below 36

  3. Characterization of ceramic materials for electrochemical hydrogen sensors

    Energy Technology Data Exchange (ETDEWEB)

    Serret, P.; Colominas, S. [Electrochemical Methods Laboratory - Analytical Chemistry Department ETS Institut Quimic de Sarria, Universitat Ramon Llull, Via Augusta, 390, 08017 Barcelona (Spain); Reyes, G. [Industrial Engineering Department ETS Institut Quimic de Sarria, Universitat Ramon Llull, Via Augusta, 390, 08017 Barcelona (Spain); Abella, J., E-mail: [Electrochemical Methods Laboratory - Analytical Chemistry Department ETS Institut Quimic de Sarria, Universitat Ramon Llull, Via Augusta, 390, 08017 Barcelona (Spain)


    Accurate and reliable tritium management is of basic importance for the correct operation conditions of the blanket tritium cycle. The Electrochemical Methods Lab at Institut Quimic de Sarria (IQS) is working in the design and development of tritium sensors, based on proton solid state electrolytes to be used in molten lithium-lead eutectic. Different solid electrolyte proton conductors have been synthesized (Sr{sub 3}CaZr{sub 0.9}Ta{sub 1.1}O{sub 8.55}, SrCe{sub 0.95}Yb{sub 0.05}O{sub 3-{alpha}}, CaZr{sub 0.9}In{sub 0.1}O{sub 3-{alpha}}, Ba{sub 3}(Ca{sub 1.18}Nb{sub 1.82})O{sub 9-{alpha}}) in order to be evaluated in a testing apparatus for hydrogen gas. Potentiometric measurements of the synthesized ceramic elements have been performed. In all experiments the working temperature was 500 {sup o}C. The sensors constructed using the proton conductor element Sr{sub 3}CaZr{sub 0.9}Ta{sub 1.1}O{sub 8.55} exhibited stable output potential and its value was close to the theoretical value calculated with the Nernst equation. When the proton conductor elements SrCe{sub 0.95}Yb{sub 0.05}O{sub 3-{alpha}} and CaZr{sub 0.9}In{sub 0.1}O{sub 3-{alpha}} and Ba{sub 3}(Ca{sub 1.18}Nb{sub 1.82})O{sub 9-{alpha}} were used a deviation higher than 100 mV between theoretical and experimental data was obtained.

  4. Alkaloids and other constituents from Xylopia langsdorffiana (Annonaceae); Alcaloides e outros constituintes de Xylopia langsdorffiana (Annonaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Marcelo Sobral da; Tavares, Josean Fechine; Queiroga, Karine Formiga; Agra, Maria de Fatima; Barbosa Filho, Jose Maria [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Dept. de Ciencias Farmaceuticas], e-mail:; Almeida, Jackson Roberto Guedes da Silva [Universidade Federal do Vale do Sao Francisco, Petrolina, PE (Brazil). Colegiado de Medicina; Silva, Samia Andricia Souza da [Universidade Federal de Alagoas (UFAL), Maceio, AL (Brazil). Escola de Enfermagem e Farmacia


    The phytochemical investigation of Xylopia langsdorffiana led to the isolation of corytenchine, xylopinine, discretamine, xylopine, ent-atisan-16{alpha}-hydroxy-18-oic acid, 13{sup 2} (S) hydroxy-17{sup 3}-ethoxyphaephorbide and quercetin-3-{alpha}-rhamnoside. Their structures were assigned based on spectroscopic analyses, including two-dimensional NMR techniques. Antioxidant activities of discretamine were measured using the 1,2-diphenyl- 2-picryl-hydrazyl (DPPH) free radical scavenging assay. (author)

  5. Electroweak corrections to three-jet production in e{sup +}e{sup -} annihilation

    Energy Technology Data Exchange (ETDEWEB)

    Denner, Ansgar [Paul Scherrer Institut, CH-5232 Villigen PSI (Switzerland); Dittmaier, Stefan [Physikalisches Institut, Albert-Ludwigs-Universitaet Freiburg, D-79104 Freiburg (Germany); Max-Planck-Institut fuer Physik (Werner-Heisenberg-Institut), D-80805 Muenchen (Germany); Gehrmann, Thomas [Institut fuer Theoretische Physik, Universitaet Zuerich, CH-8057 Zuerich (Switzerland)], E-mail:; Kurz, Christian [Paul Scherrer Institut, CH-5232 Villigen PSI (Switzerland); Institut fuer Theoretische Physik, Universitaet Zuerich, CH-8057 Zuerich (Switzerland)


    We compute the electroweak O({alpha}{sup 3}{alpha}{sub s}) corrections to three-jet production and related event-shape observables at electron-positron colliders. We properly account for the experimental photon isolation criteria and for the corrections to the total hadronic cross section. Corrections to the three-jet rate and to normalised event-shape distributions turn out to be at the few-percent level.

  6. Electroweak corrections to three-jet production in electron-positron annihilation

    CERN Document Server

    Denner, Ansgar; Gehrmann, Thomas; Kurz, Christian


    We compute the electroweak ${\\cal O}(\\alpha^3\\alpha_s)$ corrections to three-jet production and related event-shape observables at electron-positron colliders. We properly account for the experimental photon isolation criteria and for the corrections to the total hadronic cross section. Corrections to the three-jet rate and to normalised event-shape distributions turn out to be at the few-per-cent level.

  7. Impaired insulin activation and dephosphorylation of glycogen synthase in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Nicoline Resen


    . No significant abnormalities in GSK-3alpha or -3beta were found in PCOS subjects. Pioglitazone treatment improved insulin-stimulated glucose metabolism and GS activity in PCOS (all P ... of GS including absent dephosphorylation at sites 2+2a contributes to insulin resistance in skeletal muscle in PCOS. The ability of pioglitazone to enhance insulin sensitivity, in part, involves improved insulin action on GS activity and dephosphorylation at NH2-terminal sites....

  8. Comparison of osteoblast-like cell responses to calcium silicate and tricalcium phosphate ceramics in vitro. (United States)

    Ni, Siyu; Chang, Jiang; Chou, Lee; Zhai, Wanyin


    Calcium silicate ceramics have been proposed as new bone repair biomaterials, since they have proved to be bioactive, degradable, and biocompatible. Beta-tricalcium phosphate ceramic is a well-known degradable material for bone repair. This study compared the effects of CaSiO3 (alpha-, and beta-CaSiO3) and beta-Ca3(PO4)2 (beta-TCP) ceramics on the early stages of rat osteoblast-like cell attachment, proliferation, and differentiation. Osteoblast-like cells were cultured directly on CaSiO3 (alpha-, and beta-CaSiO3) and beta-TCP ceramics. Attachment of a greater number of cells was observed on CaSiO3 (alpha-, and beta-CaSiO3) ceramics compared with beta-TCP ceramics after incubation for 6 h. SEM observations showed an intimate contact between cells and the substrates, significant cells adhesion, and that the cells spread and grew on the surfaces of all the materials. In addition, the proliferation rate and alkaline phosphatase (ALP) activity of the cells on the CaSiO3 (alpha-, and beta-CaSiO3) ceramics were improved when compared with the beta-TCP ceramics. In the presence of CaSiO3, elevated levels of calcium and silicon in the culture medium were observed throughout the 7-day culture period. In conclusion, the results of the present study revealed that CaSiO3 ceramics showed greater ability to support cell attachment, proliferation, and differentiation than beta-TCP ceramic. 2006 Wiley Periodicals, Inc.

  9. Coincident expression of the chemokine receptors CCR6 and CCR7 by pathologic Langerhans cells in Langerhans cell histiocytosis. (United States)

    Fleming, Mark D; Pinkus, Jack L; Fournier, Marcia V; Alexander, Sarah W; Tam, Carmen; Loda, Massimo; Sallan, Stephen E; Nichols, Kim E; Carpentieri, David F; Pinkus, Geraldine S; Rollins, Barrett J


    It has been suggested that a switch in chemokine receptor expression underlies Langerhans cell migration from skin to lymphoid tissue. Activated cells are thought to down-regulate CCR6, whose ligand macrophage inflammatory protein-3 alpha (MIP-3 alpha)/CCL20 is expressed in skin, and up-regulate CCR7, whose ligands are in lymphoid tissues. In Langerhans cell histiocytosis (LCH), pathologic Langerhans cells (LCs) accumulate in several tissues, including skin, bone, and lymphoid organs. We have examined 24 LCH cases and find that pathologic LCs expressed CCR6 and CCR7 coincidentally in all cases. Furthermore, MIP-3 alpha/CCL20 is expressed by keratinocytes in involved skin and by macrophages and osteoblasts in involved bone. Expression of CCR6 by pathologic LCs may contribute to their accumulation in nonlymphoid organs such as skin and bone, whereas CCR7 expression may direct them to lymphoid tissue. Histiocytes in Rosai-Dorfman disease and hemophagocytic syndrome also coexpressed CCR6 and CCR7, suggesting that this may be a general attribute of abnormal histiocytes.

  10. Effects of sulpiride on prolactin and mRNA levels of steroid 5alpha-reductase isozymes in adult rat brain. (United States)

    Sánchez, Pilar; Torres, Jesús M; Vílchez, Pablo; Del Moral, Raimundo G; Ortega, Esperanza


    Prolactin (PRL) promotes maternal behavior (MB), a complex pattern of behavior aimed at maximizing offspring survival. 3alpha,5alpha-reduced neurosteroids may also regulate MB. Indeed, PRL, 3alpha,5alpha-reduced neurosteroids, and 5alpha-reductase (5alpha-R), the key enzyme in the biosynthesis of these neuroactive steroids, are all increased in stress situations These facts led us to hypothesize a possible interrelation between PRL levels and 5alpha-R. In the present study we quantified mRNA levels of both 5alpha-R isozymes in prefrontal cortex of male and female rats after administration of sulpiride, an inductor of PRL secretion. Our results demonstrated that mRNA levels of both 5alpha-R isozymes were significantly increased in male and female rats by sulpiride, directly or via sulpiride-induced hyperprolactinemia. Since 3alpha,5alpha-reduced neurosteroids and PRL exert anxiolytic effects in response to stress, these molecules and 5alpha-R may possibly participate in a common pathway of significant adaptation to stress situations.

  11. Novel lanostane and rearranged lanostane-type triterpenoids from Abies sachalinensis - II -. (United States)

    Gao, Hui Yuan; Wu, Li Jun; Nakane, Takahisa; Shirota, Osamu; Kuroyanagi, Masonori


    In the previous work we reported five A-seco-rearranged lanostane triterpenoids as antibacterial constituents from the ethyl acetate soluble fraction of Abies sachalinensei leaves. In further study on the isolation of constituents from the ethyl acetate soluble fraction, two new rearranged lanostane and lanostane-type triterpenoids (3, 4) and three reported compound (1, 2, 5) were isolated. The structures of new compound 3 and 4 were determined to be 3,4-seco-4(28),6,8(14),24-mariesatetraen-26,23-olide-23-hydroxy-3-oic acid and 3,4-seco-4(28),7,24-lanostatrien-26,23-olide-23-hydroxy-3-oic acid, respectively, by spectral studies on HR-MS, (1)H-NMR, (13)C-NMR, and 2D-NMR spectra. Compound 1 was identified with pindrolactone and its structure was revised as 7,14,22Z,24-mariesatetraen-26,23-olide-3alpha-ol. Structures of 2 and 5 were determined as 7,14,24-mariesatrien-26,23-olide-3alpha,23-diol and 3alpha-hydroxy-7,14,24E-mariesatrien-23-oxo-26-oic acid. Of these compounds, 2, 3 and 4 were obtained as lactol tautomer mixtures at gamma-lactone structures of side chains.

  12. Negative regulation of opioid receptor-G protein-Ca2+ channel pathway by the nootropic nefiracetam. (United States)

    Yoshii, Mitsunobu; Furukawa, Taiji; Ogihara, Yoshiyasu; Watabe, Shigeo; Shiotani, Tadashi; Ishikawa, Yasuro; Nishimura, Masao; Nukada, Toshihide


    It has recently been reported that nefiracetam, a nootropic agent, is capable of attenuating the development of morphine dependence and tolerance in mice. The mechanism of this antimorphine action is not clear. The present study was designed to address this issue using Xenopus oocytes expressing delta-opioid receptors, G proteins (G(i3alpha) or G(o1alpha)), and N-type (alpha1B) Ca2+ channels. Membrane currents through Ca2+ channels were recorded from the oocytes under voltage-clamp conditions. The Ca2+ channel currents were reduced reversibly by 40-60% in the presence of 1 microM leucine-enkephalin (Leu-Enk). The Leu-Enk-induced current inhibition was recovered promptly by nefiracetam (1 microM), while control currents in the absence of Leu-Enk were not influenced by nefiracetam. A binding assay revealed that 3H-nefiracetam preferentially bound to the membrane fraction of oocytes expressing G(i3alpha). When delta-opioid receptors were coexpressed, the binding was significantly increased. However, an additional expression of alpha1B Ca2+ channels decreased the binding. The results suggest that nefiracetam preferentially binds to G(i3alpha) associated with delta-opioid receptors, thereby inhibiting the association of G proteins with Ca2+ channels. In conclusion, nefiracetam negatively regulates the inhibitory pathway of opioid receptor-G protein-Ca2+ channel.

  13. Stromal laminin chain distribution in normal, hyperplastic and malignant oral mucosa: relation to myofibroblast occurrence and vessel formation. (United States)

    Franz, Marcus; Wolheim, Anke; Richter, Petra; Umbreit, Claudia; Dahse, Regine; Driemel, Oliver; Hyckel, Peter; Virtanen, Ismo; Kosmehl, Hartwig; Berndt, Alexander


    The contribution of stromal laminin chain expression to malignant potential, tumour stroma reorganization and vessel formation in oral squamous cell carcinoma (OSCC) is not fully understood. Therefore, the expression of the laminin chains alpha2, alpha3, alpha4, alpha5 and gamma2 in the stromal compartment/vascular structures in OSCC was analysed. Frozen tissue of OSCC (9x G1, 24x G2, 8x G3) and normal (2x)/hyperplastic (11x) oral mucosa was subjected to laminin chain and alpha-smooth muscle actin (ASMA) immunohistochemistry. Results were correlated to tumour grade. The relation of laminin chain positive vessels to total vessel number was assessed by immunofluorescence double labelling with CD31. Stromal laminin alpha2 chain significantly decreases and alpha3, alpha4, alpha5 and gamma2 chains and also ASMA significantly increase with rising grade. The amount of stromal alpha3, alpha4 and gamma2 chains significantly increased with rising ASMA positivity. There is a significant decrease in alpha3 chain positive vessels with neoplastic transformation. Mediated by myofibroblasts, OSCC development is associated with a stromal up-regulation of laminin isoforms possibly contributing to a migration promoting microenvironment. A vascular basement membrane reorganization concerning alpha3 and gamma2 chain laminins during tumour angioneogenesis is suggested.

  14. Implication of STAT3 signaling in human colonic cancer cells during intestinal trefoil factor 3 (TFF3) -- and vascular endothelial growth factor-mediated cellular invasion and tumor growth. (United States)

    Rivat, Christine; Christine, Rivat; Rodrigues, Sylvie; Sylvie, Rodrigues; Bruyneel, Erik; Erik, Bruyneel; Piétu, Geneviève; Geneviève, Piétu; Robert, Amélie; Amélie, Robert; Redeuilh, Gérard; Gérard, Redeuilh; Bracke, Marc; Marc, Bracke; Gespach, Christian; Christian, Gespach; Attoub, Samir; Samir, Attoub


    Signal transducer and activator of transcription (STAT) 3 is overexpressed or activated in most types of human tumors and has been classified as an oncogene. In the present study, we investigated the contribution of the STAT3s to the proinvasive activity of trefoil factors (TFF) and vascular endothelial growth factor (VEGF) in human colorectal cancer cells HCT8/S11 expressing VEGF receptors. Both intestinal trefoil peptide (TFF3) and VEGF, but not pS2 (TFF1), activate STAT3 signaling through Tyr(705) phosphorylation of both STAT3alpha and STAT3beta isoforms. Blockade of STAT3 signaling by STAT3beta, depletion of the STAT3alpha/beta isoforms by RNA interference, and pharmacologic inhibition of STAT3alpha/beta phosphorylation by cucurbitacin or STAT3 inhibitory peptide abrogates TFF- and VEGF-induced cellular invasion and reduces the growth of HCT8/S11 tumor xenografts in athymic mice. Differential gene expression analysis using DNA microarrays revealed that overexpression of STAT3beta down-regulates the VEGF receptors Flt-1, neuropilins 1 and 2, and the inhibitor of DNA binding/differentiation (Id-2) gene product involved in the neoplastic transformation. Taken together, our data suggest that TFF3 and the essential tumor angiogenesis regulator VEGF(165) exert potent proinvasive activity through STAT3 signaling in human colorectal cancer cells. We also validate new therapeutic strategies targeting STAT3 signaling by pharmacologic inhibitors and RNA interference for the treatment of colorectal cancer patients.

  15. AKT/SGK-sensitive phosphorylation of GSK3 in the regulation of L-selectin and perforin expression as well as activation induced cell death of T-lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bhavsar, Shefalee K.; Merches, Katja; Bobbala, Diwakar [Department of Physiology, University of Tuebingen (Germany); Lang, Florian, E-mail: [Department of Physiology, University of Tuebingen (Germany)


    Highlights: Black-Right-Pointing-Pointer Akt/SGK dependent phosphorylation of GSK3{alpha},{beta} regulates T lymphocytes. Black-Right-Pointing-Pointer T cells from mice expressing Akt/SGK insensitive GSK3{alpha},{beta} (gsk3{sup KI}) release less IL-2. Black-Right-Pointing-Pointer CD4{sup +} cells from gsk3{sup KI} mice express less CD62L. Black-Right-Pointing-Pointer CD8{sup +} cells from gsk3{sup KI} mice are relatively resistant to activation induced cell death. Black-Right-Pointing-Pointer Perforin expression is enhanced in gsk3{sup KI} T cells. -- Abstract: Survival and function of T-lymphocytes critically depends on phosphoinositide (PI) 3 kinase. PI3 kinase signaling includes the PKB/Akt and SGK dependent phosphorylation and thus inhibition of glycogen synthase kinase GSK3{alpha},{beta}. Lithium, a known unspecific GSK3 inhibitor protects against experimental autoimmune encephalomyelitis. The present study explored, whether Akt/SGK-dependent regulation of GSK3 activity is a determinant of T cell survival and function. Experiments were performed in mutant mice in which Akt/SGK-dependent GSK3{alpha},{beta} inhibition was disrupted by replacement of the serine residue in the respective SGK/Akt-phosphorylation consensus sequence by alanine (gsk3{sup KI}). T cells from gsk3{sup KI} mice were compared to T cells from corresponding wild type mice (gsk3{sup WT}). As a result, in gsk3{sup KI} CD4{sup +} cells surface CD62L (L-selectin) was significantly less abundant than in gsk3{sup WT} CD4{sup +} cells. Upon activation in vitro T cells from gsk3{sup KI} mice reacted with enhanced perforin production and reduced activation induced cell death. Cytokine production was rather reduced in gsk3{sup KI} T cells, suggesting that GSK3 induces effector function in CD8{sup +} T cells. In conclusion, PKB/Akt and SGK sensitive phosphorylation of GSK3{alpha},{beta} is a potent regulator of perforin expression and activation induced cell death in T lymphocytes.

  16. Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass spectrometric identification of urinary metabolites. (United States)

    Kohler, Maxie; Parr, Maria K; Opfermann, Georg; Thevis, Mario; Schlörer, Nils; Marner, Franz-Josef; Schänzer, Wilhelm


    4-Hydroxyandrost-4-ene-3,17-dione is a second generation, irreversible aromatase inhibitor and commonly used as anti breast cancer medication for postmenopausal women. 4-Hydroxytestosterone is advertised as anabolic steroid and does not have any therapeutic indication. Both substances are prohibited in sports by the World Anti-Doping Agency, and, due to a considerable increase of structurally related steroids with anabolic effects offered via the internet, the metabolism of two representative candidates was investigated. Excretion studies were conducted with oral applications of 100mg of 4-hydroxyandrostenedione or 200mg of 4-hydroxytestosterone to healthy male volunteers. Urine samples were analyzed for metabolic products using conventional gas chromatography-mass spectrometry approaches, and the identification of urinary metabolites was based on reference substances, which were synthesized and structurally characterized by nuclear magnetic resonance spectroscopy and high resolution/high accuracy mass spectrometry. Identified phase-I as well as phase-II metabolites were identical for both substances. Regarding phase-I metabolism 4-hydroxyandrostenedione (1) and its reduction products 3beta-hydroxy-5alpha-androstane-4,17-dione (2) and 3alpha-hydroxy-5beta-androstane-4,17-dione (3) were detected. Further reductive conversion led to all possible isomers of 3xi,4xi-dihydroxy-5xi-androstan-17-one (4, 6-11) except 3alpha,4alpha-dihydroxy-5beta-androstan-17-one (5). Out of the 17beta-hydroxylated analogs 4-hydroxytestosterone (18), 3beta,17beta-dihydroxy-5alpha-androstan-4-one (19), 3alpha,17beta-dihydroxy-5beta-androstan-4-one (20), 5alpha-androstane-3beta,4beta,17beta-triol (21), 5alpha-androstane-3alpha,4beta,17beta-triol (26) and 5alpha-androstane-3alpha,4alpha,17beta-triol (28) were identified in the post administration urine specimens. Furthermore 4-hydroxyandrosta-4,6-diene-3,17-dione (29) and 4-hydroxyandrosta-1,4-diene-3,17-dione (30) were determined as

  17. The oestrogenic effects of gestodene, a potent contraceptive progestin, are mediated by its A-ring reduced metabolites. (United States)

    Lemus, A E; Zaga, V; Santillán, R; García, G A; Grillasca, I; Damián-Matsumura, P; Jackson, K J; Cooney, A J; Larrea, F; Pérez-Palacios, G


    Gestodene (17 alpha-ethynyl-13 beta-ethyl-17 beta-hydroxy-4, 15-gonadien-3-one) is the most potent synthetic progestin currently available and it is widely used as a fertility regulating agent in a number of contraceptive formulations because of its high effectiveness, safety and acceptability. The observation that contraceptive synthetic progestins exert hormone-like effects other than their progestational activities, prompted us to investigate whether gestodene (GSD) administration may induce oestrogenic effects, even though the GSD molecule does not interact with intracellular oestrogen receptors (ER). To assess whether GSD may exert oestrogenic effects through some of its neutral metabolites, a series of experimental studies were undertaken using GSD and three of its A-ring reduced metabolites. Receptor binding studies by displacement analysis confirmed that indeed GSD does not bind to the ER, whereas its 3 beta,5 alpha-tetrahydro reduced derivative (3 beta GSD) interacts with a relative high affinity with the ER. The 3 alpha,5 alpha GSD isomer (3 alpha GSD) also binds to the ER, though to a lesser extent. The ability of the A-ring reduced GSD derivatives to induce oestrogenic actions was evaluated by the use of two different molecular bioassays: (a) transactivation of a yeast system co-transfected with the human ER alpha (hER alpha) gene and oestrogen responsive elements fused to the beta-galactosidase reporter vector and (b) transactivation of the hER alpha-mediated transcription of the chloramphenicol acetyl transferase (CAT) reporter gene in a HeLa cells expression system. The oestrogenic potency of 3 beta GSD was also assessed by its capability to induce oestrogen-dependent progestin receptors (PR) in the anterior pituitary of castrated female rats. The results demonstrated that 3 beta GSD and 3 alpha GSD were able to activate, in a dose-dependent manner, the hER alpha-mediated transcription of both the beta-galactosidase and the CAT reporter genes in the

  18. Females of the sea urchin Strongylocentrotus purpuratus differ in the structures of their egg jelly sulfated fucans. (United States)

    Alves, A P; Mulloy, B; Moy, G W; Vacquier, V D; Mourão, P A


    The egg jelly coats of sea urchins contain sulfated fucans which bind to a sperm surface receptor glycoprotein to initiate the signal transduction events resulting in the sperm acrosome reaction. The acrosome reaction is an ion channel regulated exocytosis which is an obligatory event for sperm binding to, and fusion with, the egg. Approximately 90% of individual females of the sea urchin Strongylocentrotus purpuratus spawned eggs having only one of two possible sulfated fucan electrophoretic isotypes, a slow migrating (sulfated fucan I), or a fast migrating (sulfated fucan II) isotype. The remaining 10% of females spawned eggs having both sulfated fucan isotypes. The two sulfated fucan isotypes were purified from egg jelly coats and their structures determined by NMR spectroscopy and methylation analysis. Both sulfated fucans are linear polysaccharides composed of 1-->3-linked alpha-L-fucopyranosyl units. Sulfated fucan I is entirely sulfated at the O -2 position but with a heterogeneous sulfation pattern at O -4 position. Sulfated fucan II is composed of a regular repeating sequence of 3 residues, as follows: [3-alpha-L-Fuc p -2,4(OSO3)-1-->3-alpha-L-Fuc p -4(OSO3)-1-->3-alpha-L-Fuc p -4(OSO3)-1]n. Both purified sulfated fucans have approximately equal potency in inducing the sperm acrosome reaction. The significance of two structurally different sulfated fucans in the egg jelly coat of this species could relate to the finding that the sperm receptor protein which binds sulfated fucan contains two carbohydrate recognition modules of the C-type lectin variety which differ by 50% in their primary structure.

  19. Sexuality and fertility in women with Addison's disease. (United States)

    Erichsen, Martina M; Husebye, Eystein S; Michelsen, Trond M; Dahl, Alv A; Løvås, Kristian


    Females with primary adrenal insufficiency (Addison's disease) have reduced levels of circulating androgens, which are allegedly important for sexual functioning. The aim was to determine peripheral androgen status, sexual functioning, and birth rates in Addison's disease females. In a postal survey, all 269 females in the Norwegian Addison's registry were invited to complete the Sexual Activity Questionnaire (SAQ) and registration of childbirths. Blood samples were analyzed for 5alpha-androstane-3alpha,17beta-diol-3-glucuronide (3alpha-Diol-G) and compared with blood donor levels. The SAQ scores were compared with 740 age-matched controls from the general population and 234 women subjected to risk-reducing salpingo-oophorectomy. Fertility was estimated as standardized incidence ratio for birth; the expected number of births was estimated from population statistics. The SAQ was completed by 174 (65%) of the Addison's patients. Those not taking DHEA had significantly lower 3alpha-Diol-G levels than blood donors (mean, 0.53 vs. 2.2 ng/ml; P Addison's disease females were equally sexually active as the controls, but they reported significantly higher pleasure and less discomfort. They reported lower pleasure but less discomfort than the risk-reducing salpingo-oophorectomy women. The fertility was significantly reduced in females with Addison's disease; 54 children were born to mothers with established diagnosis (87.5 expected), yielding a standardized incidence ratio for birth of 0.69 (confidence interval, 0.52-0.86). Despite androgen depletion, females with Addison's disease do not report impaired sexuality. The fertility is reduced after the diagnosis is made; the reasons for this remain unknown.

  20. Skin of the male African catfish, Clarias gariepinus: a source of steroid glucuronides

    Energy Technology Data Exchange (ETDEWEB)

    Ali, S.A.; Schoonen, W.G.; Lambert, J.G.; Van den Hurk, R.; Van Oordt, P.G.


    Steroid metabolism in the skin of mature male African catfish, Clarias gariepinus, reared in the laboratory, was studied in vitro by tissue incubations with (/sup 3/H)pregnenolone, (/sup 3/H)dehydroepiandrosterone, (/sup 3/H)17 alpha-hydroxyprogesterone, (/sup 3/H)androstenedione, (/sup 14/C)11 beta-hydroxyandrostenedione, and (/sup 3/H)testosterone as precursors. While pregnenolone was not converted to any other steroid, dehydroepiandrosterone was transformed mainly to 5-androstene-3 beta, 17 beta-diol. The products of 17 alpha-hydroxyprogesterone incubations were 5 beta-pregnane-3 alpha,17 alpha-diol-20-one, 5 beta-pregnane-3 alpha,17 alpha, 20 beta-triol, and 5 beta-pregnan-17 alpha-o1-3,20-dione. The major steroids of androstenedione incubations were etiocholanolone, testosterone, and androsterone. Testosterone was converted mainly to etiocholanolone and androstenedione, and only small quantities of 11 beta-hydroxytestosterone, 11-ketotestosterone, and 11-ketoandrostenedione were the metabolites found in 11 beta-hydroxyandrostenedione incubation. These results demonstrated the presence of the enzymes 5 alpha- and 5 beta-reductases and 3 alpha-, 11 beta-, 17 beta-, and 20 beta-hydroxysteroid dehydrogenases in the skin. From enzymehistochemical results it appeared that the steroid conversions take place in the epithelial cells. Moreover, the presence of UDP-glucose dehydrogenase, an enzyme involved in the synthesis of glucuronic acid, in these cells indicates the possibility of steroid glucuronide formation. Indeed significant amounts of water-soluble steroid conjugates, particularly 5 beta-dihydrotestosterone- and testosterone-glucuronide, were found in the incubations with androstenedione and testosterone, indicating the presence of the UDP-glucuronosyl transferase in the catfish skin.

  1. Inactivation by UDP-glucuronosyltransferase enzymes: the end of androgen signaling. (United States)

    Chouinard, Sarah; Yueh, Mei-Fei; Tukey, Robert H; Giton, Frank; Fiet, Jean; Pelletier, Georges; Barbier, Olivier; Bélanger, Alain


    Conjugation by UDP-Glucuronosyltransferase (UGT) is the major pathway of androgen metabolism and elimination in the human. High concentrations of glucuronide conjugates of androsterone (ADT) and androstane-3alpha,17beta-diol (3alpha-diol) are present in circulation and several studies over the last 30 years have concluded that the serum levels of these metabolites might reflect the androgen metabolism in several tissues, including the liver and androgen target tissues. Three UGT2B enzymes are responsible for the conjugation of DHT and its metabolites ADT and 3alpha-diol: UGT2B7, B15 and B17. UGT2B7 is expressed in the liver and skin whereas UGT2B15 and B17 were found in the liver, prostate and skin. Very specific antibodies against each UGT2B enzyme have been obtained and used for immunohistochemical studies in the human prostate. It was shown that UGT2B17 is expressed in basal cells whereas UGT2B15 is only localized in luminal cells, where it inactivates DHT. By using LNCaP cells, we have also demonstrated that the expression and activity of UGT2B15 and B17 are modulated by several endogenous prostate factors including androgen. Finally, to study the physiological role of UGT2B enzymes, transgenic mice bearing the human UGT2B15 gene were recently obtained. A decrease in reproductive tissue weight from transgenic animals compared to those from control animals was observed. In conclusion, the conjugation by UGT2B7, B15 and B17, which represents a non-reversible step in androgen metabolism, is an important means by which androgens are regulated locally. It is also postulated that UGT enzymes protect the tissue from deleteriously high concentrations of active androgen.

  2. Complete mapping of crystallization pathways during cholesterol precipitation from model bile: influence of physical-chemical variables of pathophysiologic relevance and identification of a stable liquid crystalline state in cold, dilute and hydrophilic bile salt-containing systems. (United States)

    Wang, D Q; Carey, M C


    Using complementary physical-chemical techniques we defined five different crystallization pathways as functions of time (30 days) and increasing lecithin (egg yolk) content in pathophysiologically relevant model biles super-saturated (cholesterol saturation indices, 1.2 - 2.7) by dilution of approximately equal to 29 g/dl bile salt-lecithin-cholesterol micellar solutions. As evidenced by quasi-elastic light-scattering spectroscopy, supersaturation was heralded by the appearance of unilamellar vesicles. With the lowest lecithin contents, arc-like crystals with habit and density (d 1.030 g/mL) consistent with anhydrous cholesterol appeared first and evolved via helical and tubular crystals to form plate-like cholesterol monohydrate crystals (d 1.045 g/mL). With higher lecithin fractions, cholesterol monohydrate crystals appeared earlier than arc and other transitional crystals. With typical physiological lecithin contents, early liquid crystals (d 1.020 g/mL) were followed by cholesterol monohydrate crystals and subsequent appearances of arc and other intermediate crystals. With higher lecithin contents, liquid crystals were followed by cholesterol monohydrate crystals only, and at the highest lecithin mole fractions, liquid crystals appeared that did not generate solid crystals. Added calcium increased solid crystal number in proportion to its concentration (5 - 20 mM) but did not influence appearance times, crystallization pathways, or micellar cholesterol solubilities. Decreases in temperature (37 degrees --> 4 degrees C), total lipid concentration (7.3 --> 2.4 g/dL), and bile salt hydrophobicity (3 alpha, 12 alpha --> 3 alpha, 7 alpha, 12 alpha --> 3 alpha, 7 beta hydroxylated taurine conjugates) progressively shifted all crystallization pathways to lower lecithin contents, retarded crystallization, and decreased micellar cholesterol solubilities. The lecithin content of mother biles decreased markedly during crystallization especially where liquid crystals were

  3. Distinct epitopes for anti-glomerular basement membrane alport alloantibodies and goodpasture autoantibodies within the noncollagenous domain of alpha3(IV) collagen: a janus-faced antigen. (United States)

    Wang, Xu-Ping; Fogo, Agnes B; Colon, Selene; Giannico, Giovanna; Abul-Ezz, Sameh R; Miner, Jeffrey H; Borza, Dorin-Bogdan


    Alport posttransplantation anti-glomerular basement membrane (GBM) nephritis is mediated by alloantibodies against the noncollagenous (NC1) domains of the alpha3alpha4alpha5(IV) collagen network, which is present in the GBM of the allograft but absent from Alport kidneys. The specificity of kidney-bound anti-GBM alloantibodies from a patient who had autosomal recessive Alport syndrome (ARAS) and developed posttransplantation nephritis was compared with that of Goodpasture autoantibodies from patients with autoimmune anti-GBM disease. Allograft-eluted alloantibodies reacted specifically with alpha3alpha4alpha5 NC1 hexamers, targeting their alpha3NC1 and alpha4NC1 subunits, and recognized a noncontiguous alloepitope formed jointly by the E(A) and E(B) regions of alpha3NC1 domain. In contrast, human Goodpasture autoantibodies recognized the separate E(A) and E(B) autoepitopes of alpha3NC1 but not the composite alloepitope. Molecular modeling of alpha3NC1 revealed that the alloepitope is more accessible within the NC1 hexamers than the partially sequestered Goodpasture autoepitopes. Overall, the specificity of alloantibodies indicated a selective lack of immune tolerance toward the alpha3 and alpha4(IV) collagen chains not expressed in patients with ARAS. Using COL4A3 knockout mice, a model of ARAS, it was shown further that acid-dissociated rather than native alpha3alpha4alpha5 NC1 hexamers elicited murine anti-GBM antibodies most closely resembling human ARAS alloantibodies. In contrast, alpha3NC1 monomers elicited Goodpasture-like murine antibodies, targeting the E(A) and E(B) autoepitopes. Thus, the identity of alpha3NC1 epitopes targeted by anti-GBM antibodies is strongly influenced by the molecular organization of the immunogen. These findings suggest that different isoforms of alpha3(IV) collagen may be implicated in the pathogenesis of ARAS posttransplantation anti-GBM nephritis and Goodpasture disease.

  4. [Study on the chemical constituents in Pouzolzia zeylanica]. (United States)

    Fu, Ming; Niu, You-Ya; Yu, Juan; Kong, Qing-Tong


    To study the chemical constituents of Pouzolzia zeylanica. Many chromatography means were used in separation and purification, and the structures of all compounds were identified by the means of spectroscopic analysis and physicochemical properties. 14 compounds were elucidated as: beta-sitosterol (1), daucosterol (2), oleanolic acid (3), epicatechin (4), alpha-amyrin (5), eugenyl-beta-rutinoside (6), 2alpha, 3alpha, 19alpha-trihydroxyurs-12-en-28-oic (7), scopolin (8), scutellarein-7-O-alpha-L-rhamnoside (9), scopoletin (10), quercetin (11), quercetin-3-O-beta-D-glucoside (12), apigenin (13), 2alpha-hydroxyursolic acid (14). All compounds are obtained from this plant for the first time.

  5. (n, {alpha}) cross section measurement of light nuclei using gridded ionization chamber and gaseous sample

    Energy Technology Data Exchange (ETDEWEB)

    Sanami, Toshiya; Baba, Mamoru; Saito, Keiichiro; Ibara, Yasutaka; Yamazaki, Tetsuro; Sato, Jun; Hirakawa, Naohiro [Tohoku Univ., Sendai (Japan)


    We have developed a measuring method of (n, {alpha}) cross section by using gaseous sample in a gridded ionization chamber. In this study, we measured the {sup 12}C(n, {alpha}{sub 0}) and the {sup 16}O(n, {alpha}{sub 0}), (n, {alpha}{sub 123}) cross sections for En=11.5 and 12.8 MeV neutrons. We also deduced the {sup 12}C(n, x{alpha}) spectrum and analyzed the data by a kinematic calculation combined with the reaction data of the {sup 12}C(n, n`3{alpha}). (author)

  6. Characteristics of sterol uptake in Saccharomyces cerevisiae.


    Lorenz, R T; Rodriguez, R J; Lewis, T A; Parks, L W


    A Saccharomyces cerevisiae sterol auxotroph, FY3 (alpha hem1 erg7 ura), was used to probe the characteristics of sterol uptake in S. cerevisiae. The steady-state cellular concentration of free sterol at the late exponential phase of growth could be adjusted within a 10-fold range by varying the concentration of exogenously supplied sterol. When cultured on 1 microgram of sterol ml-1, the cells contained a minimal cellular free-cholesterol concentration of 0.85 nmol/mg (dry weight) and were te...

  7. Calystegins of Physalis alkekengi var. francheti (Solanaceae). Structure determination and their glycosidase inhibitory activities. (United States)

    Asano, N; Kato, A; Oseki, K; Kizu, H; Matsui, K


    Five calystegins were extracted from the roots of Physalis alkekengi var. francheti (Solanaceae) with hot water and purified to homogeneity by the combination of a variety of ion-exchange column chromatographies. Their structures have been determined from the 1H- and 13C-NMR spectral data, and two of the compounds were identified as calystegins A3 and B2, which have been isolated from the roots of Calystegia sepium (Convolvulaceae). Two of the remaining three were found to be 1 alpha, 3 alpha, 4 beta-trihydroxy-nor-tropane and 1 alpha, 2 alpha, 3 alpha, 4 beta-tetrahydroxy-nor-tropane and given the trivial name calystegins A5 and B3, respectively. The last calystegin was assigned as 1 alpha, 2 beta, 3 alpha, 6 alpha-tetrahydroxy-nor-tropane, which was the same as the relative configuration proposed in the literature for calystegin B1 isolated from C. sepium. However, the 13C-NMR spectral data for the compound from C. sepium differed substantially from our results. From a personal communication with the authors of the original paper on calystegins, it was clarified that the 13C-NMR chemical shifts of calystegin B1 in the original paper had been erroneous. Since their corrected 13C-NMR data of calystegin B1 and its 1H-NMR chemical shifts in the original paper are very close to our present data, we concluded that both compounds from C. sepium and P. alkekengi are identical. Calystegin B2 has been known to be a potent competitive inhibitor of almond beta-glucosidase (Ki = 1.2 microM) and coffee bean alpha-galactosidase (Ki = 0.86 microM). In this study calystegin B1 (1 alpha, 2 beta, 3 alpha, 6 alpha-tetrahydroxy-nor-tropane) proved to be a potent competitive inhibitor of almond beta-glucosidase (Ki = 1.9 microM) and bovine liver beta-galactosidase (Ki = 1.6 microM), but not an inhibitor of alpha-galactosidases. Calystegin A3 was found to be a weaker inhibitor compared to calystegin B2 but with the same inhibitory spectrum. Calystegin A5, a 2-deoxy derivative of

  8. Lanostane triterpenoids from the inedible mushroom Fomitopsis spraguei. (United States)

    Quang, Dang Ngoc; Arakawa, Yuuki; Hashimoto, Toshihiro; Asakawa, Yoshinori


    Investigation of the methanolic extract of the inedible mushroom Fomitopsis spraguei (Polyporaceae) led to the isolation of five lanostane-type triterpenoids (1-5): three new compounds named fomitopsins A-C (2-4), and two known compounds, quercinic acid C (1) and 3alpha-carboxyacetyl-12beta-hydroxyquercinic acid (5). Their structures were determined by 2D NMR, MS, IR, UV spectra, and X-ray crystallographic analyses. An X-ray crystal structure analysis of quercinic acid C (1) established its stereochemistry as 3R,12R-dihydroxy-24R-methyl-23-oxo-25S-lanost-8-en-26-oic acid.

  9. Lamb shift in the muonic deuterium atom

    Energy Technology Data Exchange (ETDEWEB)

    Krutov, A. A.; Martynenko, A. P. [Samara State University, Pavlov street 1, 443011, Samara (Russian Federation); Samara State University, Pavlov Street 1, 443011, Samara, Russia and Samara State Aerospace University named after academician S.P. Korolyov, Moskovskoye Shosse 34, 443086, Samara (Russian Federation)


    We present an investigation of the Lamb shift (2P{sub 1/2}-2S{sub 1/2}) in the muonic deuterium ({mu}D) atom using the three-dimensional quasipotential method in quantum electrodynamics. The vacuum polarization, nuclear-structure, and recoil effects are calculated with the account of contributions of orders {alpha}{sup 3}, {alpha}{sup 4}, {alpha}{sup 5}, and {alpha}{sup 6}. The results are compared with earlier performed calculations. The obtained numerical value of the Lamb shift at 202.4139 meV can be considered a reliable estimate for comparison with forthcoming experimental data.

  10. Lamb shift in muonic helium ion

    CERN Document Server

    Martynenko, A P


    The Lamb shift (2P_{1/2}-2S_{1/2}) in the muonic helium ion (mu ^4_2He)^+ is calculated with the account of contributions of orders alpha^3, alpha^4, alpha^5 and alpha^6. Special attention is given to corrections of the electron vacuum polarization, the nuclear structure and recoil effects. The obtained numerical value of the Lamb shift 1381.716 meV can be considered as a reliable estimate for the comparison with experimental data.

  11. Lamb shift in muonic deuterium atom

    CERN Document Server

    Krutov, A A


    We present new investigation of the Lamb shift (2P_{1/2}-2S_{1/2}) in the muonic deuterium (mu d) atom using the three-dimensional quasipotential method in quantum electrodynamics. The vacuum polarization, nuclear structure and recoil effects are calculated with the account of contributions of orders alpha^3, alpha^4, alpha^5 and alpha^6. The results are compared with earlier performed calculations. The obtained numerical value of the Lamb shift 202.3616 meV can be considered as a reliable estimate for the comparison with forthcoming experimental data.

  12. Synthesis and nicotinic receptor activity of a hydroxylated tropane

    DEFF Research Database (Denmark)

    Bremner, John B; Godfrey, Colette A; Jensen, Anders A.


    (+/-)-3alpha-hydroxy homoepibatidine 4 has been synthesized from the alkaloid scopolamine 5 and its properties as a nicotinic agonist assessed. While still binding strongly, the compound showed reduced agonist potency for the alpha(4)beta(2) nAChR compared with the parent compound epibatidine 1....... Compound 4 also displayed generally similar binding and selectivity profiles at alpha(4)beta(2), alpha(2)beta(4), alpha(3)beta(4), and alpha(4)beta(4) nAChR subtypes to those for nicotine....

  13. Attenuation of mild hyperandrogenic activity in postpubertal acne by a triphasic oral contraceptive containing low doses of ethynyl estradiol and d,l-norgestrel. (United States)

    Lemay, A; Dewailly, S D; Grenier, R; Huard, J


    The effect of a low dose triphasic oral contraceptive (OC) was evaluated during a 6-month treatment period in 41 patients (mean age, 25.4 +/- 0.7 yr) who had grade I-IV postpubertal acne and normal menses. The OC contained three dose levels of ethynyl estradiol and dl-norgestrel. Acne lesions were assessed, and serum androgen levels were measured during a control cycle and between days 17-21 of treatment cycles 1, 2, 3, and 6. Four patients dropped out after 3 months of treatment. Acne was significantly improved after the first OC cycle. After six cycles, the number of comedones had decreased by 79.6 +/- 3.2% (range, 50-100%) in 69.4% of the patients. Mean baseline levels of testosterone, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate were in the upper third of the normal range, with elevated individual values in 18.9%, 36.5%, and 26.8% of the women, respectively. Mean baseline levels of androstenedione, free testosterone (T), and 3 alpha-androstanediol glucuronide (3 alpha-diol-G) were above the normal range, with elevated individual values in 51.2%, 75.0%, and 85.4% of the patients, respectively. Sex hormone-binding globulin (SHBG) levels were below the normal range in 26.8% of the cases. At the end of the first OC cycle, there was a significant (P less than 0.01) decrease in all androgen precursors and a 2-fold increase in SHBG. Androstenedione and free T decreased into the normal range during OC intake. Serum 3 alpha-diol-G levels remained elevated, but had decreased by 34.5% at cycle 6 (P less than 0.05). These results show that the triphasic OC has significantly improved acne in postpubertal women for whom acne was the main manifestation of mild hyperandrogenic activity. The improvement in acne corresponded to a decrease in adrenal/ovarian androgens and free T, which led to a decreased metabolism to 3 alpha-diol-G, presumably by the sebaceous glands. The increase in SHBG is considered an estrogenic effect, and the triphasic formulation containing

  14. Escher in the Sky

    CERN Document Server

    Kallosh, Renata


    The cosmological models called $\\alpha$-attractors provide an excellent fit to the latest observational data. Their predictions $n_{s} = 1-2/N$ and $r = 12\\alpha/N^{2}$ are very robust with respect to the modifications of the inflaton potential. An intriguing interpretation of $\\alpha$-attractors is based on a geometric moduli space with a boundary: a Poincare disk model of a hyperbolic geometry with the radius $\\sqrt{3\\alpha}$, beautifully represented by the Escher's picture Circle Limit IV. In such models, the amplitude of the gravitational waves is proportional to the square of the radius of the Poincare disk.

  15. Structure of an extracellular polysaccharide produced by Lactobacillus rhamnosus strain C83

    Energy Technology Data Exchange (ETDEWEB)

    Vanhaverbeke, C.; Bosso, C.; Colin-Morel, P.; Gey, C.; Heyraud, A. [Centre de Recherches sur les Macromolecules Vegetales, CNRS and Universite Joseph Fourier, B.P.53, F-38041 Grenoble (France); Gamar-Nourani, L.; Blondeau, K.; Simonet, J.-M. [Institut de Genetique et Microbiologie, Laboratoire de Genetique Moleculaire des Bacteries d' Interet Industriel, CNRS URA 2225, Batiment 360, Universite de Paris Sud, F-91405 Orsay (France)


    The extracellular polysaccharide produced by Lactobacillus rhamnosus strain C83 was found to be composed of d-glucose and d-galactose in a molar ratio of 2:3. The primary structure of the polysaccharide was shown by sugar analysis, methylation analysis, FABMS, partial acid hydrolysis and nuclear magnetic resonance (NMR) spectroscopy to consist of a pentasaccharide repeating unit having the following structure:-3)-{alpha}-d-Glcp-(1-2)-{beta}-d-Galf-(1-6)-{alpha}-d-Galp-(1-6) -{alpha}-d-Glcp-(1-3)-{beta}-d-Galf-(1-. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  16. Thermodynamics of Third Order Lovelock-Born-Infeld Black Holes


    Li, Peng; Yue, Rui-Hong; Zou, De-Cheng


    We here explore black holes in the third order Lovelock gravity coupling with nonlinear Born-Infeld electromagnetic field. Considering special second and third order coefficients ($\\hat{\\alpha}_2^2=3\\hat{\\alpha}_3=\\alpha^2$), we analyze the thermodynamics of third order Lovelock-Born-Infeld black holes and, in 7-dimensional AdS space-time, discuss the stability of black holes in different event horizon structures. We find that the cosmological constant $\\Lambda$ plays an important role in the...

  17. Thermodynamics of Third Order Lovelock-Born-Infeld Black Holes

    CERN Document Server

    Li, Peng; Zou, De-Cheng


    We here explore black holes in the third order Lovelock gravity coupling with nonlinear Born-Infeld electromagnetic field. Considering special second and third order coefficients ($\\hat{\\alpha}_2^2=3\\hat{\\alpha}_3=\\alpha^2$), we analyze the thermodynamics of third order Lovelock-Born-Infeld black holes and, in 7-dimensional AdS space-time, discuss the stability of black holes in different event horizon structures. We find that the cosmological constant $\\Lambda$ plays an important role in the distribution of stable regions of black holes.

  18. Uncertainties in the use of periodate oxidation for determination of dextran structure. (United States)

    Leonard, G J


    A glucan of high molecular weight isolated from stale sugar-cane, and previously shown to have a marked effect on sucrose crystallisation processes-1, is a relatively linear dextran. Approximately 96-97% of its D-glucose residues are involved in (1 yields 6)-alpha-D linkages and constitute the linear backbone of the polymer. The remaining 3-4% of D-glucose residues form branch-points by (1 yields 3)-alpha-D linkages. The periodate-oxidation technique, which has been extensively used by other workers to determine dextran structure, gave erroneous results when applied to the dextran from stale sugar-cane.

  19. Alkaloid content of the seeds from Erythroxylum Coca var. Coca. (United States)

    Casale, John F; Toske, Steven G; Colley, Valerie L


    Alkaloid extracts from the seeds of Erythroxylum Coca var. Coca grown in the Chapare Valley of Bolivia were subjected to gas and liquid chromatographic-mass spectrometric analyses. Several alkaloids from these seeds were detected and characterized, including methylecgonidine, tropine, 3alpha-acetoxytropane, ecgonine methyl ester, cuscohygrine, N-norbenzoyltropine, benzoyltropine, hexanoylecgonine methyl ester, cocaine, cis-cinnamoylcocaine, and trans-cinnamoylcocaine. Methylecgonidine was determined to be the primary constituent and not an analytical artifact. Additionally, two significant new uncharacterized alkaloids were established as present. Recent evidence suggests that some cocaine processors are adding this seed extraction material to cocaine extracted from coca leaf and may impact cocaine impurity signature profiles.

  20. [Effect of a new derivative of glutamic and apovincaminic acids on brain metabolism in post-ischemic period]. (United States)

    Makarova, L M; Prikhod'ko, M A; Pogorelyĭ, V E; Skachilova, S Ia; Mirzoian, R S


    Neuroprotective properties of the new derivative of glutamic and apovincaminic acids, ethyl -(3-alpha,16-alpha)-eburnamenin-14-carbopxylate of 2-aminopentadionic acid (LHT 1-02) were studied on a model of acute brain ischemia in cats. LHT 1-02 has proved to be more effective than the reference drugs vinpocetin and glycine in preventing the reperfusive damage, which was manifested by decreased postischemic hyperglycemia, activated utilization of oxygen in the brain, and suppressed postischemic metabolic lactate acidosis. Thus, the results of this comparative study show expediency of further investigations of LHT 1 - 02 as a potential neuroprotective drug.

  1. Optical transitions in hybrid perovskite solar cells: Ellipsometry, density functional theory, and quantum efficiency analyses for CH3NH3PbI3


    Shirayama, Masaki; Kadowaki, Hideyuki; Miyadera, Tetsuhiko; Sugita, Takeshi; Tamakoshi, Masato; Kato, Masato; Fujiseki, Takemasa; Murata, Daisuke; Hara, Shota; Murakami, Takurou N.; Fujimoto, Shohei; Chikamatsu, Masayuki; FUJIWARA, HIROYUKI


    We report artifact-free CH3NH3PbI3 optical constants extracted from ultra-smooth perovskite layers without air exposure and assign all the optical transitions in the visible/ultraviolet region unambiguously based on density functional theory (DFT) analysis that assumes a simple pseudo-cubic crystal structure. From the self-consistent spectroscopic ellipsometry analysis of the ultra-smooth CH3NH3PbI3 layers, we find that the absorption coefficients of CH3NH3PbI3 (alpha = 3.8 x 10^4 cm-1 at 2.0...

  2. Observation of isolated high-E_T photons in deep inelastic scattering

    CERN Document Server

    Chekanov, S; Krakauer, D A; Loizides, J H; Magill, S; Miglioranzi, S; Musgrave, B; Repond, J; Yoshida, R; Mattingly, M C K; Antonioli, P; Bari, G; Basile, M; Bellagamba, L; Boscherini, D; Bruni, A; Bruni, G; Cara Romeo, G; Cifarelli, Luisa; Cindolo, F; Contin, A; Corradi, M; De Pasquale, S; Giusti, P; Iacobucci, G; Margotti, A; Montanari, A; Nania, R; Palmonari, F; Pesci, A; Sartorelli, G; Zichichi, A; Aghuzumtsyan, G; Bartsch, D; Brock, I; Goers, S; Hartmann, H; Hilger, E; Irrgang, P; Jakob, H P; Kind, O; Meyer, U; Paul, E; Rautenberg, J; Renner, R; Stifutkin, A; Tandler, J; Voss, K C; Wang, M; Bailey, D S; Brook, N H; Cole, J E; Heath, G P; Namsoo, T; Robins, S; Wing, M; Capua, M; Mastroberardino, A; Schioppa, M; Susinno, G; Kim, J Y; Kim, Y K; Lee, J H; Lim, I T; Pac, M Y; Caldwell, A; Helbich, M; Liu, X; Mellado, B; Ning, Y; Paganis, S; Ren, Z; Schmidke, W B; Sciulli, F; Chwastowski, J; Eskreys, Andrzej; Figiel, J; Galas, A; Olkiewicz, K; Stopa, P; Zawiejski, L; Adamczyk, L; Bold, T; Grabowska-Bold, I; Kisielewska, D; Kowal, A M; Kowal, M; Kowalski, T; Przybycien, M B; Suszycki, L; Szuba, D; Szuba, J; Kotanski, A; Slominski, W; Adler, V; Behrens, U; Bloch, I; Borras, K; Chiochia, V; Dannheim, D; Drews, G; Fourletova, J; Fricke, U; Geiser, A; Göttlicher, P; Gutsche, O; Haas, T; Hain, W; Hillert, S; Kahle, B; Kötz, U; Kowalski, H; Kramberger, G; Labes, H; Lelas, D; Lim, H; Löhr, B; Mankel, R; Melzer-Pellmann, I A; Nguyen, C N; Notz, D; Nuncio-Quiroz, A E; Polini, A; Raval, A; Rurua, L; Schneekloth, U; Stösslein, U; Wolf, G; Youngman, C; Zeuner, W; Schlenstedt, S; Barbagli, G; Gallo, E; Genta, C; Pelfer, P G; Bamberger, A; Benen, A; Karstens, F; Dobur, D; Vlasov, N N; Bell, M; Bussey, P J; Doyle, A T; Ferrando, J; Hamilton, J; Hanlon, S; Saxon, D H; Skillicorn, I O; Gialas, I; Carli, T; Gosau, T; Holm, U; Krumnack, N; Lohrmann, E; Milite, M; Salehi, H; Schleper, P; Schörner-Sadenius, T; Stonjek, S; Wichmann, K; Wick, K; Ziegler, A; Collins-Tooth, C; Foudas, C; Goncalo, R; Long, K R; Tapper, A D; Cloth, P; Filges, D; Kataoka, M; Nagano, K; Tokushuku, K; Yamada, S; Yamazaki, Y; Barakbaev, A N; Boos, E G; Pokrovskiy, N S; Zhautykov, B O; Son, D; Piotrzkowski, K; Barreiro, F; Glasman, C; González, O; Labarga, L; Del Peso, J; Tassi, E; Terron, J; Vázquez, M; Zambrana, M; Barbi, M; Corriveau, F; Gliga, S; Lainesse, J; Padhi, S; Stairs, D G; Walsh, R; Tsurugai, T; Antonov, A; Danilov, P; Dolgoshein, B A; Gladkov, D; Sosnovtsev, V V; Suchkov, S; Dementiev, R K; Ermolov, P F; Katkov, I I; Khein, L A; Korzhavina, I A; Kuzmin, V A; Levchenko, B B; Lukina, O Yu; Proskuryakov, A S; Shcheglova, L M; Zotkin, S A; Coppola, N; Grijpink, S; Koffeman, E; Kooijman, P; Maddox, E; Pellegrino, A; Schagen, S; Tiecke, H G; Velthuis, J J; Wiggers, L; De Wolf, E; Brümmer, N; Bylsma, B; Durkin, L S; Ling, T Y; Cooper-Sarkar, A M; Cottrell, A; Devenish, R C E; Foster, B; Grzelak, G; Gwenlan, C; Patel, S; Straub, P B; Walczak, R; Bertolin, A; Brugnera, R; Carlin, R; Dal Corso, F; Dusini, S; Garfagnini, A; Limentani, S; Longhin, A; Parenti, A; Posocco, M; Stanco, L; Turcato, M; Heaphy, E A; Metlica, F; Oh, B Y; Whitmore, J J; Iga, Y; D'Agostini, Giulio; Marini, G; Nigro, A; Cormack, C; Hart, J C; McCubbin, N A; Heusch, C A; Park, I H; Pavel, N; Abramowicz, H; Gabareen, A; Kananov, S; Kreisel, A; Levy, A; Kuze, M; Fusayasu, T; Kagawa, S; Kohno, T; Tawara, T; Yamashita, T; Hamatsu, R; Hirose, T; Inuzuka, M; Kaji, H; Kitamura, S; Matsuzawa, K; Ferrero, M I; Monaco, V; Sacchi, R; Solano, A; Arneodo, M; Ruspa, M; Koop, T; Martin, J F; Mirea, A; Butterworth, J M; Hall-Wilton, R; Jones, T W; Lightwood, M S; Sutton, M R; Targett-Adams, C; Ciborowski, J; Ciesielski, R; Luzniak, P; Nowak, R J; Pawlak, J M; Sztuk, J; Tymieniecka, T; Ukleja, A; Ukleja, J; Zarnecki, A F; Adamus, M; Plucinsky, P P; Eisenberg, Y; Hochman, D; Riveline, U; Karshon, M; Gladilin, L K; Kcira, D; Lammers, S; Li, L; Reeder, D D; Rosin, M; Savin, A A; Smith, W H; Deshpande, Abhay A; Dhawan, S; Bhadra, S; Catterall, C D; Fourletov, S; Hartner, G; Menary, S R; Soares, M; Standage, J


    First measurements of cross sections for isolated prompt photon production in deep inelastic ep scattering have been made using the ZEUS detector at the HERA electron-proton collider using an integrated luminosity of 121 pb^-1. A signal for isolated photons in the transverse energy and rapidity ranges 5 35 GeV^2. Cross sections are presented for inclusive prompt photons and for those accompanied by a single jet in the range E_T^jet \\geq 6 GeV and -1.5 \\leq eta^jet < 1.8. Calculations at order alpha^3alpha_s describe the data reasonably well.

  3. Molecular mechanism of antioxidant synergism of tocotrienols and carotenoids in palm oil. (United States)

    Schroeder, Maria T; Becker, Eleonora Miquel; Skibsted, Leif H


    During repeated deep-fat frying of potato slices at 163 degrees C in yellow or red palm olein of comparable fatty acid profiles, the oxidative stability (peroxide value and anisidine value) of the palm oleins was similar, and in yellow palm olein, the rate of antioxidant depletion decreased in the order gamma-T3 > alpha-T3 > delta-T3 (T3, tocotrienol). In red palm olein, which had a total tocopherol/tocotrienol content of 1260 vs 940 ppm in yellow palm olein and a corresponding longer induction period in the Rancimat stability test at 120 degrees C, only depletion of gamma-T3 was significant among the phenols during frying and slower as compared to that in yellow palm olein. The carotenes in the red palm olein were depleted linearly with the number of fryings, apparently yielding an overall protection of the phenols. In antioxidant-depleted palm olein and in phospholipid liposomes with added increasing concentrations of phenols, gamma-T3 was found to be a better antioxidant than alpha-T3. alpha-T3 and alpha-T (T, tocopherol) had a similar antioxidant effect in antioxidant-depleted palm olein in the Rancimat stability test, while in the liposomes the ordering as determined by induction period for the formation of conjugated dienes was gamma-T3 > alpha-T3 > alpha-T. The addition of 100-1000 ppm beta-carotene to antioxidant-depleted palm olein or liposomes (lycopene also tested) did not provide any protection against oxidation. In the liposomes, synergistic interactions were observed between beta-carotene or lycopene and alpha-T, alpha-T3, or gamma-T3 for carotene/phenol ratios of 1:10 and 1:2 but not for 1:1. In chloroform, carotenes were regenerated by tocopherols/tocotrienols from carotene radicals generated by laser flash photolysis as shown by transient absorption spectroscopy, suggesting that carotenes rather than phenols are the primary substrate for lipid-derived radicals in red palm olein, in effect depleting carotenes prior to phenols during frying

  4. A triterpenoid saponin from Albizia julibrissin. (United States)

    Zou, K; Zhao, Y Y; Tu, G Z; Guo, D A; Zhang, R Y; Zheng, J H


    A triterpenoid saponin (1) was obtained from the stem barks of Albizia julibrissin Durazz. Its structure was elucidated as 3-O-[beta-D-xylopyranosyl-(1 --> 2)-alpha-L-arabinopyranosyl-(1 --> 6)-beta-D-glucopyranosyl]-21-O-[(6S)-2-trans-2-hydroxymethyl-6-methyl-6-O-beta-D-quinovopyranosyl-2, 7-octadienoyl]-16-deoxy-acacic acid 28-O-beta-D-glucopyranosyl-(1 --> 3)-[alpha-L-arabinofuranosyl-(1 --> 4)]-alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranosyl ester (1), named as Julibroside J26, based on the chemical and spectral methods.

  5. Electroweak corrections to hadronic event shapes

    CERN Document Server

    Denner, Ansgar; Gehrmann, Thomas; Kurz, Christian


    We report on a recent calculation of the electroweak O(\\alpha^3\\alpha_s) corrections to 3-jet production and related event-shape observables at e+e- colliders. The calculation properly accounts for the experimental photon isolation criteria and for the corrections to the total hadronic cross section. Corrections to the normalised event-shape distributions, which are exemplarily discussed here for the thrust distribution at LEP and linear-collider energies, turn out to be at the few-per-cent level and show remnants of the radiative return to the Z pole even after inclusion of appropriate cuts.

  6. Characterization of the seed oils from kiwi (Actinidia chinensis, passion fruit (Passiflora edulis and guava (Psidium guajava

    Directory of Open Access Journals (Sweden)

    Piombo Georges


    Full Text Available Oils extracted from three exotic fruits, guava, kiwi and passion fruit were analyzed to evaluate the possible commercial interest for these waste materials from fruit juices industry. Results showed interesting fatty acids compositions with high amounts of essential fatty acids such as 62.3% alpha linolenic acid for kiwi seed oil, and respectively 73.4% and 77.0% for omega 6 linoleic acid in passion fruit and guava seed oils. Fatty acids regiodistribution, sterols and tocopherols contents were also analyzed to try to establish the potential nutritional interest of such oils.

  7. The depolarizing action of 5-hydroxytryptamine on rabbit vagal afferent and sympathetic neurones in vitro and its selective blockade by ICS 205-930.



    Depolarizing responses to 5-hydroxytryptamine (5-HT) were recorded from rabbit nodose (NG) and superior cervical (SCG) ganglia using the sucrose-gap technique. The antagonist potency and selectivity of ICS 205-930 ([3 alpha-tropanyl]-1H-indole-3-carboxylic acid ester) were investigated. In NG, 5-HT (5 to 80 nmol) evoked depolarizations of graded amplitude. The ED50 was 18.2 (10.9-30.5) nmol (geometric mean, 95% confidence limits). Responses were blocked surmountably by ICS 205-930, 10(-11) an...

  8. Terpenoid constituents from leaves of Guarea kunthiana

    Energy Technology Data Exchange (ETDEWEB)

    Garcez, Fernanda R.; Garcez, Walmir S.; Bazzo, Rita de Cassia [Mato Grosso do Sul Univ., Campo Grande, MS (Brazil). Dept. de Quimica]. E-mail:; Silva, Ana Francisca G. da [Universidade Estadual de Mato Grosso do Sul, Mundo Novo, MS (Brazil). Unidade Universitaria de Mundo Novo; Resende, Ubirazilda M. [Mato Grosso do Sul Univ., Campo Grande, MS (Brazil). Dept. de Biologia


    From leaves of Guarea kunthiana one new kaurene diterpene (ent-kaur-16-en-2-one) was isolated along with eight known diterpenes (ent-kaur-16-ene, ent-3{alpha}- and 3{beta}-hydroxykaur-16-ene, kolavelool, kolavenol, kolavenal, ent-13-epi-manoyloxide and (-)-nephthenol), four sesquiterpenes (alismol, alismoxide, spathulenol and 4{beta},10{alpha}-aromadendranediol), polyprenol-12 and {alpha}- and {delta}-tocopherols. Kolavenal is reported for the first time as a natural product, as well as the occurrence of cembrane- and ent-kaurane-type diterpenes in the Meliaceae. (author)

  9. Triterpenos de Styrax camporum (styracaceae

    Directory of Open Access Journals (Sweden)

    Pauletti Patrícia Mendonça


    Full Text Available Chemical investigation of the leaves of Styrax camporum (Styracaceae resulted in the isolation of the lignan lariciresinol and six triterpenes: ursolic acid, 2alpha,3alpha-dihydroxy-urs-12-en-28-oic acid and mixtures of uvaol and erythrodiol, as well as 3beta-O-trans-p-coumaroyl-2alpha-hydroxy-urs-12-en-28-oic acid and 3b-O-trans-p-coumaroylmaslinic acid. The structures of these compounds were established by spectroscopic analysis. This paper deals with the first report of these compounds in S. camporum.

  10. Antifungal iridoids, triterpenes and phenol compounds from Alibertia myrciifolia Sprunge Ex. Schum

    Energy Technology Data Exchange (ETDEWEB)

    Luciano, Joao Henrique S.; Lima, Mary Anne S.; Silveira, Edilberto Rocha [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Centro de Ciencias. Dept. de Quimica Organica e Inorganica; Vasconcelos, Ilka Maria; Fernandes, Georgia Sampaio [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Dept. de Bioquimica e Biologia Molecular; Souza, Elnatan Bezerra de [Universidade do Vale do Acarau, Sobral, CE (Brazil). Coord. de Biologia


    The new iridoid glucoside 10-O-vanilloyl-geniposidic acid has been isolated from the aerial parts of Alibertia myrciifolia along with hydroxyhopanone, 3{alpha},22-dihydroxyhopane, ursolic acid, luteolin-3',4'-dimethyl ether, caffeic acid and geniposidic acid. The structures of the isolated compounds were determined by means of mass spectrometry and nuclear magnetic resonance spectral analyses. The antifungal activities of the iridoids 10-O-vanilloyl-geniposidic acid and geniposidic acid were evaluated against the phytopathogenic fungi strains Colletotrichum gloeosporioides, Fusarium solani and Aspergillus niger. (author)

  11. Structural investigation of resin glycosides from Ipomoea lonchophylla. (United States)

    MacLeod, J K; Ward, A; Oelrichs, P B


    A fraction from Ipomoea lonchophylla, which was toxic to mice, contained an inseparable mixture of resin glycosides with differing numbers of C5 ester groups on the hexasaccharide chain. After alkaline hydrolysis of the esters, the structure of the major component (1) was elucidated using high-field NMR spectroscopy, mass spectrometry, chemical studies, and comparison with known resin glycosides. Compound 1 was identified as 3,11-dihydroxytetradecanoic acid 11-O-beta-quinovopyranosyl-(1-->2)-beta-glucopyranosyl-(1-->3)- [alpha-rhamnopyranosyl- (1-->4)]-quinovopyranosyl-(1-->2)-beta-glucopyranosyl-(1-->2)-beta -fucopyranoside.

  12. Arabidopsis thaliana RGXT1 and RGXT2 Encode Golgi-Localized (1,3)--D-Xylosyltransferases Involved in the Synthesis of Pectic Rhamnogalacturonan-II

    DEFF Research Database (Denmark)

    Egelund, Jack; Petersen, Bent Larsen; Motawia, M S


    Two homologous plant-specific Arabidopsis thaliana genes, RGXT1 and RGXT2, belong to a new family of glycosyltransferases (CAZy GT-family-77) and encode cell wall (1,3)-alpha-d-xylosyltransferases. The deduced amino acid sequences contain single transmembrane domains near the N terminus, indicative...... in rhamnogalacturonan-II, a complex polysaccharide essential to vascular plants, and is conserved across higher plant families. Rhamnogalacturonan-II isolated from both RGXT1 and RGXT2 T-DNA insertional mutants functioned as specific acceptor molecules in the xylosyltransferase assay. Expression of RGXT1- and RGXT2...

  13. Biotransformation of sclareolide by filamentous fungi: cytotoxic evaluations of the derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Cano, Arturo [Universidad Nacional Autonoma de Mexico, D.F. (Mexico). Facultad de Estudios Superiores Zaragoza; Ramirez-Apan, Maria Teresa; Delgado, Guillermo, E-mail: delgado@unam.m [Universidad Nacional Autonoma de Mexico, D.F. (Mexico)


    Sclareolide (1) was incubated with eight different species of filamentous fungi conventionally used for bio-oxidations. Compound 1 was metabolized with Aspergillus niger in medium A to yield 3-ketosclareolide (2) and 3b-hydroxysclareolide (4), while in medium B (containing major number of nutrients with respect to medium A), compounds 2, 4, 3{alpha},6{beta}-dihydroxysclareolide (16), 1-ketosclareolide (17), 3-keto-15-hydroxysclareolide (18) and 3{beta},15-dihydroxysclareolide (19) were obtained. The biotransformation products 16-19 were found to be new substances. Fermentation of 1 with Cunninghamella blackesleeana using medium A afforded 2 and 4, while using medium B yielded 2, 4, 16 and 17. Compounds 2, 4 and 17 were also obtained with Curvularia lunata. Biotransformation of 1 with Beauveria bassiana yielded 4 in satisfactory yield, with Rhizopus oligosporus and Mucor miehei afforded 2 and 4, while with R. nigricans and Fusarium moliniforme yielded 2, 4 and 16. Cytotoxic evaluation of 1 and the obtained products against selected human cancer cell lines (U251, PC-3, K562, HCT-15, MCF-7 and SKUL-1) indicated that 16 (3{alpha},6{beta}-dihydroxysclareolide) displayed moderate cytotoxic (IC{sub 50} < 100 {mu}M) against U251, PC-3, HCT-15 and MCF-7. (author)

  14. The enzymic and chemical synthesis of ursodeoxycholic and chenodeoxycholic acid from cholic acid. (United States)

    Sutherland, J D; Macdonald, I A; Forrest, T P


    Three approaches to the synthesis of ursodeoxycholic acid (UDC) from cholic acid have been investigated: (i) oxidation of cholic acid to 3 alpha, 7 alpha-dihydroxy-12 keto-5 beta-cholanoic acid (12K-CDC) with Clostridium group P 12 alpha-hydroxysteroid dehydrogenase (HSDH), isomerization of 12K-CDC to 3 alpha, 7 beta-dihydroxy-12 keto-5 beta-cholanoic acid (12K-UDC) with Clostridium absonum 7 alpha- and 7 beta-HSDH and reduction of 12K-UDC by Wolff-Kishner to UDC; (ii) isomerization of cholic acid to ursocholic acid (UC) by C. absonum 7 alpha- and 7 beta-HSDH, oxidation of UC to 12K-UDC with Clostridium group P 12 alpha-HSDH and Wolff-Kishner reduction of 12K-UDC to UDC; (iii) oxidation of cholic acid to 12K-CDC by Clostridium group P 12 alpha-HSDH, Wolff-Kishner reduction of 12K-CDC to chenodeoxycholic acid (CDC) and isomerization of CDC to UDC using whole cell cultures of C. absonum. In the first two approaches (using cell free systems) the yields of desired product were relatively low primarily due to the formation of various side products. The third method proved the most successful giving an overall yield of 37% (UDC) whose structure was verified by mass spectroscopy of the methyl ester.

  15. Combined chemical-enzymic synthesis of deoxygenated oligosaccharide analogs: transfer of deoxygenated D-GlcpNAc residues from their UDP-GlcpNAc derivatives using N-acetylglucosaminyltransferase I. (United States)

    Srivastava, G; Alton, G; Hindsgaul, O


    The 3''-, 4''-, and 6''-deoxy analogs of UDP-GlcpNAc have been synthesized chemically and found to act as donor-substrates for N-acetylglucosaminyltransferase-I (GnT-I) from human milk. Incubation of UDP-GlcpNAc and these deoxy analogs with GnT-I in the presence of alpha-D-Manp-(1----3)-[alpha-D-Manp-(1----6)]-beta-D-Manp -O(CH2)8COOMe gave beta-D-GlcpNAc-(1----2)-alpha-D-Manp-(1----3)-[alpha-D-Manp- (1----6)]- beta-D-Manp-O(CH2)8COOMe (6), and the deoxy analogs 12-14 where HO-3, HO-4, and HO-6, respectively, of the beta-D-GlcNAc residue were replaced by hydrogen. The tetrasaccharide glycosides 6 and 12-14 were characterized by 1H-n.m.r. spectroscopy and evaluated as acceptors for GnT-II, the next enzyme in the pathway of biosynthesis of Asn-linked oligosaccharides. Deoxygenation of the 3-position of the beta-D-GlcNAc residue of 6 completely abolished its acceptor activity, whereas removal of HO-4 or HO-6 caused only modest decreases in activity.

  16. [Triterpenoid saponins from flower bud of Jasminum officinale var. grandiflorum]. (United States)

    Zhao, Gui-Qin; Dong, Jun-Xing


    To study the chemical constituent bud of the flowers of Jasminum officinale var. grandiflorum. The compounds were isolated and purified by recrystallization and chromatography on silica gel and Sephadex LH - 20 column. Their structures were elucidated on the basis of physicochemical properties and spectral analysis. Six triterpenoid saponins were identified as 3-O-alpha-L-rhamnopyranosyl (1 --> 2)-beta-D-xylopyranosyl- hederagenin-28-O-beta-D-galactopyranosyl (1 --> 6)-beta-D-galactopyranosyl ester (1), hederagenin-3-O-beta-D-glucopyranosyl (1 --> 3)-alpha-L-arabinopyranoside (2), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-oic-O-beta-D-glucopyranosyl ester (3), hederagenin-3-O-beta-D-xylopyranosyl (1 --> 3)-alpha-L-rhamnopyranosyl (1 --> 2)-alpha-L-arabinopyranoside (4), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-oic-O-alpha-L-rhamnopyranosyl (1 --> 4)-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranosyl ester (5), hederagenin-3-O-alpha-L-rhamnopyranosyl (1 --> 2)-alpha-L-arabinopyranoside (6). Compound 1 is a new compound. Compounds 2, 3, 4, 5, 6 were isolated from the genus Jasminum for the first time.

  17. New constituents from the trunk bark of Tabebuia heptaphylla; Novos constituintes quimicos das cascas do caule de Tabebuia heptaphylla

    Energy Technology Data Exchange (ETDEWEB)

    Garcez, Fernanda Rodrigues; Garcez, Walmir Silva; Mahmoud, Talal Suleiman; Figueiredo, Patricia de Oliveira [Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS (Brazil). Dept. de Quimica]. E-mail:; Resende, Ubirazilda Maria [Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS (Brazil). Dept. de Biologia


    A new triterpene, 3beta,6beta,21beta-trihydroxyolean-12-ene and a new iridoid, 8alpha-methyl-8beta-hydroxy-6beta-(3',4'-dimethoxy)benzoyloxy-1alpha, 3alpha-dimethoxy-octahydro-cyclopenta[c]pyran were isolated from the trunk bark of a specimen of Tabebuia heptaphylla (Bignoniaceae) collected in the 'Pantanal' of Mato Grosso do Sul, Brazil. Twelve known compounds were also obtained in this work, comprising four iridoids, 6-O-p-hydroxybenzoylajugol, 6-O-p-methoxybenzoylajugol, 6-O-3{sup ,}4{sup -}dimethoxybenzoylajugol, 8alpha-methyl-8beta-hydroxy-6beta-(4'-hydroxy)benzoyloxy-1alpha, 3alpha-dimethoxy-octahydro-cyclopenta[c]pyran, a cyclopentene dialdehyde, 2-formyl-5-(3',4'-dimethoxybenzoyloxy) -3-methyl-2-cyclopentene-1-acetaldehyde, a phenylethanoid glycoside, verbascoside and three benzoic acid derivatives, p-hydroxybenzoic, pmethoxybenzoic and 3,4-dimethoxybenzoic acids, in addition to squalene, sitostenone and sitosterol. The antioxidant properties of the isolated compounds were also evaluated in this work. (author)

  18. Sialic acid-containing sugar chains of hen ovalbumin and ovomucoid. (United States)

    Yamashita, K; Tachibana, Y; Hitoi, A; Kobata, A


    The acidic oligosaccharide fractions released from hen ovalbumin and ovomucoid by hydrazinolysis contain both sialyloligosaccharides and sulfated oligosaccharides. The sialyloligosaccharides were converted into neutral oligosaccharides by sialidase digestion, and separated from sulfated oligosaccharides by paper electrophoresis. Structural studies of these neutral oligosaccharides showed that the oligosaccharides of ovalbumin have different structural characteristics from those of ovomucoid, i.e., all sialyloligosaccharides from ovomucoid contain a pentasaccharide, alpha-D-Manp-(1----3)-[alpha-D-Manp-(1----6)]-beta-D-Manp -(1----4)-GlcpNAc- (1----4)-GlcpNAc, as a common core, and the smallest oligomannosyl core of the sugar chains from ovalbumin is alpha-D-Manp-(1----3)-alpha-D-Manp-(1----6)-[alpha-D-Manp -(1----3)]-beta-D- Manp-(1----4)-GlcpNAc-(1----4)-GlcpNAc. By methanolysis followed by N-acetylation, sialyl oligosaccharides, free from sulfated oligosaccharides, were recovered quantitatively from the acidic fractions of ovalbumin and ovomucoid. Methylation analysis of these sialyloligosaccharide mixtures, before and after sialidase digestion, showed that all sialic acid of both glycoproteins occurs as a alpha-Sia-(2----3)-D-Galp group.

  19. Testosterone metabolism of fibroblasts grown from prostatic carcinoma, benign prostatic hyperplasia and skin fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Schweikert, H.U.; Hein, H.J.; Romijn, J.C.; Schroeder, F.H.


    The metabolism of (1,2,6,7-3H)testosterone was assessed in fibroblast monolayers derived from tissue of 5 prostates with benign hyperplasia (BPH), 4 prostates with carcinoma (PC), and 3 biopsy samples of skin, 2 nongenital skin (NG) and 1 genital skin. The following metabolites could be identified: androstanedione androstenedione, dihydrotestosterone, androsterone, epiandrosterone, androstane-3 alpha, 17 beta-diol and androstane-3 beta, 17 beta-diol. Testosterone was metabolized much more rapidly in fibroblasts originating from prostatic tissue than in fibroblasts derived from NG. A significantly higher formation of 5 alpha-androstanes and 3 alpha-hydroxysteroids could be observed in fibroblasts from BPH as compared to PC. 17-ketosteroid formation exceeded 5 alpha-androstane formation in BPH, whereas 5 alpha-reduction was the predominant pathway in fibroblasts grown from PC and NG. Since testosterone metabolism in fibroblasts of prostatic origin therefore resembles in many aspects that in whole prostatic tissue, fibroblasts grown from prostatic tissues might be a valuable tool for further investigation of the pathogenesis of human BPH and PC.

  20. Expression of PGE2 EP3 receptor subtypes in the mouse preoptic region. (United States)

    Vasilache, Ana Maria; Andersson, Josefin; Nilsberth, Camilla


    Inflammatory-induced fever is dependent on prostaglandin E(2) (PGE(2)) binding to its EP(3) receptor in the thermoregulatory region of the hypothalamus, but it is not known which EP(3) receptor isoform(s) that is/are involved. We identified the EP(3) receptor expression in the mouse preoptic region by in situ hybridization and isolated the corresponding area by laser capture microdissection. Real-time RT-PCR analysis of microdissected tissue revealed a predominant expression of the EP(3alpha) isoform, but there was also considerable expression of EP(3gamma), corresponding to approximately 15% of total EP(3) receptor expression, whereas EP(3beta) was sparsely expressed. This distribution was not changed by immune challenge induced by peripheral administration of LPS, indicating that EP(3) receptor splicing and distribution is not activity dependent. Considering that EP(3alpha) and EP(3gamma) are associated with inhibitory and stimulatory G-proteins, respectively, the present data demonstrate that the PGE(2) response of the target neurons is intricately regulated.


    Directory of Open Access Journals (Sweden)

    Davide Vito Moretti


    Full Text Available Objective: temporo-parietal cortex thinning is associated to mild cognitive impairment (MCI due to Alzheimer disease (AD. The increase of EEG upper/low alpha power ratio has been associated with AD-converter MCI subjects. We investigated the association of alpha3/alpha2 ratio with patterns of cortical thickness in MCI.Methods: 74 adult subjects with MCI underwent clinical and neuropsychological evaluation, electroencephalogram (EEG recording and high resolution 3D magnetic resonance imaging (MRI. Alpha3/alpha2 power ratio as well as cortical thickness was computed for each subject. Three MCI groups were detected according to increasing tertile values of upper/low alpha power ratio . Difference of cortical thikness among the groups was estimated. Pearson’s r was used to assess the topography of the correlation between cortical thinning and memory impairment.Results: High upper/low alpha power ratio group had total cortical grey matter (CGM volume reduction of 471 mm2 than low upper/low alpha power ratio group (p

  2. Riemannian geometry of thermodynamics and systems with repulsive power-law interactions. (United States)

    Ruppeiner, George


    A Riemannian geometric theory of thermodynamics based on the postulate that the curvature scalar R is proportional to the inverse free energy density is used to investigate three-dimensional fluid systems of identical classical point particles interacting with each other via a power-law potential energy gamma r(-alpha) . Such systems are useful in modeling melting transitions. The limit alpha-->infinity corresponds to the hard sphere gas. A thermodynamic limit exists only for short-range (alpha>3) and repulsive (gamma>0) interactions. The geometric theory solutions for given alpha>3 , gamma>0 , and any constant temperature T have the following properties: (1) the thermodynamics follows from a single function b (rho T(-3/alpha) ) , where rho is the density; (2) all solutions are equivalent up to a single scaling constant for rho T(-3/alpha) , related to gamma via the virial theorem; (3) at low density, solutions correspond to the ideal gas; (4) at high density there are solutions with pressure and energy depending on density as expected from solid state physics, though not with a Dulong-Petit heat capacity limit; (5) for 33.7913 a phase transition is required to go between these regimes; (7) for any alpha>3 we may include a first-order phase transition, which is expected from computer simulations; and (8) if alpha-->infinity, the density approaches a finite value as the pressure increases to infinity, with the pressure diverging logarithmically in the density difference.

  3. Effect of 1,1-dimethylphenyl 1,4-piperazinium on mouse tracheal smooth muscle responsiveness. (United States)

    Dorion, G; Israël-Assayag, E; Beaulieu, M J; Cormier, Y


    Bronchial hyperresponsiveness is one of the main features of asthma. A nicotinic receptor agonist, 1,1-dimethylphenyl 1,4-piperazinium (DMPP), has been shown to have an inhibitory effect on airway response to methacholine in an in vivo model of asthma. The aims of this study were to 1) verify whether nicotinic acetylcholine receptors (nAChR) were present on mouse tracheal smooth muscle, 2) verify whether bronchoprotection observed in mice was due to a direct effect on airway smooth muscle, and 3) compare the effects of nicotinic agonists to that of salbutamol. Alpha3-, alpha4-, and alpha7-nAChR subunits were detected by immunofluorescence on tracheal tissues from normal BALB/c mice. The effect of DMPP on tracheal responsiveness was verified by an isometric method. Tracheas were isolated from normal mice, placed in organ baths, and contracted with a single dose of methacholine. Cumulative doses of DMPP or salbutamol were added to the baths. Results show that mouse tracheal smooth muscle is positive for alpha4- and alpha7-nAChR subunits and that the epithelium is positive for alpha3-, alpha4-, and alpha7-subunits. DMPP induced a greater dose-dependent relaxation of tracheal smooth muscles precontracted with methacholine than with salbutamol. These results suggest that the smooth muscle-relaxing effect of DMPP could have some interest in the treatment of obstructive pulmonary diseases.

  4. Novos constituintes químicos das cascas do caule de Tabebuia heptaphylla New constituents from the trunk bark of Tabebuia heptaphylla

    Directory of Open Access Journals (Sweden)

    Fernanda Rodrigues Garcez


    Full Text Available A new triterpene, 3beta,6beta,21beta-trihydroxyolean-12-ene and a new iridoid, 8alpha-methyl-8beta-hydroxy-6beta-(3',4'-dimethoxybenzoyloxy-1 alpha,3alpha-dimethoxy-octahydro-cyclopenta[c]pyran were isolated from the trunk bark of a specimen of Tabebuia heptaphylla (Bignoniaceae collected in the "Pantanal" of Mato Grosso do Sul, Brazil. Twelve known compounds were also obtained in this work, comprising four iridoids, 6-O-p-hydroxybenzoylajugol, 6-O-p-methoxybenzoylajugol, 6-O-3",4"-dimethoxybenzoylajugol, 8alpha-methyl-8beta-hydroxy-6beta-(4'-hydroxybenzoyloxy-1alpha,3 alpha-dimethoxy-octahydro-cyclopenta[c]pyran, a cyclopentene dialdehyde, 2-formyl-5-(3',4'-dimethoxybenzoyloxy-3-methyl-2-cyclopentene-1-acetaldehyde, a phenylethanoid glycoside, verbascoside and three benzoic acid derivatives, p-hydroxybenzoic, p-methoxybenzoic and 3,4-dimethoxybenzoic acids, in addition to squalene, sitostenone and sitosterol. The antioxidant properties of the isolated compounds were also evaluated in this work.

  5. Improved expression of His(6)-tagged strictosidine synthase cDNA for chemo-enzymatic alkaloid diversification. (United States)

    Yang, Liuqing; Zou, Hongbin; Zhu, Huajian; Ruppert, Martin; Gong, Jingxu; Stöckigt, Joachim


    Strictosidine synthase (STR1) catalyzes the stereoselective formation of 3alpha(S)-strictosidine from tryptamine and secologanin. Strictosidine is the key intermediate in the biosynthesis of 2,000 plant monoterpenoid indole alkaloids, and it is a key precursor of enzyme-mediated synthesis of alkaloids. An improved expression system is described which leads to optimized His(6)-STR1 synthesis in Escherichia coli. Optimal production of STR1 was achieved by determining the impact of co-expression of chaperones pG-Tf2 and pG-LJE8. The amount and activity of STR1 was doubled in the presence of chaperone pG-Tf2 alone. His(6)-STR1 immobilized on Ni-NTA can be used for enzymatic synthesis of strictosidines on a preparative scale. With the newly co-expressed His(6)-STR1, novel 3alpha(S)-12-azastrictosidine was obtained by enzymatic catalysis of 7-azatryptamine and secologanin. The results obtained are of significant importance for application to chemo-enzymatic approaches leading to diversification of alkaloids with novel improved structures.

  6. Evolution of Low-Mass Population III Stars

    CERN Document Server

    Suda, T; Itoh, N; Suda, Takuma; Fujimoto, Masayuki Y.


    The evolution of low-mass Pop.III of mass 0.8-1.1 Msun is followed from the main sequence to the onset of H mixing into a convective zone driven by the He core flash. We examine the dependence of stellar structure on the adopted input physics and find that consideration of the non-resonant term in the 3-alpha reaction rate is crucial, since the CN cycle is activated when the abundance by number of 12C produced by this reaction is no larger than 10^-11-10^-9. This explains why recent computations of Pop.III do not find a He flash occurring at the bottom of the H-burning shell at the beginning of the H shell burning phase, as first found by Fujimoto et al.(1990) who did not include the non-resonant term in their calculations. We confirm that, if the non-resonant term of the 3-alpha reaction rate is not included in the input physics, the He-H flash in the shell occurs for M >= 1.0 Msun. We also find that the treatment of the EOS for the Coulomb liquid region, where electron conduction and radiation compete, is i...

  7. Acne and hirsutism in polycystic ovary syndrome: clinical, endocrine-metabolic and ultrasonographic differences. (United States)

    Falsetti, L; Gambera, A; Andrico, S; Sartori, E


    The aim of this study was to investigate whether the absence or presence of acne or hirsutism in 248 women with polycystic ovary syndrome was associated with different clinical, endocrine, metabolic and ultrasonographic factors. Patients were divided into three groups: 96 (38.7%) without any androgenic symptoms; 94 (37.9%) with only hirsutism; and 58 (23.4%) with only acne. The cycle alterations (oligomenorrhea or amenorrhea) and the echographic ovarian morphology (polycystic or multifollicular ovaries) showed no significant differences between the three groups. Hirsutism was associated with a greater incidence of obesity and insulin resistance, with an increase of 17-hydroxyprogesterone, ovarian and adrenal androgens, 3alpha-androstanediol glucuronide, insulin, insulin-like growth factor-I and low luteinizing hormone, sex hormone binding globulins and insulin-like growth factor binding protein-1 levels. Acne was associated only with the lowest 3alpha-androstanediol glucuronide levels. Therefore, two different pathogenetic mechanisms may play a role in the onset of acne and hirsutism.

  8. Antioxidant and free radical scavenging activity of flavonol glycosides from different Aconitum species. (United States)

    Braca, Alessandra; Fico, Gelsomina; Morelli, Ivano; De Simone, Francesco; Tomè, Franca; De Tommasi, Nunziatina


    Bioassay-guided fractionation by 1,1-diphenyl-2-dipicrylhydrazyl (DPPH) radical scavenging test of polar extracts of some Italian Aconitum species (A. napellus subsp. tauricum, A. napellus subsp. neomontanum, A. paniculatum, A. vulparia) led to the isolation of 13 flavonol glycosides: quercetin 3-O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->2)-beta-glucopyranoside-7-O-alpha-rhamnopyranoside (1), kaempferol 3-O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->2)-beta-glucopyranoside-7-O-alpha-rhamnopyranoside (2), quercetin 3-O-(6-trans-p-coumaroyl)-beta-glucopyranosyl-(1-->2)-beta-glucopyranoside-7-O-alpha-rhamnopyranoside (3), kaempferol 3-O-(6-trans-p-coumaroyl)-beta-glucopyranosyl-(1-->2)-beta-glucopyranoside-7-O-alpha-rhamnopyranoside (4), quercetin 7-O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->3)-alpha-rhamnopyranoside-3-O-beta-glucopyranoside (5), kaempferol 7-O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->3)-alpha-rhamnopyranoside-3-O-beta-glucopyranoside (6), kaempferol 7-O-(6-trans-p-coumaroyl)-beta-glucopyranosyl-(1-->3)-alpha-rhamnopyranoside-3-O-beta-glucopyranoside (7), kaempferol 3-O-beta-(2"-acetyl)galactopyranoside (8), kaempferol 3-O-beta-(2"-acetyl)galactopyranoside-7-O-alpha-arabinopyranoside (9), quercetin 3-O-beta-(2"-acetyl)galactopyranoside-7-O-alpha-arabinopyranoside (10), quercetin 3,7-di-O-alpha-rhamnopyranoside (11), kaempferol 3,7-di-O-alpha-rhamnopyranoside (12) and quercetin 3-O-beta-glucopyranoside-7-O-alpha-rhamnopyranoside (13). Their antioxidant activity (AA) was determined by measuring free radical scavenging activity by DPPH test and the coupled oxidation of beta-carotene and linoleic acid assay. The results showed that 5 is the most active compound in the DPPH free-radical scavenging test (IC(50) 1.9 microM) while in the coupled oxidation of beta-carotene and linoleic acid assay compound 1 has the highest inhibitory ratio after 1h (58.9%). Some structure-activity relationships on the AA were obtained.

  9. Synovial tissue hypoxia and inflammation in vivo.

    LENUS (Irish Health Repository)

    Ng, C T


    INTRODUCTION: Hypoxia is a microenvironmental feature in the inflamed joint, which promotes survival advantage for cells. The aim of this study was to examine the relationship of partial oxygen pressure in the synovial tissue (tPO(2)) in patients with inflammatory arthritis with macroscopic\\/microscopic inflammation and local levels of proinflammatory mediators. METHODS: Patients with inflammatory arthritis underwent full clinical assessment and video arthroscopy to quantify macroscopic synovitis and measure synovial tPO(2) under direct visualisation. Cell specific markers (CD3 (T cells), CD68 (macrophages), Ki67 (cell proliferation) and terminal deoxynucleotidyl transferase dUTP nick end labelling (cell apoptosis)) were quantified by immunohistology. In vitro migration was assessed in primary and normal synoviocytes (synovial fibroblast cells (SFCs)) using a wound repair scratch assay. Levels of tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), interferon gamma (IFNgamma), IL6, macrophage inflammatory protein 3alpha (MIP3alpha) and IL8 were quantified, in matched serum and synovial fluid, by multiplex cytokine assay and ELISA. RESULTS: The tPO(2) was 22.5 (range 3.2-54.1) mm Hg and correlated inversely with macroscopic synovitis (r=-0.421, p=0.02), sublining CD3 cells (-0.611, p<0.01) and sublining CD68 cells (r=-0.615, p<0.001). No relationship with cell proliferation or apoptosis was found. Primary and normal SFCs exposed to 1% and 3% oxygen (reflecting the median tPO(2) in vivo) induced cell migration. This was coupled with significantly higher levels of synovial fluid tumour necrosis factor alpha (TNFalpha), IL1beta, IFNgamma and MIP3alpha in patients with tPO(2) <20 mm Hg (all p values <0.05). CONCLUSIONS: This is the first study to show a direct in vivo correlation between synovial tPO(2), inflammation and cell migration, thus it is proposed that hypoxia is a possible primary driver of inflammatory processes in the arthritic joint.

  10. Molecular cloning and characterization of CIDE-3, a novel member of the cell-death-inducing DNA-fragmentation-factor (DFF45)-like effector family. (United States)

    Liang, Liang; Zhao, Mujun; Xu, Zhenhua; Yokoyama, Kazunari K; Li, Tsaiping


    DNA fragmentation is one of the critical steps in apoptosis, which is induced by DNA fragmentation factor (DFF). DFF is composed of two subunits, a 40 kDa caspase-activated nuclease (DFF40) and a 45 kDa inhibitor (DFF45). Recently a novel family of cell-death-inducing DFF45-like effectors (CIDEs) has been identified. Among CIDEs, two from human (CIDE-A and CIDE-B) and three from mouse (CIDE-A, CIDE-B and FSP27) have been reported. In this study human CIDE-3, a novel member of CIDEs, was identified upon sequence analysis of a previously unidentified cDNA that encoded a protein of 238 amino acids. It was shown to be a human homologue of mouse FSP27, and shared homology with the CIDE-N and CIDE-C domains of CIDEs. Apoptosis-inducing activity was clearly shown by DNA-fragmentation assay of the nuclear DNA of CIDE-3 transfected 293T cells. The expression pattern of CIDE-3 was different from that of CIDE-B. As shown by Northern-blot analysis, CIDE-3 was expressed mainly in human small intestine, heart, colon and stomach, while CIDE-B showed strong expression in liver and small intestine and at a lower level in colon, kidney and spleen. Green-fluorescent-protein-tagged CIDE-3 was revealed in some cytosolic corpuscles. Alternative splicing of the CIDE-3 gene was also identified by reverse transcription PCR, revealing that two transcripts, CIDE-3 and CIDE-3alpha, were present in HepG2 and A375 cells. CIDE-3 comprised a full-length open reading frame with 238 amino acids; in CIDE-3alpha exon 3 was deleted and it encoded a protein of 164 amino acids. Interestingly the CIDE-3alpha isoform still kept the apoptosis-inducing activity and showed the same pattern of subcellular localization as CIDE-3. Consistent with its chromosome localization at 3p25, a region associated with high frequency loss of heterozygosity in many tumours, CIDE-3 may play an important role in prevention of tumorigenesis.

  11. Bioequivalence studies of tibolone in premenopausal women and effects on expression of the tibolone-metabolizing enzyme AKR1C (aldo-keto reductase) family caused by estradiol. (United States)

    Kang, Keon W; Kim, Yoon G


    This study aimed to investigate the bioequivalence of a test formulation of tibolone with the marketed reference formulation in 24 young healthy female volunteers. Tibolone is a synthetic steroid hormone for menopausal women. Volunteers were treated with the 2 formulations of tibolone (total dose of active ingredient 2.5 mg) according to a 2 x 2 crossover design with a 1-week washout period. Plasma concentrations of 3alpha- and 3beta-hydroxytibolone, which are major metabolites of tibolone, were assayed in timed samples over a 24-hour period with a validated gas chromatography/mass spectrometry (GC/MS) method that had a lower limit of quantification of 0.5 ng/mL. The reference and test formulations gave a mean 3alpha-hydroxytibolone C(max) of 5.0 and 5.2 ng/mL, respectively, and a mean 3beta-hydroxytibolone C(max) of 16.4 and 16.5 ng/mL, respectively. The mean AUC(t) of 3alpha-hydroxytibolone was 24.7 and 24.3 ng h/mL, whereas the mean AUC(t) of 3beta-hydroxytibolone was 57.6 and 54.8 ng h/mL for the test and reference formulations, respectively. The authors did not find significant differences in pharmacokinetic parameters between the 2 formulations, but metabolite formation was different from reports in postmenopausal women. The authors therefore measured the effects of estradiol on the expression of the tibolone-metabolizing enzymes, from the aldo-keto reductase (AKR1C) family, using HepG2 cell (human hepatoma cells) and MCF-7 cell (human breast cancer cells). Estradiol increased mRNA levels of AKR1C1, AKR1C2, and AKR1C3 and protein levels of total AKR1C in HepG2 cells. Estradiol selectively enhanced levels of AKR1C2 mRNA in MCF-7 cells. Thus, changes in the major metabolites of tibolone might result from changes in AKR1C family expression by patient estrogen status.

  12. Expression of 10 GABA(A) receptor subunit messenger RNAs in the motor-related thalamic nuclei and basal ganglia of Macaca mulatta studied with in situ hybridization histochemistry. (United States)

    Kultas-Ilinsky, K; Leontiev, V; Whiting, P J


    In situ hybridization histochemistry technique with [35S]UTP-labelled riboprobes was used to study the expression pattern of 10 GABA(A) receptor subunit messenger RNAs in the basal ganglia and motor thalamic nuclei of rhesus monkey. Human transcripts were used for the synthesis of alpha2, alpha4, beta2, beta3, gamma1 and delta subunit messenger RNA probes. Rat complementary DNAs were used for generating alpha1, alpha3, beta1 and gamma2 subunit messenger RNA probes. Nigral, pallidal and cerebellar afferent territories in the ventral tier thalamic nuclei all expressed alpha1, alpha2, alpha3, alpha4, beta1, beta2, beta3, delta and gamma2 subunit messenger RNAs but at different levels. Each intralaminar nucleus displayed its own unique expression pattern. In the thalamus, gamma1 subunit messenger RNA was detected only in the parafascicular nucleus. Comparison of the expression patterns with the known organization of GABA(A) connections in thalamic nuclei suggests that (i) the composition of the receptor associated with reticulothalamic synapses, except for those in the intralaminar nuclei, may be alpha1alpha4beta2delta, (ii) receptors of various other subunit compositions may operate in the local GABAergic circuits, and (iii) the composition of receptors at nigro- and pallidothalamic synapses may differ, with those at nigrothalamic probably containing beta1 and gamma2 subunits. In the medial and lateral parts of the globus pallidus, the subthalamic nucleus and the substantia nigra pars reticularis, the alpha1, beta2 and gamma2 messenger RNAs were co-expressed at a high level suggesting that this subunit composition was associated with all GABAergic synapses in the direct and indirect striatal output pathways. Various other subunit messenger RNAs were also expressed but at a lower level. In the substantia nigra pars compacta the most highly expressed messenger RNAs were alpha3, alpha4 and beta3; all other subunit messenger RNAs studied, except for gamma1, alpha1 and

  13. Impact-induced tensile waves in a kind of phase-transforming materials

    CERN Document Server

    Huang, Shou-Jun


    This paper concerns the global propagation of impact-induced tensile waves in a kind of phase-transforming materials. It is well-known that the governing system of partial differential equations is hyperbolic-elliptic and the initial-boundary value problem is not well-posed at all levels of loading. By making use of fully nonlinear stress-strain curve to model this material, Dai and Kong succeeded in constructing a physical solution of the above initial-boundary value problem. For the impact of intermediate range, they assumed that $\\beta<3\\alpha$ in the stress-response function for simplicity. In this paper, we revisit the impact problem and consider the propagation of impact-induced tensile waves for all values of the parameters $\\alpha$ and $\\beta$. The physical solutions for all levels of loading are obtained completely.

  14. Bile salts of the coelacanth, Latimeria chalumnae. (United States)

    Kihira, K; Akashi, Y; Kuroki, S; Yanagisawa, J; Nakayama, F; Hoshita, T


    Bile salts of the coelacanth, Latimeria chalumnae, Smith, have been analyzed and shown to have three bile alcohols, latimerol, 5 alpha-cyprinol, and 5 alpha-cholestane-3 beta, 7 alpha,-12 alpha,25,26-pentol, two C24 bile acids, chenodeoxycholic acid and cholic acid, one C26 bile acid, probably 3 beta, 7 alpha, 12 alpha-trihydroxy-27-nor-5 alpha-cholestan-26-oic acid, and two C27 bile acids, 3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha-cholestan-26-oic acid and 3 beta,7 alpha,12 alpha-trihydroxy-5 alpha-cholestan-26-oic acid as determined by gas-liquid chromatography and gas-liquid chromatography-mass spectrometry.

  15. Anacardic acid derivatives from Brazilian propolis and their antibacterial activity

    Energy Technology Data Exchange (ETDEWEB)

    Silva, M.S.S.; Lima, S.G. de; Lopes, J.A.D.; Chaves, M.H.; Cito, A.M.G.L. [Universidade Federal do Piaui (UFPI), Teresina, PI (Brazil). Dept. de Quimica]. E-mail:; Oliveira, E.H. [Universidade Federal do Piaui (UFPI), Teresina, PI (Brazil). Dept. de Microbiologia e Parasitologia; Reis, F.A.M. [Universidade Estadual de Campinas (UNICAMP), Campinas, SP (Brazil). Inst. de Quimica


    Propolis is a sticky, gummy, resinous substance collected by honeybees (Apis mellifera L.) from various plant sources, which has excellent medicinal properties. This paper describes the isolation and identification of triterpenoids and anacardic acid derivatives from Brazilian propolis and their antibacterial activity. Their structures were elucidated by {sup 1}H and {sup 13}C NMR, including uni- and bidimensional techniques; in addition, comparisons were made with data from academic literature. These compounds were identified as: cardanols (1a + 1b), cardols (2a + 2b), mono ene anacardic acid (3), alpha-amirine (4), beta-amirine (5), cycloartenol (6), 24-methylene-cycloartenol (7) and lupeol (8). The determination of the position of the double bond after a reaction with Dimethyl disulfide (DMDS) is described for the phenol derivatives. The ethanolic extract was tested in vitro for antimicrobial activity by using the disc diffusion method and it showed significant results against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Shigella spp. (author)

  16. Balancing omega-6 and omega-3 fatty acids in ready-to-use therapeutic foods (RUTF)

    DEFF Research Database (Denmark)

    Brenna, J Thomas; Akomo, Peter; Bahwere, Paluku


    Ready-to-use therapeutic foods (RUTFs) are a key component of a life-saving treatment for young children who present with uncomplicated severe acute malnutrition in resource limited settings. Increasing recognition of the role of balanced dietary omega-6 and omega-3 polyunsaturated fatty acids...... with altered PUFA content and looked at the effects on circulating omega-3 docosahexaenoic acid (DHA) status as a measure of overall omega-3 status. Supplemental oral administration of omega-3 DHA or reduction of RUTF omega-6 linoleic acid using high oleic peanuts improved DHA status, whereas increasing omega......-3 alpha-linolenic acid in RUTF did not. The results of these two small studies are consistent with well-established effects in animal studies and highlight the need for basic and operational research to improve fat composition in support of omega-3-specific development in young children as RUTF use...

  17. Margarines with linseed oil: nutritional interests, specificities and development

    Directory of Open Access Journals (Sweden)

    Renault Anne


    Full Text Available The last national study on individual food consumption confirmed that French consumers have a very low intake of omega 3 alpha-linolenic acid (ALA, as well as an inadequate balance between omega 6 and omega 3 fatty acids, that should be compensated with a more important intake in omega 3. Certain types of margarines and spreads offer the possibility to increase the intake in this nutriment, in particular margarines containing linseed oil. Their high content of ALA allows, on the basis of a daily consumption of 20 g, to counterbalance, partially or totally, the low intake in omega 3. However, these spreads require a quite particular attention in their development and their production, mostly because of the relative instability of the linseed oil in the oxidation process and the need to avoid developing of off tastes until the end of shelf life.

  18. Targeting the BH3 domain of Bcl-2 family proteins. A brief history from natural products to foldamers as promising cancer therapeutic avenues. (United States)

    De Giorgi, M; Voisin-Chiret, A S; Rault, S


    For many years the spotlight in drug discovery has been on a relatively small number of validated therapeutic target classes, such as G-protein coupled receptors and enzymes such as protein kinases, with well characterized enzymatic and cellular activities. However, with recent progress in genomics and proteomics, protein-protein interactions (PPIs) provide new way of finding novel bioactive molecules acting on their interfaces. This review addresses the current case studies and state of the art in the development of small chemical modulators controlling interactions of proteins that have pathological implications in various human diseases and in particular in cancer. The attention is focused on Bcl-2 family protein modulators ranging from natural products to synthetic ones with particular interest in foldamers as BH3 alpha helix mimetics.

  19. Basement membrane abnormalities in human eyes with diabetic retinopathy

    DEFF Research Database (Denmark)

    Ljubimov, A V; Burgeson, R E; Butkowski, R J


    discontinuously for laminin-1, entactin/nidogen, and alpha3-alpha4 Type IV collagen, in contrast to non-DR corneas. Major BM alterations were found in DR retinas compared to normals and non-DR diabetics. The inner limiting membrane (retinal BM) of DR eyes had accumulations of fibronectin (including cellular......) and Types I, III, IV (alpha1-alpha2), and V collagen. The BM zone of new retinal blood vessels in neovascularized areas accumulated tenascin and Type XII collagen, whereas normal, diabetic, and adjacent DR retinas showed only weak and irregular staining. In preretinal membranes, perlecan, bamacan, and Types...... VI, VIII, XII, and XIV collagen were newly identified. Diabetic BM thickening appears to involve qualitative alterations of specific BM markers at an advanced disease stage, with the appearance of DR....

  20. Turbulence statistics of Couette Poiseuille turbulent flow. 2nd Report. Higher order turbulence statistics; Couette Poiseuille gata ranryu no midare tokeiryo. 2. Koji tokeiryo

    Energy Technology Data Exchange (ETDEWEB)

    Nakabayashi, K.; Kito, O.; Kato, Y. [Nagoya Institute of Technology, Nagoya (Japan)


    Turbulence statistics in Couette Poiseuille flow are obtained by measurements. These include correlation coefficient, skewness and flatness factors and four-quadrant analysis of Reynolds shear stress -{rho}uv. In the region of y{sup +} {<=}30-40, the distributions of all these quantities are only affected by non-dimensional parameter {mu}({identical_to}u*{sup 3}/{alpha}{nu}), as the mean velocity and the turbulence intensities profiles are. The four-quadrant analysis shows that the fractional contribution from 4th-quadrant is affected largely by parameter {mu} whereas that from 2nd-quadrant remains unaffected. In the case of 0<{mu}{<=}94, the fractional contribution from 4th-quadrant is greater than that from 2nd-quadrant, unlike the conventional wall turbulent flow. 8 refs., 17 figs., 2 tabs.

  1. Turbulence statistics of Couette Poiseuille turbulent flow. 1st Report. Turbulence intensities; Couette Poiseuille gata ranryu no midare tokeiryo. 1. Midare tsuyosa

    Energy Technology Data Exchange (ETDEWEB)

    Nakabayashi, K.; Kito, O.; Kato, Y. [Nagoya Institute of Technology, Nagoya (Japan)


    Turbulence intensities in Couette Poiseuille flow, developed between stationary and moving walls, have been measured by I- and X-type hot wires. The intensities in the wall region are affected by non-dimensional shear stress gradient parameter {mu} ({identical_to} u*{sup 3}/{alpha}{nu}), but not by Reynolds number Re* ({identical_to} hu*/{nu}). As |{mu}| decreases, distributions of streamwise and wall-normal turbulence intensities shift upward or downward from those of plane-Couette flow depending on the sign of {mu}. In the turbulent core region, turbulence intensities of Poiseuille-type flow distribute quite differently from that of Couette-type flow. The effective parameter in this region is 13, but the effect of 13 on the turbulence intensities is obscured by the low Reynolds number effect. 13 refs., 12 figs., 2 tabs.

  2. Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health? (United States)

    Leikin-Frenkel, Alicia I.


    The role of ω3 alpha linolenic acid (ALA) in the maternal diet during pregnancy and lactation, and its effect on the prevention of disease and programming of health in offspring, is largely unknown. Compared to ALA, ω3 docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids have been more widely researched due to their direct implication in fetal neural development. In this literature search we found that ALA, the essential ω3 fatty acid and metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In light of new and evolving findings, this review proposes that ALA may have an intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal development as a regulator of gene programming for the prevention of metabolic disease and promotion of health in offspring. PMID:27023621

  3. [Glycosides from flowers of Jasminum officinale L. var. grandiflorum]. (United States)

    Zhao, Gui-qin; Xia, Jing-jing; Dong, Jun-xing


    To study the chemical constituents of the flower of Jasminum officinale L. var. grandiflorum. The compounds were isolated and purified by re-crystallization and chromatography on silica gel and Sephadex LH-20 column. Their structures were elucidated on the physicochemical properties and spectral analysis. Seven glycosides were identified as kaempferol-3-O-alpha-L-rhamnopyranosyl (1-->3)-[alpha-L-rhamnopyranosyl (1-->6)]-beta-D-galactopyranoside (I), kaempferol-3-O-rutinoside (II), 7-ketologanin (III), oleoside-11-methyl ester (IV), 7-glucosyl-l1-methyl oleoside (V), ligstroside (VI), oleuropein (VII). Compound I is a new compound. Compounds III and V were isolated from the family of Jasminum for the first time and compounds II, IV and VI were isolated from Jasminum officinale L. var. grandiflorum for the first time.

  4. Calculation of energy spectrum of $^{12}$C isotope with modified Yukawa potential by cluster models

    Indian Academy of Sciences (India)



    In this paper, we have calculated the energy spectrum of 12C isotope in two-cluster models, $3\\alpha$ cluster model and $^8$Be + $\\alpha$ cluster model. We use the modified Yukawa potential for interaction between theclusters and solve the Schrödinger equation using Nikiforov–Uvarov method to calculate the energy spectrum. Then, we increase the accuracy by adding spin-orbit coupling and tensor force and solve them by perturbationtheory in both models. Finally, the calculated results for both models are compared with each other and with the experimental data. The results show that the isotope $^{12}$C should be considered as a three-$\\alpha$ cluster and themodified Yukawa potential is adaptable for cluster interactions.

  5. Hydroxylation of a hederagenin derived saponin by a Xylareaceous fungus found in fruits of Sapindus saponaria

    Energy Technology Data Exchange (ETDEWEB)

    Murgu, Michael; Santos, Luiz F. Arruda; Souza, Gezimar D. de; Daolio, Cristina; Ferreira, Antonio Gilberto; Rodrigues-Filho, Edson [Universidade Federal de Sao Carlos (UFSCAR), SP (Brazil). Dept. de Quimica; Schneider, Bernd [Max Planck Institute for Chemical Ecology, Beutenberg Campus, Jena (Germany)


    During our screening of tropical plants for endophyte microorganisms, a Xylareaceous fungus was found living on the internal part of Sapindus saponaria fruits. The fruits of S. saponaria accumulate great amounts of triterpenoidal and sesquiterpenoidal saponins. The saponin 3-O-({beta}-D-xylopyranosyl)-(1{yields}3)-{alpha}-L -rhamnopyranosyl-(1{yields}2)-{alpha}-L-arabinopyranosyl-hederagenin was isolated using chromatographic methods, after alkaline hydrolysis of the crude extract obtained from S. saponaria fruits and added to the culture medium used to grows the fungus. A new saponin was isolated from this experiment by preparative scale HPLC and characterized as a 22{alpha}-hydroxy derivative. The structure of this hydroxylated saponin was elucidated based on interpretation of MS/MS data and NMR spectra. (author)

  6. Radical-scavenging activities of new hydroxylated ursane triterpenes from cv. Annurca apples. (United States)

    D'Abrosca, Brigida; Fiorentino, Antonio; Monaco, Pietro; Pacifico, Severina


    Two new ursolic acid triterpene derivatives, compounds 2 and 3, have been isolated from cv. Annurca apple fruit, a high-quality apple variety widely cultivated in southern Italy, together with the known 2-oxopomolic acid (1). The new compounds were identified by means of different spectroscopic techniques as 3-epi-2-oxopomolic acid (= (3alpha)-3,19-dihydroxy-2-oxours-12-en-28-oic acid; 2) and (1alpha)-1-hydroxy-3-oxours-12-en-28-oic acid (3). Compounds 1-3 were tested for their radical-scavenging activities with the aid of a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay (Fig. 2). All three constituents showed activities similar to that of the reference antioxidant alpha-tocopherol (vitamin E).

  7. Steroid metabolism in the hormone dependent MCF-7 human breast carcinoma cell line and its two hormone resistant subpopulations MCF-7/LCC1 and MCF-7/LCC2

    DEFF Research Database (Denmark)

    Jørgensen, L; Brünner, N; Spang-Thomsen, M


    and 17beta-hydroxysteroid oxidoreductase were investigated isolating the following steroids: estriol (E3), estradiol (E2), estrone (E1), 3alpha/beta-androstanediol (A-diol), testosterone (T), dihydrotestosterone (DHT), androsterone (AND), androstenedion (4-AD) and androstanedione (A-dion). For all......, and preincubation with cortisol had no effect on the enzyme activity. With [14C]T as the substrate, the metabolized level of DHT was very similar in the three cell lines, though MCF-7/LCC1 and MCF-7/LCC2 utilized the substrate to a much lesser extent. The amount of DHT and 4-AD produced were comparable in the two...... to the parent MCF-7. However, since treatment with DHT and T inhibited cell growth equally well in all three tumor cell lines, it is unlikely that the found differences in steroid metabolism was involved in the acquisition of the endocrine resistance of the two MCF-7 sublines....

  8. A linear temperature-to-frequency converter

    DEFF Research Database (Denmark)

    Løvborg, Leif


    The possibility of converting temperature into a frequency signal by means of a thermistor which is part of the frequency-determining network of an RC oscillator is investigated. It is shown that a temperature - frequency characteristic which has a point of inflection may be realized, and that th......The possibility of converting temperature into a frequency signal by means of a thermistor which is part of the frequency-determining network of an RC oscillator is investigated. It is shown that a temperature - frequency characteristic which has a point of inflection may be realized......, and that the maximum value of the temperature-frequency coefficient beta in this point is-1/3 alpha, where a is the temperature coefficient of the thermistor at the corresponding temperature. Curves showing the range in which the converter is expected to be linear to within plusmn0.1 degC are given. A laboratory...

  9. O carater de Chern-Connes para C$^*$-sistemas dinamicos calculado em algumas algebras de operadores pseudodiferenciais

    CERN Document Server

    Dias, David P


    Given a C$^*$-dynamical system $(A, G, \\alpha)$ one defines a homomorphism, called the Chern-Connes character, that take an element in $K_0(A) \\oplus K_1(A)$, the K-theory groups of the C$^*$-algebra $A$, and maps it into $H_{\\mathbb{R}}^*(G)$, the real deRham cohomology ring of $G$. We explictly compute this homomorphism for the examples $(\\overline{\\Psi_{cl}^0(S^1)}, S^1, \\alpha)$ and $(\\overline{\\Psi_{cl}^0(S^2)}, SO(3), \\alpha)$, where $\\overline{\\Psi_{cl}^0(M)}$ denotes the C$^*$-algebra generated by the classical pseudodifferential operators of zero order in the manifold $M$ and $\\alpha$ the action of conjugation by the regular representation (translations).

  10. Functional characterisation of a putative rhamnogalacturonan II specific xylosyltransferase. (United States)

    Egelund, Jack; Damager, Iben; Faber, Kirsten; Olsen, Carl-Erik; Ulvskov, Peter; Petersen, Bent Larsen


    An Arabidopsis thaliana gene, At1g56550, was expressed in Pichia pastoris and the recombinant protein was shown to catalyse transfer of D-xylose from UDP-alpha-D-xylose onto methyl alpha-L-fucoside. The product formed was shown by 1D and 2D 1H NMR spectroscopy to be Me alpha-D-Xyl-(1,3)-alpha-L-Fuc, which is identical to the proposed target structure in the A-chain of rhamnogalacturonan II. Chemically synthesized methyl L-fucosides derivatized by methyl groups on either the 2-, 3- or 4 position were tested as acceptor substrates but only methyl 4-O-methyl-alpha-L-fucopyranoside acted as an acceptor, although to a lesser extent than methyl alpha-L-fucoside. At1g56550 is suggested to encode a rhamnogalacturonan II specific xylosyltransferase.

  11. Durangite from the Black Range, New Mexico, and new data on durangite from Durango and Cornwall. (United States)

    Foord, E.E.; Oakman, M.R.; Maxwell, C.H.


    Durangite, associated with cassiterite, hematite, quartz, tridymite, cristobalite and clinopyroxene, occurs in small veinlets within flows, ash-flow tuffs and lithic tuffs in a tin mine near Boiler Peak, New Mexico. It is clear to semi-translucent, pale yellow-orange to medium orange-red with a vitreous lustre, pale yellow streak; H. 5-5.5%; irregular to conchoidal fracture and a good (110) cleavage; elongate along c with (110), (010), (021) and (111) the prominent forms; Dmeas 3.90, Dcalc 3.92 g/cm3; alpha medium yellow orange 1.634(3), beta pale yellow orange 1.663(3), gamma colourless 1.685(3); weak to moderate dispersion r C2/c; Z = 4. Additional X-ray and chemical data on durangite from Durango and Cornwall are also included.-L.T.T.

  12. Kerr-Newman Black Hole In Quintessence

    CERN Document Server

    Xu, Zhaoyi


    We study the Kerr-Newman solutions of the Einstein-Maxwell equation in quintessence field around a black hole by Newman-Janis algorithm. From the horizon structure and stationary limit surfaces, we find that Kerr-Newman black hole exists an ergosphere with $r^{+} < r < r^{L}$, which is related to the parameters $\\omega$ and $\\alpha$. We obtain the general expression between $\\alpha$ and $\\omega$ if the cosmological horizon exists, in which for $\\omega=-1/2$, $\\alpha\\leq\\sqrt{2}/5$, and for $\\omega=-2/3$, $\\alpha\\leq 1/6$. For $\\omega=-2/3$, the result is same with rotational black hole in quintessence. The singularity of the black holes is the same with that of Kerr black hole. We also discuss the rotation velocity of the black holes on the equatorial plane for $\\omega =-2/3$ and $-1/2$.

  13. Evaluation of antinociceptive and anti-inflammatory activities of a new triterpene saponin from Bauhinia variegata leaves. (United States)

    Mohamed, Mona A; Mammoud, Madeha R; Hayen, Heiko


    A new triterpene saponin, named as 23-hydroxy-3alpha-[O-alpha-L-1C4-rhamnopyranosyl-(1"-->4')-O-alpha-L-4C1-arabinopyranosyl-oxy]olean-12-en-28-oic acid O-alpha-L-1C4-rhamnopyranosyl-(1"'-->4")-O-beta-D-4C1-glucopyranosyl-(1"-->6"')-O-beta-D-4C1-glucopyranosyl ester (9), was isolated from the leaves of Bauhinia variegata Linn. In addition, six flavonoid compounds along with two cinnamic acid derivatives were isolated and identified based on their chromatographic properties, and chemical and spectral data (ESI-high resolution-MSn, 1H NMR, 13C NMR, 1H-1H COSY, HSQC, and HMBC). Compound 9 was found to be nontoxic (LD50) and to have significant anti-inflammatory and antinociceptive activities. It also showed a slight antischistosomal activity.

  14. Isolation and characterization of Exodus-2, a novel C-C chemokine with a unique 37-amino acid carboxyl-terminal extension. (United States)

    Hromas, R; Kim, C H; Klemsz, M; Krathwohl, M; Fife, K; Cooper, S; Schnizlein-Bick, C; Broxmeyer, H E


    Chemokines are a group of small, homologous proteins that regulate leukocyte migration, hemopoiesis, and HIV-1 absorption. We report here the cloning and characterization of a novel murine and human C-C chemokine termed Exodus-2 for its similarity to Exodus-1/MIP-3alpha/LARC, and its chemotactic ability. This novel chemokine has a unique 36 or 37 (murine and human, respectively) amino acid carboxyl-terminal extension not seen in any other chemokine family member. Purified recombinant Exodus-2 was found to have two activities classically associated with chemokines: inhibiting hemopoiesis and stimulating chemotaxis. However, Exodus-2 also had unusual characteristics for C-C chemokines. It selectively stimulated the chemotaxis of T-lymphocytes and was preferentially expressed in lymph node tissue. The combination of these characteristics may be a functional correlate for the unique carboxyl-terminal structure of Exodus-2.

  15. Spectroscopy of {sup 40}Ca and negative-parity bands

    Energy Technology Data Exchange (ETDEWEB)

    Torilov, S.; Oertzen, W. von; Kokalova, Tz [Fachbereich Physik, Freie Universitaet Berlin, Arnimallee 14, D-14195, Berlin (Germany); Hahn-Meitner-Institut Berlin, Glienicker Strasse 100, D-14109, Berlin (Germany); Thummerer, S.; Bohlen, H.G. [Hahn-Meitner-Institut Berlin, Glienicker Strasse 100, D-14109, Berlin (Germany); Angelis, [Hahn-Meitner-Institut Berlin, Glienicker Strasse 100, D-14109, Berlin (Germany); INFN-Laboratori Nazionali di Legnaro, Legnaro (Italy); Tumino, A. [Hahn-Meitner-Institut Berlin, Glienicker Strasse 100, D-14109, Berlin (Germany); INFN-Laboratori Nazionali del Sud and Universita di Catania, Via S. Sofia 44, I-95123, Catania (Italy); Axiotis, M.; Marginean, N.; Martinez, T.; Napoli, D.R.; Poli, M.De [INFN-Laboratori Nazionali di Legnaro, Legnaro (Italy); Farnea, E.; Lenzi, S.M.; Ur, C. [Dipartimento di Fisica and INFN, Padova (Italy); Rousseau, M.; Papka, P. [Institut de Recherches Subatomiques, IReS, Strasbourg (France)


    We have studied the reactions {sup 28}Si+{sup 24}Mg{yields}{sup 52}Fe{yields}{sup 4}0Ca{sup *}+3{alpha} as well as the binary channel {sup 52}Fe{yields}{sup 4}0Ca{sup *}+{sup 12}C{sup *}, in order to search for deformed states, which form rotational bands in {sup 40}Ca. We observe positive- and negative-parity bands. The negative-parity band is proposed to be a partner of an inversion doublet with the positive-parity states being based on 4p-4h configurations. The properties of the positive-parity states are discussed on the basis of the shell model and the parity doublet on the basis of a cluster model with intrinsic reflection asymmetric shapes. (orig.)

  16. Sintering of nano sized powders on the basis of silicon nitride in a solar furnace

    Energy Technology Data Exchange (ETDEWEB)

    Zhilinska, N.; Zalite, I.; Grabis, J.; Rodriguez, J.; Martinez, D.


    A study of the sintering of Si{sub 3}N{sub 4}-Y{sub 2}O{sub 3}-Al{sub 2}O{sub 3} and Si{sub 3}N{sub 4}-AIN-Al{sub 2}O{sub 3}-Y{sub 2}O{sub 3} ({alpha}/{beta}-SiAION) nano powders with the specific surface area of 65-70 m''2/g and average particle size of 30-35 nm is reported. The powders have been prepared by the plasma chemical synthesis. This work relates to an innovative method of sintering in the solar furnace at Plataforma Solar de Almeria. The influence of sintering temperature, sintering time and heating rate on the densification behaviour of the plasma synthesized powder compositions was investigated. The results were compared with the data obtained using commercial powder. (Author) 3 refs.

  17. Reversal of bone loss in mice by nongenotropic signaling of sex steroids. (United States)

    Kousteni, S; Chen, J R; Bellido, T; Han, L; Ali, A A; O'Brien, C A; Plotkin, L; Fu, Q; Mancino, A T; Wen, Y; Vertino, A M; Powers, C C; Stewart, S A; Ebert, R; Parfitt, A M; Weinstein, R S; Jilka, R L; Manolagas, S C


    We show that sex steroids protect the adult murine skeleton through a mechanism that is distinct from that used to preserve the mass and function of reproductive organs. The classical genotropic actions of sex steroid receptors are dispensable for their bone protective effects, but essential for their effects on reproductive tissues. A synthetic ligand (4-estren-3alpha,17beta-diol) that reproduces the nongenotropic effects of sex steroids, without affecting classical transcription, increases bone mass and strength in ovariectomized females above the level of the estrogen-replete state and is at least as effective as dihydrotestosterone in orchidectomized males, without affecting reproductive organs. Such ligands merit investigation as potential therapeutic alternatives to hormone replacement for osteoporosis in both women and men [corrected].

  18. Rye polyphenols and the metabolism of n-3 fatty acids in rats: a dose dependent fatty fish-like effect (United States)

    Ounnas, Fayçal; de Lorgeril, Michel; Salen, Patricia; Laporte, François; Calani, Luca; Mena, Pedro; Brighenti, Furio; Del Rio, Daniele; Demeilliers, Christine


    As long-chain fatty acids (LCFA) of the n-3 series are critically important for human health, fish consumption has considerably increased in recent decades, resulting in overfishing to respond to the worldwide demand, to an extent that is not sustainable for consumers’ health, fisheries economy, and marine ecology. In a recent study, it has been shown that whole rye (WR) consumption improves blood and liver n-3 LCFA levels and gut microbiota composition in rats compared to refined rye. The present work demonstrates that specific colonic polyphenol metabolites may dose dependently stimulate the synthesis of n-3 LCFA, possibly through their microbial and hepatic metabolites in rats. The intake of plant n-3 alpha-linolenic acid and WR results in a sort of fatty fish-like effect, demonstrating that the n-3 LCFA levels in blood and tissues could be increased without eating marine foods, and therefore without promoting unsustainable overfishing, and without damaging marine ecology. PMID:28071699

  19. Steroidal geminal dihydroperoxides and 1,2,4,5-tetraoxanes: structure determination and their antimalarial activity. (United States)

    Todorović, N M; Stefanović, M; Tinant, B; Declercq, J P; Makler, M T; Solaja, B A


    Cholestane-derived gem-dihydroperoxides and tetraoxanes were synthesized starting from 5 alpha- and 5 beta-cholestan-3-ones by acid-catalyzed addition of hydrogen peroxide to the ketone. They were characterized by IR, NMR, and mass spectroscopy analysis aided by molecular mechanics calculations, and, in the instance of 5 beta-cholestane-3 alpha,3 beta-dihydroperoxide (6), by x-ray analysis. The synthesized compounds were tested in vitro against Plasmodium falciparum Sierra Leone (D6) and Indochina (W2) malaria clones. All compounds were inactive to both clones, with the exception of tetraoxane 7a, which exhibited modest activity toward D6 clone with IC50 = 155 nM.

  20. Nonlinear optics of astaxanthin thin films (United States)

    Esser, A.; Fisch, Herbert; Haas, Karl-Heinz; Haedicke, E.; Paust, J.; Schrof, Wolfgang; Ticktin, Anton


    Carotinoids exhibit large nonlinear optical properties due to their extended (pi) -electron system. Compared to other polyenes which show a broad distribution of conjugation lengths, carotinoids exhibit a well defined molecular structure, i.e. a well defined conjugation length. Therefore the carotinoid molecules can serve as model compounds to study the relationship between structure and nonlinear optical properties. In this paper the synthesis of four astaxanthins with C-numbers ranging from 30 to 60, their preparation into thin films, wavelength dispersive Third Harmonic Generation (THG) measurements and some molecular modelling calculations will be presented. Resonant (chi) (3) values reach 1.2(DOT)10-10 esu for C60 astaxanthin. In the nonresonant regime a figure of merit (chi) (3)/(alpha) of several 10-13 esu-cm is demonstrated.

  1. Evidence That GABA Mediates Dopaminergic and Serotonergic Pathways Associated with Locomotor Activity in Juvenile Chinook Salmon (Oncorhynchus tshawytscha) (United States)

    Clements, S.; Schreck, C.B.


    The authors examined the control of locomotor activity in juvenile salmon (Oncorhynchus tshawytscha) by manipulating 3 neurotransmitter systems-gamma-amino-n-butyric acid (GABA), dopamine, and serotonin-as well as the neuropeptide corticotropin releasing hormone (CRH). Intracerebroventricular (ICV) injections of CRH and the GABAAagonist muscimol stimulated locomotor activity. The effect of muscimol was attenuated by administration of a dopamine receptor antagonist, haloperidol. Conversely, the administration of a dopamine uptake inhibitor (4???,4??? -difluoro-3-alpha-[diphenylmethoxy] tropane hydrochloride [DUI]) potentiated the effect of muscimol. They found no evidence that CRH-induced hyperactivity is mediated by dopaminergic systems following concurrent injections of haloperidol or DUI with CRH. Administration of muscimol either had no effect or attenuated the locomotor response to concurrent injections of CRH and fluoxetine, whereas the GABAA antagonist bicuculline methiodide potentiated the effect of CRH and fluoxetine.

  2. Robust Models for Operator Workload Estimation (United States)


    48 Appendix C: Physiological Features List No. Name Category No. Name Category 1 F7 Alpha EEG 40 T3 Gamma EEG 2 F8 Alpha EEG 41 Pz Gamma EEG...3 Fz Alpha EEG 42 O2 Gamma EEG 4 T3 Alpha EEG 43 F7 Delta EEG 5 Pz Alpha EEG 44 F8 Delta EEG 6 O2 Alpha EEG 45 Fz Delta EEG 7 T4 Alpha EEG 46 T3...Delta EEG 8 F7 Beta EEG 47 Pz Delta EEG 9 F8 Beta EEG 48 O2 Delta EEG 10 Fz Beta EEG 49 T4 Delta EEG 11 T3 Beta EEG 50 F7 Theta EEG 12 Pz Beta

  3. Influence of reaction channel on the isomeric cross-section ratio


    Qaim, S. M.; Sudár, S.; Fessler, A.


    The influence of reaction channel on the isomeric cross-section ratio was investigated by analysing the experimental data on the reactions Cr-52(p, n)Mn-52m,Mn-g, Cr-52(He-3, t)Mn-52m.g, Fe-54(d, alpha)Mn-52m.g, Fe-54(n, t)Mn-52m.g and Fe-54(He-3, alpha p)Mn-52m.g over the incident particle energy range extending up to 35MeV. The influence is most pronounced when the channels differ widely, for example (p,n) and (He-3, t) processes, i.e. when the reaction mechanisms are different. The nuclear...

  4. Polysaccharides in Fungi. XXXIV. A polysaccharide from the fruiting bodies of Amanita muscaria and the antitumor activity of its carboxymethylated product. (United States)

    Kiho, T; Yoshida, I; Katsuragawa, M; Sakushima, M; Usui, S; Ukai, S


    A water-insoluble, alkali-soluble, glucan (AM-APP), [alpha]D +160 degrees in 0.4 M NaOH, was isolated from the alkaline extract of the fruiting bodies of Amanita muscaria. The results of chemical and spectroscopic investigations indicate that AM-APP is a linear (1 --> 3)-alpha-D-glucan with a molecular weigh estimated by gel chromatography of about 42000. Its carboxymethylated product (AM-APP-CM) showed potent antitumor activity against sarcoma 180 in mice, although the native polysaccharide (AM-APP) had little effect. The distribution of carboxymethyl groups in the molecule was analyzed by gas chromatography and mass spectrometry. The degree of substitution of carboxymethyl groups was 0.95 and the substituents were located at O-2, at O-4, at O-6, at O-2 and O-6, and at O-4 and O-6 on glucose.

  5. Mathematical Perspectives on the Federal Thrift Savings Plan (TSP) (United States)


    3 Alpha = 5 Alpha = 10 © 2008 Scott T. Nestler 38 Performance (Reward-Risk) Measures • Sharpe Ratio • STARR Ratio • R- Ratio ( Rachev ) ( ) ( ) E XSTARR...Similar to R- Ratio but use Alpha-VaR and Beta-VaR in place of CVaR • AVaR- Ratio : • BVaR- Ratio : 1 2 ( ) ( ) AVaR X AVR AVaR X α α − = 1 1 2 2...87,754 Beta VaR(50,5) $ 43,938 $ 44,010 $ 60,203 $ 67,757 Performance Measure (↑ better) VG-ICA TSP MP L 2030 L 2040 Sharpe Ratio 0.94 0.63 0.57

  6. Cytotoxic glycosides from Albizia julibrissin. (United States)

    Ikeda, T; Fujiwara, S; Araki, K; Kinjo, J; Nohara, T; Miyoshi, T


    During the course of a study of leguminous plants, cytotoxicity was demonstrated by the crude saponin fraction of Albizia julibrissin. Following chromatographic purification, the structures of three novel saponins, julibrosides I-III (1-3), inclusive of a cytotoxic principle, were elucidated. A comparison of the cytotoxicity of julibrosides (1-3) and their prosapogenins (4-15) prepared by alkaline hydrolysis clearly indicated that both an alpha-L-arabinofuranosyl-(1-->4)-[beta-D-glucopyranosyl-(1-->3)]-alpha- L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl ester unit and a monoterpene-quinovopyranosyl moiety are crucial substituents for cytotoxicity among this class of compounds. The hydroxy group at C-16 of aglycon may play an important role in mediating cytotoxicity, and the N-acetyl-glucosamine moiety at C-3 seems to enhance activity because 3 showed the strongest cytotoxicity.

  7. A new triterpenoid saponin from Albizia julibrissin Durazz. (United States)

    Xu, Tun-Hai; Li, Hai-Tao; Xu, Ya-Juan; Zhao, Hong-Feng; Xie, Sheng-Xu; Han, Dong; Si, Yun-Shan; Li, Yu; Niu, Jian-Zhao; Xu, Dong-Ming


    A new triterpenoid, saponin hehuanoside A, was isolated together with the known triterpenoid saponins 2, 3, and 4 from the stem bark of Albizia julibrissin. With the help of chemical and spectral analyzes (IR, MS, 1D-NMR, and 2D-NMR), the structure of the new triterpenoid saponin was elucidated as 21-O-[(6S)-2-trans-2,6-dimethyl-6-O-beta-d-quinovopyranosyl-2,7-octadienoyl]-3-O-beta-d-xylopyranosyl-(1 --> 2)-beta-d-fucopyranosyl-(1 --> 6)-beta-d-2-deoxy-2-acetamidoglucopyrasyl acacic acid 28-O-alpha-l-arabinofuranosyl-(1 --> 4)-[-beta-d-glucopyranosyl-(1 --> 3)]-alpha-l-rhamnopyranosyl-(1 --> 2)-beta-d-glucopyranosyl ester (1). Three known triterpenoid saponins 2-4 were identified on the basis of spectroscopic data.

  8. The synthesis and characterization of analogs of the antimicrobial compound squalamine: 6 beta-hydroxy-3-aminosterols synthesized from hyodeoxycholic acid. (United States)

    Jones, S R; Kinney, W A; Zhang, X; Jones, L M; Selinsky, B S


    Analogs of the aminosterol antimicrobial agent squalamine have been synthesized beginning from hyodeoxycholic acid. After carboxylic acid esterification and oxidation of both alcohol functions to ketones, the A/B ring junction was converted from cis to trans by acid-catalyzed isomerization. Different polyamines were added to the 3-keto group by reductive amination, yielding both the 3 alpha and 3 beta addition products. The synthetic products exhibited potent, broad-spectrum antimicrobial activity similar to that of the parent compound. Changing the identity of the polyamine or the stereochemistry of addition has little effect upon antimicrobial activity but appears to change the selectivity of the agents. The analogs are synthesized with high yield from inexpensive starting materials and are promising alternatives to squalamine as potential antibiotics.

  9. Grassmann Duality and the Particle Spectrum

    CERN Document Server

    Delbourgo, Robert


    Schemes based on anticommuting scalar coordinates, corresponding to properties, lead to generations of particles naturally. The application of Grassmannian duality cuts down the number of states substantially and is vital for constructing sensible Lagrangians anyhow. We apply duality to all of the subgroups within the {\\em classification} group SU(3)$\\times$SU(2)$_L\\times$SU(2)$_R$, which encompasses the standard model gauge group, and thereby determine the full state inventory; this includes the definite prediction of quarks with charge -4/3 and other exotic states. Assuming universal gravitational coupling to the gauge fields and parity even property curvature, we also obtain $4\\sin^2\\theta_w = 1 - 2\\alpha/3\\alpha_s$ which is not far from the experimental value around the $M_Z$ mass.

  10. Electroweak corrections to hadronic event shapes and jet production in e{sup +}e{sup -} annihilation

    Energy Technology Data Exchange (ETDEWEB)

    Denner, Ansgar [Paul Scherrer Institut, CH-5232 Villigen PSI (Switzerland); Dittmaier, Stefan [Physikalisches Institut, Albert-Ludwigs-Universitaet Freiburg, D-79104 Freiburg (Germany); Gehrmann, Thomas, E-mail: thomas.gehrmann@physik.uzh.c [Institut fuer Theoretische Physik, Universitaet Zuerich, CH-8057 Zuerich (Switzerland); Kurz, Christian [Paul Scherrer Institut, CH-5232 Villigen PSI (Switzerland); Institut fuer Theoretische Physik, Universitaet Zuerich, CH-8057 Zuerich (Switzerland)


    We present a complete calculation of the electroweak O(alpha{sup 3}alpha{sub s}) corrections to three-jet production and related event-shape observables at electron-positron colliders. The Z-boson resonance is described within the complex-mass scheme, rendering the calculation valid both in the resonance and off-shell regions. Higher-order initial-state radiation is included in the leading-logarithmic approximation. We properly account for the corrections to the total hadronic cross section and for the experimental photon isolation criteria. To this end we implement contributions of the quark-to-photon fragmentation function both in the slicing and subtraction formalism. The effects of the electroweak corrections on various event-shape distributions and on the three-jet rate are studied. They are typically at the few-percent level, and remnants of the radiative return are found even after inclusion of appropriate cuts.

  11. Electroweak corrections to hadronic event shapes and jet production in e+e- annihilation

    CERN Document Server

    Denner, Ansgar; Gehrmann, Thomas; Kurz, Christian


    We present a complete calculation of the electroweak O(alpha^3 alpha_s) corrections to three-jet production and related event-shape observables at electron--positron colliders. The Z-boson resonance is described within the complex-mass scheme, rendering the calculation valid both in the resonance and off-shell regions. Higher-order initial-state radiation is included in the leading-logarithmic approximation. We properly account for the corrections to the total hadronic cross section and for the experimental photon isolation criteria. To this end we implement contributions of the quark-to-photon fragmentation function both in the slicing and subtraction formalism. The effects of the electroweak corrections on various event-shape distributions and on the three-jet rate are studied. They are typically at the few-per-cent level, and remnants of the radiative return are found even after inclusion of appropriate cuts.

  12. Alpha-thalassemia in northern Thailand. Frequency of deletional types characterized at the DNA level. (United States)

    Hundrieser, J; Sanguansermsri, T; Papp, T; Flatz, G


    The frequency of alpha-thalassemias in northern Thailand was estimated using DNA techniques. Among 106 healthy adult Thais from the Chiangmai area, 28 were shown to carry alpha-globin gene anomalies. There were 19 heterozygotes and 1 homozygote for alpha-thalassemia-2. One of the alpha-thalassemia-2 deletions was of the -alpha 4.2 type and the remaining 20 of the -alpha 3.7 type (subtype I). Deletions of both alpha-globin genes on one chromosome (alpha-thalassemia-1) of the Southeast Asian type were observed in 5 cases, and 3 alpha-globin gene triplications were identified. Compared with a previous report on alpha-thalassemia in northern Thailand which was based on the determination of hemoglobin Bart's in cord blood, the present DNA study reveals a similar frequency of alpha-thalassemia-2 but a considerably lower frequency of alpha-thalassemia-1.

  13. Triterpenoid saponins from Lippia alba (Mill.) N. E. Brown

    Energy Technology Data Exchange (ETDEWEB)

    Farias, Mareni R.; Pertile, Roberto; Correa, Melissa M.; Schenkel, Eloir P., E-mail: [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil). Dept. de Ciencias Farmaceuticas. Programa de Pos-graduacao em Farmacia; Almeida, Maria Tereza R. de; Palermo, Jorge A. [Universidad de Buenos Aires (Argentina). Facultad de Ciencias Exactas y Naturales. Dept. de Quimica Organica


    Two saponins were isolated from the leaves of Lippia alba. Their structures were established using one- and two-dimensional NMR spectroscopy and mass spectrometry. These new compounds were elucidated as 3-O-beta-D-glucopyranosyl-28-O-(alpha-L-rhamnopyranosyl-(1->3)-beta-D-xylopyranosyl -(1->4)-alpha-L-rhamnopyranosyl-(1->2)-alpha-L-arabinopyranosyl)-16alpha, 23-dihydroxy-olean -12-en-28-oic acid, named as Lippiasaponin I (2) and as 3-O-beta-D-glucopyranosyl-28-O-(alpha-L-rhamnopyranosyl-(1->3)-beta-D-xylopyranosyl- (1->4)-alpha-L-rhamnopyranosyl-(1->3)-alpha-Larabinopyranosyl)-16alpha,23-dihydroxy-olean -12-en-28-oic acid, named Lippiasaponin II (3). (author)

  14. Quantum Dot-Induced Phase Stabilization of ..alpha..-CsPbI3 Perovskite for High-Efficiency Photovoltaics

    Energy Technology Data Exchange (ETDEWEB)

    Swarnkar, Abhishek; Marshall, Ashley R.; Sanehira, Erin M.; Chernomordik, Boris D.; Moore, David T.; Christians, Jeffrey A.; Chakrabarti, Tamoghna; Luther, Joseph M.


    We show nanoscale phase stabilization of CsPbI3 quantum dots (QDs) to low temperatures that can be used as the active component of efficient optoelectronic devices. CsPbI3 is an all-inorganic analog to the hybrid organic cation halide perovskites, but the cubic phase of bulk CsPbI3 (..alpha..-CsPbI3) -- the variant with desirable band gap -- is only stable at high temperatures. We describe the formation of ..alpha..-CsPbI3 QD films that are phase-stable for months in ambient air. The films exhibit long-range electronic transport and were used to fabricate colloidal perovskite QD photovoltaic cells with an open-circuit voltage of 1.23 volts and efficiency of 10.77%. These devices also function as light-emitting diodes with low turn-on voltage and tunable emission.

  15. Production of $\\alpha$-particle condensate states in heavy-ion collisions

    CERN Document Server

    Raduta, Ad R; Geraci, E; Neindre, N Le; Napolitani, P; Rivet, M F; Alba, R; Amorini, F; Cardella, G; Chatterjee, M; De Filippo, E; Guinet, D; Lautesse, P; La Guidara, E; Lanzalone, G; Lanzano, G; Lombardo, I; Lopez, O; Maiolino, C; Pagano, A; Pirrone, S; Politi, G; Porto, F; Rizzo, F; Russotto, P; Wieleczko, J P


    The fragmentation of quasi-projectiles from the nuclear reaction $^{40}Ca$ + $^{12}C$ at 25 MeV/nucleon was used to produce excited states candidates to $\\alpha$-particle condensation. The experiment was performed at LNS-Catania using the CHIMERA multidetector. Accepting the emission simultaneity and equality among the $\\alpha$-particle kinetic energies as experimental criteria for deciding in favor of the condensate nature of an excited state, we analyze the $0_2^+$ and $2_2^+$ states of $^{12}$C and the $0_6^+$ state of $^{16}$O. A sub-class of events corresponding to the direct 3-$\\alpha$ decay of the Hoyle state is isolated.

  16. Layered cathode materials for lithium ion rechargeable batteries (United States)

    Kang, Sun-Ho; Amine, Khalil


    A number of materials with the composition Li.sub.1+xNi.sub..alpha.Mn.sub..beta.Co.sub..gamma.M' zF.sub.z (M'=Mg,Zn,Al,Ga,B,Zr,Ti) for use with rechargeable batteries, wherein x is between about 0 and 0.3, .alpha. is between about 0.2 and 0.6, .beta. is between about 0.2 and 0.6, .gamma. is between about 0 and 0.3, .delta. is between about 0 and 0.15, and z is between about 0 and 0.2. Adding the above metal and fluorine dopants affects capacity, impedance, and stability of the layered oxide structure during electrochemical cycling.

  17. Purification and characterization of a 4-hydroxybiphenyl UDP-glucuronosyltransferase from rat liver microsomes

    Energy Technology Data Exchange (ETDEWEB)

    Styczynski, B.; Green, M.; Coffman, B.; Puig, J.; Tephly, T. (Univ. of Iowa, Iowa City (United States))


    A phenobarbital-inducible rat liver microsomal UDP-glucuronosyltransferase (4-HBP UDPGT) which catalyzes the glucuronidation of 4-hydroxybiphenyl has been purified to homogeneity. The apparent subunit molecular weight of this protein is 52,500 as determined by SDS-PAGE. 4-HBP UDPGT was shown to react with 4-hydroxybiphenyl, p-nitrophenol and 4-methylumbelliferone, but did not react with morphine, testosteron or chloramphenicol. Upon treatment with Endoglycosidase H, the 4-HBP UDPGT underwent about a 2,000 dalton decrease in subunit molecular weight, suggesting that this protein in N-glycosylated. Western blot analysis has revealed immunorecognition of 4-HBP UDPGT by antibodies raised in rabbit against rat 3{alpha}- and 17{beta}-hydroxysteroid UDPGTs. Additionally, the authors have obtained the N-terminal amino acid sequence of 4-HBP UDPGT. These data provide evidence which suggests that this protein is different from another UDPGT previously shown to react with 4-hydroxybiphenyl, testosterone and chloramphenicol.

  18. Papillary renal cell carcinoma with multifocal cystic and solid masses in right kidney: a case report%右肾多发囊实性乳头状肾细胞癌一例报道

    Institute of Scientific and Technical Information of China (English)

    Xingxing Wang; Yong Hu; Jian Wang; Jun Xu; Taiping Zhang


    Papillary renal cell carcinoma (PRCC) is one of the second common subtype among all renal carcinoma. In this paper, it aimed at a 67 years old male patient with right multifocal papillary renal cell carcinoma (PRCC). Histologi-cal finding concluded papillae and tubular structures covered by mild small cells with pale cytoplasm and were character-ized by small oval nuclei. The neoplastic mesenchymal consists of foamy macrophages, necrosis, and cholesterol crystal. Immunohistochemically, all papillae and tubular structures express cytokeratin 7 (CK7), CD10, CK (AE1/AE3), alpha-meth-ylacyl-coenzyme A racemase (AMACR) and EMA; but was negative for antibody S-100. All the foamy macrophages show positive reactivity for CD68. The patient underwent right radical nephrectomy and survived well six months after the operation during our follow-up.

  19. Studies on synthetic pathway of xylose-containing N-linked oligosaccharides deduced from substrate specificities of the processing enzymes in sycamore cells (Acer pseudoplatanus L.). (United States)

    Tezuka, K; Hayashi, M; Ishihara, H; Akazawa, T; Takahashi, N


    We measured the activities of alpha-1,3-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase, alpha-1,6-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase, beta-1,4-mannosyl-glycoprotein beta-1,2-xylosyltransferase and glycoprotein 3-alpha-L-fucosyltransferase in the Golgi fraction of suspension-cultured cells of sycamore (Acer pseudoplatanus L.) using fluorescence-labelled oligosaccharides as acceptor substrates for these transferase reactions. The structures of the pyridylaminated oligosaccharides produced by these reactions were analyzed by two-dimensional sugar mapping using high-performance liquid chromatography. We demonstrated that (formula; see text) was processed to produce by these in vitro reactions. On the basis of these results, we discuss a biosynthetic pathway for xylose containing N-linked oligosaccharides in plant glycoproteins.

  20. Brane assisted quintessential inflation with transient acceleration

    CERN Document Server

    Bento, M C; Santos, N M C


    A simple model of quintessential inflation with the modified exponential potential exp(-\\alpha \\phi) [A + (\\phi-\\phi_0)^2] is analyzed in the braneworld context. Considering reheating via instant preheating, it is shown that the evolution of the scalar field \\phi from inflation to the present epoch is consistent with the observational constraints in a wide region of the parameter space. The model exhibits transient acceleration at late times for 0.96 < A \\alpha^2 < 1.3 and 271 < \\phi_0 \\alpha < 273, while permanent acceleration is obtained for 2.5 10^{-9} < A \\alpha^2 < 0.98 and 252 < \\phi_0 \\alpha < 273. The steep parameter \\alpha is constrained to be in the range 5.3 < \\alpha < 11.2.

  1. Proteomic analysis of ethanol-induced embryotoxicity in cultured post-implantation rat embryos. (United States)

    Usami, Makoto; Mitsunaga, Katsuyoshi; Irie, Tomohiko; Miyajima, Atsuko; Doi, Osamu


    Protein expression changes were examined in day 10.5 rat embryos cultured for 24 hr in the presence of ethanol by using two-dimensional electrophoresis and mass spectrometry. Exposure to ethanol resulted in quantitative changes in many embryonic protein spots (16 decreased and 28 increased) at in vitro embryotoxic concentrations (130 and 195 mM); most changes occurred in a concentration-dependent manner. For these protein spots, 17 proteins were identified, including protein disulfide isomerase A3, alpha-fetoprotein, phosphorylated cofilin-1, and serum albumin. From the gene ontology classification and pathway mapping of the identified proteins, it was found that ethanol affected several biological processes involving oxidative stress and retinoid metabolism.

  2. Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health? (United States)

    Leikin-Frenkel, Alicia I


    The role of ω3 alpha linolenic acid (ALA) in the maternal diet during pregnancy and lactation, and its effect on the prevention of disease and programming of health in offspring, is largely unknown. Compared to ALA, ω3 docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids have been more widely researched due to their direct implication in fetal neural development. In this literature search we found that ALA, the essential ω3 fatty acid and metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In light of new and evolving findings, this review proposes that ALA may have an intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal development as a regulator of gene programming for the prevention of metabolic disease and promotion of health in offspring.

  3. Constituents of Pterocarpus marsupium: an ayurvedic crude drug. (United States)

    Maurya, Rakesh; Singh, Rajinder; Deepak, Mundkinajeddu; Handa, S S; Yadav, Prem P; Mishra, Pushpesh K


    Five new flavonoid C-glucosides, 6-hydroxy-2-(4-hydroxybenzyl)-benzofuran-7-C-beta-d-glucopyranoside (1), 3-(alpha-methoxy-4-hydroxybenzylidene)-6-hydroxybenzo-2(3H)-furanone-7-C-beta-d-glucopyranoside (2), 2-hydroxy-2-p-hydroxybenzyl-3(2H)-6-hydroxybenzofuranone-7-C-beta-d-glucopyranoside (4), 8-(C-beta-d-glucopyranosyl)-7,3',4'-trihydroxyflavone (5) and 1,2-bis(2,4-dihydroxy,3-C-glucopyranosyl)-ethanedione (6) and two known compounds C-beta-d-glucopyranosyl-2,6-dihydroxyl benzene (7) and sesquiterpene (8), were isolated from an aqueous extract of the heartwood of Pterocarpus marsupium. The structure has been established using spectroscopic data.

  4. Pathogenesis of Goodpasture syndrome: a molecular perspective. (United States)

    Borza, Dorin-Bogdan; Neilson, Eric G; Hudson, Billy G


    Goodpasture (GP) syndrome is a form of anti-glomerular basement membrane (GBM) disease, in which autoantibodies bind to alpha3(IV) collagen in GBM causing rapidly progressive glomerulonephritis and pulmonary hemorrhage. The conformational GP epitopes have been mapped to 2 regions within the noncollagenous (NC1) domain of the alpha3(IV) chain. Recently, we described the molecular organization of the autoantigen in the native alpha3alpha4alpha5(IV) collagen network of the GBM. The crystal structure of the NC1 domain has revealed how the GP epitopes are sequestered in the native GBM. Further insight into the pathogenesis of disease has been obtained from better animal models. These advances provide a foundation for the development of new specific therapies.

  5. Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health?

    Directory of Open Access Journals (Sweden)

    Alicia I. Leikin-Frenkel


    Full Text Available The role of ω3 alpha linolenic acid (ALA in the maternal diet during pregnancy and lactation, and its effect on the prevention of disease and programming of health in offspring, is largely unknown. Compared to ALA, ω3 docosahexaenoic (DHA and eicosapentaenoic (EPA acids have been more widely researched due to their direct implication in fetal neural development. In this literature search we found that ALA, the essential ω3 fatty acid and metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In light of new and evolving findings, this review proposes that ALA may have an intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal development as a regulator of gene programming for the prevention of metabolic disease and promotion of health in offspring.

  6. HIV-1 efficient entry in inner foreskin is mediated by elevated CCL5/RANTES that recruits T cells and fuels conjugate formation with Langerhans cells.

    Directory of Open Access Journals (Sweden)

    Zhicheng Zhou


    Full Text Available Male circumcision reduces acquisition of HIV-1 by 60%. Hence, the foreskin is an HIV-1 entry portal during sexual transmission. We recently reported that efficient HIV-1 transmission occurs following 1 h of polarized exposure of the inner, but not outer, foreskin to HIV-1-infected cells, but not to cell-free virus. At this early time point, Langerhans cells (LCs and T-cells within the inner foreskin epidermis are the first cells targeted by the virus. To gain in-depth insight into the molecular mechanisms governing inner foreskin HIV-1 entry, foreskin explants were inoculated with HIV-1-infeceted cells for 4 h. The chemokine/cytokine milieu secreted by the foreskin tissue, and resulting modifications in density and spatial distribution of T-cells and LCs, were then investigated. Our studies show that in the inner foreskin, inoculation with HIV-1-infected cells induces increased CCL5/RANTES (1.63-fold and decreased CCL20/MIP-3-alpha (0.62-fold secretion. Elevated CCL5/RANTES mediates recruitment of T-cells from the dermis into the epidermis, which is blocked by a neutralizing CCL5/RANTES Ab. In parallel, HIV-1-infected cells mediate a bi-phasic modification in the spatial distribution of epidermal LCs: attraction to the apical surface at 1 h, followed by migration back towards the basement membrane later on at 4 h, in correlation with reduced CCL20/MIP-3-alpha at this time point. T-cell recruitment fuels the continuous formation of LC-T-cell conjugates, permitting the transfer of HIV-1 captured by LCs. Together, these results reveal that HIV-1 induces a dynamic process of immune cells relocation in the inner foreskin that is associated with specific chemokines secretion, which favors efficient HIV-1 entry at this site.

  7. Structures of two O-chain polysaccharides of Citrobacter gillenii O9a,9b lipopolysaccharide. A new homopolymer of 4-amino-4,6-dideoxy-D-mannose (perosamine). (United States)

    Lipiński, Tomasz; Zatonsky, George V; Kocharova, Nina A; Jaquinod, Michel; Forest, Eric; Shashkov, Alexander S; Gamian, Andrzej; Knirel, Yuriy A


    Mild acid degradation of the lipopolysaccharide of Citro- bacter gillenii O9a,9b released a polysaccharide (PS), which was found to consist of a single monosaccharide, 4- acetamido-4,6-dideoxy-d-mannose (d-Rha4NAc, N-acetyl-d-perosamine). PS was studied by methylation analysis and (1)H-NMR and (13)C-NMR spectroscopy, using two-dimensional (1)H,(1)H COSY, TOCSY, NOESY, and H-detected (1)H,(13)C heteronuclear correlation experiments. It was found that PS includes two structurally different polysaccharides: an alpha1-->2-linked homopolymer of N-acetyl-d-perosamine [-->2)-alpha-d-Rhap4NAc-(1-->, PS2] and a polysaccharide composed of tetrasaccharide repeating units (PS1) with the following structure: -->3)-alpha-d-Rhap4NAc-(1-->2)-alpha-d-Rhap4NAc-(1-->2)-alpha-d-Rhap4NAc-(1-->3)-alpha-d-Rhap4 N Ac2Ac-(1--> where the degree of O-acetylation of a 3-substituted Rha4NAc residue at position 2 is approximately 70%. PS could be fractionated into PS1 and PS2 by gel-permeation chromatography on TSK HW-50S. Matrix-assisted laser desorption ionization MS data indicate sequential chain elongation of both PS1 and PS2 by a single sugar unit, with O-acetylation in PS1 beginning at a certain chain length. Anti-(C. gillenii O9a,9b) serum reacted with PS1 in double immunodiffusion and immunoblotting, whereas neither PS2 nor the lipopolysaccharide of Vibrio cholerae O1 with a structurally related O-chain polysaccharide were reactive.

  8. Anti-HIV activity in cervical-vaginal secretions from HIV-positive and -negative women correlate with innate antimicrobial levels and IgG antibodies.

    Directory of Open Access Journals (Sweden)

    Mimi Ghosh

    Full Text Available We investigated the impact of antimicrobials in cervicovaginal lavage (CVL from HIV(+ and HIV(- women on target cell infection with HIV. Since female reproductive tract (FRT secretions contain a spectrum of antimicrobials, we hypothesized that CVL from healthy HIV(+ and (- women inhibit HIV infection.CVL from 32 HIV(+ healthy women with high CD4 counts and 15 healthy HIV(- women were collected by gently washing the cervicovaginal area with 10 ml of sterile normal saline. Following centrifugation, anti-HIV activity in CVL was determined by incubating CVL with HIV prior to addition to TZM-bl cells. Antimicrobials and anti-gp160 HIV IgG antibodies were measured by ELISA. When CXCR4 and CCR5 tropic HIV-1 were incubated with CVL from HIV(+ women prior to addition to TZM-bl cells, anti-HIV activity in CVL ranged from none to 100% inhibition depending on the viral strains used. CVL from HIV(- controls showed comparable anti-HIV activity. Analysis of CH077.c (clone of an R5-tropic, mucosally-transmitted founder virus viral inhibition by CVL was comparable to laboratory strains. Measurement of CVL for antimicrobials HBD2, trappin-2/elafin, SLPI and MIP3alpha indicated that each was present in CVL from HIV(+ and HIV(- women. HBD2 and MIP3alpha correlated with anti-HIV activity as did anti-gp160 HIV IgG antibodies in CVL from HIV(+ women.These findings indicate that CVL from healthy HIV(+ and HIV(- women contain innate and adaptive defense mechanisms that inhibit HIV infection. Our data suggest that innate endogenous antimicrobials and HIV-specific IgG in the FRT can act in concert to contribute toward the anti-HIV activity of the CVL and may play a role in inhibition of HIV transmission to women.

  9. N-containing sugars from Morus alba and their glycosidase inhibitory activities. (United States)

    Asano, N; Oseki, K; Tomioka, E; Kizu, H; Matsui, K


    The reexamination of N-containing sugars from the roots of Morus alba by improved purification procedures led to the isolation of eighteen N-containing sugars, including seven that were isolated from the leaves of Morus bombycis. These N-containing sugars are 1-deoxynojirimycin (1), N-methyl-1-deoxynojirimycin (2), fagomine (3), 3-epi-fagomine (4), 1,4-dideoxy-1,4-imino-D-arabinitol (5), 1,4-dideoxy-1,4-imino-D-ribitol (6), calystegin B2 (1 alpha,2 beta,3 alpha,4 beta-tetrahydroxy-nor-tropane, 7), calystegin C1 (1 alpha,2 beta,3 alpha,4 beta,6 alpha-pentahydroxy-nor-tropane, 8), 1,4-dideoxy-1,4-imino-(2-O-beta-D-glucopyranosyl)-D-arabinitol (9), and nine glycosides of 1. These glycosides consist of 2-O- and 6-O-alpha-D-galactopyranosyl-1-deoxynojirimycins (10 and 11, respectively), 2-O-, 3-O- and 4-O-alpha-D-glucopyranosyl-1-deoxynojirimycins (12, 13, and 14, respectively), and 2-O-, 3-O-, 4-O- and 6-O-beta-D-glucopyranosyl-1-deoxynojirimycins (15, 16, 17, and 18, respectively). Compound 4 is a new member of polyhydroxylated piperidine alkaloids, and the isolation of 6 is the first report of its natural occurrence. It has recently been found that the polyhydroxy-nor-tropane alkaloids possess potent glycosidase inhibitory activities. Calystegin A3 is the trihydroxy-nor-tropane, and calystegins B1 and B2 are the tetrahydroxy-nor-tropane. Calystegin C1, a new member of calystegins, is the first naturally occurring pentahydroxy-nor-tropane alkaloid. The inhibitory activities of these compounds were investigated against rat digestive glycosidases and various commercially available glycosidases.

  10. Two diastereomeric saponins with cytotoxic activity from Albizia julibrissin. (United States)

    Zou, K; Zhao, Y; Tu, G; Cui, J; Jia, Z; Zhang, R


    Two diastereomeric saponins, julibrosides J1 (1) and J9 (2), both of which show cytotoxic activity, were obtained from the stem bark of Albizia julibrissin Durazz. On the basis of chemical and spectral evidence [L.B. Ma et al., Carbohydr. Res., 281 (1996) 35-46], the structure of 1 was revised as 3-O-[beta-D-xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->6) -beta-D-glucopyranosyl]-21-O-[(6S)-2-trans-2-hydroxymethyl-6-methyl-6-O- [4-O-((6R)-2-trans-2,6-dimethyl-6-O-(beta-D-quinovopyranosyl)-2,7- octadienoyl)-beta-D-quinovopyranosyl]-2,7-octadienoyl] acacic acid-28-O-beta-D-glucopyranosyl-(1-->3)-[alpha-L-arabinofuranosyl-(1-->4 )]-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl ester. The diastereoisomer 2 of 1 was identified as 3-O-[beta-D-xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->6) -beta-D-glucopyranosyl]-21-O-[(6S)-2-trans-2-hydroxymethyl-6-methyl-6-O- [4-O-((6S)-2-trans-2,6-dimethyl-6-O-(beta-D-quinovopyranosyl)-2,7- octadienoyl)-beta-D-quinovopyranosyl]-2,7-octadienoyl] acacic acid-28-O-beta-D-glucopyranosyl-(1-->3)-[alpha-L-arabinofuranosyl-(1-->4 )]-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl ester. Saponin 2 is a new saponin named julibroside J9. Both julibrosides J1 and J9 show good inhibitory action against the KB cancer cell line in vitro.

  11. Thermodynamic assessment of the La-Sb and the Ho-Sb systems using the associate model

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jinsan [School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083 (China); Li, Changrong, E-mail: [School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083 (China); Guo, Cuiping; Du, Zhenmin [School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083 (China); Zhao, Xushan; Shen, Jianyun [General Research Institute for Nonferrous Metals, Beijing 100088 (China)


    Highlights: Black-Right-Pointing-Pointer The liquid phase was described by the associate model. Black-Right-Pointing-Pointer The first-principles method was used to calculate formation enthalpies of compounds. Black-Right-Pointing-Pointer A self-consistent set of thermodynamic parameters was obtained. Black-Right-Pointing-Pointer The experimental and calculated data were well reproduced by the optimized results. - Abstract: The La-Sb and the Ho-Sb systems were thermodynamically assessed by CALPHAD (CALculation of PHAse Diagram) approach based on the available experimental data including thermodynamic properties and phase equilibria. The formation enthalpies (at 0 K) of the compounds of the La-Sb and the Ho-Sb systems were calculated by the first-principles method and used in the present thermodynamic optimization. The liquid phases of both systems were modeled as the associate model, with the constituent species La, Sb and La{sub 3}Sb{sub 2} for the La-Sb liquid and Ho, Sb and HoSb for the Ho-Sb liquid. The excess Gibbs energy was formulated with the Redlich-Kister polynomial. The intermetallics, La{sub 2}Sb, La{sub 3}Sb{sub 2}, LaSb, LaSb{sub 2}, Ho{sub 5}Sb{sub 3}, {alpha}-Ho{sub 4}Sb{sub 3}, {beta}-Ho{sub 4}Sb{sub 3}, {alpha}-HoSb, {beta}-HoSb and HoSb{sub 2}, were treated as stoichiometric compounds. The calculated results showed the good agreement with the experimental data. The inconsistency of the calculated formation enthalpy of the compound HoSb{sub 2} with the reported experimental value was analyzed.

  12. Association of EEG, MRI, and regional blood flow biomarkers is predictive of prodromal Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Moretti DV


    Full Text Available Davide Vito Moretti IRCCS S Giovanni di Dio Fatebenefratelli, Brescia, Italy Background: Thinning in the temporoparietal cortex, hippocampal atrophy, and a lower regional blood perfusion is connected with prodromal stage of Alzheimer’s disease (AD. Of note, an increase of electroencephalography (EEG upper/low alpha frequency power ratio has also been associated with these major landmarks of prodromal AD.Methods: Clinical and neuropsychological assessment, EEG recording, and high-resolution three-dimensional magnetic resonance imaging were done in 74 grown up subjects with mild cognitive impairment. This information was gathered and has been assessed 3 years postliminary. EEG recording and perfusion single-photon emission computed tomography assessment was done in 27 subjects. Alpha3/alpha2 frequency power ratio, including cortical thickness, was figured for every subject. Contrasts in cortical thickness among the groups were assessed. Pearson’s r relationship coefficient was utilized to evaluate the quality of the relationship between cortical thinning, brain perfusion, and EEG markers.Results: The higher alpha3/alpha2 frequency power ratio group corresponded with more prominent cortical decay and a lower perfusional rate in the temporoparietal cortex. In a subsequent meetup after 3 years, these patients had AD.Conclusion: High EEG upper/low alpha power ratio was connected with cortical diminishing and lower perfusion in the temporoparietal brain area. The increase in EEG upper/low alpha frequency power ratio could be helpful in recognizing people in danger of conversion to AD dementia and this may be quality information in connection with clinical assessment. Keywords: electroencephalography, mild cognitive impairment, hippocampal volume, brain rhythms, biomarkers

  13. Inhibition of 3(17)beta-hydroxysteroid dehydrogenase from Pseudomonas testosteroni by steroidal A ring fused pyrazoles. (United States)

    Levy, M A; Holt, D A; Brandt, M; Metcalf, B W


    Several 2,3- and 3,4-steroidal fused pyrazoles have been investigated as potential inhibitors of NAD(P)H-dependent steroid oxidoreductases. These compounds are proven to be potent, specific inhibitors for 3(17) beta-hydroxysteroid dehydrogenase from Pseudomonas testosteroni with Ki values of 6-100 nM. In contrast, the activities of 3 alpha,20 beta-hydroxysteroid dehydrogenase from Streptomyces hydrogenans, steroid 5 alpha-reductase from rat prostate, and 3 alpha-hydroxysteroid dehydrogenase from rat liver were unaffected by micromolar concentrations of these compounds. Product and dead-end inhibition studies indicate an ordered association to the beta-dehydrogenase with the cofactor binding prior to substrate or inhibitor. From the results of double inhibition experiments, it is proposed that inhibition occurs through formation of an enzyme-NAD+-inhibitor ternate. On the basis of pH profiles of Vm/Km, Vm, and 1/Ki and of absorbance difference spectra, a hypothetical mechanism of inhibition by the steroidal pyrazoles, drawn by analogy from the inhibition of liver alcohol dehydrogenase by alkylpyrazoles [Theorell, H., & Yonetani, T. (1963) Biochem. Z. 338, 537-553; Andersson, P., Kvassman, J. K., Lindström, A., Oldén, B., & Pettersson, G. (1981) Eur. J. Biochem. 113, 549-554], is reconsidered. The pH studies and enzyme modification experiments by diethyl pyrocarbonate suggest the involvement of histidine in binding of the inhibitor. A modified proposal for the structure of the enzyme-NAD+-steroidal pyrazole complex is proposed.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Triterpene saponins from Chenopodium quinoa Willd. (United States)

    Kuljanabhagavad, Tiwatt; Thongphasuk, Piyanut; Chamulitrat, Walee; Wink, Michael


    Twenty triterpene saponins (1-20) have been isolated from different parts of Chenopodium quinoa (flowers, fruits, seed coats, and seeds) and their structures have been elucidated by analysis of chemical and spectroscopic data including 1D- and 2D-NMR. Four compounds (1-4) were identified: 3beta-[(O-beta-d-glucopyranosyl-(1-->3)-alpha-l-arabinopyranosyl)oxy]-23-oxo-olean-12-en-28-oic acid beta-d-glucopyranoside (1), 3beta-[(O-beta-d-glucopyranosyl-(1-->3)-alpha-l-arabinopyranosyl)oxy]-27-oxo-olean-12-en-28-oic acid beta-d-glucopyranoside (2), 3-O-alpha-l-arabinopyranosyl serjanic acid 28-O-beta-d-glucopyranosyl ester (3), and 3-O-beta-d-glucuronopyranosyl serjanic acid 28-O-beta-d-glucopyranosyl ester (4). The following known compounds have not previously been reported as saponin constituents from the flowers and the fruits of this plant: two bidesmosides of serjanic acid (5,6), four bidesmosides of oleanolic acid (7-10), five bidesmosides of phytolaccagenic acid (11-15), four bidesmosides of hederagenin (16-19), and one bidesmoside of 3beta,23,30-trihydroxy olean-12-en-28-oic acid (20). The cytotoxicity of these saponins and their aglycones was tested in HeLa cells. Induction of apoptosis in Caco-2 cells by bidesmosidic saponins 1-4 and their aglycones I-III was determined by flow cytometric DNA analysis. The saponins with an aldehyde group were most active. The relationships between structure and cytotoxic activity of saponins and their aglycones are discussed.

  15. The disintegrin domain of ADAM9: a ligand for multiple beta1 renal integrins. (United States)

    Mahimkar, Rajeev M; Visaya, Orvin; Pollock, Allan S; Lovett, David H


    Renal tubular epithelial cells in all nephron segments express a distinct member of the metalloprotease-disintegrin family, ADAM9 (a disintegrin and metalloprotease 9), in a punctate basolateral distribution co-localized to the beta1 integrin chain [Mahimkar, Baricos, Visaya, Pollock and Lovett (2000) J. Am. Soc. Nephrol. 11, 595-603]. Discrete segments of the nephron express several defined beta1 integrins, suggesting that ADAM9 interacts with multiple renal integrins and thereby regulates epithelial cell-matrix interactions. Intact ADAM9 and a series of deletion constructs sequentially lacking the metalloprotease domain and the disintegrin domain were assembled as chimaeras with a C-terminal GFP (green fluorescent protein) tag. Stable expression of the ADAM9/GFP protein on the surface of HEK-293 cells (human embryonic kidney 293 cells) significantly decreased adhesion to types I and IV collagen, vitronectin and laminin, but had little effect on adhesion to fibronectin. Expression of the disintegrin/cysteine-rich/GFP construct yielded a similar, but more marked pattern of decreased adhesion. Expression of the cysteine-rich/GFP construct had no effect on adhesion, indicating that the disintegrin domain was responsible for the competitive inhibition of cell-matrix binding. To define the specific renal tubular beta1 integrins interacting with the ADAM9 disintegrin domain, a recombinant GST (glutathione S-transferase)-disintegrin protein was used as a substrate in adhesion assays in the presence or absence of specific integrin-blocking antibodies. Inclusion of antibodies to alpha1, alpha3, alpha6, alphav and beta1 blocked adhesion of HEK-293 cells to GST-disintegrin protein. Immobilized GST-disintegrin domain perfused with renal cortical lysates specifically recovered the alpha3, alpha6, alphav and beta1 integrin chains by Western analysis. It is concluded that ADAM9 is a polyvalent ligand, through its disintegrin domain, for multiple renal integrins of the beta1

  16. Determining structure and function of steroid dehydrogenase enzymes by sequence analysis, homology modeling, and rational mutational analysis. (United States)

    Duax, William L; Thomas, James; Pletnev, Vladimir; Addlagatta, Anthony; Huether, Robert; Habegger, Lukas; Weeks, Charles M


    The short-chain oxidoreductase (SCOR) family of enzymes includes over 6,000 members identified in sequenced genomes. Of these enzymes, approximately 300 have been characterized functionally, and the three-dimensional crystal structures of approximately 40 have been reported. Since some SCOR enzymes are steroid dehydrogenases involved in hypertension, diabetes, breast cancer, and polycystic kidney disease, it is important to characterize the other members of the family for which the biological functions are currently unknown and to determine their three-dimensional structure and mechanism of action. Although the SCOR family appears to have only a single fully conserved residue, it was possible, using bioinformatics methods, to determine characteristic fingerprints composed of 30-40 residues that are conserved at the 70% or greater level in SCOR subgroups. These fingerprints permit reliable prediction of several important structure-function features including cofactor preference, catalytic residues, and substrate specificity. Human type 1 3beta-hydroxysteroid dehydrogenase isomerase (3beta-HSDI) has 30% sequence identity with a human UDP galactose 4-epimerase (UDPGE), a SCOR family enzyme for which an X-ray structure has been reported. Both UDPGE and 3-HSDI appear to trace their origins back to bacterial 3alpha,20beta-HSD. Combining three-dimensional structural information and sequence data on the 3alpha,20beta-HSD, UDPGE, and 3beta-HSDI subfamilies with mutational analysis, we were able to identify the residues critical to the dehydrogenase function of 3-HSDI. We also identified the residues most probably responsible for the isomerase activity of 3beta-HSDI. We test our predictions by specific mutations based on sequence analysis and our structure-based model.

  17. Depression-like behavior of aged male and female mice is ameliorated with administration of testosterone or its metabolites. (United States)

    Frye, Cheryl A; Walf, Alicia A


    There may be a role of age-related decline in androgen production and/or its metabolism for late-onset depression disorders of men and women. Thus, the anti-depressant-like effects of testosterone (T) and its metabolites are of interest. Given that these androgens have disparate mechanisms of action, it is important to begin to characterize and compare their effects in an aged animal model. We hypothesized that there would be sex differences in depression behavior of aged mice and that androgens would reduce depression-like behaviors in the forced swim test. To investigate this, male and female mice (approximately 24 months old) were subcutaneously administered T, or one of its 5alpha-reduced metabolites (dihydrotesterone-DHT, 5alpha-androstane,17beta-diol-3alpha-diol), or aromatized metabolite (estradiol--E(2)), or oil vehicle. Mice were administered androgens (1 mg/kg) 1 h before being tested in the forced swim test, an animal model of depression. We found that males spent more time immobile, and less time swimming, than females. Administration of T, DHT, or 3alpha-diol similarly reduced time spent immobile, and increased time spent struggling, of male and female mice. E(2), compared to vehicle administration, decreased time spent immobile of males and females, but increased time spent swimming of females and time spent struggling of male mice. Together, these data suggest that T and its 5alpha-reduced and aromatized metabolites have anti-depressant-like effects in aged male and female mice.

  18. Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action

    Energy Technology Data Exchange (ETDEWEB)

    Gee, K.W.; Bolger, M.B.; Brinton, R.E.; Coirini, H.; McEwen, B.S.


    Further in vitro studies of steroids active at the gamma-aminobutyric acidA (GABAA) receptor regulated Cl- channel labeled by (35S)-t-butylbicyclophosphorothionate ((35S)TBPS) reveal additional structural requirements necessary for activity. Evaluation of selected steroids for activity against TBPS-induced convulsions show similar requirements for activity. Interestingly, steroids (e.g., 5 alpha-pregnan-3 alpha, 20 alpha-diol) were identified that have high potency but limited efficacy as modulators of (35S)TBPS binding. These characteristics are reminiscent of the clinically useful benzodiazepines (BZs) such as clonazepam. However, interactions between the prototypical anesthetic-barbiturate, sodium pentobarbital, and steroids active at the Cl- channel suggest that they do not share a common site of action as allosteric modulators of (35S)TBPS and BZ receptor binding. The most potent steroid evaluated, 5 alpha-pregnan-3 alpha-ol-20-one, modulates (35S)TBPS binding at low concentrations (IC50 approximately 17 nM) in a regionally dependent manner. All (35S)TBPS binding sites appear to be functionally coupled to a steroid modulatory site. Because several of the active steroids are metabolites of progesterone, their ability to inhibit the binding of (3H)promegestrone to the cytosolic progestin receptor in rat uterus was evaluated. Those steroids showing potent activity at the GABAA receptor-Cl- ionophore were inactive at the intracellular progestin receptor. Such specificity coupled with their high potency provide additional support for the hypothesis that some of these steroids may be involved in the homeostatic regulation of brain excitability via the GABAA-BZ receptor complex.

  19. Optical studies of nicotinic acetylcholine receptor subtypes in the guinea-pig enteric nervous system. (United States)

    Obaid, A L; Nelson, M E; Lindstrom, J; Salzberg, B M


    Nicotinic transmission in the enteric nervous system (ENS) is extensive, but the role of individual nicotinic acetylcholine receptor (nAChR) subtypes in the functional connectivity of its plexuses has been elusive. Using monoclonal antibodies (mAbs) against neuronal alpha3-, alpha4-, alpha3/alpha5-, beta2-, beta4- and alpha7-subunits, combined with radioimmunoassays and immunocytochemistry, we demonstrate that guinea-pig enteric ganglia contain all of these nAChR-subunits with the exception of alpha4, and so, differ from mammalian brain. This information alone, however, is insufficient to establish the functional role of the identified nAChR-subtypes within the enteric networks and, ultimately, their specific contributions to gastrointestinal physiology. We have used voltage-sensitive dyes and a high-speed CCD camera, in conjunction with specific antagonists to various nAChRs, to elucidate some of the distinct contributions of the individual subtypes to the behaviour of enteric networks. In the guinea-pig, the submucous plexus has the extraordinary advantage that it is virtually two-dimensional, permitting optical recording, with single cell resolution, of the electrical activity of all of its neurones. In this plexus, the block of alpha3beta2-, alpha3beta4- and/or alpha7-nAChRs always results in a decrease in the magnitude of the synaptic response. However, the magnitude of the fast excitatory post-synaptic potentials (epsps) evoked by electrical stimulation of a neighbouring ganglion varies from cell to cell, reflecting the differential expression of subunits already observed using mAbs, as well as the strengths of the activated synaptic inputs. At the same time, we observe that submucous neurones have a substantial mecamylamine (Mec)-insensitive (non-nicotinic) component to their fast epsps, which may point to the presence of purinergic or serotonergic fast epsps in this system. In the myenteric plexus, on the other hand, the antagonist-induced changes in the

  20. Nicotine induces fibrogenic changes in human liver via nicotinic acetylcholine receptors expressed on hepatic stellate cells

    Energy Technology Data Exchange (ETDEWEB)

    Soeda, Junpei; Morgan, Maelle; McKee, Chad; Mouralidarane, Angelina; Lin, ChingI [University College London, Centre for Hepatology, Royal Free Hospital, London NW3 2PF (United Kingdom); Roskams, Tania [Department of Morphology and Molecular Pathology, University of Leuven (Belgium); Oben, Jude A., E-mail: [University College London, Centre for Hepatology, Royal Free Hospital, London NW3 2PF (United Kingdom); Department of Gastroenterology and Hepatology, Guy' s and St Thomas' Hospital, London SE1 7EH (United Kingdom)


    Highlights: Black-Right-Pointing-Pointer Cigarette smoke may induce liver fibrosis via nicotine receptors. Black-Right-Pointing-Pointer Nicotine induces proliferation of hepatic stellate cells (HSCs). Black-Right-Pointing-Pointer Nicotine activates hepatic fibrogenic pathways. Black-Right-Pointing-Pointer Nicotine receptor antagonists attenuate HSC proliferation. Black-Right-Pointing-Pointer Nicotinic receptor antagonists may have utility as novel anti-fibrotic agents. -- Abstract: Background and aims: Cigarette smoke (CS) may cause liver fibrosis but possible involved mechanisms are unclear. Among the many chemicals in CS is nicotine - which affects cells through nicotinic acetylcholine receptors (nAChR). We studied the effects of nicotine, and involved pathways, on human primary hepatic stellate cells (hHSCs), the principal fibrogenic cells in the liver. We then determined possible disease relevance by assaying nAChR in liver samples from human non-alcoholic steatohepatitis (NASH). Methods: hHSC were isolated from healthy human livers and nAChR expression analyzed - RT-PCR and Western blotting. Nicotine induction of hHSC proliferation, upregulation of collagen1-{alpha}2 and the pro-fibrogenic cytokine transforming growth factor beta 1 (TGF-{beta}1) was determined along with involved intracellular signaling pathways. nAChR mRNA expression was finally analyzed in whole liver biopsies obtained from patients diagnosed with non-alcoholic steatohepatitis (NASH). Results: hHSCs express muscle type ({alpha}1, {beta}1, delta and epsilon) and neuronal type ({alpha}3, {alpha}6, {alpha}7, {beta}2 and {beta}4) nAChR subunits at the mRNA level. Among these subunits, {alpha}3, {alpha}7, {beta}1 and {epsilon} were predominantly expressed as confirmed by Western blotting. Nicotine induced hHSC proliferation was attenuated by mecamylamine (p < 0.05). Additionally, collagen1-{alpha}2 and TGF-{beta}1 mRNA expression were significantly upregulated by nicotine and inhibited by

  1. Fatty acid composition, eicosanoid production and permeability in skin tissues of rainbow trout (Oncorhynchus mykiss) fed a control or an essential fatty acid deficient diet. (United States)

    Ghioni, C; Bell, J G; Bell, M V; Sargent, J R


    4 (LTC4) and leukotriene C5 (LTC5) in skin cells challenged with the calcium ionophore A23187, and of prostaglandin F2alpha (PGF2alpha), 12-HETE and 12-HEPE in gill cells challenged similarly. Prostaglandin F3alpha (PGF3alpha) production by ionophore stimulated gill cells was significantly reduced in fish fed the EFA-deficient diet. 14-HDHE produced by gill cells was 3.3 fold higher in EFA deficient fish compared to controls.

  2. Detection of dehydroepiandrosterone misuse by means of gas chromatography- combustion-isotope ratio mass spectrometry. (United States)

    Mareck, Ute; Geyer, Hans; Flenker, Ulrich; Piper, Thomas; Thevis, Mario; Schänzer, Wilhelm


    According to World Anti-Doping Agency (WADA) rules (WADA Technical Document-TD2004EAAS) urine samples containing dehydroepiandrosterone (DHEA) concentrations greater than 100 ng ML(-1) shall be submitted to isotope ratio mass spectrometry (IRMS) analysis. The threshold concentration is based on the equivalent to the glucuronide, and the DHEA concentrations have to be adjusted for a specific gravity value of 1.020. In 2006, 11,012 doping control urine samples from national and international federations were analyzed in the Cologne doping control laboratory, 100 (0.9%) of them yielding concentrations of DHEA greater than 100 ng mL(-1). Sixty-eight percent of the specimens showed specific gravity values higher than 1.020, 52% originated from soccer players, 95% were taken in competition, 85% were male urines, 99% of the IRMS results did not indicate an application of testosterone or related prohormones. Only one urine sample was reported as an adverse analytical finding having 319 ng mL(-1) DHEA (screening result), more than 10,000 ng mL(-1) androsterone and depleted carbon isotope ratio values for the testosterone metabolites androsterone and etiocholanolone. Statistical evaluation showed significantly different DHEA concentrations between specimens taken in- and out-of- competition, whereas females showed smaller DHEA values than males for both types of control. Also a strong influence of the DHEA excretion on different sport disciplines was detectable. The highest DHEA values were detected for game sports (soccer, basketball, handball, ice hockey), followed by boxing and wrestling. In 2007, 6622 doping control urine samples were analyzed for 3alpha,5-cyclo-5alpha-androstan-6beta-ol-17-one (3alpha,5-cyclo), a DHEA metabolite which was described as a useful gas chromatography-mass spectrometry (GC-MS) screening marker for DHEA abuse. Nineteen urine specimens showed concentrations higher than the suggested threshold of 140 ng mL(-1), six urine samples yielded

  3. Expression of neuronal nicotinic acetylcholine receptor subunit mRNAs in rat hippocampal GABAergic interneurons. (United States)

    Son, Jong-Hyun; Winzer-Serhan, Ursula H


    Hippocampal inhibitory interneurons are a diverse population of cells widely scattered in the hippocampus, where they regulate hippocampal circuit activity. The hippocampus receives cholinergic projections from the basal forebrain, and functional studies have suggested the presence of different subtypes of nicotinic acetylcholine receptors (AChRs) on gamma-aminobutyric acid (GABA)ergic interneurons. Single-cell polymerase chain reaction analysis had confirmed that several nAChR subunit mRNAs are co-expressed with glutamate decarboxylase 67 (GAD67), the marker for GABAergic interneurons. In this anatomical study, we systematically investigated the co-expression of GAD67 with different nAChR subunits by using double in situ hybridization with a digoxigenin-labeled GAD67 probe and (35)S-labeled probes for nAChR subunits (alpha2, alpha3, alpha4, alpha5, alpha6, alpha7, beta2, beta3, and beta4). The results revealed that most GAD67-positive interneurons expressed beta2, and 67 % also expressed alpha7 mRNA. In contrast, mRNA expression of other subunits was limited; only 13 % of GAD67-positive neurons co-expressed alpha4, and less than 10% expressed transcripts for alpha2, alpha3, alpha5, or beta4. Most GAD67/alpha2 co-expression was located in CA1/CA3 stratum oriens, and GAD67/alpha5 co-expression was predominantly detected in CA1/CA3 stratum radiatum/lacunosum moleculare and the dentate gyrus. Expression of alpha6 and beta3 mRNAs was rarely detected in the hippocampus, and mRNAs were not co-expressed with GAD67. These findings suggest that the majority of nicotinic responses in GABAergic interneurons should be mediated by a homomeric alpha7 or heteromeric alpha7*-containing nAChRs. Other possible combinations such as alpha2beta2*, alpha4beta2*, or alpha5beta2* heteromeric nAChRs could contribute to functional nicotinic response in subsets of GABAergic interneurons but overall would have a minor role.

  4. Conversion of cassava starch to biomass, carbohydrates, and acids by Aspergillus niger. (United States)

    Tan, K H; Ferguson, L B; Carlton, C


    The filamentous fungus, Aspergillus niger, efficiently converted cassava polysaccharides to mycelial mass, simple sugars, and acids during the course of its growth. A typical 70-ml culture broth containing 2% cassava polysaccharides yielded 0.38 g dry mycelial mass, 1.14 mmol reducing sugars, and 1.17 meq acids at the end of 42 h. About 70% of the initial total carbohydrate in the medium was degraded during the same period. The sugars and acids in the culture broths were analyzed by HPLC on a single Aminex HPX-87 column at 55 degrees C, using 0.013 N H2SO4 as the eluting solvent. Cassava polysaccharides were degraded to oligosaccharides, maltotriose, maltose, and glucose beyond the 20-h growth periods, with maltotriose emerging as the major simple sugar. The appearance of citric, malic, gluconic, succinic, and fumaric acids accounted mostly for the decreasing pH in the growth media. Formation of carbohydrate species in the culture broths was closely related to the biosynthesis and secretion of several carbohydrases by A. niger. The extracellular carbohydrases were separated and identified by chromatofocusing and polyacrylamide gel electrophoresis to be amyloglucosidase (EC, alpha-amylase (EC, and alpha-glucosidase (EC, respectively.

  5. The Traveling Salesman Problem Under Squared Euclidean Distances

    CERN Document Server

    de Berg, Mark; Sitters, René; Woeginger, Gerhard J; Wolff, Alexander


    Let $P$ be a set of points in $\\mathbb{R}^d$, and let $\\alpha \\ge 1$ be a real number. We define the distance between two points $p,q\\in P$ as $|pq|^{\\alpha}$, where $|pq|$ denotes the standard Euclidean distance between $p$ and $q$. We denote the traveling salesman problem under this distance function by TSP($d,\\alpha$). We design a 5-approximation algorithm for TSP(2,2) and generalize this result to obtain an approximation factor of $3^{\\alpha-1}+\\sqrt{6}^{\\alpha}/3$ for $d=2$ and all $\\alpha\\ge2$. We also study the variant Rev-TSP of the problem where the traveling salesman is allowed to revisit points. We present a polynomial-time approximation scheme for Rev-TSP$(2,\\alpha)$ with $\\alpha\\ge2$, and we show that Rev-TSP$(d, \\alpha)$ is APX-hard if $d\\ge3$ and $\\alpha>1$. The APX-hardness proof carries over to TSP$(d, \\alpha)$ for the same parameter ranges.

  6. Incorporation of radiolabeled whey proteins into casein micelles by heat processing

    Energy Technology Data Exchange (ETDEWEB)

    Noh, B.; Richardson, T. (Univ. of California, Davis (USA))


    Skim milk was heated at .70, 95, and 140{degree}C to simulate the processes of pasteurization, forewarming, and UHT sterilization, and the specific interactions between {alpha}-lactalbumin or {beta}-lactoglobulin and the caseins studied using tracer amounts of added {sup 14}C-labeled whey protein. Radioactivities of the whey and of the washed casein pellets from renneted skim milk were measured and the extent of the interaction estimated. Upon heating skim milk at 70{degree}C for 45 s, less than 2% {beta}-lactoglobulin and less than .3% {alpha}-lactalbumin were incorporated into the curd. Heating at 95{degree}C for .5 to 20 min resulted in 58 to 85% of the {beta}-lactoglobulin and 8 to 55% of the {alpha}-lactalbumin becoming associated with the curd. Heating at 140{degree}C for 2 and 4 s caused 43 and 54% of the {beta}-lactoglobulin and 9 and 12% of the {alpha}-lactalbumin, respectively, to be bound to the curd fraction. The radiolabeling technique is very sensitive and useful for tracing low levels of interaction between whey proteins and casein in heated milk systems.

  7. [Lipid mobilization and energy metabolism: impact of molecular and cellular approaches on the treatment of obesity]. (United States)

    Lafontan, M; Berlan, M; Galitzky, J


    There is strong evidence that reduced sympathetic nervous system (SNS) activity is involved in the etiology of obesity in several animal models of obesity. In humans the situation is more complex but humans with low SNS activity, reduced beta-adrenergic sensitivity, reduced lipid mobilizing efficacy of catecholamines have lowered energy expenditure and are at greater risk of obesity. The SNS with its effect on food intake, lipid mobilization and energy expenditure has a major potential as a target for novel pharmacotherapies in weight reducing strategies. Extended cellular and molecular knowledge about the nature, the distribution and the role of the adrenergic receptors (beta(1)-, beta(2)-, beta(3)-, alpha(2)- and alpha(1)-) existing in tissue effectors involved in the control of lipid mobilization (adipose tissue) and energy expenditure (brown adipose tissue, skeletal muscle) has opened new pathways for pharmacological strategies. In this manuscript, after a summary of current knowledge on the regulation of lipid mobilization and energy expenditure in humans, we briefly review the putative targets and the most recent attempts to develop agents acting at various adrenergic receptor types in SNS effectors or on SNS activity. These include major questions about putative utilization of beta(3)-agonists, alpha(2)-antagonists and beta-antagonists in pharmacotherapy and/or prevention of obesity in humans.

  8. Polymorphism of exon 3 of the HLA-G gene

    DEFF Research Database (Denmark)

    Hviid, T V; Meldgaard, Michael; Sørensen, S


    populations have only revealed a limited polymorphism. We investigated the polymorphism of the exon 3 of HLA-G by means of Polymerase Chain Reaction (PCR)-Single Strand Conformation Polymorphism (SSCP)- and DNA sequencing analysis in a Danish population. We detected four single-base substitutions in exon 3...... rate of embryos. HLA-G seems to play an important role in the feto-maternal relationship. The polymorphism of the HLA-G locus is not fully clarified. One study has shown extensive nucleotide sequence variation in the exon 3 (alpha-2 domain) in healthy African Americans. A few studies in other...... compared to the sequence of HLA-6.0 (G*01011); one of these has not been reported before. We also found a deletion of the first base of codon 130 or the third of codon 129 in a heterozygous individual. This study, together with previous results, suggests that the polymorphism of exon 3 of the HLA-G gene...

  9. Feeding Glycyrrhiza glabra (liquorice) and Astragalus membranaceus (AM) alters innate immune and physiological responses in yellow perch (Perca flavescens). (United States)

    Elabd, Hiam; Wang, Han-Ping; Shaheen, Adel; Yao, Hong; Abbass, Amany


    The current work assessed the potential immunomodulatory and growth-promoting effects of Astragalus membranaceus (AM) and Glycyrrhiza glabra (liquorice) in Yellow perch (Perca flavescens). In this regard, fish with an average weight of 31 ± 1.0 g were divided into five groups, and fed daily with an additive-free basal diet (control); 1, 2, and 3% (w/w) Glycyrrhiza glabra, and the fifth diet was incorporated with a combination of 1% G. glabra-AM for a four-week period. Immunological, biochemical and growth parameters were measured; and sub-groups of fish were exposed to 1-week starvation. The results showed that incorporating AM and liquorice in the diet significantly improved Immunological [superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), Lipid peroxidase (LPx) and lysozyme activities], biochemical [Aspartate Aminotransferase (AST) and Alanine Transaminase (ALT) activities; and glucose and cortisol concentrations] and growth performance parameters [body mass gain (BMG), specific growth rate (SGR), length, condition factor (K) and feed conversion ratio (FCR)]. In addition, markedly up-regulated the expression of related genes [Insulin-Like Growth Factor-1 (IGF-1), Serum amyloid A (SAA), Complement Component C3 (CCC3), Alpha 2 Macroglobulin (A2M), SOD and GPx] in treated fish groups compared to the control. Conclusively, feeding AM and liquorice diets significantly increased (P < 0.05) growth performance, antioxidant and immune response profiles throughout the entire experiment, suggesting their beneficial rule as natural anti-stress agents.

  10. A heuristic solution for the Pioneer anomaly employing an ELA metric with dark matter in the outskirts of the Solar system

    CERN Document Server

    Ferreira, P Castelo


    Considering an expanding locally anisotropic (ELA) metric with the Sun as central mass and the heuristic ansatz for the dimensionless functional exponent parameter 'alpha=3+alpha_2(r_1)(1-U_Sun)^2' with a linear ansatz 'alpha_2(r_1)=alpha_2^(2.0)+alpha_2^(2.1) r_1' above 20 AU the pioneer anomaly is fully accounted for as due to the blue-shift of the background space-time. For compatibility with orbital motion within the Solar system it is further considered a branch ansatz for which \\alpha_2(r_1)=0 below 19 AU. This construction reduces the physical acceleration correction above 20 AU down to ~10^(-14) m/s^2 outwards from the Sun such that orbital corrections to Uranus, Neptune and Pluto are less notorious than when the full Pioneer acceleration is considered to be a gravitational acceleration. It is also discussed the effective mass-energy density distribution above 20 AU due to the background corrections and the respective finite non-null total mass is computed by considering an upper cut-off for the funct...

  11. Nonlocalized cluster dynamics and nuclear molecular structure

    CERN Document Server

    Zhou, Bo; Horiuchi, Hisashi; Ren, Zhongzhou; Röpke, Gerd; Schuck, Peter; Tohsaki, Akihiro; Xu, Chang; Yamada, Taiichi


    A container picture is proposed for understanding cluster dynamics where the clusters make nonlocalized motion occupying the lowest orbit of the cluster mean-field potential characterized by the size parameter $``B"$ in the THSR (Tohsaki-Horiuchi-Schuck-R\\"{o}pke) wave function. The nonlocalized cluster aspects of the inversion-doublet bands in $^{20}$Ne which have been considered as a typical manifestation of localized clustering are discussed. So far unexplained puzzling features of the THSR wave function, namely that after angular-momentum projection for two cluster systems the prolate THSR wave function is almost 100$\\%$ equivalent to an oblate THSR wave function is clarified. It is shown that the true intrinsic two-cluster THSR configuration is nonetheless prolate. The proposal of the container picture is based on the fact that typical cluster systems, 2$\\alpha$, 3$\\alpha$, and $\\alpha$+$^{16}$O, are all well described by a single THSR wave function. It will be shown for the case of linear-chain states w...

  12. [Application of microbial enzymes in studies of steroid metabolism (author's transl)]. (United States)

    Schlegel, J; Schubert, K


    In vitro models are necessary for studying the biotransformation of new steroid drugs and to determine the structure of the metabolites and their biological activity. For that reason microorganisms and their enzymes were used to investigate the anabolic steroid Oral-Turinabol (4-chloro-17alpha-methyl-17beta-hydroxy-1,4-androstadiene-3-one). Clostridium paraputrificum transformed Oral-Turinabol into the hydrogenation products 4beta-chloro-17alpha-methyl-17beta-hydroxy-5beta-1-androstene-3-one (I) and 4beta-chloro-17alpha-methyl-5beta-1-androstene-3alpha,17beta-biol (II); Rhodotorula glutinis to 4alpha-chloro-17alpha-methyl-5alpha-1-androstene-3beta,17beta-hydroxy-5alpha-1-androstene-3-one (III) and 4alpha-chloro-17alpha-methyl-5alpha-1-androstene-3beta,17beta-diol (IV). The hydroxylation products 6beta-hydroxy- (V), 7beta-hydroxy- (VI), 15alpha- (VII) and 15beta-hydroxy-Oral-Turinabol (VIII) resulted from Absidia glauca and Aspergillus flavus. The metabolites II-V were isolated until now from mammals.

  13. Proper Eighth-Order Vacuum-Polarization Function and its Contribution to the Tenth-Order Lepton g-2

    CERN Document Server

    Aoyama, T; Kinoshita, T; Nio, M


    This paper reports the Feynman-parametric representation of the vacuum-polarization function consisting of 105 Feynman diagrams of the eighth order, and its contribution to the gauge-invariant set called Set I(i) of the tenth-order lepton anomalous magnetic moment. Numerical evaluation of this set is carried out using FORTRAN codes generated by an automatic code generation system gencodevpN developed specifically for this purpose. The contribution of diagrams containing electron loop to the electron g-2 is 0.017 47 (11) (alpha/pi)^5. The contribution of diagrams containing muon loop is 0.000~001 67 (3) (alpha/pi)^5. The contribution of tau-lepton loop is negligible at present. The sum of all these terms is 0.017 47 (11) (alpha/pi)^5. The contribution of diagrams containing electron loop to the muon g-2 is 0.087 1 (59) (alpha/pi)^5. That of tau-lepton loop is 0.000 237 (1) (alpha/pi)^5. The total contribution to a_mu, the sum of these terms and the mass-independent term, is 0.104 8 (59) (alpha/pi)^5.

  14. Exploration of cone cyclic nucleotide-gated channel-interacting proteins using affinity purification and mass spectrometry. (United States)

    Ding, Xi-Qin; Matveev, Alexander; Singh, Anil; Komori, Naoka; Matsumoto, Hiroyuki


    Photopic (cone) vision essential for color sensation, central vision, and visual acuity is mediated by the activation of photoreceptor cyclic nucleotide-gated (CNG) channels. Naturally occurring mutations in the cone channel subunits CNGA3 and CNGB3 are associated with achromatopsia and cone dystrophies. This work investigated the functional modulation of cone CNG channel by exploring the channel-interacting proteins. Retinal protein extracts prepared from cone-dominant Nrl (- / -) mice were used in CNGA3 antibody affinity purification, followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) separation and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analysis. The peptide mass fingerprinting of the tryptic digests and database search identified a number of proteins including spectrin alpha-2, ATPase (Na(+)/K(+) transporting) alpha-3, alpha and beta subunits of ATP synthase (H(+) transporting, mitochondrial F1 complex), and alpha-2 subunit of the guanine nucleotide-binding protein. In addition, the affinity-binding assays demonstrated an interaction between cone CNG channel and calmodulin but not cone Na(+)/Ca(2+)-K(+) exchanger in the mouse retina. Results of this study provide insight into our understanding of cone CNG channel-interacting proteins and the functional modulations.

  15. Nucleotide insertion initiated by van der Waals interaction during polymerase beta DNA replication

    CERN Document Server

    Arulsamy, Andrew Das


    Immortality will remain a fantasy for as long as aging is determined by the erroneous biochemical reactions during a particular DNA replication. The replication and base excision repair mechanism, associated to eukaryotic DNA polymerase-beta enzyme are central to maintaining a healthy cell. Here, we give a series of unambiguous theoretical analyses and prove that the exclusive biochemical reaction involved in a single nucleotide insertion into the DNA primer can be efficiently tracked using the renormalized van der Waals interaction of the stronger type, and the Hermansson blue-shifting hydrogen bond effect. We found that there are two biochemical steps involved to complete the insertion of a single dCTP into the 3' end of a DNA primer. First, the O3' (from a DNA primer) initiates the nucleophilic attack on P_alpha?(from an incoming dCTP), in response, O3_alpha (bonded to P_alpha) retaliates by interacting with H' (bonded to O3'). These interactions are shown to be strongly interdependent and require the form...

  16. HIF3A DNA Methylation Is Associated with Childhood Obesity and ALT. (United States)

    Wang, Shuo; Song, Jieyun; Yang, Yide; Zhang, Yining; Wang, Haijun; Ma, Jun


    Gene polymorphisms associated so far with body mass index (BMI) can explain only 1.18-1.45% of observed variation in BMI. Recent studies suggest that epigenetic modifications, especially DNA methylation, could contribute to explain part of the missing heritability, and two epigenetic genome-wide analysis studies (EWAS) have reported that Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) methylation was associated with BMI or BMI change. We therefore assessed whether the HIF3A methylation is associated with obesity and other obesity-related phenotypes in Chinese children. The subjects included 110 severe obese cases aged 7-17y and 110 normal-weight controls matched by age and gender for measurement of blood DNA methylation levels at the HIF3A gene locus using the Sequenom's MassARRAY system. We observed significantly higher methylation levels in obese children than in controls at positions 46801642 and 46801699 in HIF3A gene (Pobesity, and has a BMI-independent association with ALT. The results provide evidence for identifying epigenetic factors of elivated ALT and may be useful for risk assessment and personalized medicine of liver diseases such as non-alcoholic fatty liver disease (NAFLD).

  17. HIF3A DNA Methylation Is Associated with Childhood Obesity and ALT.

    Directory of Open Access Journals (Sweden)

    Shuo Wang

    Full Text Available Gene polymorphisms associated so far with body mass index (BMI can explain only 1.18-1.45% of observed variation in BMI. Recent studies suggest that epigenetic modifications, especially DNA methylation, could contribute to explain part of the missing heritability, and two epigenetic genome-wide analysis studies (EWAS have reported that Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A methylation was associated with BMI or BMI change. We therefore assessed whether the HIF3A methylation is associated with obesity and other obesity-related phenotypes in Chinese children. The subjects included 110 severe obese cases aged 7-17y and 110 normal-weight controls matched by age and gender for measurement of blood DNA methylation levels at the HIF3A gene locus using the Sequenom's MassARRAY system. We observed significantly higher methylation levels in obese children than in controls at positions 46801642 and 46801699 in HIF3A gene (P<0.05, and found positive associations between methylation and alanine aminotransferase (ALT levels adjusted by gender, age and BMI at the position 46801699 (r = 0.226, P = 0.007. These results suggest that HIF3A DNA methylation is associated with childhood obesity, and has a BMI-independent association with ALT. The results provide evidence for identifying epigenetic factors of elivated ALT and may be useful for risk assessment and personalized medicine of liver diseases such as non-alcoholic fatty liver disease (NAFLD.

  18. Ursodeoxycholic acid in the Ursidae: biliary bile acids of bears, pandas, and related carnivores. (United States)

    Hagey, L R; Crombie, D L; Espinosa, E; Carey, M C; Igimi, H; Hofmann, A F


    The biliary bile acid composition of gallbladder bile obtained from six species of bears (Ursidae), the Giant panda, the Red panda, and 11 related carnivores were determined by reversed phase liquid chromatography and gas chromatography-mass spectrometry. Bile acids were conjugated solely with taurine (in N-acyl linkage) in all species. Ursodeoxycholic acid (3 alpha, 7 beta-dihydroxy-5 beta-cholan-24-oic acid) was present in all Ursidae, averaging 1-39% of biliary bile acids depending on the species; it was not detected or present as a trace constituent (bears, and its proportion averaged 34% (range 0-62%). Ursodeoxycholic acid averaged 17% of biliary bile acids in the Polar bear (n = 4) and 18% in the Brown bear (n = 6). Lower proportions (1-8%) were present in the Sun bear (n = 2), Ceylon Sloth bear (n = 1), and the Spectacled bear (n = 1). Bile of all species contained taurine-conjugated chenodeoxycholic acid and cholic acid. In some related carnivores, deoxycholic acid, the 7-dehydroxylation product of cholic acid, was also present. To determine whether the 7 beta hydroxy group of ursodeoxycholic acid was formed by hepatic or bacterial enzymes, bile acids were determined in hepatic bile obtained from bears with chronic biliary fistulae. Fistula bile samples contained ursodeoxycholic acid, chenodeoxycholic acid, and a trace amount of cholic acid, all as taurine conjugates, indicating that ursodeoxycholic acid is a primary bile acid formed in the liver in Ursidae.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Assessing seasonal and spatial trends of persistent organic pollutants (POPs) in Indian agricultural regions using PUF disk passive air samplers

    Energy Technology Data Exchange (ETDEWEB)

    Pozo, Karla [Atmospheric Science and Technology Directorate, Environment Canada, 4905 Dufferin Street, Toronto, Ontario M3H 5T4 (Canada); Environmental Science Department, University of Siena, Via Mattioli 4, 53100 Siena (Italy); Harner, Tom, E-mail: tom.harner@ec.gc.c [Atmospheric Science and Technology Directorate, Environment Canada, 4905 Dufferin Street, Toronto, Ontario M3H 5T4 (Canada); Lee, Sum Chi [Atmospheric Science and Technology Directorate, Environment Canada, 4905 Dufferin Street, Toronto, Ontario M3H 5T4 (Canada); Sinha, Ravindra K. [Centre for Environmental Science, School of Earth Biological and Environmental Sciences, Central University of Bihar, Patna (India); Sengupta, B. [Central Pollution Control Board, Parivesh Bhavan, East Arjun Nagar, Delhi (India); Loewen, Mark [Freshwater Institute, Department of Fisheries and Oceans, Winnipeg, Manitoba (Canada); Geethalakshmi, V. [Department of Agricultural Meteorology, Tamil Nadu Agricultural University, Coimbatore, Tamil Nadu (India); Kannan, Kurunthachalam [Wadsworth Center, New York State Department of Health and Department of Environmental Health Sciences, State University of New York at Albany, New York (United States); Volpi, Valerio [Environmental Science Department, University of Siena, Via Mattioli 4, 53100 Siena (Italy)


    The first survey of persistent organic pollutant (POP) concentrations in air across several Indian agricultural regions was conducted in 2006-2007. Passive samplers comprising polyurethane foam (PUF) disks were deployed on a quarterly basis at seven stations in agricultural regions, one urban site and one background site. The project was conducted as a sub-project of the Global Atmospheric Passive Sampling (GAPS) Network. In addition to revealing new information on air concentrations of several organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), the study has demonstrated the feasibility of conducting regional-scale monitoring for POPs in India using PUF disk samplers. The following analytes were detected with relatively high concentrations in air (mean for 2006 and 2007, pg/m{sup 3}): {alpha}- and {gamma}-hexachlorocyclohexane (HCH) (292 and 812, respectively); endosulfan I and II (2770 and 902, respectively); p,p'-DDE and p,p'-DDT (247 and 931, respectively); and for the sum of 48 PCBs, 12,100 (including a site with extremely high air concentrations in 2007) and 972 (when excluding data for this site). - New data on air concentrations of POPs across Indian agricultural regions is generated using cost-effective passive air samplers.

  20. Photolysis of alpha-xylyl chlorides: an efficient deep-UV photoinitiating system for radical and cationic polymerization. (United States)

    Ponce, Patricia; Catalani, Luiz Henrique


    Photoacid generators (PAG) are chemical systems where light absorption renders strong acid formation, typically with quantum yields greater than one. Many compounds bearing halogen atoms are reported to produce hydrogen halides upon photolysis. Here, alpha-chloroxylene derivatives (ortho, meta and para) were subject of a photolysis study in order to: (i) determine the operative mechanism, (ii) identify the products formed and (iii) quantify the amount of HCl formed. Product structure and quantum yields of HCl formation where determined for the photolysis of alpha-chloro-o-xylene (1), alpha-chloro-m-xylene (2), alpha-chloro-p-xylene (3), alpha, alpha'-dichloro-o-xylene (4), alpha, alpha'-dichloro-m-xylene (5) and alpha, alpha'-dichloro-p-xylene (6) in apolar (benzene, cumene, ethylbenzene, toluene and isooctane) and polar (methanol, n-propanol, isopropyl alcohol) solvents. Some of these compounds were analysed by laser flash photolysis in argon-purged isooctane as solvent to examine the possible reaction intermediates involved. The observed products are derived from typical radical reactions like recombination, dimerization and hydrogen abstraction from the starting compound or from solvents. The formation of HCl is expected as the result of C-Cl homolysis followed by hydrogen abstraction by chlorine atom. The results showed yields ranging from 1.2 to 18, depending on the conditions used. These numbers indicate the potential use of these compounds as PAG systems for the deep UV region.

  1. Linking tricyclic antidepressants to ionotropic glutamate receptors. (United States)

    Stoll, Laura; Gentile, Lisa


    Although tricyclic antidepressants have been in existence since the 1940s when they were discovered upon screening iminodibenzyl derivatives for other potential therapeutic uses, their mechanism of action has remained unclear [A. Goodman Gilman, T.W. Rall, A.S. Nies, P. Taylor, Goodman and Gilman's The Pharmacological Basis of Therapeutics, eighth ed., Pergamon Press, New York, 1990]. In addition to their ability to hinder the reuptake of biogenic amines, there is mounting evidence that the tricyclic antidepressants inhibit glutamate transmission. Here, intrinsic tryptophan fluorescence spectroscopy is used to document the binding of desipramine, a member of the tricyclic antidepressant family, to a well-defined extracellular glutamate binding domain (S1S2) of the GluR2 subunit of the amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. The binding is distinct from those of other known effectors of the receptor, including the endogenous sulfated neurosteroids pregnenolone sulfate and 3alpha-hydroxy-5beta-pregnan-20-one sulfate, and is consistent with a conformational change upon binding that is allosterically transmitted to the channel region of the receptor.

  2. Measurement of the Electrical Conductivity of He{sup 3} Plasma Induced by Neutron Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Braun, J.; Nygaard, K.


    The conductivity of a He plasma created by the inelastic reaction with thermal neutrons: {sup 3}He + n{sub th} -> {sup 3}H + p + 0.76 MeV is studied as a function of neutron flux, gas temperature and gas density. Using reported values of the electron mobility the electron density is calculated from experimental conductivity values. Further, by accepting a reasonable value for the mean energy lost in creating one ion-pair, the recombination coefficient is estimated. The measurements performed so far cover temperatures between 300 - 1600 K and densities between 0.25 - 1 times the density at atmospheric pressure and 300 K. The neutron flux is varied between 10{sup 10} - 10{sup 11} n/cm{sup 2}/s. As a sample of results achieved at 1600 K and the lowest density (corresponding to about atmospheric pressure) and the highest neutron flux the following values are obtained for the conductivity, the electron density and the recombination coefficient respectively: {sigma} 0.2 S/m, n{sub e} 6x10{sup 11}/cm{sup 3}, {alpha} = 2xl0{sup -10} cm{sup 3}/s. An extrapolation of data obtained shows that the concept of neutron induced conductivity should be attractive for MHD power generation.

  3. The pharmacology of spontaneously open alpha 1 beta 3 epsilon GABA A receptor-ionophores. (United States)

    Maksay, Gábor; Thompson, Sally A; Wafford, Keith A


    Human alpha(1)beta(3) epsilon GABA(A) receptors were expressed in Xenopus oocytes and examined using the conventional two-electrode voltage-clamp technique and compared to alpha(1)beta(3)gamma(2) receptors. The effects of several GABA(A) agonists were studied, and the allosteric modulation of the channel by a number of GABAergic modulators investigated. The presence of the epsilon subunit increased the potency and efficacy of direct activation by partial GABA(A) agonists (piperidine-4-sulphonic acid and thio-4-PIOL), pentobarbital and neuro-steroids. Direct activation by 3-hydroxylated neurosteroids was restricted to 3alpha epimers, while chirality at C5 was indifferent. The 3beta-sulfate esters of pregnenolone and dehydroepiandrosterone inhibited the spontaneous currents with efficacies higher, while bicuculline methiodide and SR 95531 did so lower than picrotoxin and TBPS. Furosemide, fipronil, triphenylcyanoborate and Zn(2+) blocked the spontaneous currents of alpha(1)beta(3) epsilon receptors with different efficacies. Flunitrazepam and 4'-chlorodiazepam inhibited the spontaneous currents with micromolar potencies. In conclusion, spontaneously active alpha(1)beta(3) epsilon GABA(A) receptors can be potentiated and blocked by GABAergic agents within a broad range of efficacy.

  4. The structure of {sup l2}C and stellar helium burning

    Energy Technology Data Exchange (ETDEWEB)

    Gai, Moshe, E-mail: [Laboratory for Nuclear Science at Avery Point University of Connecticut, 1084 Shennecossett Rd, Groton, CT 06340-6097 (United States)


    The rate of stellar formation of carbon at high temperatures (T > 3 GK) may increase beyond that which is expected from the Hoyle state at 7.654 MeV due to contributions from higher lying states in {sup 12}C. The long sought for second 2{sup +} state predicted at 9 - 10 MeV excitation energy in {sup 12}C was predicted to significantly increase the production of {sup 12}C. An Optical Readout Time Projection Chamber (O-TPC) operating with the gas mixture of CO{sub 2} (80%) + N{sub 2}(20%) at 100 torr with gamma beams from the HI{gamma}S facility of TUNL at Duke was used to study the formation of carbon (and oxygen) during helium burning. Preliminary measurements were carried out at beam energies: E = 9.51, 9.61, 9.72, 10.00, 10.54, 10.84 and 11.14 MeV. Extra attention was paid for separating the carbon dissociation events, {sup 12}C({gamma},3{alpha}), from the oxygen dissociation events, {sup 16}O({gamma}, {alpha}){sup 12}C. Complete angular distributions were measured giving credence to a newly identified 2{sup +} state just below 10.0 MeV.

  5. RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability. (United States)

    Xu, Dongyi; Guo, Rong; Sobeck, Alexandra; Bachrati, Csanad Z; Yang, Jay; Enomoto, Takemi; Brown, Grant W; Hoatlin, Maureen E; Hickson, Ian D; Wang, Weidong


    BLM, the helicase mutated in Bloom syndrome, associates with topoisomerase 3alpha, RMI1 (RecQ-mediated genome instability), and RPA, to form a complex essential for the maintenance of genome stability. Here we report a novel component of the BLM complex, RMI2, which interacts with RMI1 through two oligonucleotide-binding (OB)-fold domains similar to those in RPA. The resulting complex, named RMI, differs from RPA in that it lacks obvious DNA-binding activity. Nevertheless, RMI stimulates the dissolution of a homologous recombination intermediate in vitro and is essential for the stability, localization, and function of the BLM complex in vivo. Notably, inactivation of RMI2 in chicken DT40 cells results in an increased level of sister chromatid exchange (SCE)--the hallmark feature of Bloom syndrome cells. Epistasis analysis revealed that RMI2 and BLM suppress SCE within the same pathway. A point mutation in the OB domain of RMI2 disrupts the association between BLM and the rest of the complex, and abrogates the ability of RMI2 to suppress elevated SCE. Our data suggest that multi-OB-fold complexes mediate two modes of BLM action: via RPA-mediated protein-DNA interaction, and via RMI-mediated protein-protein interactions.

  6. Radio recombination lines from obscured quasars with the SKA

    CERN Document Server

    Manti, Serena; Ferrara, Andrea; Feruglio, Chiara; Graziani, Luca; Bernardi, Gianni


    We explore the possibility of detecting hydrogen radio recombination lines from 0 < z < 10 quasars. We compute the expected Hnalpha flux densities as a function of absolute magnitude and redshift by considering (i) the range of observed AGN spectral indices from UV to X-ray bands, (ii) secondary ionizations from X-ray photons, and (iii) stimulated emission due to nonthermal radiation. All these effects are important to determine the line fluxes. We find that the combination of slopes: alpha_X,hard = -1.11, alpha_X,soft = -0.7, alpha_EUV = -1.3, alpha_UV = -1.7, maximizes the expected flux, f_Hnalpha = 10 microJy for z = 7 quasars with M_AB = -27 in the n = 50 lines; allowed SED variations produce variations by a factor of 3 around this value. Secondaries boost the line intensity by a factor of 2 to 4, while stimulated emission in high-z quasars with M_AB = -26 provides an extra boost to RRL flux observed at nu = 1 GHz if recombinations arise in HII regions with T_e = 10^3-5 K, n_e = 10^3-5 cm^-3. We com...

  7. Effect of pressure on nanomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Uma D. [Department of Physics, G.B. Pant University of Agriculture and Technology, Pantnagar-263145 (India); Kumar, M., E-mail: [Department of Physics, G.B. Pant University of Agriculture and Technology, Pantnagar-263145 (India)


    A simple theory is proposed to predict the effect of pressure on nanomaterials, which gets support from the Mie-Gruneisen theory of thermal expansivity as formulated by Born and Huang. We considered LiAlSi{sub 2}O{sub 6} to study the effect of pressure in the light of other formulations, viz. Murnaghan, Birch-Murnaghan, Vinet and Kumar. The results obtained are found to present a good agreement with the experimental data as well as other formulations. To confirm the validity of the formulation, we applied the method to study the compression behaviour of a number of nanomaterials, viz. CdSe, Rb{sub 3}C{sub 60}, Ni(20 nm), carbon nanotube, {gamma}-Fe{sub 2}O{sub 3}, {epsilon}-Fe (Hexagonal iron), MgO, CuO, {gamma}-Al{sub 2}O{sub 3} (67 nm), {alpha}-Fe{sub 2}O{sub 3}, {alpha}-Fe (filled nanotube), TiO{sub 2} (anatase), 3C-SiC (30 nm), TiO{sub 2} (rutile phase), Zr{sub 0.1}Ti{sub 0.9}O{sub 2}, AlN (hexagonal), {gamma}-Si{sub 3}N{sub 4}, Ni-filled MWCNT and Fe-filled MWCNT. The results obtained are compared with the experimental data. A good agreement between theory and experiment demonstrates the validity of the present approach.

  8. Ficusonic acid: a new cytotoxic triterpene isolated from Maytenus royleanus (Wall. ex M. A. Lawson) cufodontis

    Energy Technology Data Exchange (ETDEWEB)

    Din, Ala Ud; Uddin, Ghias [Center for Phytomedicine and Medicinal Organic Chemistry, Institute of Chemical Sciences, University of Peshawar(Pakistan); Hussain, Nusrat; Choudary, Mohammad Iqbal, E-mail: [International Center for Chemical and Biological Sciences, HEJ Research Institute of Chemistry, University of Karachi (Pakistan)


    Phytochemical investigation of the roots of Maytenus royleanus resulted into the isolation of a new cytotoxic triterpene ficusonic acid, 3{beta},21{beta}-dihydroxyolean-12-en-29-oic acid, together with three known compounds, 3{alpha},22{beta}-dihydroxyolean-12-en-29-oic acid, salaspermic acid and orthosphenic acid, reported for the first time from this source. Their structures were established on the basis of extensive spectroscopic techniques. The cytotoxic activity of compound 3{beta},21{beta}-dihydroxyolean-12-en-29-oic acid was evaluated against two cancer cell lines, PC-3 prostate and HeLa cervical cancer lines. 3{beta},21{beta}-dihydroxyolean-12-en-29-oic acid showed weak activity against PC-3 (IC{sub 50} = 35.42 Greek-Small-Letter-Mu mol L{sup -1}) however against HeLa (IC{sub 50} = 20.47 Greek-Small-Letter-Mu mol L{sup -1}), its activity was moderate. (author)

  9. Influence of the semisynthetic bile acid MKC on the ileal permeation of gliclazide in vitro in healthy and diabetic rats treated with probiotics. (United States)

    Al-Salami, H; Butt, G; Tucker, I; Mikov, M


    The aim of this study was to investigate the influence of sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate (MKC) on the ileal permeation of gliclazide in healthy and diabetic rats treated with probiotics. Male Wistar rats (2-3 months, 350 +/- 50 g) were randomly allocated into four groups (n = 32); Groups 1 and 2 were healthy controls and Groups 3 and 4 were diabetic rats (alloxan 30 mg/kg was administered i.v.), which were administered probiotics for three days after the rats became diabetics. The rats were sacrificed and tissues were mounted on Ussing chambers. Then, gliclazide (200 microg/ml) was added to all the groups, while MKC (50 microg/ml) was given to Groups 2 and 4, for the measurement of the mucosal to serosal absorption Jss(MtoS) and serosal to mucosal secretion Jss(StoM) of gliclazide. In the tissues of healthy rats treated with probiotics, MKC stimulated the net absorption of gliclazide by stimulating the absorptive and reducing the secretory unidirectional fluxes, while in tissues from diabetic rats treated with probiotics, MKC had no effect. In healthy rats treated with probiotics, the degradation of MKC by bacterial polypeptides produced divalent bile salts that inhibited Mrp2, which resulted in reducing secretion and stimulating the absorption of gliclazide. In contrast, in diabetic rats treated with probiotics, MKC had no effect possibly due to a difference in the metabolic profile and resulting in no net flux.

  10. Spectral properties of large gradual solar energetic particle events - II -Systematic Q/M-dependence of heavy ion spectral breaks

    CERN Document Server

    Desai, M I; Dayeh, M A; Ebert, R W; McComas, D J; Li, G; Cohen, C M S; Mewaldt, R A; Schwadron, N A; Smith, C W


    We fit the $\\sim$0.1-500 MeV/nucleon H-Fe spectra in 46 large SEP events surveyed by Desai et al. (2016) with the double power-law Band function to obtain a normalization constant, low- and high-energy parameters $\\gamma_a$ and $\\gamma_b$; and break energy $E_B$. We also calculate the low-energy power-law spectral slope $\\gamma_1$. We find that: 1) $\\gamma_a$, $\\gamma_1$, and $\\gamma_b$ are species-independent within a given SEP event, and the spectra steepen with increasing energy; 2) $E_B$'s are well ordered by Q/M ratio, and decrease systematically with decreasing Q/M, scaling as (Q/M)$^\\alpha$ with $\\alpha$ varying between $\\sim$0.2-3; 3) $\\alpha$ is well correlated with Fe/O at $\\sim$0.16-0.23 MeV/nucleon and CME speed; 4) In most events: $\\alpha$3; and 5) Seven out of 9 extreme SEP events (associated with faster CMEs and GLEs) are Fe-rich, have $\\alpha >$1.4, have flatter spectra at low and high energies with $\\gamma_b$-$\\gamma_a <$3. The species-independence of $\\gamma_a$, $\\gamma_1$, and $\\gamma_b$...

  11. 17 beta-estradiol modulates GABAergic synaptic transmission and tonic currents during development in vitro. (United States)

    Pytel, Maria; Wójtowicz, Tomasz; Mercik, Katarzyna; Sarto-Jackson, Isabella; Sieghart, Werner; Ikonomidou, Chrysanthy; Mozrzymas, Jerzy W


    Estrogens exert a variety of modulatory effects on the structure and function of the nervous system. In particular, 17 beta-estradiol was found to affect GABAergic inhibition in adult animals but its action on GABAergic currents during development has not been elucidated. In the present study, we investigated the effect of 17 beta-estradiol on hippocampal neurons developing in vitro. In this model, mIPSC kinetics showed acceleration with age along with increased alpha1 subunit expression, similarly as in vivo. Long-term treatment with 17 beta-estradiol increased mIPSC amplitudes in neurons cultured for 6-8 and 9-11DIV and prolonged the mIPSC decaying phase only in the 9-11DIV group. The time needed for the onset of 17 beta-estradiol effect on mIPSC amplitude was approximately 48 h. In the period of 9-11DIV, treatment with 17 beta-estradiol strongly reduced the tonic conductance activated by low GABA concentrations. The effects of 17 beta-estradiol on mIPSCs and tonic conductance were not correlated with any change in expression of considered GABAAR subunits (alpha1-3, alpha5-6, gamma2) while alpha4 and delta subunits were at the detection limit. In conclusion, we provide evidence that 17 beta-estradiol differentially affects the phasic and tonic components of GABAergic currents in neurons developing in vitro.

  12. Chemical composition, larvicidal action, and adult repellency of Thymus magnus against Aedes albopictus. (United States)

    Park, Young-Uk; Koo, Hyun-Na; Kim, Gil-Hah


    Thymus magnus, an endemic species, is found in the Republic of Korea. The volatile compounds extracted by SPME from T. magnus were investigated for their chemical composition and electrophysiological response against the Asian tiger mosquito, Aedes albopictus. The volatile compounds of T. magnus as determined by gas chromatography mass spectrometry were gamma-terpinene (33.0%), thymol (29.9%), beta-bisabolene (8.9%), p-cymene (8.3%), alpha-terpinene (5.0%), myrcene (4.7%), beta-caryophyllene (4.0%), alpha-thujene (2.7%), camphene (1.3%), carvacrol (1.2%), and alpha-pinene (1.1%). Among these candidates, thymol exhibited complete (100%) repellent activity against female Ae. albopictus, an effect that was confirmed through evaluating the electrophysiological response on the antenna of Ae. albopictus. The effectiveness of a binary 1:2 mixture of thymol and vanillin (0.05:0.1 microl per cm2) was found to be significantly more effective than thymol alone for a period of 120 min. In addition, thymol, alpha-terpinene, and carvacrol showed high larvicidal activity against on the third-stage larvae with LC50 values of 0.9 microl per 100 ml.

  13. A Highly Tilted Binding Mode by a Self-Reactive T Cell Receptor Results in Altered Engagement of Peptide and MHC

    Energy Technology Data Exchange (ETDEWEB)

    D Sethi; D Schubert; A Anders; A Heroux; D Bonsor; C Thomas; E Sundberg; J Pyrdol; K Wucherpfennig


    Self-reactive T cells that escape elimination in the thymus can cause autoimmune pathology, and it is therefore important to understand the structural mechanisms of self-antigen recognition. We report the crystal structure of a T cell receptor (TCR) from a patient with relapsing-remitting multiple sclerosis that engages its self-peptide-major histocompatibility complex (pMHC) ligand in an unusual manner. The TCR is bound in a highly tilted orientation that prevents interaction of the TCR-{alpha} chain with the MHC class II {beta} chain helix. In this structure, only a single germline-encoded TCR loop engages the MHC protein, whereas in most other TCR-pMHC structures all four germline-encoded TCR loops bind to the MHC helices. The tilted binding mode also prevents peptide contacts by the short complementarity-determining region (CDR) 3{beta} loop, and interactions that contribute to peptide side chain specificity are focused on the CDR3{alpha} loop. This structure is the first example in which only a single germline-encoded TCR loop contacts the MHC helices. Furthermore, the reduced interaction surface with the peptide may facilitate TCR cross-reactivity. The structural alterations in the trimolecular complex are distinct from previously characterized self-reactive TCRs, indicating that there are multiple unusual ways for self-reactive TCRs to bind their pMHC ligand.

  14. Regulation of nicotinic receptor subtypes following chronic nicotinic agonist exposure in M10 and SH-SY5Y neuroblastoma cells

    DEFF Research Database (Denmark)

    Warpman, U; Friberg, L; Gillespie, A


    The present study further investigated whether nicotinic acetylcholine receptor (nAChR) subtypes differ in their ability to up-regulate following chronic exposure to nicotinic agonists. Seven nicotinic agonists were studied for their ability to influence the number of chick alpha4beta2 n......AChR binding sites stably transfected in fibroblasts (M10 cells) following 3 days of exposure. The result showed a positive correlation between the Ki values for binding inhibition and EC50 values for agonist-induced alpha4beta2 nAChR up-regulation. The effects of epibatidine and nicotine were further...... investigated in human neuroblastoma SH-SY5Y cells (expressing alpha3, alpha5, beta2, and beta4 nAChR subunits). Nicotine exhibited a 14 times lower affinity for the nAChRs in SH-SY5Y cells as compared with M10 cells, whereas epibatidine showed similar affinities for the nAChRs expressed in the two cell lines...

  15. Investigation of nanostructural, thermal and magnetic properties of yttrium iron garnet synthesized by mechanochemical method

    Energy Technology Data Exchange (ETDEWEB)

    Karami, M.A. [Materials Science and Engineering Department, School of Engineering, Shiraz University, Shiraz (Iran, Islamic Republic of); Shokrollahi, H., E-mail: [Electroceramics Group, Materials Science and Engineering Department, Shiraz University of Technology, 71555-313 Shiraz (Iran, Islamic Republic of); Hashemi, B. [Materials Science and Engineering Department, School of Engineering, Shiraz University, Shiraz (Iran, Islamic Republic of)


    This paper focuses on the magnetic, structural and thermal properties of mechanically alloyed Y{sub 2}O{sub 3}/{alpha}-Fe{sub 2}O{sub 3} mixed powders and investigates the effects of the mechanical milling and heat treatment on the synthesis of yttrium iron garnet from the primary materials. The morphological and structural studies were carried out by scanning electron microscope and X-ray diffraction, respectively. The thermal activities were measured by differential thermal analysis. The magnetic properties were studied by vibrating sample magnetometer. The results showed that high-energy milling does not lead to the garnet formation and even does not decrease the temperature of the garnet formation. Furthermore, the orthoferrite phase can be achieved slightly during the milling process (up to 96 h) and completely by the heat treatment at lower temperatures (850 Degree-Sign C). - Highlights: Black-Right-Pointing-Pointer The results showed that high energy milling did not lead to the garnet formation. Black-Right-Pointing-Pointer The milling process did not decrease the temperature of the garnet formation. Black-Right-Pointing-Pointer The orthoferrite phase can be achieved slightly during the mechanical milling. Black-Right-Pointing-Pointer The milling process can lower the temperature of orthoferrite formation. Black-Right-Pointing-Pointer The milled powder for 96 h completely transforms to orthoferrite below 700 Degree-Sign C.

  16. Transport and metabolic effects of alpha-aminoisobutyric acid in Saccharomyces cerevisiae. (United States)

    Kim, K W; Roon, R J


    alpha-Aminoisobutyric acid is actively transported into yeast cells by the general amino acid transport system. The system exhibits a Km for alpha-aminoisobutyric acid of 270 microM, a Vmax of 24 nmol/min per mg cells (dry weight), and a pH optimum of 4.1-4.3. alpha-Aminoisobutyric acid is also transported by a minor system(s) with a Vmax of 1.7 nmol/min per mg cells. Transport occurs against a concentration gradient with the concentration ratio reaching over 1000:1 (in/out). The alpha-aminoisobutyric acid is not significantly metabolized or incorporated into protein after an 18 h incubation. alpha-Aminoisobutyric acid inhibits cell growth when a poor nitrogen source such as proline is provided but not with good nitrogen sources such as NH+4. During nitrogen starvation alpha-aminoisobutyric acid strongly inhibits the synthesis of the nitrogen catabolite repression sensitive enzyme, asparaginase II. Studies with a mutant yeast strain (GDH-CR) suggest that alpha-aminoisobutyric acid inhibition of asparaginase II synthesis occurs because alpha-aminoisobutyric acid is an effective inhibitor of protein synthesis in nitrogen starved cells.

  17. A new value for the Lamb shift

    CERN Document Server

    Petermann, Andreas


    A recent analytic value of the alpha /sup 2/ slope of the Dirac form, factor of the free electron, from the crossed ladder diagram, is added to the contributions of the fourth order diagrams already evaluated by different workers. The sum is found to be F/sub 1/(0)/sub total/=( alpha /sup 2// pi /sup 2/)(- 4819/5184-49 pi /sup 2//432+/sup 1///sub 2/ pi /sup 2/ log 2-/sup 3///sub 4/ zeta (3))=( alpha /sup 2// pi /sup 2/)(0.4699). This contributes to the Lamb shift inH: ( alpha /sup 2// pi /sup 2/) alpha /sup 2//sub 1/2/m alpha /sup 2/ 0.4699=0.444 MHz. The total Lamb shift in H is then: S/sub H/=(2S/sub 1/2/-2P/sub 1/2/) /sub H/=1057.911+or-0.011 MHz (s.d.), and the separation Delta E/sub H /-S/sub H/: (2S/sub 3/2/-2S/sub 1/2/)/sub H/ =9911.115+or-0.031 MHz (s.d.). (15 refs).

  18. Immunohistochemical characterization of basal cell adenomas of the salivary gland. (United States)

    Takahashi, H; Fujita, S; Okabe, H; Tsuda, N; Tezuka, F


    Seven cases of basal cell adenomas of the salivary gland were analyzed by immunohistochemical methods with a broad panel of routinely used antibodies. Histologically the epithelial elements were classified as tubuloglandular, trabecular and solid patterns. The authors' results indicated the following: 1) The duct lining cells of tubuloglandular and trabecular patterns have distinct epithelial features with cytokeratins (KL 1, PKK 1, *PKK 2 and PKK 3), alpha-one-antichymotrypsin (alpha 1-ACT), carcinoembryonic antigen (CEA) and S-100 alpha subunit positivity. 2) The basaloid cells in the trabecular and solid patterns expressed two immunophenotypes: one had actin, neuron-specific enolase (NSE), S-100 protein and S-100 beta subunit patterns typical of myoepithelial cells in normal glands. The other basaloid cells had vimentin and S-100 protein patterns. The former cell type could be found in 4 of 7 cases and the latter was found in 7 cases. This represents a minor participation of the myoepithelial cells in the basal cell adenoma. 3) The basement membrane and stromal connective tissue around the neoplastic cells were positive for alpha-one-antitrypsin (alpha 1-AT). This antibody is a good marker in identifying the basement membrane-like material.

  19. Characterization of rapeseed (Brassica napus) oils by bulk C, O, H, and fatty acid C stable isotope analyses. (United States)

    Richter, Eva Katharina; Spangenberg, Jorge E; Kreuzer, Michael; Leiber, Florian


    Rapeseed ( Brassica napus ) oils differing in cultivar, sites of growth, and harvest year were characterized by fatty acid concentrations and carbon, hydrogen, and oxygen stable isotope analyses of bulk oils (delta(13)C(bulk), delta(2)H(bulk), delta(18)O(bulk) values) and individual fatty acids (delta(13)C(FA)). The delta(13)C(bulk), delta(2)H(bulk), and delta(18)O(bulk) values were determined by continuous flow combustion and high-temperature conversion elemental analyzer-isotope ratio mass spectrometry (EA/IRMS, TC-EA/IRMS). The delta(13)C(FA) values were determined using gas chromatography--combustion-isotope ratio mass spectrometry (GC/C/IRMS). For comparison, other C(3) vegetable oils rich in linolenic acid (flax and false flax oils) and rich in linoleic acid (poppy, sunflower, and safflower oils) were submitted to the same chemical and isotopic analyses. The bulk and molecular delta(13)C values were typical for C(3) plants. The delta(13)C value of palmitic acid (delta(13)C(16:0)) and n-3 alpha-linolenic acid (delta(13)C(18:3n-3)) differed (p oils. Also within species, significant differences of delta(13)C(FA) were observed (p oil differed between cultivars (p oil and specific fatty acid stable isotope analysis might be useful in tracing dietary lipids differing in their origin.

  20. Dielectric properties of betaine phosphite and deuterated betaine phosphite films

    Energy Technology Data Exchange (ETDEWEB)

    Balashova, E. V., E-mail:; Krichevtsov, B. B.; Zaitseva, N. V. [Russian Academy of Sciences, Ioffe Physicotechnical Institute (Russian Federation); Pankova, G. A. [Russian Academy of Sciences, Institute of Macromolecular Compounds (Russian Federation); Frederiks, I. D.; Lemanov, V. V. [Russian Academy of Sciences, Ioffe Physicotechnical Institute (Russian Federation)


    Polycrystalline films of betaine phosphite (BPI) and deuterated BPI have been grown by evaporation on LiNbO{sub 3}, {alpha}-SiO{sub 2}, {alpha}-Al{sub 2}O{sub 3}, and NdGaO{sub 3} substrates. These films consist of large single-crystal blocks in which the polar axis (b) lies in the substrate plane. The results of studying the dielectric properties of the films using interdigital electrodes, X-ray diffraction, and block images in a polarized-light microscope in reflection are reported. The film transition into the ferroelectric state at T = T{sub c} is accompanied by strong anomalies of the capacitance of the film/interdigital structure/substrate structure. The deuteration of BPI films leads to an increase in their temperature T{sub c}: from T{sub c} = 200 K for BPI-based structures to T{sub c} = 280 K for structures with a high degree of deuteration (d {approx} 90%).

  1. Efecto de diferentes plaguicidas sobre el crecimiento de Azotobacter chroococcum

    Directory of Open Access Journals (Sweden)

    Diego Rivera


    dichlorovinyl-2,2-dimethylcyclopropane carboxylate (RS-cyano-3-phenoxybenzyl; S-metolachlor:(S-2-chloro-N-(2-ethyl-6-methyl-phenyl-N-(2-methoxy-1-methyl-ethyl-acetamide; Fluometuron: 1,1-dimethyl-3 (alpha, alpha, alpha-trifluoro-m-tolyl urea and Glyphosate: (N-(phosphonomethyl glycine on the viability of biological inoculant Monibac ® - Corpoica whose active ingredient is based on non-symbiotic diazotrophic bacteria Azotobacter chroococcum AC1, applying the minimum inhibitory concentration and compatibility techniques. The results demonstrated the susceptibility of the organism Cypermethrin 50% and when it is mixed with other pesticides in the rate used in the field regularly. It was found that there were no significant effects (P< 0,05 of pesticides (Carboxin, Thiram, Imidacloprid, S-metolachlor, Fluometuron and Glyphosate under the different concentrations tested suggesting that this bacterium is able to tolerate these chemicals by different physiological mechanisms without affecting their growth in laboratory level. Key words: Azotobacter chroococcum, agrochemicals, bacteria, biofertilizer, inhibition

  2. Maximum geometrical hindrance to diffusion in brain extracellular space surrounding uniformly spaced convex cells. (United States)

    Tao, L; Nicholson, C


    Brain extracellular space (ECS) constitutes a porous medium in which diffusion is subject to hindrance, described by tortuosity, lambda = (D/D*)1/2, where D is the free diffusion coefficient and D* is the effective diffusion coefficient in brain. Experiments show that lambda is typically 1.6 in normal brain tissue although variations occur in specialized brain regions. In contrast, different theoretical models of cellular assemblies give ambiguous results: they either predict lambda-values similar to experimental data or indicate values of about 1.2. Here we constructed three different ECS geometries involving tens of thousands of cells and performed Monte Carlo simulation of 3-D diffusion. We conclude that the geometrical hindrance in the ECS surrounding uniformly spaced convex cells is independent of the cell shape and only depends on the volume fraction alpha (the ratio of the ECS volume to the whole tissue volume). This dependence can be described by the relation lambda = ((3-alpha)/2)1/2, indicating that the geometrical hindrance in such ECS cannot account for lambda > 1.225. Reasons for the discrepancy between the theoretical and experimental tortuosity values are discussed.

  3. Determination of astrophysical 12N(p,g)13O reaction rate from the 2H(12N, 13O)n reaction and its astrophysical implications

    CERN Document Server

    Guo, B; Li, Zhihong; Wang, Y B; Yan, S Q; Li, Y J; Shu, N C; Han, Y L; Bai, X X; Chen, Y S; Liu, W P; Yamaguchi, H; Binh, D N; Hashimoto, T; Hayakawa, S; Kahl, D; Kubono, S; He, J J; Hu, J; Xu, S W; Iwasa, N; Kume, N; Li, Zhihuan


    The evolution of massive stars with very low-metallicities depends critically on the amount of CNO nuclides which they produce. The $^{12}$N($p$,\\,$\\gamma$)$^{13}$O reaction is an important branching point in the rap-processes, which are believed to be alternative paths to the slow 3$\\alpha$ process for producing CNO seed nuclei and thus could change the fate of massive stars. In the present work, the angular distribution of the $^2$H($^{12}$N,\\,$^{13}$O)$n$ proton transfer reaction at $E_{\\mathrm{c.m.}}$ = 8.4 MeV has been measured for the first time. Based on the Johnson-Soper approach, the square of the asymptotic normalization coefficient (ANC) for the virtual decay of $^{13}$O$_\\mathrm{g.s.}$ $\\rightarrow$ $^{12}$N + $p$ was extracted to be 3.92 $\\pm$ 1.47 fm$^{-1}$ from the measured angular distribution and utilized to compute the direct component in the $^{12}$N($p$,\\,$\\gamma$)$^{13}$O reaction. The direct astrophysical S-factor at zero energy was then found to be 0.39 $\\pm$ 0.15 keV b. By considering ...

  4. A comparison between pre- and posthibernation morphometry, hematology, and blood chemistry in viperid snakes. (United States)

    Dutton, Christopher J; Taylor, Peter


    Snakes from temperate climates are often made to hibernate in zoos to stimulate reproduction. Unfortunately, deaths have occurred during and after hibernation. This study evaluated the health status, pre- and posthibernation, of 31 adult viperid snakes. It included morphometric measurements, hematology, and blood chemistry. No differences were seen in body weights and weight to length ratios between pre- and posthibernation examinations, suggesting that the overall condition of the snakes did not change. No differences were seen in hematologic and blood chemistry parameters, except that bile acids (3alpha-hydroxybile acids) decreased, the implications of which are unknown. Three individuals had markedly high plasma uric acid levels posthibernation; of these, two individuals died from extensive visceral gout and one recovered with fluid therapy. Viperid snakes should be clinically healthy, well hydrated, and in good body condition when they are put into hibernation. They should be maintained in an environment with sufficient humidity and should have access to water. Blood samples should be collected on arousal for measuring plasma uric acid levels. Changes in morphometry, hematology, and blood chemistry appear to be abnormal and should be investigated thoroughly.

  5. Antifungal and molluscicidal saponins from Serjania salzmanniana. (United States)

    Ekabo, O A; Farnsworth, N R; Henderson, T O; Mao, G; Mukherjee, R


    An investigation of Serjania salzmanniana for biologically active substances has led to the isolation of two novel saponins, salzmannianoside A (3-O-[[beta-D- glucopyranosyl-(1-->4)]-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L- arabinopyranosyl] gypsogenin) [3] and salzmannianoside B (3-O-[[beta-D-glucopyranosyl-(1-->4)]-[alpha-L- arabinopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)] -alpha-L-arabinopyranosyl] hederagenin) (4). Two known saponins, pulsatilla saponin D (3-O-[[beta-D- glucopyranosyl-(1-->4)]-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L- arabinopyranosyl] hederagenin) (1) and 3-O-[[beta-D-glucopyranosyl-(1-->4)]-[alpha-L-rhamnopyranosyl-(1-->2)]-a lpha-L- arabinopyranosyl] oleanolic acid (2) were also isolated from this plant. The structures of 3 and 4 were elucidated by FABMS and 2D NMR techniques. All these four saponins were mollusicidal, causing 70-100% mortality at 10 ppm against Biomphalaria alexandrina, a vector of Schistosoma mansoni in the Nile Valley. The saponins also showed antifungal activity against Cryptococcus neoformans and Candida albicans at minimal inhibitory concentrations of 8 and 16 micrograms/mL, respectively.

  6. Roles of Wnt/{beta}-catenin signaling in epithelial differentiation of mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yajing; Sun, Zhaorui; Qiu, Xuefeng [Immunology and Reproductive Biology Laboratory, Medical College of Nanjing University, Nanjing 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093 (China); Li, Yan [Jiangsu Centers for Diseases Prevention and Control, Nanjing 210009 (China); Qin, Jizheng [Immunology and Reproductive Biology Laboratory, Medical College of Nanjing University, Nanjing 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093 (China); Han, Xiaodong, E-mail: [Immunology and Reproductive Biology Laboratory, Medical College of Nanjing University, Nanjing 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing 210093 (China)


    Bone marrow-derived mesenchymal stem cells (MSCs) have been demonstrated to be able to differentiate into epithelial lineage, but the precise mechanisms controlling this process are unclear. Our aim is to explore the roles of Wnt/{beta}-catenin in the epithelial differentiation of MSCs. Using indirect co-culture of rat MSCs with rat airway epithelial cells (RTE), MSCs expressed several airway epithelial markers (cytokeratin 18, tight junction protein occudin, cystic fibrosis transmembrance regulator). The protein levels of some important members in Wnt/{beta}-catenin signaling were determined, suggested down-regulation of Wnt/{beta}-catenin with epithelial differentiation of MSCs. Furthermore, Wnt3{alpha} can inhibit the epithelial differentiation of MSCs. A loss of {beta}-catenin induced by Dickkopf-1 can enhance MSCs differentiation into epithelial cells. Lithium chloride transiently activated {beta}-catenin expression and subsequently decreased {beta}-catenin level and at last inhibited MSCs to differentiate into airway epithelium. Taken together, our study indicated that RTE cells can trigger epithelial differentiation of MSCs. Blocking Wnt/{beta}-catenin signaling may promote MSCs to differentiate towards airway epithelial cells.

  7. A highly tilted binding mode by a self-reactive T cell receptor results in altered engagement of peptide and MHC

    Energy Technology Data Exchange (ETDEWEB)

    Sethi, D.K.; Heroux, A.; Schubert, D. A.; Anders, A.-K.; Bonsor, D. A.; Thomas, C. P.; Sundberg, E. J.; Pyrdol, J.; Wucherpfennig, K. W.


    Self-reactive T cells that escape elimination in the thymus can cause autoimmune pathology, and it is therefore important to understand the structural mechanisms of self-antigen recognition. We report the crystal structure of a T cell receptor (TCR) from a patient with relapsing-remitting multiple sclerosis that engages its self-peptide-major histocompatibility complex (pMHC) ligand in an unusual manner. The TCR is bound in a highly tilted orientation that prevents interaction of the TCR-{alpha} chain with the MHC class II {beta} chain helix. In this structure, only a single germline-encoded TCR loop engages the MHC protein, whereas in most other TCR-pMHC structures all four germline-encoded TCR loops bind to the MHC helices. The tilted binding mode also prevents peptide contacts by the short complementarity-determining region (CDR) 3{beta} loop, and interactions that contribute to peptide side chain specificity are focused on the CDR3{alpha} loop. This structure is the first example in which only a single germline-encoded TCR loop contacts the MHC helices. Furthermore, the reduced interaction surface with the peptide may facilitate TCR cross-reactivity. The structural alterations in the trimolecular complex are distinct from previously characterized self-reactive TCRs, indicating that there are multiple unusual ways for self-reactive TCRs to bind their pMHC ligand.

  8. Integrin alpha chains exhibit distinct temporal and spatial localization patterns in epithelial cells of the Drosophila ovary. (United States)

    Dinkins, Michael B; Fratto, Victoria M; Lemosy, Ellen K


    Integrins are heterodimeric transmembrane receptors that modulate cell adhesion, migration, and signaling. Multiple integrin chains contribute to development and morphogenesis of a given tissue. Here, we analyze the expression of Drosophila integrin alpha chains in the ovarian follicular epithelium, a model for tissue morphogenesis and cell migration. We find expression throughout development of the beta chain, betaPS. Alpha chains, however, exhibit both spatial and temporal expression differences. alphaPS1 and alphaPS2 integrins are detected during early and mid-oogenesis on apical, lateral, and basal membranes with the betaPS chain, whereas alphaPS3-family integrins (alphaPS3, alphaPS4, alphaPS5) are expressed in anterior cells late in oogenesis. Surprisingly, we find that alphaPS3-family integrins are dispensable for dorsal appendage morphogenesis but play a role in the final length of the egg, suggesting redundant functions of integrins in a simple tissue. We also demonstrate roles for alphaPS3betaPS integrin in border cell migration and in stretch cells.

  9. Morphological effects on IR band profiles: Experimental spectroscopic analysis with application to observed spectra of oxygen-rich AGB stars

    CERN Document Server

    Tamanai, A; Blum, J; Posch, Th; Koike, C; Ferguson, J W


    To trace the source of the unique 13, 19.5, and 28 $\\mu$m emission features in the spectra of oxygen-rich circumstellar shells around AGB stars, we have compared dust extinction spectra obtained by aerosol measurements. We have measured the extinction spectra for 19 oxide powder samples of eight different types, such as Ti-compounds (TiO, TiO$_2$, Ti$_2$O$_3$, Ti$_3$O$_5$, Al$_2$TiO$_5$, CaTiO$_3$), $\\alpha$-, $\\gamma$-, $\\chi$-$\\delta$-$\\kappa$-Al$_2$O$_3$, and MgAl$_2$O$_4$ in the infrared region (10 - 50 $\\mu$m) paying special attention to the morphological (size, shape, and agglomeration) effects and the differences in crystal structure. Anatase (TiO$_2$) particles with rounded edges are the possible 13, 19.5 and 28 $\\mu$m band carriers as the main contributor in the spectra of AGB stars, and spherically shaped nano-sized spinel and Al$_2$TiO$_5$ dust grains are possibly associated with the anatase, enhancing the prominence of the 13 $\\mu$m feature and providing additional features at 28 $\\mu$m. The extin...

  10. Solvability of fractional multi-point boundary-value problems with p-Laplacian operator at resonance

    Directory of Open Access Journals (Sweden)

    Tengfei Shen


    Full Text Available In this article, we consider the multi-point boundary-value problem for nonlinear fractional differential equations with $p$-Laplacian operator: $$\\displaylines{ D_{0^+}^\\beta \\varphi_p (D_{0^+}^\\alpha u(t = f(t,u(t,D_{0^+}^{\\alpha - 2} u(t,D_{0^+}^{\\alpha - 1} u(t, D_{0^+}^\\alpha u(t,\\quad t \\in (0,1, \\cr u(0 = u'(0=D_{0^+}^\\alpha u(0 = 0,\\quad D_{0^+}^{\\alpha - 1} u(1 = \\sum_{i = 1}^m {\\sigma_i D_{0^+}^{\\alpha - 1} u(\\eta_i } , }$$ where $2 < \\alpha \\le 3$, $0 < \\beta \\le 1$, $3 < \\alpha + \\beta \\le 4$, $\\sum_{i = 1}^m {\\sigma_i } = 1$, $D_{0^+}^\\alpha$ is the standard Riemann-Liouville fractional derivative. $\\varphi_{p}(s=|s|^{p-2}s$ is p-Laplacians operator. The existence of solutions for above fractional boundary value problem is obtained by using the extension of Mawhin's continuation theorem due to Ge, which enrich konwn results. An example is given to illustrate the main result.

  11. Development of gluten-free bread using tartary buckwheat and chia flour rich in flavonoids and omega-3 fatty acids as ingredients. (United States)

    Costantini, Lara; Lukšič, Lea; Molinari, Romina; Kreft, Ivan; Bonafaccia, Giovanni; Manzi, Laura; Merendino, Nicolò


    In this study, chia seed flour, which is rich in omega-3 alpha-linolenic acid, and common and tartary buckwheat flour, which has a high antioxidant activity, were integrated into different types of bread with the aim of improving their nutritional value and healthy features. Our results indicate that bread made with chia and tartary buckwheat flour was more acceptable in many nutritional aspects compared to the control (common wheat bread); it contained a higher amount of protein (20%), insoluble dietary fibres (74%), ash (51%), and alpha-linolenic acid (67.4%). Moreover, this bread possessed lower energy (14%) and carbohydrate contents (24%) compared to the control. Tartary buckwheat also improved the total antioxidant capacity of the bread (about 75%) and provided a considerable amount of flavonoids, which are healthy non-nutritional compounds. Overall, chia and tartary buckwheat represent excellent raw materials for the formulation of gluten-free bread with high nutritional value. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Glycogen Synthase Kinase 3 (GSK-3) influences epithelial barrier function by regulating Occludin, Claudin-1 and E-cadherin expression

    Energy Technology Data Exchange (ETDEWEB)

    Severson, Eric A.; Kwon, Mike; Hilgarth, Roland S.; Parkos, Charles A. [Epithelial Pathobiology Research Unit, Dept. of Pathology, Emory University, Atlanta, GA 30322 (United States); Nusrat, Asma, E-mail: [Epithelial Pathobiology Research Unit, Dept. of Pathology, Emory University, Atlanta, GA 30322 (United States)


    The Apical Junctional Complex (AJC) encompassing the tight junction (TJ) and adherens junction (AJ) plays a pivotal role in regulating epithelial barrier function and epithelial cell proliferative processes through signaling events that remain poorly characterized. A potential regulator of AJC protein expression is Glycogen Synthase Kinase-3 (GSK-3). GSK-3 is a constitutively active kinase that is repressed during epithelial-mesenchymal transition (EMT). In the present study, we report that GSK-3 activity regulates the structure and function of the AJC in polarized model intestinal (SK-CO15) and kidney (Madin-Darby Canine Kidney (MDCK)) epithelial cells. Reduction of GSK-3 activity, either by small molecule inhibitors or siRNA targeting GSK-3 alpha and beta mRNA, resulted in increased permeability to both ions and bulk solutes. Immunofluorescence labeling and immunoblot analyses revealed that the barrier defects correlated with decreased protein expression of AJC transmembrane proteins Occludin, Claudin-1 and E-cadherin without influencing other TJ proteins, Zonula Occludens-1 (ZO-1) and Junctional Adhesion Molecule A (JAM-A). The decrease in Occludin and E-cadherin protein expression correlated with downregulation of the corresponding mRNA levels for these respective proteins following GSK-3 inhibition. These observations implicate an important role of GSK-3 in the regulation of the structure and function of the AJC that is mediated by differential modulation of mRNA transcription of key AJC proteins, Occludin, Claudin-1 and E-cadherin.

  13. Iron: a versatile element to produce materials for environmental applications

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, Ana Paula C.; Araujo, Maria H.; Oliveira, Luiz C.A.; Moura, Flavia C.C.; Lago, Rochel M., E-mail:, E-mail: [Departamento de Quimica, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Tristao, Juliana C. [Universidade Federal de Vicosa, Florestal, MG (Brazil); Ardisson, Jose D. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Lab. de Fisica Aplicada; Amorim, Camila C., E-mail: [Departamento de Engenharia Sanitaria e Ambiental, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)


    Iron is a versatile element forming several phases with different oxidation states and {sup s}tructures, such as Fe{sup 0}, FeO, Fe{sub 3}O{sub 4}, {gamma}-Fe{sub 2}O{sub 3}, {alpha}-Fe{sub 2}O{sub 3} and FeOOH. All these phases have unique physicochemical properties which can be used for different applications. In this work, it is described the use of different iron compounds, synthetic and also from natural and waste sources, in environmental and technological applications. Two main research areas are described. The first one is related to strategies to increase the reactivity of Fe phases, mainly by the formation of Fe{sup 0}/iron oxide composites and by the introduction of new metals in the iron oxide structure to promote new surface reactions. The second area is the use of the magnetic properties of some iron phases to produce versatile magnetic materials with focus in adsorption, catalysis and emulsions. (author)

  14. Regulation of naïve fetal T-cell migration by the chemokines Exodus-2 and Exodus-3. (United States)

    Christopherson, K; Brahmi, Z; Hromas, R


    We and other workers have recently isolated three novel CC chemokines termed Exodus-1/LARC/Mip-3alpha, Exodus-2/6Ckine/SLC/TCA4, and Exodus-3/Mip-3beta/CKbeta11/ELC. These chemokines share an amino terminal Asp-Cys-Cys-Leu sequence, unique among all chemokines. They also selectively regulate migration of adult T cells. Indeed, there is evidence that Exodus-2 and -3 are critical for adult T-cell adhesion to high endothelial venules in lymph nodes, a rate-limiting step for T-cell trafficking through nodal tissue. Less is known of the factors controlling migration of naïve human fetal T cells. We tested whether these chemokines could regulate chemotaxis in cord blood T-cell populations, and compared that efficacy with normal peripheral blood adult T cells. The findings indicated that naive CD45RA+ cord blood T-cell migration is stimulated by Exodus-2 and -3, and CD4+ cord blood T cells are attracted preferentially by Exodus-2 or -3 as compared with CD8+. Exodus-2 and -3 are likely to be critical in regulating the flux of naive CD4 + fetal T-cell population of secondary lymphoid tissue.

  15. The exodus subfamily of CC chemokines inhibits the proliferation of chronic myelogenous leukemia progenitors. (United States)

    Hromas, R; Cripe, L; Hangoc, G; Cooper, S; Broxmeyer, H E


    Chemokines are a family of related proteins that regulate leukocyte infiltration into inflamed tissue and play important roles in disease processes. Among the biologic activities of chemokines is inhibition of proliferation of normal hematopoietic progenitors. However, chemokines that inhibit normal progenitors rarely inhibit proliferation of hematopoietic progenitors from patients with chronic myelogenous leukemia (CML). We and others recently cloned a subfamily of CC chemokines that share similar amino-terminal peptide sequences and a remarkable ability to chemoattract T cells. These chemokines, Exodus-1/LARC/MIP-3alpha, Exodus-2/SLC/6Ckine/TCA4, and Exodus-3/CKbeta11/MIP-3beta, were found to inhibit proliferation of normal human marrow progenitors. The study described here found that these chemokines also inhibited the proliferation of progenitors in every sample of marrow from patients with CML that was tested. This demonstration of consistent inhibition of CML progenitor proliferation makes the 3 Exodus chemokines unique among chemokines. (Blood. 2000;95:1506-1508)

  16. Development of a spectroscopic assay for bifunctional ligand-protein conjugates based on copper

    Energy Technology Data Exchange (ETDEWEB)

    Brady, Erik D. E-mail:; Chong, Hyun-Soon; Milenic, Diane E.; Brechbiel, Martin W


    A simple, non-radioactive method for the determination of ligand-to-protein ratio (L/P) for novel ligand-antibody conjugates has been developed based on an exchange equilibrium with the purple Cu(II) complex of arsenazo III. The method requires a UV/Vis spectrometer and has been verified for monoclonal antibody Herceptin conjugates of a variety of ligand modalities, including common macrocyclic compounds NOTA and TETA, and with a new bifunctional tachpyridine (1H-Pyrrole-1-butanamide,N-[4-[[(1{alpha},3{alpha},5{alpha})-3,5-bis[(2-pyridi= nylmethyl) amino]cyclohexyl](2-pyridinylmethyl)amino]butyl]-2,5-dihydro-2, 5-dioxo-(9CI)). The spectroscopically derived values for L/P were verified by titration of the ligand-antibody conjugate with {sup 64}Cu. In each case, the value obtained by UV/Vis spectroscopy matches that found by radiolabeling. The method is rapid, taking less than 30 minutes with each ligand in this study.

  17. Structural investigations of the Bacillus subtilis SPP1 phage G39P helicase inhibitor loading protein

    CERN Document Server

    Bailey, S


    The Bacillus subtilis SPPI phage encoded protein G39P is a loader and inhibitor of the phage G40P replicative helicase involved in the initiation of phage DNA replication. The 2.4A crystal structure of a C-terminal truncated variant of G39P was solved using multiple wavelength anomalous dispersion exploiting the anomalous signal of seleno- methionine substituted protein. Inspection of the electron density maps revealed the asymmetric unit contained three independent G39P monomers, composed of 3 alpha-helices and their connecting loops. However, the model only accounted for the first 67 residues of the protein, as there was no interpretable electron density for residues 68 to 112. A preliminary NMR investigation revealed the C-terminal region of the protein had rapid internal motion and formed no well-defined stable fold that involved immobilized side chains. This is consistent with the X-ray analysis that displayed no electron density for these residues. A detailed comparison of NMR spectra from the C-termina...

  18. Substitutional and Interstitial Diffusion in alpha2-Ti3Al(O) (United States)

    Copland, Evan; Young, David J.; Gleeson, Brian; Jacobson, Nathan


    The reaction between Al2O3 and alpha2-Ti3Al was studied with a series of Al2O3/alpha2-Ti3Al multiphase diffusion couples annealed at 900, 1000 and 1100 C. The diffusion-paths were found to strongly depend on alpha2- Ti3Al(O) composition. For alloys with low oxygen concentrations the reaction involved the reduction of Al2O3, the formation of a gamma-TiAl reaction-layer and diffusion of Al and O into the alpha2-Ti3Al substrate. Measured concentration profiles across the interaction-zone showed "up-hill" diffusion of O in alpha2-Ti3Al(O) indicating a significant thermodynamic interaction between O and Al, Ti or both. Diffusion coefficients for the interstitial O in alpha2-Ti3Al(O) were determined independently from the interdiffusion of Ti and Al on the substitutional lattice. Diffusion coefficients are reported for alpha2-Ti3Al(O) as well as gamma-TiAl. Interpretation of the results were aided with the subsequent measurement of the activities of Al, Ti and O in alpha 2-Ti3Al(O) by Knudsen effusion-cell mass spectrometry.

  19. Measurement of differential (n,x{alpha}) cross section using 4{pi} gridded ionization chamber

    Energy Technology Data Exchange (ETDEWEB)

    Sanami, Toshiya; Baba, Mamoru; Matsuyama, Shigeo; Kiyosumi, Takehide; Nauchi, Yasushi; Saito, Keiichiro; Hirakawa, Naohiro [Tohoku Univ., Sendai (Japan). Faculty of Engineering; Kawano, Toshihiko


    We carried out the measurements of high resolution {alpha} emission spectra of {sup 58}Ni and {sup nat}Ni between 4.5 and 6.5 MeV, and {sup 12}C(n,x{alpha}) cross section using a 4{pi} gridded ionization chamber. In Ni measurement, overall energy resolution was improved to around 200 keV by optimizing a sample thickness and a neutron source width. Measured alpha spectra showed separate peaks corresponding to the ground and low-lying excited states of the residual nucleus ({sup 55}Fe). These results were compared with another direct measurement and statistical model calculations. In {sup 12}C measurement, GIC was applied for (n,x{alpha}) reactions of light nuclei. This application is difficult to (n,x{alpha}) cross sections of light nuclei, because of the influences of large recoil energy and multi-body break-up. We developed new methods which eliminate the effects of recoil nuclei and multi-body break-up and applied them to {sup 12}C(n,x{alpha}) reaction at En=14.1 MeV. In our experiment, the {sup 12}C(n,{alpha}{sub 0}){sup 9}Be angular differential cross section and {sup 12}C(n,n`3{alpha}) cross section were obtained. (author)

  20. [Pharmacology of the bronchospasmolytic oxitropium bromide]. (United States)

    Bauer, V R


    The anticholinergic substance (8r)-6 beta, 7 beta-epoxy-8-ethyl-3 alpha-[(-)-tropoyloxyl]-1 alpha H, 5 alpha H-tropanium bromide (oxitropium bromide, Ba 253 BR, Ventilat) is a competitive antagonist of acetylcholine. In vitro, it is many times as effective as atropine. In vivo, oxitropium bromide, following i.v. administration, is also more effective than atropine. Due to its quaternary structure, a central anticholinergic effect cannot be demonstrated. Furthermore, poor enteral resorption is to be expected. Locally administered, as an aqueous aerosol, the effect of the substance is distinctly greater than that of atropine, both in potency and duration of action. This is also true when administered by metered-dose inhaler compared with ipratropium bromide. As, following aerosol administration, the margin between major effect and the most sensitive side-effect is in the ratio 1 : 100, side-effects are unlikely even with marked inhalational overdosage. Oxitropium bromide can be described, therefore, as a preparation free of side-effects which represents in prophylactic use in many cases of obstructive airway disease, an alternative to beta-mimetics and xanthine derivatives.

  1. Pharmacology of the anticholinergic bronchospasmolytic agent flutropium bromide. (United States)

    Bauer, R; Fügner, A


    The anticholinergic agent (8r)-8-(2-fluoroethyl)-3 alpha-hydroxy-1 alpha H,tropanium bromide benzilic acid ester (flutropium bromide, Ba 598 BR) is a classic competitive antagonist of acetylcholine. In in vitro experiments it is more effective than atropine. In addition there are indications, that flutropium bromide may interfere with the anaphylactic reaction in a certain dose range in vitro. In in vivo experiments for the characterization of the anticholinergic properties flutropium bromide is also somewhat more effective than atropine after parenteral administration. Because of its quaternary structure no central anticholinergic effect is detectable. Furthermore, a poor enteral absorption is to be expected; this can be concluded from the low relative effectiveness after oral administration. After systemic administration, flutropium bromide is only slightly more effective than atropine. The duration of action is longer. After local administration as an aerosol it is superior to atropine with regard to both effectiveness and duration of action. Since in aerosol administration the ratio of the main effect to the most sensitive side effects, inhibition of salivary secretion, is 1:100, no side effects are to be expected even after high inhalational overdoses. Flutropium bromide can therefore be described as a preparation which is free of side effects. When used prophylactically it represents a therapeutic alternative to beta-mimetics and xanthine derivatives for most cases of obstructive airway diseases.

  2. Predictions on the alpha decay half lives of Superheavy nuclei with Z = 113 in the range 255 l.e. A l.e. 314

    CERN Document Server

    Santhosh, K P; Nithya, C; Priyanka, B


    An intense study of the alpha decay properties of the isotopes of superheavy element Z=113 have been performed within the Coulomb and proximity potential model for deformed nuclei (CPPMDN) within the wide range 255 l.e. A l.e. 314. The predicted alpha decay half lives of $^{278}$113 and $^{282}$113 and the alpha half lives of their decay products are in good agreement with the experimental data. 6{\\alpha) chains and 4{\\alpha} chains predicted respectively for $^{278}$113 and $^{282}$113 are in agreement with the experimental observation. Our study shows that the isotopes in the mass range 278 l.e. A l.e. 286 will survive fission and can be synthesized and detected in the laboratory via alpha decay. In our study, we have predicted 6{\\alpha} chains from $^{279}$113, 4{\\alpha} chains from $^{286}$113, 3{\\alpha} chains from $^{280,281,283}$113, 2{\\alpha} chains from $^{284}$113 and 1{\\alpha} chain from $^{285}$113. We hope that these predictions will be a guideline for future experimental investigations.

  3. Sgs1 regulates gene conversion tract lengths and crossovers independently of its helicase activity. (United States)

    Lo, Yi-Chen; Paffett, Kimberly S; Amit, Or; Clikeman, Jennifer A; Sterk, Rosa; Brenneman, Mark A; Nickoloff, Jac A


    RecQ helicases maintain genome stability and suppress tumors in higher eukaryotes through roles in replication and DNA repair. The yeast RecQ homolog Sgs1 interacts with Top3 topoisomerase and Rmi1. In vitro, Sgs1 binds to and branch migrates Holliday junctions (HJs) and the human RecQ homolog BLM, with Top3alpha, resolves synthetic double HJs in a noncrossover sense. Sgs1 suppresses crossovers during the homologous recombination (HR) repair of DNA double-strand breaks (DSBs). Crossovers are associated with long gene conversion tracts, suggesting a model in which Sgs1 helicase catalyzes reverse branch migration and convergence of double HJs for noncrossover resolution by Top3. Consistent with this model, we show that allelic crossovers and gene conversion tract lengths are increased in sgs1Delta. However, crossover and tract length suppression was independent of Sgs1 helicase activity, which argues against helicase-dependent HJ convergence. HJs may converge passively by a "random walk," and Sgs1 may play a structural role in stimulating Top3-dependent resolution. In addition to the new helicase-independent functions for Sgs1 in crossover and tract length control, we define three new helicase-dependent functions, including the suppression of chromosome loss, chromosome missegregation, and synthetic lethality in srs2Delta. We propose that Sgs1 has helicase-dependent functions in replication and helicase-independent functions in DSB repair by HR.

  4. The development of an integrated platform to identify breast cancer glycoproteome changes in human serum. (United States)

    Zeng, Zhi; Hincapie, Marina; Haab, Brian B; Hanash, Samir; Pitteri, Sharon J; Kluck, Steven; Hogan, Jason M; Kennedy, Jacob; Hancock, William S


    Protein glycosylation represents one of the major post-translational modifications and can have significant effects on protein function. Moreover, changes in the carbohydrate structure are increasingly being recognized as an important modification associated with cancer etiology. In this report, we describe the development of a proteomics approach to identify breast cancer related changes in either concentration and/or the carbohydrate structures of glycoprotein(s) present in blood samples. Diseased and healthy serum samples were processed by an optimized sample preparation protocol using multiple lectin affinity chromatography (M-LAC) that partitions serum proteins based on glycan characteristics. Subsequently, three separate procedures, 1D SDS-PAGE, isoelectric focusing and an antibody microarray, were applied to identify potential candidate markers for future study. The combination of these three platforms is illustrated in this report with the analysis of control and cancer glycoproteomic fractions. Firstly, a molecular weight based separation of glycoproteins by 1D SDS-PAGE was performed, followed by protein, glycoprotein staining, lectin blotting and LC-MS analysis. To refine or confirm the list of interesting glycoproteins, isoelectric focusing (targeting sialic acid changes) and an antibody microarray (used to detect neutral glycan shifts) were selected as the orthogonal methods. As a result, several glycoproteins including alpha-1B-glycoprotein, complement C3, alpha-1-antitrypsin and transferrin were identified as potential candidates for further study.

  5. 异常凝血酶原和肝细胞癌%Des-gamma-carboxy-prothrombin and Hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    袁联文; 唐伟; 幕内·雅敏


    目前肝细胞癌(hepatocellular carcinoma,HCC)的诊断主要有影像学诊断和血清肿瘤标志物的检测.异常凝血酶原(des-gamma-carboxy-prothrombin,DCP)又被称为PIVKA-Ⅱ(protein induced by vita-min K absence or antagonist-Ⅱ),与AFP(alpha-fetoprotein)和AFP-L3(alpha-fetoprotein L3 fraction)一样被认为是一种很有价值的肝细胞癌血清肿瘤标志物.在HCC的检测诊断上,它们之间无明显相关关系,而表现为一定的互补性,结合影像学诊断,动态观测HCC高危(肝炎、肝硬化)人群,这些血清肿瘤标志物有助于HCC的早期发现,同时对HCC的手术疗效的评价、预后的估评有着一定的指导意义.

  6. Predictions on the alpha decay chains of superheavy nuclei with Z =121 within the range 290 $\\leq$ A $\\leq$ 339

    CERN Document Server

    Santhosh, K P


    A systematic study on the alpha decay half lives of various isotopes of superheavy element \\textit{Z} = 121 within the range 290 $\\leq$ A $\\leq$ 339 is presented for the first time using Coulomb and proximity potential model for deformed nuclei (CPPMDN). The calculated $\\alpha$ decay half lives of the isotopes within our formalism match well with the values computed using Viola-Seaborg systematic, Universal curve of Poenaru et al., and the analytical formula of Royer. In our study by comparing the $\\alpha$ decay half lives with the spontaneous fission half lives, we have predicted $2\\alpha$ chain from $^{309, 311, 312}$121, $3\\alpha$ chain from $^{310}$121 and $1\\alpha$ chain from $^{313, 314}$121. Clearly our study shows that the isotopes of superheavy element \\textit{Z} = 121 within the mass range 309 $\\leq$ A $\\leq$ 314 will survive fission and can be synthesized and detected in the laboratory via alpha decay. We hope that our predictions will provide a new guide to future experiments.

  7. Changes in proteasome structure and function caused by HAMLET in tumor cells. (United States)

    Gustafsson, Lotta; Aits, Sonja; Onnerfjord, Patrik; Trulsson, Maria; Storm, Petter; Svanborg, Catharina


    Proteasomes control the level of endogenous unfolded proteins by degrading them in the proteolytic core. Insufficient degradation due to altered protein structure or proteasome inhibition may trigger cell death. This study examined the proteasome response to HAMLET, a partially unfolded protein-lipid complex, which is internalized by tumor cells and triggers cell death. HAMLET bound directly to isolated 20S proteasomes in vitro and in tumor cells significant co-localization of HAMLET and 20S proteasomes was detected by confocal microscopy. This interaction was confirmed by co-immunoprecipitation from extracts of HAMLET-treated tumor cells. HAMLET resisted in vitro degradation by proteasomal enzymes and degradation by intact 20S proteasomes was slow compared to fatty acid-free, partially unfolded alpha-lactalbumin. After a brief activation, HAMLET inhibited proteasome activity in vitro and in parallel a change in proteasome structure occurred, with modifications of catalytic (beta1 and beta5) and structural subunits (alpha2, alpha3, alpha6 and beta3). Proteasome inhibition was confirmed in extracts from HAMLET-treated cells and there were indications of proteasome fragmentation in HAMLET-treated cells. The results suggest that internalized HAMLET is targeted to 20S proteasomes, that the complex resists degradation, inhibits proteasome activity and perturbs proteasome structure. We speculate that perturbations of proteasome structure might contribute to the cytotoxic effects of unfolded protein complexes that invade host cells.

  8. Achromatopsia as a potential candidate for gene therapy. (United States)

    Pang, Ji-Jing; Alexander, John; Lei, Bo; Deng, Wentao; Zhang, Keqing; Li, Qiuhong; Chang, Bo; Hauswirth, William W


    Achromatopsia is an autosomal recessive retinal disease involving loss of cone function that afflicts approximately 1 in 30,000 individuals. Patients with achromatopsia usually have visual acuities lower than 20/200 because of the central vision loss, photophobia, complete color blindness and reduced cone-mediated electroretinographic (ERG) amplitudes. Mutations in three genes have been found to be the primary causes of achromatopsia, including CNGB3 (beta subunit of the cone cyclic nucleotide-gated cation channel), CNGA3 (alpha subunit of the cone cyclic nucleotide-gated cation channel), and GNAT2 (cone specific alpha subunit of transducin). Naturally occurring mouse models with mutations in Cnga3 (cpfl5 mice) and Gnat2 (cpfl3 mice) were discovered at The Jackson Laboratory. A natural occurring canine model with CNGB3 mutations has also been found. These animal models have many of the central phenotypic features of the corresponding human diseases. Using adeno-associated virus (AAV)-mediated gene therapy, we and others show that cone function can be restored in all three models. These data suggest that human achromatopsia may be a good candidate for corrective gene therapy.

  9. Role of Triton X-100 in chemiluminescent enzyme immunoassays capable of diagnosing genetic disorders. (United States)

    Chong, Richard; Rho, Jee-Eun R; Yoon, Hye-Joo; Park, Paul S; Rho, Tae-Ho D; Park, Jee Y; Park, Lucienne; Kim, Young-Hwan; Lee, Ji Hoon


    The use of Triton X surfactants in developing 1,1'-oxalylimidazole chemiluminescent enzyme immunoassays (ODI CEIs) with extended linear response range for the quantification of unconjugated estriol (uE3), alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) is reported for the first time. The wider linear dynamic range in ODI CLEIA results from Triton X series (e.g., Triton X-100, -114, -405, -705) acting as an inhibitor in the interaction between Amplex Red (hydrophobic substrate) and horseradish peroxidase (hydrophilic enzyme) to produce resorufin (hydrophobic fluorescent dye). Triton X-100 acts as the appropriate inhibitor in ODI CLEIA. The maximum concentrations of AFP and hCG quantified with sandwich ODI CLEIA in the presence of Triton X-100 were 8 times higher than when analyzed with the same system in the absence of Triton X-100. In addition, the lowest concentration of uE3 determined using competitive ODI CLEIA in the presence of Triton X-100 was 20 times lower than that measured with competitive ODI CLEIA in the absence of Triton X-100. These results indicate that rapid quantification of AFP, uE3, and hCG using cost effective and highly sensitive ODI CLEIAs in the presence of Triton X-100 can be applied as an accurate, precise, and reproducible method to diagnose genetic disorders (e.g., trisomy 18 and trisomy 21) in fetuses. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Higher order Larmor radius corrections to guiding-centre equations and application to fast ion equilibrium distributions (United States)

    Lanthaler, S.; Pfefferlé, D.; Graves, J. P.; Cooper, W. A.


    An improved set of guiding-centre equations, expanded to one order higher in Larmor radius than usually written for guiding-centre codes, are derived for curvilinear flux coordinates and implemented into the orbit following code VENUS-LEVIS. Aside from greatly improving the correspondence between guiding-centre and full particle trajectories, the most important effect of the additional Larmor radius corrections is to modify the definition of the guiding-centre’s parallel velocity via the so-called Baños drift. The correct treatment of the guiding-centre push-forward with the Baños term leads to an anisotropic shift in the phase-space distribution of guiding-centres, consistent with the well-known magnetization term. The consequence of these higher order terms are quantified in three cases where energetic ions are usually followed with standard guiding-centre equations: (1) neutral beam injection in a MAST-like low aspect-ratio spherical equilibrium where the fast ion driven current is significantly larger with respect to previous calculations, (2) fast ion losses due to resonant magnetic perturbations where a lower lost fraction and a better confinement is confirmed, (3) alpha particles in the ripple field of the European DEMO where the effect is found to be marginal.

  11. Four Dimensional Graphene

    CERN Document Server

    Drissi, L B; Bousmina, M


    Mimicking pristine 2D graphene, we revisit the BBTW model for 4D lattice QCD given in ref.[5] by using the hidden SU(5) symmetry of the 4D hyperdiamond lattice H_4. We first study the link between the H_4 and SU(5); then we refine the BBTW 4D lattice action by using the weight vectors \\lambda_1, \\lambda_2, \\lambda_3, \\lambda_4, \\lambda_5 of the 5-dimensional representation of SU(5) satisfying {\\Sigma}_i\\lambda_i=0. After that we study explicitly the solutions of the zeros of the Dirac operator D in terms of the SU(5) simple roots \\alpha_1, \\alpha_2, \\alpha_3, \\alpha_4 generating H_4; and its fundamental weights \\omega_1, \\omega_2, \\omega_3, \\omega_4 which generate the reciprocal lattice H_4^\\ast. It is shown, amongst others, that these zeros live at the sites of H_4^\\ast; and the continuous limit D is given by ((id\\surd5)/2) \\gamma^\\muk_\\mu with d, \\gamma^\\mu and k_\\mu standing respectively for the lattice parameter of H_4, the usual 4 Dirac matrices and the 4D wave vector. Other features such as differences ...

  12. Interpreting EEG alpha activity. (United States)

    Bazanova, O M; Vernon, D


    Exploring EEG alpha oscillations has generated considerable interest, in particular with regards to the role they play in cognitive, psychomotor, psycho-emotional and physiological aspects of human life. However, there is no clearly agreed upon definition of what constitutes 'alpha activity' or which of the many indices should be used to characterize it. To address these issues this review attempts to delineate EEG alpha-activity, its physical, molecular and morphological nature, and examine the following indices: (1) the individual alpha peak frequency; (2) activation magnitude, as measured by alpha amplitude suppression across the individual alpha bandwidth in response to eyes opening, and (3) alpha "auto-rhythmicity" indices: which include intra-spindle amplitude variability, spindle length and steepness. Throughout, the article offers a number of suggestions regarding the mechanism(s) of alpha activity related to inter and intra-individual variability. In addition, it provides some insights into the various psychophysiological indices of alpha activity and highlights their role in optimal functioning and behavior.

  13. In vitro metabolism of gestodene in target organs: formation of A-ring reduced derivatives with oestrogenic activity. (United States)

    Lemus, A E; Santillán, R; Damián-Matsumura, P; García, G A; Grillasca, I; Pérez-Palacios, G


    Gestodene (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4,5-gonadien-3-one), the most potent progestin ever synthesized, stimulates breast cancer cell growth through an oestrogen receptor-mediated mechanism, and its use in hormonal contraception has been associated with side effects attributable to oestrogenic actions. These observations have remained controversial, since gestodene does not bind to the oestrogen receptor or exert oestrogen-like activities. Recently, we have demonstrated that non-phenolic gestodene derivatives interact with oestrogen receptors and induce oestrogenic effects in cell expression systems. To assess whether gestodene is biotransformed to metabolites with intrinsic oestrogenic potency, [3H]- and [14C]-labelled gestodene were incubated in vitro with rat anterior pituitary, hypothalamus and ventral prostate homogenates under different experimental conditions. The most remarkable finding was the isolation and identification of 3beta,5alpha-tetrahydrogestodene and 3alpha,5alpha-tetrahydrogestodene as metabolic conversion products of gestodene, presumably with 5alpha-dihydrogestodene as intermediate. The overall results seem to indicate that the weak oestrogenic effects attributable to gestodene could be mediated by its tetrahydro metabolites.

  14. Darwin's evolution theory, brain oscillations, and complex brain function in a new "Cartesian view". (United States)

    Başar, Erol; Güntekin, Bahar


    Comparatively analyses of electrophysiological correlates across species during evolution, alpha activity during brain maturation, and alpha activity in complex cognitive processes are presented to illustrate a new multidimensional "Cartesian System" brain function. The main features are: (1) The growth of the alpha activity during evolution, increase of alpha during cognitive processes, and decrease of the alpha entropy during evolution provide an indicator for evolution of brain cognitive performance. (2) Human children younger than 3 years are unable to produce higher cognitive processes and do not show alpha activity till the age of 3 years. The mature brain can perform higher cognitive processes and demonstrates regular alpha activity. (3) Alpha activity also is significantly associated with highly complex cognitive processes, such as the recognition of facial expressions. The neural activity reflected by these brain oscillations can be considered as constituent "building blocks" for a great number of functions. An overarching statement on the alpha function is presented by extended analyzes with multiple dimensions that constitute a "Cartesian Hyperspace" as the basis for oscillatory function. Theoretical implications are considered.

  15. Cytotoxicity of cardenolides and cardenolide glycosides from Asclepias curassavica. (United States)

    Li, Jun-Zhu; Qing, Chen; Chen, Chang-Xiang; Hao, Xiao-Jiang; Liu, Hai-Yang


    A new cardenolide, 12beta,14beta-dihydroxy-3beta,19-epoxy-3alpha-methoxy-5alpha-card-20(22)-enolide (6), and a new doubly linked cardenolide glycoside, 12beta-hydroxycalotropin (13), together with eleven known compounds, coroglaucigenin (1), 12beta-hydroxycoroglaucigenin (2), calotropagenin (3), desglucouzarin (4), 6'-O-feruloyl-desglucouzarin (5), calotropin (7), uscharidin (8), asclepin (9), 16alpha-hydroxyasclepin (10), 16alpha-acetoxycalotropin (11), and 16alpha-acetoxyasclepin (12), were isolated from the aerial part of ornamental milkweed, Asclepias curassavica and chemically elucidated through spectral analyses. All the isolates were evaluated for their cytotoxic activity against HepG2 and Raji cell lines. The results showed that asclepin (9) had the strongest cytotoxic activity with an IC(50) value of 0.02 microM against the two cancer cell lines and the new compound 13 had significant cytotoxic activity with IC(50) values of 0.69 and 1.46 microM, respectively.

  16. Chemical composition and antioxidant, antimicrobial, and larvicidal activities of the essential oils of Annona salzmannii and A. pickelii (Annonaceae). (United States)

    Costa, Emmanoel Vilaça; Dutra, Lívia Macedo; de Jesus, Hugo César Ramos; Nogueira, Paulo Cesar de Lima; Moraes, Valéria Regina de Souza; Salvador, Marcos José; Cavalcanti, Sócrates Cabral de Holanda; dos Santos, Roseli La Corte; Prata, Ana Paula do Nacimento


    The essential oils from the leaves of Annona salzmannii and A. pickelii (Annonaceae) growing in Sergipe, northeastern region of Brazil, were obtained by hydrodistillation using a Clevenger-type apparatus, and analyzed by GC/MS and GC/FID. Thirty-four compounds were identified in the essential oil of A. salzmannii and twenty-seven in that of A. pickelii; sesquiterpenes predominated in both essential oils. Bicyclogermacrene (20.3%), (E)-caryophyllene (19.9%), delta-cadinene (15.3%), alpha-copaene (10.0%), and allo-aromadendrene (5.7%) were the main components of A. salzmannii, and bicyclogermacrene (45.4%), (E)-caryophyllene (14.6%), and alpha-copaene (10.6%) of A. pickelii. The essential oils showed significant antioxidant capacity in the ORAC(FL) and DPPH assays. The antimicrobial activity of these essential oils was also evaluated against bacteria and fungi, as well as the larvicidal activity against Aedes aegypti larvae.

  17. Acute myeloid leukemia with DNMT3A mutations. (United States)

    Li, Yunlong; Zhu, Baosheng


    Acute myeloid leukemia (AML), a type of blood cancer, is characterized by an increase in the number of abnormal white blood cells in the bone marrow, frequently causing hematopoietic insufficiency. It is a heterogeneous disease featuring cytogenetic aberrations, recurrent somatic mutations and alterations in gene expression. DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A) is closely associated with epigenetic modifications in mammalian development and disease. More recent studies have identified recurrent somatic mutations in DNMT3A in AML, most of which are heterozygous. The DNMT3A R882 codon is a mutational hotspot. The frequency of DNMT3A mutations varies among different countries, but mutations have been found to be associated with cytogenetics, age, white blood cell (WBC) count, prognosis and response of patients to chemotherapy. The normal function of DNMT3A can be disrupted by these mutations, which subsequently results in an abnormality of epigenetic modification. These data suggest that mutations in the DNMT3A gene represent a novel class of mutations in AML with distinct biological and clinical features. Further studies are needed to elucidate the exact molecular mechanism and function of DNMT3A mutations in leukemogenesis.

  18. Epigenetic modifications of interleukin-6 in synovial fibroblasts from osteoarthritis patients (United States)

    Yang, Fei; Zhou, Song; Wang, Chuandong; Huang, Yan; Li, Huiwu; Wang, You; Zhu, Zhenan; Tang, Jian; Yan, Mengning


    Osteoarthritis (OA) is the most common degenerative disease of the synovial joint. The synovial membrane is responsible for the inflammatory reaction leading to the secretion of macrophage-derived pro-inflammatory cytokines, such as IL-6. Suppressing IL-6 over-expression in synovial fibroblasts (SF) is a promising method to prevent OA development and progression, in which the prerequisite is the elucidation of the molecular mechanisms underlying IL-6 over-expression in SF. Currently, there are few reports concerning epigenetic modifications in IL-6 in OA SF. In the present study, we attempted to investigate this phenomenon. SF over-expressing IL-6 was collected from OA patients. DNA hypomethylation and histone hyperacetylation were observed in the IL-6 promoter regions in OA SF compared with normal SF. No differences in the status of H3K9 di-methylation, H3K27 tri-methylation and H3K4 tri-methylation were observed in the IL-6 promoter regions between normal and OA SF. DNA (cytosine-5-)-methyltransferase 3 alpha (Dnmt3a) overexpression and anacardic acid (histone acetyltransferase inhibitor) treatment increased DNA methylation and decreased histone acetylation in the IL-6 promoter, and IL-6 over-expression in OA SF was suppressed. These observations provide deeper insight into the pathogenesis of OA and can be used to design new drugs and develop new therapeutic methods to treat OA. PMID:28262826

  19. Systematics of even-even T{sub z}= 1 nuclei in the A= 80 region: High-spin rotational bands in {sup 74}Kr, {sup 78}Sr, and {sup 82}Zr

    Energy Technology Data Exchange (ETDEWEB)

    Rudolph, D.; Baktash, C.; Gross, C.J.; Jin, H.; Yu, C.H. [Physics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States); Rudolph, D. [Sektion Physik der Ludwig-Maximilians-Universitaet Muenchen, D-85748 Garching (Germany); Gross, C.J. [Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee 37831 (United States); Satula, W. [Department of Physics, University of Tennessee, Knoxville, Tennessee 37996 (United States); Satula, W. [Joint Institute for Heavy Ion Research, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831 (United States); Satula, W. [Institute of Theoretical Physics, Warsaw University, PL-00681 Warsaw (Poland); Wyss, R. [The Royal Institute of Technology, Physics Department Frescati, S-104 05 Stockholm (Sweden); Birriel, I.; Saladin, J.X.; Winchell, D.F.; Wood, V.Q. [Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, Pennsylvania 15260 (United States); Devlin, M.; LaFosse, D.R.; Lerma, F.; Sarantites, D.G. [Chemistry Department, Washington University, St. Louis, Missouri 63130 (United States); Sylvan, G.N.; Tabor, S.L. [Department of Physics, Florida State University, Tallahassee, Florida 32306 (United States)


    High-spin states of T{sub z}=1 nuclei were studied with the reactions {sup 58}Ni({sup 28}Si,3{alpha}){sup 74}Kr, {sup 58}Ni({sup 28}Si,2{alpha}){sup 78}Sr, and {sup 58}Ni({sup 28}Si,2p2n){sup 82}Zr at 130 MeV beam energy. The Gammasphere array in conjunction with the 4{pi} charged-particle detector array Microball was used to detect {gamma} rays in coincidence with evaporated light charged particles. The known {pi}=+, {alpha}=0 yrast bands were extended to I=28{h_bar} at 20 MeV excitation energy. For all three nuclei, a number of positive- and negative-parity sidebands were established; altogether 15 new rotational bands were found. The data are discussed using the pairing-and-deformation self-consistent total Routhian surface (TRS) model: High-spin structures of {sup 74}Kr and {sup 78}Sr are governed by the shell gaps at large prolate deformation while {sup 82}Zr seems to exhibit shape coexistence. Nearly identical bands were established which may be explained as arising from the fp orbits acting as spectators at very elongated shapes. The experimental data in these T{sub z}=1 nuclei are in good agreement with predictions of the TRS model using conventional T=1 like-nucleon pairing correlations. {copyright} {ital 1997} {ital The American Physical Society}

  20. Sequence-Based Appraisal of the Genes Encoding Neck and Carbohydrate Recognition Domain of Conglutinin in Blackbuck (Antilope cervicapra and Goat (Capra hircus

    Directory of Open Access Journals (Sweden)

    Sasmita Barik


    Full Text Available Conglutinin, a collagenous C-type lectin, acts as soluble pattern recognition receptor (PRR in recognition of pathogens. In the present study, genes encoding neck and carbohydrate recognition domain (NCRD of conglutinin in goat and blackbuck were amplified, cloned, and sequenced. The obtained 488 bp ORFs encoding NCRD were submitted to NCBI with accession numbers KC505182 and KC505183. Both nucleotide and predicted amino acid sequences were analysed with sequences of other ruminants retrieved from NCBI GenBank using DNAstar and Megalign5.2 software. Sequence analysis revealed maximum similarity of blackbuck sequence with wild ruminants like nilgai and buffalo, whereas goat sequence displayed maximum similarity with sheep sequence at both nucleotide and amino acid level. Phylogenetic analysis further indicated clear divergence of wild ruminants from the domestic ruminants in separate clusters. The predicted secondary structures of NCRD protein in goat and blackbuck using SWISSMODEL ProtParam online software were found to possess 6 beta-sheets and 3 alpha-helices which are identical to the result obtained in case of sheep, cattle, buffalo, and nilgai. However, quaternary structure in goat, sheep, and cattle was found to differ from that of buffalo, nilgai, and blackbuck, suggesting a probable variation in the efficiency of antimicrobial activity among wild and domestic ruminants.

  1. Lipid content and fatty acid composition of green algae Scenedesmus obliquus grown in a constant cell density apparatus (United States)

    Choi, K. J.; Nakhost, Z.; Barzana, E.; Karel, M.


    The lipids of alga Scenedesmus obliquus grown under controlled conditions were separated and fractionated by column and thin-layer chromatography, and fatty acid composition of each lipid component was studied by gas-liquid chromatography (GLC). Total lipids were 11.17%, and neutral lipid, glycolipid and phospholipid fractions were 7.24%, 2.45% and 1.48% on a dry weight basis, respectively. The major neutral lipids were diglycerides, triglycerides, free sterols, hydrocarbons and sterol esters. The glycolipids were: monogalactosyl diglyceride, digalactosyl diglyceride, esterified sterol glycoside, and sterol glycoside. The phospholipids included: phosphatidyl choline, phosphatidyl glycerol and phosphatidyl ethanolamine. Fourteen fatty acids were identified in the four lipid fractions by GLC. The main fatty acids were C18:2, C16:0, C18:3(alpha), C18:1, C16:3, C16:1, and C16:4. Total unsaturated fatty acid and essential fatty acid compositions of the total algal lipids were 80% and 38%, respectively.

  2. Additional spectra of asteroid 1996 FG3, backup target of the ESA MarcoPolo-R mission

    CERN Document Server

    de Leon, J; Ali-Lagoa, V; Licandro, J; Pinilla-Alonso, N; Campins, H


    Near-Earth binary asteroid (175706) 1996 FG3 is the current backup target of the ESA MarcoPolo-R mission, selected for the study phase of ESA M3 missions. It is a primitive (C-type) asteroid that shows significant variation in its visible and near-infrared spectra. Here we present new spectra of 1996 FG3 and we compare our new data with other published spectra, analysing the variation in the spectral slope. The asteroid will not be observable again over the next three years at least. We obtained the spectra using DOLORES and NICS instruments at the Telescopio Nazionale Galileo (TNG), a 3.6m telescope located at El Roque de los Muchachos Observatory in La Palma, Spain. To compare with other published spectra of the asteroid, we computed the spectral slope S', and studied any plausible correlation of this quantity with the phase angle (alpha). In the case of visible spectra, we find a variation in spectral slope of Delta S' = 0.15 +- 0.10 %/10^3 A/degree for 3 < alpha < 18 degrees, in good agreement with ...

  3. Quantitative EEG Markers in Mild Cognitive Impairment: Degenerative versus Vascular Brain Impairment

    Directory of Open Access Journals (Sweden)

    D. V. Moretti


    Full Text Available We evaluated the relationship between brain rhythmicity and both the cerebrovascular damage (CVD and amygdalohippocampal complex (AHC atrophy, as revealed by scalp electroencephalography (EEG in a cohort of subjects with mild cognitive impairment (MCI. All MCI subjects underwent EEG recording and magnetic resonance imaging. EEGs were recorded at rest. Relative power was separately computed for delta, theta, alpha1, alpha2, and alpha3 frequency bands. In the spectral band power the severity of CVD was associated with increased delta power and decreased alpha2 power. No association of vascular damage was observed with alpha3 power. Moreover, the theta/alpha1 ratio could be a reliable index for the estimation of the individual extent of CV damage. On the other side, the group with moderate hippocampal atrophy showed the highest increase of alpha2 and alpha3 power. Moreover, when the amygdalar and hippocampal volumes are separately considered, within amygdalohippocampal complex (AHC, the increase of theta/gamma ratio is best associated with amygdalar atrophy whereas alpha3/alpha2 ratio is best associated with hippocampal atrophy. CVD and AHC damages are associated with specific EEG markers. So far, these EEG markers could have a prospective value in differential diagnosis between vascular and degenerative MCI.

  4. Anatomical substrate and scalp EEG markers are correlated in subjects with cognitive impairment and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    davide v Moretti


    Full Text Available Dementia is a syndromic diagnosis, encompassing various stage of severity and different anatomo-physiological substrates. The hippocampus is one of the first and most affected brain regions affected by both Alzheimer’s disease (AD and mild cognitive impairment (MCI. Morevoer, cronic cerebrovascular disease (CVD is one of the major risk factor for developing dementia. Recent studies have demonstrated different relationship between the anatomical substrate and scalp electroencephalography (EEG markers. Indeed, modifications of EEG rhythmicity is not proportional to the hippocampal atrophy, whereas changes in EEG activity are directly proportional to the load of subcortical CVD.Quantitative EEG have been demonstrated a reliable tool in identifying specific patterns in dementia research (Coburn et al., 2006; John and Prichep, 2006. The computation of the spectral power and the analysis of the functional coupling of brain areas, through linear coherence, are two of the most known processing methods in EEG research. Two specific EEG markers, theta/gamma and alpha3/alpha2 frequency ratio have been reliable associated to the atrophy of amygdalo-hippocampal complex. Moreover, theta/gamma ratio has been related to MCI conversion i

  5. Epigenetic Guardian: A Review of the DNA Methyltransferase DNMT3A in Acute Myeloid Leukaemia and Clonal Haematopoiesis (United States)

    Chaudry, Sabah F.


    Acute myeloid leukaemia (AML) is a haematological malignancy characterized by clonal stem cell proliferation and aberrant block in differentiation. Dysfunction of epigenetic modifiers contributes significantly to the pathogenesis of AML. One frequently mutated gene involved in epigenetic modification is DNMT3A (DNA methyltransferase-3-alpha), a DNA methyltransferase that alters gene expression by de novo methylation of cytosine bases at CpG dinucleotides. Approximately 22% of AML and 36% of cytogenetically normal AML cases carry DNMT3A mutations and around 60% of these mutations affect the R882 codon. These mutations have been associated with poor prognosis and adverse survival outcomes for AML patients. Advances in whole-exome sequencing techniques have recently identified a large number of DNMT3A mutations present in clonal cells in normal elderly individuals with no features of haematological malignancy. Categorically distinct from other preleukaemic conditions, this disorder has been termed clonal haematopoiesis of indeterminate potential (CHIP). Further insight into the mutational landscape of CHIP may illustrate the consequence of particular mutations found in DNMT3A and identify specific “founder” mutations responsible for clonal expansion that may contribute to leukaemogenesis. This review will focus on current research and understanding of DNMT3A mutations in both AML and CHIP. PMID:28286768

  6. Mechanisms of stem cell osteogenic differentiation on TiO2 nanotubes. (United States)

    Yu, Weiqiang; Qian, Chao; Jiang, Xinquan; Zhang, Fuqiang; Weng, Weimin


    TiO2 nanotubes could stimulate osteogenic differentiation of stem cells, but the molecular mechanisms underlying the interactions between nanotubes and stem cells remain unclear. In this study, we investigated the response of bone marrow stromal cells to nanotubes of different diameters using microarray-based bioinformatics approach. Gene ontology (GO) and GO enrichment network analysis indicated that larger TiO2 nanotubes were more potent than smaller nanotubes in inducing the expression of genes involved in cell proliferation, differentiation, and immune responses, and inhibiting that of genes responsible for cell adhesion. The analysis of the signaling network containing significantly affected genes suggested that Na(+)/K(+) transporting ATPases ATP1A2 (alpha 2 polypeptide) and ATP1A3 (alpha 3 polypeptide), and MAP3K11 (mitogen-activated protein kinase kinase kinase 11) were important for inducing osteogenic differentiation of bone marrow stromal cells without additional osteogenic stimuli. The upregulation of the ATP1A2 and MAP3K11 genes confirmed by real-time PCR indicates that the response of bone marrow stromal cells to nanotube cues may be mediated by the pathways previously implicated in transducing mechanical stress signals. Our results revealed some molecular mechanisms by which TiO2 nanotubes may direct osteogenic differentiation of stem cells.

  7. Dependence of the dielectric constant of electrolyte solutions on ionic concentration

    CERN Document Server

    Gavish, Nir


    We study the dependence of the static dielectric constant of aqueous electrolyte solutions upon the concentration of salt in the solution and temperature. The model takes into account the orientation of the solvent dipoles due to the electric field created by ions, the ionic response to an applied field, and the effect of thermal fluctuations. The analysis suggests that the formation of ion pairs by a small fraction of disassociated ions can have a significant effect on the static dielectric constant. The model predicts the dielectric has the functional dependence $\\varepsilon(c)=\\varepsilon_w-\\beta L(3\\alpha c/\\beta)$ where $L$ is the Langevin function, $c$ is the salt concentration, $\\varepsilon_w$ is the dielectric of the pure water, $\\alpha$ is the total excess polarization of the ions and $\\beta$ is the relative difference between the water dipole moment and the effective dipole moment of ion pairs as weighted by the density of ion pairs and their structural rigidity. The functional form gives an extreme...

  8. Neutron- and proton-induced nuclear data evaluation of thorium, uranium and curium isotopes for energies up to 250 MeV

    CERN Document Server

    Young, Ouk Lee; Jonghwa, Chang; Konobeyev, A Yu


    The evaluation of neutron- and proton nuclear data for thorium-232, U-233,234,236, and Cm-243,244,245,246 isotopes have been performed at energies up to 250 MeV. Neutron data was evaluated at energies from 20 MeV to 250 MeV, and combined with the JENDL-3.3 data at 20 MeV while proton data was obtained for energies from 1 to 250 MeV. Nuclear model parameters are largely based on the IAEA-RIPL recommendation, and adjusted to better reproduce the available measurements. The coupled channel optical model was applied to calculate the total, reaction, elastic, and direct inelastic cross sections, and to obtain the transmission coefficients. Decay of excited nuclei was described with the Hauser-Feshbach and exciton models using the GNASH code to simultaneously handle neutron, proton, deuteron, triton, helium-3, alpha , gamma emissions and fissions. Special attention was paid on the fission cross sections for energies where experimental data are scant, using appropriate systematics and fittings. Particles and gamma e...

  9. Prostaglandins in human semen during fish oil ingestion: evidence for in vivo cyclooxygenase inhibition and appearance of novel trienoic compounds. (United States)

    Knapp, H R


    Marine oils may offer cardiovascular benefits, but inhibition of prostaglandin E and prostaglandin F synthesis by fish oil has been found in animal studies, and such effects could alter physiological responses in man to a clinically significant degree. Since greater amounts of E and F-type prostaglandins are made in human seminal vesicles than in the rest of the body combined, the influence of n-3 supplements upon semen prostaglandins was assessed in 10 subjects before and after one month of taking 50 ml menhaden oil daily. Prostaglandins E1, E2 and their 19-hydroxy derivatives were measured by HPLC-UV as PGB's, and prostaglandin E3, 19-OH PGE3, and analogous PGF's by gas chromatography/mass spectrometry. Fish oil ingestion reduced concentrations of one- and two series prostaglandins (mean reduction in PGE's = 37%, in PGF's = 20%, p less than 0.05), while more than doubling the low amounts of PGE3 and PGF3 alpha, and their previously undescribed 19-hydroxy derivatives. Semen phospholipids were enriched in eicosapentaenoic acid after dietary fish oil, but sperm counts and motility were not altered during the study. Since dietary fish oil reduces prostaglandin concentration in semen, clinical trials of n-3 fatty acids should also evaluate other possible results of in vivo cyclooxygenase inhibition.

  10. Direct Three-body Triple-$\\alpha$ in Helium Novae

    CERN Document Server

    Connolly, Ryan; Brown, Edward F


    In AM CVn binaries, a white dwarf primary accretes material from a helium-rich white dwarf or stellar companion. The unstable ignition of nuclear burning via the $3\\alpha$ reaction in an accumulated helium layer powers a thermonuclear runaway near accretion rates $\\dot{M} \\lesssim 10^{-6} \\, \\mathrm{M_{\\odot} \\ yr^{-1}}$ that may be observed as helium nova or .Ia supernova. Helium burning in the primary's envelope at temperatures $T \\lesssim 10^{8} \\, \\mathrm{K}$ may proceed via the direct three-body fusion of $\\alpha$-particles. Here we show that the direct three-body rate by Nguyen et al. (2012) -- which is reduced relative to the extrapolated resonant rate at temperatures $T \\gtrsim 5 \\times 10^{7} \\, \\mathrm{K}$ -- results in novae with longer recurrence times and larger ignition masses. By contrast, we find that the enhancement in the direct three-body rate at temperatures below $T \\lesssim 5 \\times 10^{7} \\, \\mathrm{K}$ does not result in significant differences in nova outburst properties. The most mas...

  11. Laminin isoforms and their integrin receptors in glioma cell migration and invasiveness: Evidence for a role of alpha5-laminin(s) and alpha3beta1 integrin. (United States)

    Kawataki, Tomoyuki; Yamane, Tetsu; Naganuma, Hirofumi; Rousselle, Patricia; Andurén, Ingegerd; Tryggvason, Karl; Patarroyo, Manuel


    Glioma cell infiltration of brain tissue often occurs along the basement membrane (BM) of blood vessels. In the present study we have investigated the role of laminins, major structural components of BMs and strong promoters of cell migration. Immunohistochemical studies of glioma tumor tissue demonstrated expression of alpha2-, alpha3-, alpha4- and alpha5-, but not alpha1-, laminins by the tumor vasculature. In functional assays, alpha3 (Lm-332/laminin-5)- and alpha5 (Lm-511/laminin-10)-laminins strongly promoted migration of all glioma cell lines tested. alpha1-Laminin (Lm-111/laminin-1) displayed lower activity, whereas alpha2 (Lm-211/laminin-2)- and alpha4 (Lm-411/laminin-8)-laminins were practically inactive. Global integrin phenotyping identified alpha3beta1 as the most abundant integrin in all the glioma cell lines, and this laminin-binding integrin exclusively or largely mediate the cell migration. Moreover, pretreatment of U251 glioma cells with blocking antibodies to alpha3beta1 integrin followed by intracerebral injection into nude mice inhibited invasion of the tumor cells into the brain tissue. The cell lines secreted Lm-211, Lm-411 and Lm-511, at different ratios. The results indicate that glioma cells secrete alpha2-, alpha4- and alpha5-laminins and that alpha3- and alpha5-laminins, found in brain vasculature, selectively promote glioma cell migration. They identify alpha3beta1 as the predominant integrin and laminin receptor in glioma cells, and as a brain invasion-mediating integrin.

  12. The influence of Tribenoside on expression and deposition of epidermal laminins in HaCaT cells. (United States)

    Kikkawa, Yamato; Takaki, Shu; Matsuda, Yuji; Okabe, Koichi; Taniguchi, Masakazu; Oomachi, Kengo; Samejima, Teruyuki; Katagiri, Fumihiko; Hozumi, Kentaro; Nomizu, Motoyoshi


    Tribenoside has been used clinically for hemorrhoidal disease associated with coagulation, inflammation, and wounds. However, the pharmacological mechanism of tribenoside activity has never been clear. In this study we examined whether tribenoside affected expression and deposition of laminins that are required for reconstruction of basement membranes (BMs) during wound healing in hemorrhoidal disease. HaCaT cells, which are derived from human epidermis, were treated in growth media supplemented with tribenoside. Reverse transcriptase-polymerase chain reaction (RT-PCR) using primers specific for laminin chains showed that HaCaT cells constitutively expressed laminin alpha3, alpha5, beta1, beta3, gamma1, and gamma2 chains. Tribenoside treatment of HaCaT cells did not induce expression of other laminin chains. We also quantified the expression of laminin chains in tribenoside-treated cells using real-time PCR. The expression level of laminin alpha3, beta1, beta3, gamma1, and gamma2 chains was not affected. In contrast, the expression of laminin alpha5 in the tribenoside-treated cells was four times higher than that of control cells. Immunocytochemistry also showed that tribenoside accelerated the focal deposition of laminin-332 (alpha3, beta3, gamma2). These results suggest that tribenoside interacts with epidermal cells and regulates the expression and localization of laminins to help reconstruct BMs in wound healing of hemorrhoids.

  13. Characterization of local chemistry and disorder in synthetic and natural {alpha}-Al{sub 2}O{sub 3} materials by X-ray absorption near edge structure spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Mottana, A. [Rome, Univ. `Roma Tre` (Italy). Dip. di Scienze Geologiche]|[INFN, Laboratori Nazionali di Frascati, Rome (Italy); Murata, T. [Kyoto, Univ. of Education (Japan). Dept. of Physics; Marcelli, A. [INFN, Laboratori Nazionali di Frascati, Rome (Italy)] [and others


    X-ray absorption fine spectra at the Al K-edge were measured experimentally on and calculated theoretically via the multiple-scattering formalism for a chemically pure and physically perfect synthetic {alpha}-Al{sub 2}O{sub 3} ({alpha}-alumina), a natural `ruby/sapphire` (corundum) and a series of artificial `corundum` produced for technical purposes and used as geochemical standards. The Al K-edge spectra differ despite of the identical coordination (short-range arrangement) assumed by O around Al, and vary slightly in relation to the slightly different chemistries of the materials (substitutional defects) as well as on account of the location taken by foreign atoms in the structural lattices (positional defects). A quantitative treatment of the observed changes is made in terms of short-range modification of the coordination polyhedron and of medium- to long-range modifications in the overall structure; both of them induced by substitutions. In some technical `corundums`, the impurities of admixed `{beta}-alumina`, where Al is both in four- and six-fold coordination, produce another small but detectable effect on Al K-edges. Therefore, XAFS spectroscopy proves its potentials for both measuring a light element such as Al, and detecting minor coordination changes and substitutions (ca. 1{approx}3 wt.% as oxide) of the absorber by dilute other atoms, at least under favorable conditions as those occurring in this system are.

  14. Effect of enzyme preparation from the marine mollusk Littorina kurila on fucoidan from the brown alga Fucus distichus. (United States)

    Bilan, M I; Kusaykin, M I; Grachev, A A; Tsvetkova, E A; Zvyagintseva, T N; Nifantiev, N E; Usov, A I


    A fucoidanase preparation from the marine mollusk Littorina kurila cleaved some glycosidic bonds in fucoidan from the brown alga Fucus distichus, but neither fucose nor lower oligosaccharides were produced. The main product isolated from the incubation mixture was a polysaccharide built up of disaccharide repeating units -->3)-alpha-L-Fucp-(2,4-di-SO3(-))-(1-->4)-alpha-L-Fucp-(2SO3(-))-(1-->, the structure coinciding with the idealized formula proposed for the initial substance. A polymer fraction with the same carbohydrate chain but sulfated only at positions 2 and nonstoichiometrically acetylated at positions 3 and 4 of fucose residues was isolated as a minor component. It is suggested that the native polysaccharide should contain small amounts of non-sulfated and non-acetylated fucose residues, and only their glycosidic bonds are cleaved by the enzyme. The enzymatic hydrolysis showed that irregular regions of the native polysaccharide containing acetylated and partially sulfated repeating units were assembled in blocks.

  15. Method and apparatus for preparation of spherical metal carbonates and lithium metal oxides for lithium rechargeable batteries (United States)

    Kang, Sun-Ho; Amine, Khalil


    A number of materials with the composition Li.sub.1+xNi.sub..alpha.Mn.sub..beta.Co.sub..gamma.M' zF.sub.z (M'=Mg,Zn,Al,Ga,B,Zr,Ti) for use with rechargeable batteries, wherein x is between about 0 and 0.3, .alpha. is between about 0.2 and 0.6, .beta. is between about 0.2 and 0.6, .gamma. is between about 0 and 0.3, .delta. is between about 0 and 0.15, and z is between about 0 and 0.2. Adding the above metal and fluorine dopants affects capacity, impedance, and stability of the layered oxide structure during electrochemical cycling. Another aspect of the invention includes materials with the composition Li.sub.1+xNi.sub..alpha.Co.sub..beta.Mn.sub..gamma.M' .sub.z (M'=Mg,Zn,Al,Ga,B,Zr,Ti), where the x is between 0 and 0.2, the .alpha. between 0 and 1, the .beta. between 0 and 1, the .gamma. between 0 and 2, the .delta. between about 0 and about 0.2, the y is between 2 and 4, and the z is between 0 and 0.5.

  16. Steroidal glycosides from the underground parts of Helleborus caucasicus. (United States)

    Bassarello, Carla; Muzashvili, Tamara; Skhirtladze, Alexandre; Kemertelidze, Ether; Pizza, Cosimo; Piacente, Sonia


    Four polyhydroxylated and polyunsaturated furostanol glycosides (1-4), named caucasicosides A (1), B (2), C (3) and D (4), were isolated from the MeOH extract of the underground parts of Helleborus caucasicus, along with four spirostanol derivatives, a furostanol glycoside, a furospirostanol glycoside, 20-hydroxyecdysone and the bufadienolides hellebrigenin and deglucohellebrin. The structures of 1-4 were elucidated as furosta-5,20(22),25(27)-triene-1beta,3beta,11alpha,26-tetrol 26-O-beta-D-glucopyranoside (1), 26-O-beta-D-glucopyranosylfurosta-5,20(22),25(27)-triene-1beta,3beta,11alpha,26-tetrol 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside (2), 26-O-beta-d-glucopyranosyl-22alpha-methoxyfurosta-5,25(27)-diene-1beta,3beta,11alpha,26-tetrol 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside (3), 26-O-beta-D-glucopyranosylfurosta-5,20(22),25(27)-triene-1beta,3beta,26-triol 3-O-beta-D-xylopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-4-O-sulfo-alpha-L-arabinopyranoside (4). Structure elucidation was accomplished through the extensive use of 1D- and 2D NMR experiments including 1H-1H (COSY, 1D-TOCSY) and 1H-13C (HSQC, HMBC) spectroscopy along with ESI-MS and HR-ESI-MS. The aglycones of 1-4 have never been reported before.

  17. Human periodontal ligament cells facilitate leukocyte recruitment and are influenced in their immunomodulatory function by Th17 cytokine release. (United States)

    Konermann, A; Beyer, M; Deschner, J; Allam, J P; Novak, N; Winter, J; Jepsen, S; Jäger, A


    The objective of this in vitro study was to examine the immunomodulatory impact of human periodontal ligament (PDL) cells on the nature and magnitude of the leukocyte infiltrate in periodontal inflammation, particularly with regard to Th17 cells. PDL cells were challenged with pro-inflammatory cytokines (IL-1ß, IL-17A, and IFN-γ) and analyzed for the expression of cytokines involved in periodontal immunoinflammatory processes (IL-6, MIP-3 alpha, IL-23A, TGFß1, IDO, and CD274). In order to further investigate a direct involvement of PDL cells in leukocyte function, co-culture experiments were conducted. The expression of the immunomodulatory cytokines studied was significantly increased under pro-inflammatory conditions in PDL cells. Although PDL cells did not stimulate leukocyte proliferation or Th17 differentiation, these cells induced the recruitment of leukocytes. The results of our study suggest that PDL cells might be involved in chronic inflammatory mechanisms in periodontal tissues and thus in the transition to an adaptive immune response in periodontitis.

  18. Overexpression of TEAD-1 in transgenic mouse striated muscles produces a slower skeletal muscle contractile phenotype. (United States)

    Tsika, Richard W; Schramm, Christine; Simmer, Gretchen; Fitzsimons, Daniel P; Moss, Richard L; Ji, Juan


    TEA domain (TEAD) transcription factors serve important functional roles during embryonic development and in striated muscle gene expression. Our previous work has implicated a role for TEAD-1 in the fast-to-slow fiber-type transition in response to mechanical overload. To investigate whether TEAD-1 is a modulator of slow muscle gene expression in vivo, we developed transgenic mice expressing hemagglutinin (HA)-tagged TEAD-1 under the control of the muscle creatine kinase promoter. We show that striated muscle-restricted HA-TEAD-1 expression induced a transition toward a slow muscle contractile protein phenotype, slower shortening velocity (Vmax), and longer contraction and relaxation times in adult fast twitch extensor digitalis longus muscle. Notably, HA-TEAD-1 overexpression resulted in an unexpected activation of GSK-3alpha/beta and decreased nuclear beta-catenin and NFATc1/c3 protein. These effects could be reversed in vivo by mechanical overload, which decreased muscle creatine kinase-driven TEAD-1 transgene expression, and in cultured satellite cells by TEAD-1-specific small interfering RNA. These novel in vivo data support a role for TEAD-1 in modulating slow muscle gene expression.

  19. Wet hydrogen peroxide catalytic oxidation of phenol with FeAC (iron-embedded activated carbon) catalysts. (United States)

    Liou, Rey-May; Chen, Shih-Hsiung; Huang, Cheng-Hsien; Hung, Mu-Ya; Chang, Jing-Song; Lai, Cheng-Lee


    This investigation aims at exploring the catalytic oxidation activity of iron-embedded activated carbon (FeAC) and the application for the degradation of phenol in the wet hydrogen peroxide catalytic oxidation (WHPCO). FeAC catalysts were prepared by pre-impregnating iron in coconut shell with various iron loadings in the range of 27.5 to 46.5% before they were activated. The FeAC catalysts were characterised by measuring their surface area, pore distribution, functional groups on the surface, and X-ray diffraction patterns. The effects of iron loading strongly inhibited the pore development of the catalyst but benefited the oxidation activity in WHPCO. It was found that the complete conversion of phenol was observed with all FeAC catalysts in oxidation. High level of chemical oxygen demand (COD) abatement can be achieved within the first 30 minutes of oxidation. The iron embedded in the activated carbon showed good performance in the degradation and mineralisation of phenol during the oxidation due to the active sites as iron oxides formed on the surface of the activated carbon. It was found that the embedding irons were presented in gamma-Fe(2)O(3), alpha-Fe(2)O(3), and alpha-FeCOOH forms on the activated carbon. The aging tests on FeAC catalysts showed less activity loss, and less iron leaching was found after four oxidation runs.

  20. Polymorphism of Alprazolam (Xanax): a review of its crystalline phases and identification, crystallographic characterization, and crystal structure of a new polymorph (form III). (United States)

    de Armas, Héctor Novoa; Peeters, Oswald M; Van den Mooter, Guy; Blaton, Norbert


    A new polymorphic form of Alprazolam (Xanax), 8-chloro-1-methyl-6-phenyl-4H-[1,2,4]triazolo-[4,3-alpha][1,4]benzodiazepine, C(17)H(13)ClN(4), has been investigated by means of X-ray powder diffraction (XRPD), single crystal X-ray diffraction, and differential scanning calorimetry (DSC). This polymorphic form (form III) was obtained during DSC experiments after the exothermic recrystallization of the melt of form I. The crystal unit cell dimensions for form III were determined from diffractometer methods. The monoclinic unit cell found for this polymorph using XRPD after indexing the powder diffractogram was confirmed by the cell parameters obtained from single crystal X-ray diffractometry on a crystal isolated from the DSC pans. The single crystal unit cell parameters are: a = 28.929(9), b = 13.844(8), c = 7.361(3) angstroms, beta = 92.82(3) degrees , V = 2944(2) angstroms(3), Z = 8, space group P2(1) (No.4), Dx = 1.393 Mg/m(3). The structure obtained from single crystal X-ray diffraction was used as initial model for Rietveld refinement on the powder diffraction data of form III. The temperature phase transformations of alprazolam were also studied using high temperature XRPD. A review of the different phases available in the Powder Diffraction File (PDF) database for this drug is described bringing some clarification and corrections.

  1. Chia (Salvia hispanica L.) seed as an n-3 fatty acid source for finishing pigs: effects on fatty acid composition and fat stability of the meat and internal fat, growth performance, and meat sensory characteristics. (United States)

    Coates, W; Ayerza, R


    Coronary heart disease is caused by arteriosclerosis, which is triggered by an unbalanced fatty acid profile in the body. Today, Western diets are typically low in n-3 fatty acids and high in SFA and n-6 fatty acids; consequently, healthier foods are needed. Chia seed (Salvia hispanica L.), which contains the greatest known plant source of n-3 alpha-linolenic acid, was fed at the rate of 10 and 20% to finishing pigs, with the goal to determine if this new crop would increase the n-3 content of the meat as has been reported for other n-3 fatty acid-rich crops. The effects of chia on fatty acid composition of the meat, internal fats, growth performance, and meat sensory characteristics were determined. Productive performance was unaffected by dietary treatment. Chia seed modified the fatty acid composition of the meat fat, but not of the internal fat. Significantly (P < 0.05) less palmitic, stearic, and arachidic acids were found with both chia treatments. This is different than trials in which flaxseed, another plant based source of omega-3 fatty acid, has been fed. Alpha-linolenic acid content increased with increasing chia content of the diet; however, only the effect of the 20% ration was significantly (P < 0.05) different from that of the control. Chia seed increased panel member preferences for aroma and flavor of the meat. This study tends to show that chia seems to be a viable feed that can produce healthier pork for human consumption.

  2. Association of HLA-DR3 with human immune response to Lol p I and Lol p II allergens in allergic subjects. (United States)

    Freidhoff, L R; Ehrlich-Kautzky, E; Meyers, D A; Ansari, A A; Bias, W B; Marsh, D G


    Associations between HLA type and IgE or IgG antibody (Ab) responses to two well-characterized, antigenetically non-crossreactive components of Lolium perenne (rye grass) pollen extract, Lol p I (Rye I) and Lol p II (Rye II) were studied in two groups of skin-test positive (ST+) Caucasoid adults. By both nonparametric and parametric statistical methods, significant associations were found between Ab responses to both Lol I and Lol II and the possession of HLA-DR3. In view of the well-known associations of both DR3 and B8 (which are in linkage disequilibrium) with many autoimmune diseases, differences in anti-Lol I and anti-Lol II mean log[Ab] levels between B8+, DR3- vs B8-, DR3- subjects and B8+, DR3+ vs B8-, DR3+ subjects were investigated. No differences were found. Our data, along with recent RFLP and DNA sequence studies, suggest that an Ia molecule involved in immune recognition of a similar major Ia recognition site of both the Lol molecules may consist of a DR3 alpha-beta I pair. Abbreviations used: Ab: Antibody. HLA: Human leukocyte antigen. Lol p I, Lol I: Group I allergen from Lolium perenne pollen (Rye I). Lol p II, Lol II: Group II allergen from Lolium perenne pollen (Rye II). Mr: Relative molecular mass. Rx: Immunotherapy with grass pollen extracts. ST: Skin test.

  3. The structure of the carbohydrate backbone of the lipopolysaccharide of Pectinatus frisingensis strain VTT E-79104. (United States)

    Vinogradov, Evgeny; Li, Jianjun; Sadovskaya, Irina; Jabbouri, Said; Helander, Ilkka M


    The structure of the carbohydrate backbone of the lipopolysaccharide from Pectinatus frisingensis strain VTT E-79104 was analyzed using chemical degradations, NMR spectroscopy, mass spectrometry, and chemical methods. The LPS contains two major structural variants, differing in the presence or absence of an octasaccharide fragment. The largest structure of the carbohydrate backbone of the LPS, that could be deduced from experimental results, consists of 20 monosaccharides arranged in a nonrepetitive sequence: [carbohydrate structure: see text] where R is H or 4-O-Me-alpha-L-Fuc-(1-2)-4-O-Me-beta-Hep-(1-3)-alpha-GlcNAc-(1-2)-beta-Man-(1-3)-beta-ManNAc-(1-4)-alpha-Gal-(1-4)-beta-Hep-(1-3)-beta-GalNAc-(1- where Hep is a residue of D-glycero-D-galacto-heptose; all monosaccharides have the D-configuration except for 4-O-Me-L-Fuc and L-Ara4N. This structure is architecturally similar to the oligosaccharide system reported previously in P. frisingensis VTT E-82164 LPS, but differs from the latter in composition and also in the size of the outer region.

  4. La filière lin oléagineux française : panorama et perspectives

    Directory of Open Access Journals (Sweden)

    Labalette Françoise


    Full Text Available Linseed oil crop production does not succeed in reaching stable acreage in France and does not meet the demand coming from users which incorporate linseeds, which display high content in omega 3 (alpha-linolenic acid, in animal feeding in order to deliver food enriched in omega 3 by natural way (dairy products, eggs, ham.... However, several driving forces should encourage this crop, like the shortfall in linseeds in the European Union and the environmental changes expected from agriculture. That is why the French oilseed crop organisation (Onidol and the French technical institute for oilseed crops (Cetiom launched in 2008 a study about the linseed situation in France. Aim of this work was to get a better understanding of each stage of the linseed chain production from the linseed cultivation to the users and to draw perspectives for the future of this crop in France. To do that a large survey was carried out according to methods adapted to each considered sector. A great attention was given to the progress of the variety offer because the yield gap between linseed and other crops in the rotation is probably one of the most important factors explaining the crop stagnation in France. The synthesis presented in the present paper allows identifying encouraging signals for the future and points the major drawbacks to overcome and the main advantages to take advantage from for developing linseed in France.

  5. Breathing-like excited state of the Hoyle state in ${^{12}{\\rm C}}$

    CERN Document Server

    Zhou, Bo; Horiuchi, Hisashi; Ren, Zhongzhou


    The existence of the $0_3^+$ and $0_4^+$ states around 10 MeV excitation energy in ${^{12}{\\rm C}}$ is confirmed by a fully microscopic 3$\\alpha$ cluster model. Firstly, a GCM (generator coordinate method) calculation is performed by superposing optimized 2$\\alpha$+$\\alpha$ THSR (Tohsaki-Horiuchi-Schuck-R\\"{o}pke) wave functions with the radius-constraint method. The obtained two excited $0^+$ states above the Hoyle state are consistent with the recently observed states by experiment. Secondly, a variational calculation using the single 2$\\alpha$+$\\alpha$ THSR wave function orthogonalized to the ground and Hoyle states is made and it also supports the existence of the $0_3^+$ state obtained by the GCM calculation. The analysis of the obtained $0_3^+$ state is made by studying its 2$\\alpha$-$\\alpha$ reduced width amplitude, its 2$\\alpha$ correlation function, and the large monopole matrix element between this state and the Hoyle state, which shows that this $0_3^+$ state is a breathing-like excited state of th...

  6. Changes of learning and memory ability and brain nicotinic receptors of rat offspring with coal burning fluorosis

    Energy Technology Data Exchange (ETDEWEB)

    Gui, C.Z.; Ran, L.Y.; Li, J.P.; Guan, Z.Z. [Guiyang Medical College, Guiyang (China). Dept. of Pathology


    The purpose of the investigation is to reveal the mechanism of the decreased ability of learning and memory induced by coal burning fluorosis. Ten offspring SD rats aged 30 days, who were born from the mothers with chronic coal burning fluorosis, and ten offspring with same age from the normal mothers as controls were selected. Spatial learning and memory of the rats were evaluated by Morris Water Maze test. Cholinesterase activity was detected by photometric method. The expressions of nicotinic acetylcholine receptors (nAChRs) at protein and mRNA levels were detected by Western blotting and Real-time PCR, respectively. The results showed that in the rat offspring exposed to higher fluoride as compared to controls, the learning and memory ability declined; the cholinesterase activities in the brains were inhibited; the protein levels of alpha 3, alpha 4 and alpha 7 nAChR subunits were decreased which showed certain significant correlations with the declined learning and memory ability; and the mRNA levels of alpha 3 and alpha 4 nAChRs were decreased, whereas the alpha 7 mRNA increased. The data indicated that coal burning fluorosis can induce the decreased ability of learning and memory of rat offspring, in which the mechanism might be connected to the changed nAChRs and cholinesterase.

  7. Lysophospholipid presentation by CD1d and recognition by a human Natural Killer T-cell receptor

    Energy Technology Data Exchange (ETDEWEB)

    López-Sagaseta, Jacinto; Sibener, Leah V.; Kung, Jennifer E.; Gumperz, Jenny; Adams, Erin J. (UC); (UW-MED)


    Invariant Natural Killer T (iNKT) cells use highly restricted {alpha}{beta} T cell receptors (TCRs) to probe the repertoire of lipids presented by CD1d molecules. Here, we describe our studies of lysophosphatidylcholine (LPC) presentation by human CD1d and its recognition by a native, LPC-specific iNKT TCR. Human CD1d presenting LPC adopts an altered conformation from that of CD1d presenting glycolipid antigens, with a shifted {alpha}1 helix resulting in an open A pocket. Binding of the iNKT TCR requires a 7-{angstrom} displacement of the LPC headgroup but stabilizes the CD1d-LPC complex in a closed conformation. The iNKT TCR CDR loop footprint on CD1d-LPC is anchored by the conserved positioning of the CDR3{alpha} loop, whereas the remaining CDR loops are shifted, due in part to amino-acid differences in the CDR3{beta} and J{beta} segment used by this iNKT TCR. These findings provide insight into how lysophospholipids are presented by human CD1d molecules and how this complex is recognized by some, but not all, human iNKT cells.

  8. Inhibition of GSK3 by lithium, from single molecules to signaling networks

    Directory of Open Access Journals (Sweden)

    Laure eFreland


    Full Text Available For more than 60 years, the mood stabilizer lithium has been used alone or in combination for the treatment of bipolar disorder, schizophrenia, depression and other mental illnesses. Despite this long history, the molecular mechanisms trough which lithium regulates behavior are still poorly understood. Among several targets, lithium has been shown to directly inhibit glycogen synthase kinase 3 alpha and beta (GSK3α and GSK3β. However in vivo, lithium also inhibits GSK3 by regulating the activity of other mechanisms like the formation of a signaling complex comprised of beta-arrestin 2 and Akt. Here, we provide an overview of in vivo evidence supporting a role for inhibition of GSK3 in some behavioral effects of lithium. We also explore how regulation of GSK3 by lithium within a signaling network involving several molecular targets and cell surface receptors (e.g. G protein coupled receptors and receptor tyrosine kinases may provide cues to its relative pharmacological selectivity and its effects on disease mechanisms. A better understanding of these intricate actions of lithium at a systems level may allow the rational development of better mood stabilizer drugs with enhanced selectivity, efficacy and lesser side effects.

  9. Channelopathies in Cav1.1, Cav1.3, and Cav1.4 voltage-gated L-type Ca2+ channels. (United States)

    Striessnig, Jörg; Bolz, Hanno Jörn; Koschak, Alexandra


    Voltage-gated Ca2+ channels couple membrane depolarization to Ca2+-dependent intracellular signaling events. This is achieved by mediating Ca2+ ion influx or by direct conformational coupling to intracellular Ca2+ release channels. The family of Cav1 channels, also termed L-type Ca2+ channels (LTCCs), is uniquely sensitive to organic Ca2+ channel blockers and expressed in many electrically excitable tissues. In this review, we summarize the role of LTCCs for human diseases caused by genetic Ca2+ channel defects (channelopathies). LTCC dysfunction can result from structural aberrations within their pore-forming alpha1 subunits causing hypokalemic periodic paralysis and malignant hyperthermia sensitivity (Cav1.1 alpha1), incomplete congenital stationary night blindness (CSNB2; Cav1.4 alpha1), and Timothy syndrome (Cav1.2 alpha1; reviewed separately in this issue). Cav1.3 alpha1 mutations have not been reported yet in humans, but channel loss of function would likely affect sinoatrial node function and hearing. Studies in mice revealed that LTCCs indirectly also contribute to neurological symptoms in Ca2+ channelopathies affecting non-LTCCs, such as Cav2.1 alpha1 in tottering mice. Ca2+ channelopathies provide exciting disease-related molecular detail that led to important novel insight not only into disease pathophysiology but also to mechanisms of channel function.

  10. The alpha 3 chain of type IV collagen induces autoimmune Goodpasture syndrome. (United States)

    Kalluri, R; Gattone, V H; Noelken, M E; Hudson, B G


    Human Goodpasture syndrome is a lethal form of autoimmune disease that is characterized by pulmonary hemorrhage and glomerulonephritis. The tissue injury is mediated by autoantibodies that bind to glomerular and alveolar basement membrane. The target autoantigen is alpha 3(IV) collagen, one of six genetically distinct chains that comprise type IV collagen, and the epitope is sublocalized to the noncollagenous domain (NC1) of the alpha 3 chain. The present study reports the unique capacity of alpha 3(IV)NC1 dimer from bovine kidney to aberrantly engage the immune system of rabbits to respond to self, mimicking the organ-specific form of the human disease, whereas the other chains of type IV collagen are nonpathogenic. However, alpha 3(IV)NC1 hexamer was nonpathogenic, suggesting the exposure of a pathogenic epitope upon dissociation of hexamer into dimers. Exposure of the pathogenic epitope by infection or organic solvents, events which are thought to precede Goodpasture syndrome, may be the principal factor in the etiology of the disease. The pathogenicity of alpha 3(IV) collagen brings full circle a decade of research that has identified four novel chains (alpha 3-alpha 6) of type IV collagen.

  11. Overview of the magnetic properties experiments on the Mars Exploration Rovers (United States)

    Madsen, M.B.; Goetz, W.; Bertelsen, P.; Binau, C.S.; Folkmann, F.; Gunnlaugsson, H.P.; Hjollum, J.I.; Hviid, S.F.; Jensen, J.; Kinch, K.M.; Leer, K.; Madsen, D.E.; Merrison, J.; Olsen, M.; Arneson, H.M.; Bell, J.F.; Gellert, Ralf; Herkenhoff, K. E.; Johnson, J. R.; Johnson, M.J.; Klingelhofer, G.; McCartney, E.; Ming, D. W.; Morris, R.V.; Proton, J.B.; Rodionov, D.; Sims, M.; Squyres, S. W.; Wdowiak, T.; Yen, A. S.


    The Mars Exploration Rovers have accumulated airborne dust on different types of permanent magnets. Images of these magnets document the dynamics of dust capture and removal over time. The strongly magnetic subset of airborne dust appears dark brown to black in Panoramic Camera (Pancam) images, while the weakly magnetic one is bright red. Images returned by the Microscopic Imager reveal the formation of magnetic chains diagnostic of magnetite-rich grains with substantial magnetization (>8 Am2 kg-1). On the basis of M??ssbauer spectra the dust contains magnetite, olivine, pyroxene, and nanophase oxides in varying proportions, depending on wind regime and landing site. The dust contains a larger amount of ferric iron (Fe3+/Fe tot ??? 0.6) than rocks in the Gusev plains (???0.1-0.2) or average Gusev soil (???0.3). Alpha Particle X-Ray Spectrometer data of the dust show that some of the iron in magnetite is substituted by titanium and chromium. The good correlation of the amount of calcium and sulfur in the dust may be caused by the presence of a calcium sulfate related phase. The overall mineralogical composition points to a basaltic origin of the airborne dust, although some alteration has taken place as indicated by the large degree of oxidation. Copyright 2009 by the American Geophysical Union.

  12. Estrogen receptor ligands counteract cognitive deficits caused by androgen deprivation in male rats. (United States)

    Lagunas, Natalia; Calmarza-Font, Isabel; Grassi, Daniela; Garcia-Segura, Luis M


    Androgen deprivation causes impairment of cognitive tasks in rodents and humans, and this deficit can be reverted by androgen replacement therapy. Part of the effects of androgens in the male may be mediated by their local metabolism to estradiol or 3-alpha androstanediol within the brain and the consequent activation of estrogen receptors. In this study we have assessed whether the administration of estradiol benzoate, the estrogen receptor β selective agonist diarylpropionitrile or the estrogen receptor α selective agonist propyl pyrazole triol affect performance of androgen-deprived male Wistar rats in the cross-maze test. In addition, we tested the effect of raloxifene and tamoxifen, two selective estrogen receptor modulators used in clinical practice. The behavior of the rats was assessed 2 weeks after orchidectomy or sham surgery. Orchidectomy impaired acquisition in the cross-maze test. Estradiol benzoate and the selective estrogen receptor β agonist significantly improved acquisition in the cross-maze test compared to orchidectomized animals injected with vehicle. Raloxifene and tamoxifen at a dose of 1mg/kg, but not at doses of 0.5 or 2mg/kg, also improved acquisition of orchidectomized animals. Our findings suggest that estrogenic compounds with affinity for estrogen receptor β and selective estrogen receptor modulators, such as raloxifene and tamoxifen, may represent good candidates to promote cognitive performance in androgen-deprived males.

  13. What do we really know about the ubiquitin-proteasome pathway in muscle atrophy? (United States)

    Jagoe, R. T.; Goldberg, A. L.


    Studies of many different rodent models of muscle wasting have indicated that accelerated proteolysis via the ubiquitin-proteasome pathway is the principal cause of muscle atrophy induced by fasting, cancer cachexia, metabolic acidosis, denervation, disuse, diabetes, sepsis, burns, hyperthyroidism and excess glucocorticoids. However, our understanding about how muscle proteins are degraded, and how the ubiquitin-proteasome pathway is activated in muscle under these conditions, is still very limited. The identities of the important ubiquitin-protein ligases in skeletal muscle, and the ways in which they recognize substrates are still largely unknown. Recent in-vitro studies have suggested that one set of ubquitination enzymes, E2(14K) and E3(alpha), which are responsible for the 'N-end rule' system of ubiquitination, plays an important role in muscle, especially in catabolic states. However, their functional significance in degrading different muscle proteins is still unclear. This review focuses on the many gaps in our understanding of the functioning of the ubiquitin-proteasome pathway in muscle atrophy, and highlights the strengths and limitations of the different experimental approaches used in such studies.

  14. Soluble factor cross-talk between human bone marrow-derived hematopoietic and mesenchymal cells enhances in vitro CFU-F and CFU-O growth and reveals heterogeneity in the mesenchymal progenitor cell compartment. (United States)

    Baksh, Dolores; Davies, John E; Zandstra, Peter W


    The homeostatic adult bone marrow (BM) is a complex tissue wherein physical and biochemical interactions serve to maintain a balance between the hematopoietic and nonhematopoietic compartments. To focus on soluble factor interactions occurring between mesenchymal and hematopoietic cells, a serum-free adhesion-independent culture system was developed that allows manipulation of the growth of both mesenchymal and hematopoietic human BM-derived progenitors and the balance between these compartments. Factorial experiments demonstrated a role for stem cell factor (SCF) and interleukin 3 (IL-3) in the concomitant growth of hematopoietic (CD45+) and nonhematopoietic (CD45-) cells, as well as their derivatives. Kinetic tracking of IL-3alpha receptor (CD123) and SCF receptor (CD117) expression on a sorted CD45- cell population revealed the emergence of CD45-CD123+ cells capable of osteogenesis. Of the total fibroblast colony-forming units (CFU-Fs) and osteoblast colony-forming units (CFU-O), approximately 24% of CFU-Fs and about 22% of CFU-Os were recovered from this population. Cell-sorting experiments demonstrated that the CD45+ cell population secreted soluble factors that positively affect the survival and proliferation of CFU-Fs and CFU-Os generated from the CD45- cells. Together, our results provide insight into the intercellular cytokine network between hematopoietic and mesenchymal cells and provide a strategy to mutually culture both mesenchymal and hematopoietic cells in a defined scalable bioprocess.

  15. Hot accretion flow with radiative cooling: state transitions in black hole X-ray binaries

    CERN Document Server

    Wu, Mao-Chun; Yuan, Ye-Fei; Gan, Zhao-Ming


    We investigate state transitions in black hole X-ray binaries through different parameters by using two-dimensional axisymmetric hydrodynamical simulation method. For radiative cooling in hot accretion flow, we take into account the bremsstrahlung, synchrotron and synchrotron-self Comptonization self-consistently in the dynamics. Our main result is that the state transitions occur when the accretion rate reaches a critical value $\\dot M \\sim 3\\alpha\\ \\dot M_{\\rm Edd}$, above which cold and dense clumpy/filamentary structures are formed, embedded within the hot gas. We argued this mode likely corresponds to the proposed two-phase accretion model, which may be responsible for the intermediate state of black hole X-ray binaries. When the accretion rate becomes sufficiently high, the clumpy/filamentary structures gradually merge and settle down onto the mid-plane. Eventually the accretion geometry transforms to a disc-corona configuration. In summary our results are consistent with the truncated accretion scenari...

  16. CDP-choline (citicoline) attenuates brain damage in a rat model of birth asphyxia. (United States)

    Fiedorowicz, Michał; Makarewicz, Dorota; Stańczak-Mrozek, Kinga I; Grieb, Paweł


    To estimate protective potential of citicoline in a model of birth asphyxia, the drug was given to 7-day old rats subjected to permanent unilateral carotid artery occlusion and exposed for 65 min to a hypoxic gas mixture. Daily citicoline doses of 100 or 300 m/kg, or vehicle, were injected intraperitoneally for 7 consecutive days beginning immediately after the end of the ischemic-hypoxic insult, and brain damage was assessed by gross zorphology score and weight deficit two weeks after the insult. Caspase-3, alpha-fodrin, Bcl-2, and Hsp70 levels were assessed at 0, 1, and 24 h after the end of the hypoxic insult in another group of rat pups subjected to the same insult and given a single dose of 300 m/kg of citicoline or the vehicle. Citicoline markedly reduced caspase-3 activation and Hsp70 expression 24 h after the insult, and dose-dependently attenuated brain damage. In the context of the well-known excellent safety profile of citicoline, these data suggest that clinical evaluation of the efficacy of the drug in human birth asphyxia may be warranted.

  17. Seasonal and spatial variability of {sup 210}Po, {sup 238}U and {sup 239+240}Pu levels in the river catchment area assessed by application of neural-network based classification

    Energy Technology Data Exchange (ETDEWEB)

    Skwarzec, Bogdan [University of Gdansk, Faculty of Chemistry, Chair of Analytical Chemistry, 18/19 Sobieskiego Street, 80-952 Gdansk (Poland)], E-mail:; Kabat, Krzysztof [University of Gdansk, Faculty of Chemistry, Chair of Analytical Chemistry, 18/19 Sobieskiego Street, 80-952 Gdansk (Poland); Astel, Aleksander [Pomeranian Academy, Biology and Environmental Protection Institute, Environmental Chemistry Research Unit, 22a Arciszewskiego Street, 76-200 Slupsk (Poland)


    The present study deals with the application of self-organizing maps (SOM) in order to model, classify and interpret seasonal and spatial variability of {sup 210}Po, {sup 238}U and {sup 239+240}Pu levels in the Vistula river basin. The data set represents concentration values for 3 alpha emitters ({sup 210}Po, {sup 238}U and {sup 239+240}Pu) measured in surface water samples collected at 19 different sampling locations (8 in major Vistula stream while 11 in right or left Vistula tributaries) during four seasons (winter, spring, summer and autumn) in the framework of a one-year quality monitoring study. The advantages of an SOM algorithm, its classification and visualization ability for environmental data sets, are stressed. The neural-network based classification made it possible to reveal specific patterns related to both seasonal and spatial variability. In the middle and upper part of Vistula catchment as well as in the right-shore tributaries, concentrations of {sup 210}Po and {sup 238}U during summer and winter are the lowest. Concentrations of {sup 210}Po and {sup 238}U increase significantly during spring and autumn in the Vistula river catchment, especially in the delta of Vistula river. High concentration of anthropogenic originated {sup 239+240}Pu indicates 'site-specific' character of pollution in two large left-shore tributaries located in the middle part of the Vistula drainage area. Efficient classification of sampling locations could lead to an optimization of river radiochemical sampling networks and to a better tracing of natural and anthropogenic changes along Vistula river stream.

  18. 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:; Silva, Antonio A. [Universidade Federal de Vicosa (UFV), MG (Brazil). Dept. de Fitotecnia


    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)

  19. Variability of the needle essential oils of Pinus heldreichii from different populations in Montenegro and Serbia. (United States)

    Nikolić, Biljana; Ristić, Mihailo; Bojović, Srdjan; Marin, Petar D


    The essential-oil compositions of Pinus heldreichii Christ. from Montenegro and Serbia are reported at the population level. Whitebark pine is a sub-endemic high-mountain Balkan pine relict of an anthropogenically reduced area, with large morphological diversity and insufficiently clear taxonomic position. In the pine-needle terpene profile from three populations from Montenegro, and one from Serbia, 101 compounds were detected, 72 of which could be identified (Table 3). The dominant constituents are limonene (26.3%), alpha-pinene (17.5%), germacrene D (13.5%), and beta-caryophyllene (10.4%), comprising ca. 67.7% of the essential oil. Medium-to-high contents (0.5-10%) of the following 16 additional components were found: beta-pinene, beta-myrcene, alpha-humulene, delta-cadinene, alpha-muurolene, (E)-hex-2-enal, beta-gurjunene, gamma-muurolene, isopimarol, camphene, gamma-cadinene, aromadendrene, beta-bisabolene, trans-beta-farnesene, alpha-cadinene, and (Z)-hex-3-en-1-ol. The similarity of the populations and the within-population variability was visualized by principle-component analysis (PCA) of eleven selected terpenes in 97 tree samples. Cluster and genetic analyses suggest closest connection between the two spatially most-distant populations I (Montenegro) and IV (Serbia). Based on the profile of the main sesquiterpene components, the studied populations from Montenegro and Serbia are more similar to the populations from Greece and the Central Balkan peninsula (Bosnia and Serbia-Kosovo) than to those on the furthest eastern margin of their natural range (Bulgaria).

  20. Identification and characterization of genes required for compensatory growth in Drosophila. (United States)

    Gerhold, Abigail R; Richter, Daniel J; Yu, Albert S; Hariharan, Iswar K


    To maintain tissue homeostasis, some organs are able to replace dying cells with additional proliferation of surviving cells. Such proliferation can be localized (e.g., a regeneration blastema) or diffuse (compensatory growth). The relationship between such growth and the growth that occurs during development has not been characterized in detail. Drosophila melanogaster larval imaginal discs can recover from extensive damage, producing normally sized adult organs. Here we describe a system using genetic mosaics to screen for recessive mutations that impair compensatory growth. By generating clones of cells that carry a temperature-sensitive cell-lethal mutation, we conditionally ablate patches of tissue in the imaginal disc and assess the ability of the surviving sister clones to replace the lost tissue. We have used this system together with a modified whole-genome resequencing (WGS) strategy to identify several mutations that selectively compromise compensatory growth. We find specific alleles of bunched (bun) and Ribonucleoside diphosphate reductase large subunit (RnrL) reduce compensatory growth in the imaginal disc. Other genes identified in the screen, including two alleles of Topoisomerase 3-alpha (Top3α), while also required for developmental growth, appear to have an enhanced requirement during compensatory growth. Compensatory growth occurs at a higher rate than normal growth and may therefore have features in common with some types of overgrowth. Indeed, the RnrL allele identified compromises both these types of altered growth and mammalian ribonucleotide reductase and topoisomerases are targets of anticancer drugs. Finally, the approach we describe is applicable to the study of compensatory growth in diverse tissues in Drosophila.

  1. Unexpected Inflammatory Effects of Intravaginal Gels (Universal Placebo Gel and Nonoxynol-9 on the Upper Female Reproductive Tract: A Randomized Crossover Study.

    Directory of Open Access Journals (Sweden)

    Karen Smith-McCune

    Full Text Available Intravaginal anti-HIV microbicides could provide women with a self-controlled means for HIV prevention, but results from clinical trials have been largely disappointing. We postulated that unrecognized effects of intravaginal gels on the upper female reproductive tract might contribute to the lower-than-expected efficacy of HIV microbicides. Our objective was to study the effects of intravaginal gels on the immune microenvironment of the cervix and uterus. In this randomized crossover study, 27 healthy female volunteers used a nightly application of intravaginal nonoxynol-9 (N9 gel as a "failed" microbicide or the universal placebo gel (UPG as a "safe" gel (intervention cycles, or nothing (control cycle from the end of menses to the mid-luteal phase. At a specific time-point following ovulation, all participants underwent sample collection for measurements of T-cell phenotypes, gene expression, and cytokine/chemokine protein concentrations from 3 anatomic sites above the vagina: the cervical transformation zone, the endocervix and the endometrium. We used hierarchical statistical models to estimate mean (95% CI intervention effects, for N9 and UPG relative to control. Exposure to N9 gel and UPG generated a common "harm signal" that included transcriptional up-regulation of inflammatory genes chemokine (C-C motif ligand 20 (macrophage inflammatory factor-3alpha and interleukin 8 in the cervix, decreased protein concentrations of secretory leukocyte protease inhibitor, and transcriptional up-regulation of inflammatory mediators glycodelin-A and osteopontin in the endometrium. These results need to be replicated with a larger sample, but underscore the need to consider the effects of microbicide agents and gel excipients on the upper female reproductive tract in studies of vaginal microbicides.

  2. Vascular Tone Regulation Induced by C-Type Natriuretic Peptide: Differences in Endothelium-Dependent and -Independent Mechanisms Involved in Normotensive and Spontaneously Hypertensive Rats (United States)

    Caniffi, Carolina; Cerniello, Flavia M.; Gobetto, María N.; Sueiro, María L.; Arranz, Cristina


    Given that the role of C-type natriuretic peptide (CNP) in the regulation of vascular tone in hypertensive states is unclear, we hypothesized that impaired response of the nitric oxide system to CNP in spontaneously hypertensive rats (SHR) could affect vascular relaxation induced by the peptide in this model of hypertension, and that other endothelial systems or potassium channels opening could also be involved. We examined the effect of CNP on isolated SHR aortas, and the hindlimb vascular resistance (HVR) in response to CNP administration compared to normotensive rats. Aortas were mounted in an isometric organ bath and contracted with phenylephrine. CNP relaxed arteries in a concentration-dependent manner but was less potent in inducing relaxation in SHR. The action of CNP was diminished by removal of the endothelium, inhibition of nitric oxide synthase by Nω-nitro-L-arginine methyl ester, and inhibition of soluble guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one in both groups. In contrast, blockade of cyclooxygenase or subtype 2 bradykinin receptor increased CNP potency only in SHR. In both Wistar and SHR, CNP relaxation was blunted by tetraethylammonium and partially inhibited by BaCl2 and iberiotoxin, indicating that it was due to opening of the Kir and BKCa channels. However, SHR seem to be more sensitive to Kir channel blockade and less sensitive to BKCa channel blockade than normotensive rats. In addition, CNP decreases HVR in Wistar and SHR, but the effect of CNP increasing blood flow was more marked in SHR. We conclude that CNP induces aorta relaxation by activation of the nitric oxide system and opening of potassium channels, but the response to the peptide is impaired in conductance vessel of hypertensive rats. PMID:27936197

  3. Cintichem modified process - {sup 99}Mo precipitation step: application of statistical analysis tools over the reaction parameters

    Energy Technology Data Exchange (ETDEWEB)

    Teodoro, Rodrigo; Dias, Carla R.B.R.; Osso Junior, Joao A., E-mail: jaosso@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Fernandez Nunez, Eutimio Gustavo [Universidade de Sao Paulo (EP/USP), SP (Brazil). Escola Politecnica. Dept. de Engenharia Quimica


    Precipitation of {sup 99}Mo by {alpha}-benzoin oxime ({alpha}-Bz) is a standard precipitation method for molybdenum due the high selectivity of this agent. Nowadays, statistical analysis tools have been employed in analytical systems to prove its efficiency and feasibility. IPEN has a project aiming the production of {sup 99}Mo by the fission of {sup 235}U route. The processing uses as the first step the precipitation of {sup 99}Mo with {alpha}-Bz. This precipitation step involves many key reaction parameters. The aim of this work is based on the development of the already known acidic route to produce {sup 99}Mo as well as the optimization of the reactional parameters applying statistical tools. In order to simulate {sup 99}Mo precipitation, the study was conducted in acidic media using HNO{sub 3}, {alpha}Bz as precipitant agent and NaOH /1%H{sub 2}O{sub 2} as dissolver solution. Then, a Mo carrier, KMnO{sub 4} solutions and {sup 99}Mo tracer were added to the reaction flask. The reactional parameters ({alpha}-Bz/Mo ratio, Mo carrier, reaction time and temperature, and cooling reaction time before filtration) were evaluated under a fractional factorial design of resolution V. The best values of each reactional parameter were determined by a response surface statistical planning. The precipitation and recovery yields of {sup 99}Mo were measured using HPGe detector. Statistical analysis from experimental data suggested that the reactional parameters {alpha}-Bz/Mo ratio, reaction time and temperature have a significant impact on {sup 99}Mo precipitation. Optimization statistical planning showed that higher {alpha}Bz/Mo ratios, room temperature, and lower reaction time lead to higher {sup 99}Mo yields. (author)

  4. Systematic determination of the peptide acceptor preferences for the human UDP-Gal:glycoprotein-alpha-GalNAc beta 3 galactosyltransferase (T-synthase). (United States)

    Perrine, Cynthia; Ju, Tongzhong; Cummings, Richard D; Gerken, Thomas A


    Mucin-type protein O-glycosylation is initiated by the addition of alpha-GalNAc to Ser/Thr residues of a polypeptide chain. The addition of beta-Gal to GalNAc by the UDP-Gal:glycoprotein-alpha-GalNAc beta 3 galactosyltransferase (T-synthase), forming the Core 1 structure (beta-Gal(1-3)-alpha-GalNAc-O-Ser/Thr), is a common and biologically significant subsequent step in O-glycan biosynthesis. What dictates the sites of Core 1 glycosylation is poorly understood; however, the peptide sequence and neighboring glycosylation effects have been implicated. To systematically address the role of the peptide sequence on the specificity of T-synthase, we used the oriented random glycopeptide: GAGAXXXX(T-O-GalNAc)XXXXAGAG (where X = G, A, P, V, I, F, Y, S, N, D, E, H, R, and K) as a substrate. The Core 1 glycosylated product was isolated on immobilized PNA (Arachis hypogaea) lectin and its composition determined by Edman amino acid sequencing for comparison with the initial substrate composition, from which transferase preferences were obtained. From these studies, elevated preferences for Gly at the +1 position with moderately high preferences for Phe and Tyr in the +3 position relative to the acceptor Thr-O-GalNAc were found. A number of smaller Pro enhancements were also observed. Basic residues, i.e., Lys, Arg, and His, in any position were disfavored, suggesting electrostatic interactions as an additional important component modulating transferase specificity. This work suggests that there are indeed subtle specific and nonspecific protein-targeting sequence motifs for this transferase.

  5. Doping-control analysis of the 5alpha-reductase inhibitor finasteride: determination of its influence on urinary steroid profiles and detection of its major urinary metabolite. (United States)

    Thevis, Mario; Geyer, Hans; Mareck, Ute; Flenker, Ulrich; Schänzer, Wilhelm


    5alpha-Reductase inhibitors such as finasteride are prohibited in sports according to the World Anti-Doping Agency. This class of drugs is used therapeutically to treat benign prostatic hyperplasia, as well as male baldness, by decreasing 5alpha-reductase activity. Accordingly, metabolic pathways of endogenous as well as synthetic steroids are influenced, which complicates the evaluation of steroid profiles in sports drug testing. The possibility of manipulating steroid excretion profiles and, presumably, to mask steroid abuse was investigated in 5 administration studies with use of finasteride at different doses, with and without coadministration of 19-norandrostenedione. The evaluation of urinary steroid profiles demonstrated the intense effect of finasteride on numerous crucial analytical parameters, in particular the production of 5alpha-steroids such as androsterone and 5alpha-androstane-3alpha,17beta-diol, which was significantly reduced. In addition, the excretion of the main metabolite of norandrostenedione, norandrosterone, was significantly suppressed, by up to 84%, in elimination studies. For doping-control analysis the use of 5alpha-reductase inhibitors causes considerable problems because steroid profile parameters, which are commonly considered stable, are highly affected and complicate the detection of steroid abuse. In addition, the suppression of production and renal excretion of 5alpha-steroids such as 19-norandrosterone generated from anabolic agents such as 19-norandrostenedione may lead to false-negative doping-control results, because urine specimens are reported positive only when a threshold level of 2 ng/mL is exceeded. Finally, a method for the determination of the major urinary metabolite of finasteride (carboxy-finasteride) in routine doping-control screening with use of liquid chromatography-tandem mass spectrometry is described, allowing the detection of carboxy-finasteride for up to 94 hours in urine specimens collected after an oral

  6. Protection against TGF-β1-induced fibrosis effects of IL-10 on dermal fibroblasts and its potential therapeutics for the reduction of skin scarring. (United States)

    Shi, Ji-Hong; Guan, Hao; Shi, Shan; Cai, Wei-Xia; Bai, Xiao-Zhi; Hu, Xiao-Long; Fang, Xiao-Bin; Liu, Jia-Qi; Tao, Ke; Zhu, Xiong-Xiang; Tang, Chao-Wu; Hu, Da-Hai


    Scarring, tightly associated with fibrosis, is a significant symptomatic clinical problem. Interleukin 10 (IL-10) has been identified as a candidate scar-improving therapy based on preclinical studies. However, the molecular mechanism of IL-10 in scar improvement is still uncertain. In this study, human dermal fibroblasts stimulated with TGF-β1 were treated with IL-10 to analyze the mRNA and some of proteins' expression levels of type I collagen (Col1), type III collagen (Col3), alpha-smooth muscle actin (α-SMA), matrix metalloproteinase-1 (MMP1), MMP2, MMP8 and tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP2 by real-time PCR and Western blot, to observe α-SMA-positive fibroblasts by immunocytochemistry. The contracture and improvement of fibroblast-populated collagen lattice (FPCL) and a murine model of wound healing were used to evaluate the scar-improving effects by histological staining. The results showed that IL-10 can significantly down-regulate the mRNA and protein expression levels of Col1, Col3, α-SMA, and up-regulate the mRNA expression levels of MMP1 and MMP8, and decrease α-SMA-positive fibroblasts. FPCL analysis showed that the IL-10 (20 ng/ml) can significantly inhibit the contracture, improve the architecture of FPCL. Wounds injected with IL-10 demonstrated that the appearance of scar was improved, the wound margin of scarring was narrow, and the deposition of collagens (Col1 and Col3) in regenerated tissue was relieved. These results provide direct evidences that IL-10 has the inhibitory effects on the excessive deposition of extracellular matrix components and fibroblast-to-myofibroblast transition, and show that IL-10 has the potential therapy in prevention and reduction of skin scarring.

  7. Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Ali, S.F.; Newport, G.D.; Scallet, A.C.; Gee, K.W.; Paule, M.G.; Brown, R.M.; Slikker, W. Jr. (National Center for Toxicological Research, Jefferson, Arkansas (USA))

    THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the rat brain. In Experiment 1, male Sprague-Dawley rats were gavaged with vehicle, 10 or 20 mg THC/kg body weight daily, 5 days/week for 90 days. Animals were killed either 24 hours or two months after the last dose. Brains were dissected into different regions for neurochemical analyses. Two months after the cessation of chronic administration, there was a significant decrease in GABA receptor binding in the hippocampus of animals in the high dose group. However, no other significant changes were found in neurotransmitter receptor binding characteristics in the hippocampus or in neurotransmitter concentrations in the caudate nucleus, hypothalamus or septum after chronic THC administration. In an attempt to replicate the GABA receptor binding changes and also to determine the (35S)TBPS binding in hippocampus, we designed Experiment 2. In this experiment, we dosed the animals by gavage with 0, 5, 10 or 20 mg THC/kg daily, 5 days/week or with 20 mg THC/kg Monday through Thursday and 60 mg/kg on Friday for 90 days. Results from this experiment failed to replicate the dose-dependent effect of THC on GABA receptor binding in hippocampus. Modulation of (35S)TBPS binding by GABA or 3 alpha-OH-DHP or inhibition by cold TBPS in frontal cortex did not show any significant dose-related effects.

  8. Sleep-related modifications of EEG connectivity in the sensory-motor networks in Huntington Disease: An eLORETA study and review of the literature. (United States)

    Piano, Carla; Imperatori, Claudio; Losurdo, Anna; Bentivoglio, Anna Rita; Cortelli, Pietro; Della Marca, Giacomo


    To evaluate EEG functional connectivity in the sensory-motor network, during wake and sleep, in patients with Huntington Disease (HD). 23 patients with HD and 23 age- and sex-matched healthy controls were enrolled. EEG connectivity analysis was performed by means of exact Low Resolution Electric Tomography (eLORETA). In wake, HD patients showed an increase of delta lagged phase synchronization (T=3.60; p<0.05) among Broadman's Areas (BA) 6-8 bilaterally; right BA 6-8 and right BA 1-2-3; left BA 1-2-3 and left BA 4. In NREM, HD patients showed an increase of delta lagged phase synchronization (T=3.56; p<0.05) among left BA 1-2-3 and right BA 6-8. In REM, HD patients showed an increase of lagged phase synchronization (T=3.60; p<0.05) among the BA 6-8 bilaterally (delta band); left BA 1-2-3 and right BA 1-2-3 (theta); left BA 1-2-3 and right BA 4 (theta); left BA 1-2-3 and right BA 1-2-3 (alpha). Our results may reflect an abnormal function of the motor areas or an effort to counterbalance the pathological motor output. Our results may help to understand the pathophysiology of sleep-related movement disorders in Huntington's Disease, and to define therapeutically strategies. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  9. Comparative analysis of the noncollagenous NC1 domain of type IV collagen: identification of structural features important for assembly, function, and pathogenesis. (United States)

    Netzer, K O; Suzuki, K; Itoh, Y; Hudson, B G; Khalifah, R G


    Type IV collagen alpha1-alpha6 chains have important roles in the assembly of basement membranes and are implicated in the pathogenesis of Goodpasture syndrome, an autoimmune disorder, and Alport syndrome, a hereditary renal disease. We report comparative sequence analyses and structural predictions of the noncollagenous C-terminal globular NC1 domain (28 sequences). The inferred tree verified that type IV collagen sequences fall into two groups, alpha1-like and alpha2-like, and suggested that vertebrate alpha3/alpha4 sequences evolved before alpha1/alpha2 and alpha5/alpha6. About one fifth of NC1 residues were identified to confer either the alpha1 or alpha2 group-specificity. These residues accumulate opposite charge in subdomain B of alpha1 (positive) and alpha2 (negative) sequences and may play a role in the stoichiometric chain selection upon type IV collagen assembly. Neural network secondary structure prediction on multiple aligned sequences revealed a subdomain core structure consisting of six hydrophobic beta-strands and one short alpha-helix with a significant hydrophobic moment. The existence of opposite charges in the alpha-helices may carry implications for intersubdomain interactions. The results provide a rationale for defining the epitope that binds Goodpasture autoantibodies and a framework for understanding how certain NC1 mutations may lead to Alport syndrome. A search algorithm, based entirely on amino acid properties, yielded a possible similarity of NC1 to tissue inhibitor of metalloproteinases (TIMP) and prompted an investigation of a possible functional relationship. The results indicate that NC1 preparations decrease the activity of matrix metalloproteinases 2 and 3 (MMP-2, MMP-3) toward a peptide substrate, though not to [14C]-gelatin. We suggest that an ancestral NC1 may have been incorporated into type IV collagen as an evolutionarily mobile domain carrying proteinase inhibitor function.

  10. First stars evolution and nucleosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Bahena, D. [Institute of Astronomy of the Academy of Sciences, Bocni II 1401, 14131 Praha 4, (Czech Republic); Klapp, J. [ININ, 52750 La Marquesa, Estado de Mexico (Mexico); Dehnen, H. [Fachbereich Physik, Universitat Konstanz, 78457 Konstanz (Germany)]. e-mail:


    The first stars in the universe were massive and luminous with typical masses M {>=} 100M. Metal-free stars have unique physical characteristics and exhibit high effective temperatures and small radii. These so called Population III stars were responsible for the initial enrichment of the intergalactic medium with heavy elements. In this work, we study the structure, evolution and nucleosynthesis of 100, 200, 250 and 300M galactic and pregalactic Population III mass losing stars with metallicities Z 10{sup -6} and Z = 10{sup -9}, during the hydrogen and helium burning phases. Using a stellar evolution code, a system of 10 structure and evolution equations together with boundary conditions, and a set of 30 nuclear reactions, are solved simultaneously, obtaining the star's structure, evolution, isotopic abundances and their ratios. Motivated by recent stability analysis, almost all very massive star (VMS) calculations during the past few years have been performed with no mass loss. However, it has recently been claimed that VMS should have strong mass loss. We present in this work new VMS calculations that includes mass loss. The main difference between zero-metal and metal-enriched stars lies in the nuclear energy generation mechanism. For the first stars, nuclear burning proceeds in a non-standard way. Since Population III stars can reach high central temperatures, this leads to the first synthesis of primary carbon through the 3 {alpha} reaction activating the CNO-cycles. Zero-metal stars produce light elements, such as He, C, N and O. Thus, very massive pregalactic Population III stars experienced self-production of C, either at the zero-age main sequence or in later phases of central hydrogen burning. In advanced evolutionary phases, these stars contribute to the chemical enrichment of the intergalactic medium through supernova explosions. (Author)

  11. Release of arginine, glutamate and glutamine in the hippocampus of freely moving rats: Involvement of nitric oxide. (United States)

    Watts, Jo; Fowler, Leslie; Whitton, Peter S; Pearce, Brian


    Using in vivo microdialysis, we have monitored the release of three amino acids (arginine, glutamate and glutamine) in the hippocampus of freely moving rats in response to various drugs. In response to N-methyl-d-aspartate (NMDA) infusion, extracellular glutamate was increased, glutamine was decreased and arginine remained unchanged. By contrast, alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) elicited an increase in arginine release but had no effect on either glutamate or glutamine. When S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO) donor, was infused into the hippocampus, an increase in glutamate, a decrease in glutamine and no change in arginine were recorded. The effect of SNAP on extracellular glutamine levels was reversed by prior infusion of the guanylate cyclase inhibitor oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), however its effect on glutamate release was unchanged. Interestingly, SNAP was found to promote the release of arginine in the presence of ODQ. We also assessed the effect of two nitric oxide synthase inhibitors, N-nitro-l-arginine methylester (l-NAME) and 7-nitroindazole (7-NI), on the release of these amino acids. l-NAME was found to increase arginine and glutamate levels but decrease those of glutamine. In contrast, 7-NI reduced the release of all three amino acids. The results presented here confirm some but not all of the findings previously obtained using in vitro preparations. In addition, they suggest that complex relationships exist between the release of these amino acids, and that endogenous NO plays an important role in regulating their release.

  12. Solution structure of recombinant somatomedin B domain from vitronectin produced in Pichia pastoris. (United States)

    Kjaergaard, Magnus; Gårdsvoll, Henrik; Hirschberg, Daniel; Nielbo, Steen; Mayasundari, Anand; Peterson, Cynthia B; Jansson, Anna; Jørgensen, Thomas J D; Poulsen, Flemming M; Ploug, Michael


    The cysteine-rich somatomedin B domain (SMB) of the matrix protein vitronectin is involved in several important biological processes. First, it stabilizes the active conformation of the plasminogen activator inhibitor (PAI-1); second, it provides the recognition motif for cell adhesion via the cognate integrins (alpha(v)beta(3), alpha(v)beta(5), and alpha(IIb)beta(3)); and third, it binds the complex between urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR). Previous structural studies on SMB have used recombinant protein expressed in Escherichia coli or SMB released from plasma-derived vitronectin by CNBr cleavage. However, different disulfide patterns and three-dimensional structures for SMB were reported. In the present study, we have expressed recombinant human SMB by two different eukaryotic expression systems, Pichia pastoris and Drosophila melanogaster S2-cells, both yielding structurally and functionally homogeneous protein preparations. Importantly, the entire population of our purified, recombinant SMB has a solvent exposure, both as a free domain and in complex with PAI-1, which is indistinguishable from that of plasma-derived SMB as assessed by amide hydrogen ((1)H/(2)H) exchange. This solvent exposure was only reproduced by one of three synthetic SMB products with predefined disulfide connectivities corresponding to those published previously. Furthermore, this connectivity was also the only one to yield a folded and functional domain. The NMR structure was determined for free SMB produced by Pichia and is largely consistent with that solved by X-ray crystallography for SMB in complex with PAI-1.

  13. Influence of mycotoxin zearalenone and its derivatives (alpha and beta zearalenol on apoptosis and proliferation of cultured granulosa cells from equine ovaries

    Directory of Open Access Journals (Sweden)

    Minoia Paolo


    Full Text Available Abstract Background The mycotoxin zearalenone (ZEA and its derivatives, alpha and beta-zearalenol (alpha and beta-ZOL, synthesized by genera Fusarium, often occur as contaminants in cereal grains and animal feeds. The importance of ZEA on reproductive disorders is well known in domestic animals species, particularly in swine and cattle. In the horse, limited data are available to date on the influence of dietary exposure to ZEA on reproductive health and on its in vitro effects on reproductive cells. The aim of this study was to evaluate the effects of ZEA and its derivatives, alpha and beta-ZOL, on granulosa cells (GCs from the ovaries of cycling mares. Methods The cell proliferation was evaluated by using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT test after 3 days exposure at different concentrations of ZEA and its derivatives (from 1 × 10-7 to 0.1 microM. The apoptosis induction was evaluated after 1 day exposure, by DNA analysis using flow cytometry. Results An increase in cell proliferation with respect to the control was observed in the presence of ZEA at 1 × 10-3 and 1 × 10-4 microM and apoptosis was induced by all mycotoxins at different concentrations. Conclusion The simultaneous presence of apoptosis and proliferation in GC cultures treated with zearalenones could indicate that these mycotoxins could be effective in inducing follicular atresia. These effects of zearalenones may result from both direct interaction with oestrogen-receptors as well as interaction with the enzymes 3alpha (beta-hydroxysteroid dehydrogenase (HSD, involved in the synthesis and metabolism of endogenous steroid hormones. These cellular disturbances, described for the first time in equine GCs cultured in vitro, could be hypothesized as referred to reproductive failures of unknown ethiology in the mare.

  14. Influence of mycotoxin zearalenone and its derivatives (alpha and beta zearalenol) on apoptosis and proliferation of cultured granulosa cells from equine ovaries (United States)

    Minervini, Fiorenza; Giannoccaro, Alessandra; Fornelli, Francesca; Dell'Aquila, Maria Elena; Minoia, Paolo; Visconti, Angelo


    Background The mycotoxin zearalenone (ZEA) and its derivatives, alpha and beta-zearalenol (alpha and beta-ZOL), synthesized by genera Fusarium, often occur as contaminants in cereal grains and animal feeds. The importance of ZEA on reproductive disorders is well known in domestic animals species, particularly in swine and cattle. In the horse, limited data are available to date on the influence of dietary exposure to ZEA on reproductive health and on its in vitro effects on reproductive cells. The aim of this study was to evaluate the effects of ZEA and its derivatives, alpha and beta-ZOL, on granulosa cells (GCs) from the ovaries of cycling mares. Methods The cell proliferation was evaluated by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test after 3 days exposure at different concentrations of ZEA and its derivatives (from 1 × 10-7 to 0.1 microM). The apoptosis induction was evaluated after 1 day exposure, by DNA analysis using flow cytometry. Results An increase in cell proliferation with respect to the control was observed in the presence of ZEA at 1 × 10-3 and 1 × 10-4 microM and apoptosis was induced by all mycotoxins at different concentrations. Conclusion The simultaneous presence of apoptosis and proliferation in GC cultures treated with zearalenones could indicate that these mycotoxins could be effective in inducing follicular atresia. These effects of zearalenones may result from both direct interaction with oestrogen-receptors as well as interaction with the enzymes 3alpha (beta)-hydroxysteroid dehydrogenase (HSD), involved in the synthesis and metabolism of endogenous steroid hormones. These cellular disturbances, described for the first time in equine GCs cultured in vitro, could be hypothesized as referred to reproductive failures of unknown ethiology in the mare. PMID:17137489

  15. Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain. (United States)

    Ali, S F; Newport, G D; Scallet, A C; Gee, K W; Paule, M G; Brown, R M; Slikker, W


    THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the rat brain. In Experiment 1, male Sprague-Dawley rats were gavaged with vehicle, 10 or 20 mg THC/kg body weight daily, 5 days/week for 90 days. Animals were killed either 24 hours or two months after the last dose. Brains were dissected into different regions for neurochemical analyses. Two months after the cessation of chronic administration, there was a significant decrease in GABA receptor binding in the hippocampus of animals in the high dose group. However, no other significant changes were found in neurotransmitter receptor binding characteristics in the hippocampus or in neurotransmitter concentrations in the caudate nucleus, hypothalamus or septum after chronic THC administration. In an attempt to replicate the GABA receptor binding changes and also to determine the [35S]TBPS binding in hippocampus, we designed Experiment 2. In this experiment, we dosed the animals by gavage with 0, 5, 10 or 20 mg THC/kg daily, 5 days/week or with 20 mg THC/kg Monday through Thursday and 60 mg/kg on Friday for 90 days. Results from this experiment failed to replicate the dose-dependent effect of THC on GABA receptor binding in hippocampus. Modulation of [35S]TBPS binding by GABA or 3 alpha-OH-DHP or inhibition by cold TBPS in frontal cortex did not show any significant dose-related effects. Results from these experiments suggest that chronic exposure to THC does not produce significant alterations in catecholamine or indoleamine neurotransmitter systems or in opiate or GABA receptor systems in the rat brain.

  16. Androstanediol glucuronide isomers in normal men and women and in men infused with labeled dihydrotestosterone

    Energy Technology Data Exchange (ETDEWEB)

    Rittmaster, R.S.; Thompson, D.L.; Listwak, S.; Loriaux, D.L.


    3 alpha-Androstanediol glucuronide (Adiol G) is a major metabolite of dihydrotestosterone (DHT). Adiol G actually represents 2 different compounds, since the glucuronide can be conjugated at the 3-carbon position (Adiol 3-G) or at the 17-carbon position (Adiol 17-G). To determine which glucuronide represents the predominant physiological DHT metabolite and which isomer is the major circulating form, we developed a RIA to directly measure Adiol 3-G in serum extracts. In 10 normal men, mean serum Adiol 3-G and total Adiol G levels were 4.44 +/- 0.49 (+/- SE) nmol/L (208 +/- 23 ng/dL) and 27.9 +/- 2.8 nmol/L (1310 +/- 129 ng/dL), respectively (13.9 +/- 3.0% of Adiol G was Adiol 3-G). In 10 normal women sampled during the early follicular phase, mean serum Adiol 3-G and total Adiol G levels were 2.64 +/- 0.64 nmol/L (124 +/- 30 ng/dL) and 14.9 +/- 1.5 nmol/L (697 +/- 69 ng/dL), respectively (17.4 +/- 3.6% of Adiol G was Adiol 3-G). In 4 normal men infused for 8 h with tritiated DHT, 17.4 +/- 3.4% of the resulting tritiated Adiol G was Adiol 3-G. These results indicate that Adiol 17-G is the predominant circulating form of Adiol G in normal men and women and that it is also the major Adiol G isomer derived from DHT.

  17. Maternal diet, LCPUFA status and prematurity in Indian mothers: A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Prachi S. Ranade


    Full Text Available Background: Recently, certain long chain polyunsaturated fatty acids (LCPUFA have been shown to exert functional benefits with regards to gestational length. The present study examined the association of maternal LCPUFA intake, specifically Docosahexaenoic acid(DHA and Arachidonic acid (ARA, and plasma status at delivery with duration of gestation and risk of premature delivery in Indian mothers.Methods: In a cross-sectional nested case-control study, 191 mother-baby pairs [164 Full term(FT and 27 Preterm (PT] were examined for differences in maternal habitual diet pattern and plasma fatty acid composition in relation to the length of gestation.Results: The frequency of intake of n-3 fatty acid rich varieties of fish was higher (p<0.05 in FT mothers compared to PT mothers. Maternal plasma fatty acid concentration of n-3 Alpha Linolenic acid (ALA, Eicosapentaenoic acid (EPA, DHA and total n-3 fatty acids at delivery was significantly associated with intake of vegetarian ALA sources such as millets, dark whole pulses, dry fruits like walnuts, and green leafy vegetables. Among age, parity, and neonatal sex matched case-control pairs, PT mothers had significantly (p<0.01 higher levels of n-6 ARA, but lower (p<0.01 levels of n-3 DHA and total n-3 fatty acids compared to FT mothers irrespective of socioeconomic group. In fact, mothers with plasma DHA levels below median (<3.0% had ten times higher risk (OR-10.47; 95% CI: 3.03-36.48 of delivering prematurely compared to those who had plasma DHA levels above median.Conclusion: Results underscore the importance of consuming varied sources of ALA and DHAfor their role as functional lipids in determining gestational length.

  18. Psychromicrobium silvestre gen. nov., sp. nov., a novel actinobacterium isolated from alpine forest soils. (United States)

    Schumann, Peter; Zhang, De-Chao; Franca, Luís; Albuquerque, Luciana; da Costa, Milton S; Margesin, Rosa


    Two Gram-stain-variable, non-motile, catalase-positive and cytochrome c oxidase-negative bacteria, designated AK20-18T and AM20-54, were isolated from forest soil samples collected in the Italian Alps. Growth occurred at a temperature range of 5-30 °C, at pH 6-9 and in the presence of 0-5 % (w/v) NaCl. The 16S rRNA gene sequence similarity between strains AK20-18T and AM20-54 was 100 %. Phylogenetic analysis based on 16S rRNA gene sequence showed that AK20-18T had highest 16S rRNA gene sequence similarity with the type strain of Arthrobacter psychrochitiniphilus (96.9 %). The cell-wall peptidoglycan structure of strain AK20-18T was of the type A3alpha L-Lys - L-Thr - L-Ala2 (A11.27). The whole-cell sugars were galactose, ribose and lower amounts of mannose. The major respiratory quinone of the two strains was menaquinone 9(H2) (MK-9 [H2]), whereas MK-10(H2) was a minor component. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and unknown glycolipids. The major cellular fatty acids were anteiso-C15:0, iso-C15:0, iso-C16:0 and anteiso-C17:0. The genomic DNA G+C content was 59.9 mol%. Combined data of phylogenetic, phenotypic and chemotaxonomic analysis demonstrated that strains AK20-18T and AM20-54 represent a novel genus and species, for which the name Psychromicrobium silvestre gen. nov., sp. nov. is proposed. The type strain of Psychromicrobium silvestre is AK20-18T (DSM 102047T = LMG 29369 T).

  19. Zatosetron, a potent, selective, and long-acting 5HT3 receptor antagonist: synthesis and structure-activity relationships. (United States)

    Robertson, D W; Lacefield, W B; Bloomquist, W; Pfeifer, W; Simon, R L; Cohen, M L


    Antagonists of 5HT3 receptors are clinically effective in treating nausea and emesis associated with certain oncolytic drugs, including cisplatin. Moreover, these agents may be useful in pharmacological management of several central nervous system disorders, including anxiety, schizophrenia, dementia, and substance abuse. Our studies on aroyltropanamides led to the discovery that dihydrobenzofuranyl esters and amides are potent 5HT3 receptor antagonists. Simple benzoyl derivatives of tropine and 3 alpha-aminotropane possessed weak 5HT3 receptor antagonist activity, as judged by blockade of bradycardia produced by iv injection of serotonin (5HT) to anesthetized rats. Within this series, use of benzofuran-7-carboxamide as the aroyl moiety led to a substantial increase of 5HT3 receptor affinity. The optimal 5HT3 receptor antagonist identified via extensive SAR studies was endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(8-methyl-8-azabicyclo[3.2.1]oc t- 3-yl)-7-benzofurancarboxamide (Z)-2-butenedioate (zatosetron maleate). The 7-carbamyl regiochemistry, dimethyl substitution, chloro substituent, and endo stereochemistry were all crucial elements of the SAR. Zatosetron maleate was a potent antagonist of 5HT-induced bradycardia in rats (ED50 = 0.86 micrograms/kg i.v.). Low oral doses of zatosetron (30 micrograms/kg) produced long-lasting antagonism of 5HT3 receptors, as evidenced by blockade of 5HT-induced bradycardia for longer than 6 h in rats. Moreover, this compound did not produce hemodynamic effects after i.v. administration to rats, nor did it block carbamylcholine-induced bradycardia in doses that markedly blocked 5HT3 receptors. Thus, zatosetron is a potent, selective, orally effective 5HT3 receptor antagonist with a long duration of action in rats.

  20. Spatial and compositional variation in the fungal communities of organic and conventionally grown apple fruit at the consumer point-of-purchase (United States)

    Abdelfattah, Ahmed; Wisniewski, Michael; Droby, Samir; Schena, Leonardo


    The fungal diversity in harvested apples from organic or conventional management practices was analyzed in different fruit locations (stem end, calyx end, peel, and wounded flesh) shortly after fruit purchase (T1) and after 2 weeks of storage (T5). A total of 5,760,162 high-quality fungal sequences were recovered and assigned to 8,504 Operational Taxonomic Units. Members of the phylum Ascomycota were dominant in all samples and accounted for 91.6% of the total number of detected sequences. This was followed by Basidiomycota (8%), Chytridiomycota (0.1%), and unidentified fungi (0.3%). Alpha and beta diversity analyses revealed the presence of significantly different fungal populations in the investigated fruit parts. Among detected fungi, the genus Penicillium prevailed in the peel and in the wounded flesh while Alternaria spp. prevailed in the calyx and stem end samples that included apple core tissues. Several taxonomic units that appear to be closely related to pathogenic fungi associated with secondary human infections were present in peel and wounds. Moreover, significantly different populations were revealed in organic and conventional apples and this result was consistent in all investigated fruit parts (calyx end, peel, stem end, and wounded flesh). Several unique taxa were exclusively detected in organic apples suggesting that management practices may have been a contributing factor in determining the taxa present. In contrast, little differences were revealed in the two assessment times (T1 and T5). Results of the present study represent an advancement of the current knowledge on the fungal microbiota in collected fruit tissues of apple. PMID:27766161

  1. Apoptosis of human breast carcinoma cells in the presence of cis-platin and L-/D-PPMP: IV. Modulation of replication complexes and glycolipid: Glycosyltransferases. (United States)

    Boyle, Patrick J; Ma, Rui; Tuteja, Narendra; Banerjee, Sipra; Basu, Subhash


    Apoptosis of human breast carcinoma cells (SKBR-3, MCF-7, and MDA-468) has been observed after treatment of these cells with anti-cancer drug cis-platin and glycosphingolipid biosynthesis inhibitor L- and D-PPMP, respectively. These drugs initiated apoptosis in a dose-dependent manner as measured by phenotypic morphological changes, by binding of a fluorescent phophatidyl serine-specific dye (PSS-380) onto the outer leaflet of the cell membranes, and by activation of caspases, -3, -8, and -9. It was observed that in two hours very little apoptotic process had started but predominant biochemical changes occurred after 6 h. DNA degradation started after 24 hours of drug treatment. However, very little is known about the stability of the ';Replication Complexes'' during the apoptotic process. DNA helicases are motor proteins that catalyze the melting of genomic DNA during its replication, repair, and recombination processes. Previously, DNA helicase-III was characterized as a component of the replication complexes isolated from embryonic chicken brains as well as breast and colon carcinoma cells. Helicase activities were measured by a novel method (ROME assay), and DNA polymerase-alpha activities were determined by regular chain extension of the nicked ACT-DNA, by determining values obtained from +/- aphidicolin-treated incubation mixtures. In all three breast carcinoma cell lines, a common trend was observed: a decrease of activities of DNA polymerase-alpha and Helicase III. A sharp decrease of activities of the glycolipid sialyltransferases: SAT-2 (CMP-NeuAc; GD3 alpha2-8 sialyltransferase) and SAT-4 (CMP-NeuAc: GM1a alpha2-3 sialyltransferase) was observed in the apoptotic carcinoma cells treated with L-PPMP compared with cis-platin.

  2. Increased migration of Langerhans cells in response to HPV16 E6 and E7 oncogene silencing: role of CCL20. (United States)

    Caberg, Jean-Hubert; Hubert, Pascale; Herman, Ludivine; Herfs, Michael; Roncarati, Patrick; Boniver, Jacques; Delvenne, Philippe


    Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix. The persistence or progression of cervical lesions suggests that viral antigens are not adequately presented to the immune system. This hypothesis is reinforced by the observation that most squamous intraepithelial lesions (SILs) show quantitative and functional alterations of Langerhans cells (LC). The infiltration of immature LC in the squamous epithelium is mainly controlled by Macrophage Inflammatory Protein 3alpha/CCL20. After having shown that CCL20 production is altered in HPV-transformed keratinocytes (KC), the possible role of HPV16 E6 and E7 viral oncoproteins in the reduced CCL20 levels observed in SILs was investigated by silencing HPV16 E6 and E7 oncogenes by RNA interference (siRNA). This treatment not only increased CCL20 secretion but also resulted in the modulation of NF-kappaB p50, p52 and p65 precursor localization. Moreover, silencing of E6 and E7 oncogenes in HPV16-transformed KC induced a significantly higher migratory capacity of LC in a Boyden chamber assay and in an in vitro formed (pre)neoplastic epithelium reminiscent of high-grade SILs. Anti-CCL20 neutralizing antibody experiments showed that the increased migration of LC is due to the re-expression of CCL20 in E6 and E7 siRNA transfected KC. These data suggest that HPV16 E6/E7-induced down-regulation of CCL20 observed during the cervical carcinogenesis may contribute to a diminished capacity of the immune system to control HPV infection.

  3. Conjugated platinum(IV)-peptide complexes for targeting angiogenic tumor vasculature. (United States)

    Mukhopadhyay, Sumitra; Barnés, Carmen M; Haskel, Ariel; Short, Sarah M; Barnes, Katie R; Lippard, Stephen J


    The integrins alpha vbeta3 and alpha vbeta5 and the membrane-spanning surface protein aminopeptidase N (APN) are highly expressed in tumor-induced angiogenesis, making them attractive targets for therapeutic intervention. Both integrins and APN recognize a broad range of peptides containing RGD (Arg-Gly-Asp) and NGR (Asn-Gly-Arg) motifs, respectively. Here, we describe the design, synthesis, and characterization of a series of mono- and difunctionalized platinum(IV) complexes in which a conjugated peptide motif, containing RGD, (CRGDC)c, (RGDfK)c, or NGR, is appended as a "tumor-homing device" to target tumor endothelial cells selectively over healthy cells. Platinum(IV)-peptide complexes with nonspecific amino acids or peptide moieties were prepared as controls. Concentration-response curves of these compounds were evaluated against primary proliferating endothelial cells and tumor cell lines and compared to those of cisplatin, a well-described platinum-based chemotherapeutic agent. The Pt(IV)-RGD conjugates were highly and specifically cytotoxic to cell lines containing alpha vbeta3 and alpha vbeta5, approaching the activity of cisplatin. The Pt(IV)-NGR complexes were less active than Pt(IV)-RGD-containing compounds but more active than nonspecific Pt-peptide controls. Integrin alpha vbeta3 mediated, at least in part, the anti-proliferative effect of a Pt(IV)-RGD conjugate, as demonstrated by a decreased inhibitory response when endothelial cells were either (1) incubated with an excess of alpha vbeta3/alpha vbeta5-specific RGD pentapeptides or (2) transfected with RNAi for beta 3, but not beta 1, integrins. These results suggest a rational approach to improved chemotherapy with Pt(IV)-peptide conjugates by selective drug delivery to the tumor compartment.

  4. The integrin antagonist cilengitide activates alphaVbeta3, disrupts VE-cadherin localization at cell junctions and enhances permeability in endothelial cells.

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    Gian Carlo Alghisi

    Full Text Available Cilengitide is a high-affinity cyclic pentapeptdic alphaV integrin antagonist previously reported to suppress angiogenesis by inducing anoikis of endothelial cells adhering through alphaVbeta3/alphaVbeta5 integrins. Angiogenic endothelial cells express multiple integrins, in particular those of the beta1 family, and little is known on the effect of cilengitide on endothelial cells expressing alphaVbeta3 but adhering through beta1 integrins. Through morphological, biochemical, pharmacological and functional approaches we investigated the effect of cilengitide on alphaVbeta3-expressing human umbilical vein endothelial cells (HUVEC cultured on the beta1 ligands fibronectin and collagen I. We show that cilengitide activated cell surface alphaVbeta3, stimulated phosphorylation of FAK (Y(397 and Y(576/577, Src (S(418 and VE-cadherin (Y(658 and Y(731, redistributed alphaVbeta3 at the cell periphery, caused disappearance of VE-cadherin from cellular junctions, increased the permeability of HUVEC monolayers and detached HUVEC adhering on low-density beta1 integrin ligands. Pharmacological inhibition of Src kinase activity fully prevented cilengitide-induced phosphorylation of Src, FAK and VE-cadherin, and redistribution of alphaVbeta3 and VE-cadherin and partially prevented increased permeability, but did not prevent HUVEC detachment from low-density matrices. Taken together, these observations reveal a previously unreported effect of cilengitide on endothelial cells namely its ability to elicit signaling events disrupting VE-cadherin localization at cellular contacts and to increase endothelial monolayer permeability. These effects are potentially relevant to the clinical use of cilengitide as anticancer agent.

  5. Alpha-T-catenin (CTNNA3) displays tumour specific monoallelic expression in urothelial carcinoma of the bladder. (United States)

    Meehan, Maria; Melvin, Audrey; Gallagher, Emma; Smith, James; McGoldrick, Alo; Moss, Catherine; Goossens, Steven; Harrison, Michèle; Kay, Elaine; Fitzpatrick, John; Dervan, Peter; Mc Cann, Amanda


    CTNNA3 (alpha-T-catenin) is imprinted with preferential monoallelic expression of the maternal allele in placental tissue. The allelic expression pattern of CTNNA3 in adult human cancer is unknown and warrants investigation as CTNNA3 stabilizes cellular adherence, a feature which if compromised could enable cells to acquire an increased capability to detach and invade. We document the frequency of monoallelic versus biallelic expression of CTNNA3 in urothelial carcinoma of the bladder (UCB) samples and compare the observed patterns with that found in the paired normal sample. DNA PCR reactions encompassing a transcribable SNP polymorphism within exon 12 of CTNNA3 were sequence analyzed to identify heterozygous cases. A total of 96 samples were analyzed and included 22 paired normal and tumor UCB cases, 38 formalin fixed paraffin embedded (FFPE) UCB samples consisting of 18 noninvasive pTa tumors and 20 lamina propria invasive pT1 tumors and 14 cell lines of various lineages. RT-PCR analysis of 35 heterozygous samples followed by sequence analysis allowed monoallelic versus biallelic patterns to be assigned. We have provided the first demonstration that CTNNA3 displays differing allelic expression patterns in UCB. Specifically, 35% (7/20) of informative UCB, showed monoallelic expression, a feature confined to the tumor, with normal urothelial samples displaying biallelic expression. Real time RT-PCR analyses, demonstrated a significantly lower (P = 0.00039) level of CTNNA3 in the tumor samples compared with the paired normals, all of which displayed biallelic expression. In conclusion, monoallelic and biallelic CTNNA3 expression patterns are demonstrable in tumor bladder tissue, whereas normal cases show only biallelic expression.

  6. Dehydroepiandrosterone induces human CYP2B6 through the constitutive androstane receptor. (United States)

    Kohalmy, Krisztina; Tamási, Viola; Kóbori, László; Sárváry, Eniko; Pascussi, Jean-Marc; Porrogi, Pálma; Rozman, Damjana; Prough, Russell A; Meyer, Urs A; Monostory, Katalin


    Dehydroepiandrosterone (DHEA), the major precursor of androgens and estrogens, has several beneficial effects on the immune system, on memory function, and in modulating the effects of diabetes, obesity, and chemical carcinogenesis. Treatment of rats with DHEA influences expression of cytochrome P450 (P450) genes, including peroxisome proliferator-activated receptor alpha (PPAR alpha)- and pregnane X receptor (PXR)-mediated induction of CYP4As and CYP3A23, and suppression of CYP2C11. DHEA treatment elevated the expression and activities of CYP3A4, CYP2C9, CYP2C19, and CYP2B6 in primary cultures of human hepatocytes. Induction of CYP3A4 in human hepatocytes was consistent with studies in rats, but induction of CYP2Cs was unexpected. The role of PXR in this response was studied in transient transfection assays. DHEA activated hPXR in a concentration-dependent manner. Because CYP2B6 induction by DHEA in human hepatocytes might involve either PXR or constitutive androstane receptor (CAR) activation, we performed experiments in primary hepatocytes from CAR knockout mice and observed that CAR was required for maximal induction of Cyp2b10 by DHEA. Furthermore, CAR-mediated Cyp2b10 induction by DHEA was inhibited by the inverse agonist of CAR, androstanol (5 alpha-androstan-3 alpha-ol). Further evidence for CAR activation was provided by cytoplasmic/nuclear transfer of CAR upon DHEA treatment. Elucidation of CAR activation and subsequent induction of CYP2B6 by DHEA presented an additional mechanism by which the sterol can modify the expression of P450s. The effect of DHEA on the activation of the xenosensors PPAR alpha, PXR, and CAR, and the consequent potential for adverse drug/toxicant interactions should be considered in humans treated with this nutriceutical agent.

  7. Differential effect of dehydroepiandrosterone and its steroid precursor pregnenolone against the behavioural deficits in CO-exposed mice. (United States)

    Maurice, T; Phan, V; Sandillon, F; Urani, A


    The neuroactive steroids pregnenolone (3beta-hydroxy-5-pregnen-20-one) and dehydroepiandrosterone (DHEA, 3alpha-hydroxy-5-androstene-17-one) are negative allosteric modulators of the GABA(A) receptors and positive modulators of acetylcholine, NMDA and sigma(1) receptors. Pregnenolone was recently shown to potentiate the neuronal damage induced by excessive glutamate in cell culture models, whereas dehydroepiandrosterone was reported to present some neuroprotective activity. The in vivo relevance of these effects was investigated in mice submitted to an hypoxic insult, the repeated exposure to carbon monoxide (CO) gas, a model that leads to neurodegeneration in the CA(1) hippocampal area and learning deficits. Recording spontaneous alternation behaviour in the Y-maze assessed short-term memory and long-term memory was examined using a passive avoidance task. After exposure to CO, mice showed a progressive deterioration of their learning ability, reaching significance after 3 days and being maximal after 7 days. Pregnenolone administered before CO significantly facilitated the hypoxia-related deficits, which could be measured 1 day after CO and appeared maximal after 3 days. Dizocilpine blocked the deficits in vehicle- and pregnenolone-treated CO-exposed animals, showing that pregnenolone selectively facilitated the NMDA receptor-dependent excitotoxicity. Dehydroepiandrosterone blocked the appearance of the CO-induced deficits, even after 7 days. Interestingly, the sigma(1) receptor antagonist N, N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine (NE-100) failed to affect the dehydroepiandrosterone-induced protection, showing the lack of involvement of sigma(1) receptors. Cresyl violet-stained sections of the mouse hippocampal formation showed that the neurodegeneration observed in the CA(1) area after exposure to CO was augmented by pregnenolone and blocked by dehydroepiandrosterone. These results show that pregnenolone and dehydroepiandrosterone, although

  8. Benzo[a]pyrene diol epoxide suppresses retinoic acid receptor-β2 expression by recruiting DNA (cytosine-5--methyltransferase 3A

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    Xu Xiao-Chun


    Full Text Available Abstract Tobacco smoke is an important risk factor for various human cancers, including esophageal cancer. How benzo [a]pyrene diol epoxide (BPDE, a carcinogen present in tobacco smoke as well as in environmental pollution, induces esophageal carcinogenesis has yet to be defined. In this study, we investigated the molecular mechanism responsible for BPDE-suppressed expression of retinoic acid receptor-beta2 (RAR-β2 in esophageal cancer cells. We treated esophageal cancer cells with BPDE before performing methylation-specific polymerase chain reaction (MSP to find that BPDE induced methylation of the RAR-β2 gene promoter. We then performed chromatin immunoprecipitation (ChIP assays to find that BPDE recruited genes of the methylation machinery into the RAR-β2 gene promoter. We found that BPDE recruited DNA (cytosine-5--methyltransferase 3 alpha (DNMT3A, but not beta (DNMT3B, in a time-dependent manner to methylate the RAR-β2 gene promoter, which we confirmed by reverse transcription-polymerase chain reaction (RT-PCR analysis of the reduced RAR-β2 expression in these BPDE-treated esophageal cancer cell lines. However, BPDE did not significantly change DNMT3A expression, but it slightly reduced DNMT3B expression. DNA methylase inhibitor 5-aza-2'-deoxycytidine (5-Aza and DNMT3A small hairpin RNA (shRNA vector antagonized the effects of BPDE on RAR-β2 expressions. Transient transfection of the DNMT3A shRNA vector also antagonized BPDE's effects on expression of RAR-β2, c-Jun, phosphorylated extracellular signal-regulated protein kinases 1/2 (ERK1/2, and cyclooxygenase-2 (COX-2, suggesting a possible therapeutic effect. The results of this study form the link between the esophageal cancer risk factor BPDE and the reduced RAR-β2 expression.

  9. Microarray-based gene expression profiling reveals genes and pathways involved in the oncogenic function of REG3A on pancreatic cancer cells. (United States)

    Xu, Qianqian; Fu, Rong; Yin, Guoxiao; Liu, Xiulan; Liu, Yang; Xiang, Ming


    We previously reported that regenerating islet-derived protein 3 alpha (REG3A) exacerbates pancreatic malignancies. The mechanism of this effect has not been clearly elucidated. Here we first identified key differentially expressed genes (DEGs) and signal pathways in the pancreatic cancer cell line SW1990, compared to two control cell lines, by microarray analysis. We then identified key genes and pathways regulated by REG3A or the cytokine IL6 in SW1990 cells. Afterwards, these DEGs induced by REG3A or IL6 were subjected to KEGG pathway enrichment analysis and GO function analysis by the DAVID online tool. Ultimately, we constructed protein-protein interaction networks among the DEGs by Cytoscape. Among the three pancreatic cell lines, SW1990 exhibited highly deterioration with the activation of genes and pathways related to proliferation, survival, angiogenesis, and invasion. As a result, 50 DEGs enriched in 11 pathways were identified in REG3A-treated SW1990 cells, and 28 DEGs enriched in 9 pathways were detected in IL6-treated cells. Overall, results of microarray analysis followed by qRT-PCR and Western blotting suggest that REG3A regulates pancreatic cell growth by increasing the expression of at least 8 genes: JAK1, STAT3, IL10, FOXM1, KRAS, MYC, CyclinD1, and c-fos; and activation of at least 4 signal pathways: TGFβ, PDGF, angiogenesis and RAS. Similar results were obtained with IL6 treatment. Regulation network analysis confirmed the cell growth related DEGs, and further uncovered three transcription factor families with immune functions regulated by REG3A.

  10. A Genetic Variant Ameliorates β-Thalassemia Severity by Epigenetic-Mediated Elevation of Human Fetal Hemoglobin Expression. (United States)

    Chen, Diyu; Zuo, Yangjin; Zhang, Xinhua; Ye, Yuhua; Bao, Xiuqin; Huang, Haiyan; Tepakhan, Wanicha; Wang, Lijuan; Ju, Junyi; Chen, Guangfu; Zheng, Mincui; Liu, Dun; Huang, Shuodan; Zong, Lu; Li, Changgang; Chen, Yajun; Zheng, Chenguang; Shi, Lihong; Zhao, Quan; Wu, Qiang; Fucharoen, Supan; Zhao, Cunyou; Xu, Xiangmin


    A delayed fetal-to-adult hemoglobin (Hb) switch ameliorates the severity of β-thalassemia and sickle cell disease. The molecular mechanism underlying the epigenetic dysregulation of the switch is unclear. To explore the potential cis-variants responsible for the Hb switching, we systematically analyzed an 80-kb region spanning the β-globin cluster using capture-based next-generation sequencing of 1142 Chinese β-thalassemia persons and identified 31 fetal hemoglobin (HbF)-associated haplotypes of the selected 28 tag regulatory single-nucleotide polymorphisms (rSNPs) in seven linkage disequilibrium (LD) blocks. A Ly1 antibody reactive (LYAR)-binding motif disruptive rSNP rs368698783 (G/A) from LD block 5 in the proximal promoter of hemoglobin subunit gamma 1 (HBG1) was found to be a significant predictor for β-thalassemia clinical severity by epigenetic-mediated variant-dependent HbF elevation. We found this rSNP accounted for 41.6% of β-hemoglobinopathy individuals as an ameliorating factor in a total of 2,738 individuals from southern China and Thailand. We uncovered that the minor allele of the rSNP triggers the attenuation of LYAR and two repressive epigenetic regulators DNA methyltransferase 3 alpha (DNMT3A) and protein arginine methyltransferase 5 (PRMT5) from the HBG promoters, mediating allele-biased γ-globin elevation by facilitating demethylation of HBG core promoter CpG sites in erythroid progenitor cells from β-thalassemia persons. The present study demonstrates that this common rSNP in the proximal (A)γ-promoter is a major genetic modifier capable of ameliorating the severity of thalassemia major through the epigenetic-mediated regulation of the delayed fetal-to-adult Hb switch and provides potential targets for the treatment of β-hemoglobinopathy. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  11. Regulation of human natural killer cell migration and proliferation by the exodus subfamily of CC chemokines. (United States)

    Robertson, M J; Williams, B T; Christopherson, K; Brahmi, Z; Hromas, R


    Natural killer (NK) cells play an important role in innate and adaptive immune responses to obligate intracellular pathogens. Nevertheless, the regulation of NK cell trafficking and migration to inflammatory sites is poorly understood. Exodus-1/MIP-3alpha/LARC, Exodus-2/6Ckine/SLC, and Exodus-3/MIP-3beta/ELC/CKbeta-11 are CC chemokines that share a unique aspartate-cysteine-cysteine-leucine motif near their amino terminus and preferentially stimulate the migration of T lymphocytes. The effects of Exodus chemokines on human NK cells were examined. Exodus-1, -2, and -3 did not induce detectable chemotaxis of resting peripheral blood NK cells. In contrast, Exodus-2 and -3 stimulated migration of polyclonal activated peripheral blood NK cells in a dose-dependent fashion. Exodus-2 and -3 also induced dose-dependent chemotaxis of NKL, an IL-2-dependent human NK cell line. Results of modified checkerboard assays indicate that migration of NKL cells in response to Exodus-2 and -3 represents true chemotaxis and not simply chemokinesis. Exodus-1, -2, and -3 did not induce NK cell proliferation in the absence of other stimuli. Nevertheless, Exodus-2 and -3 significantly augmented IL-2-induced proliferation of normal human CD56(dim) NK cells. In contrast, Exodus-1, -2, and -3 did not affect the cytolytic activity of resting or activated peripheral blood NK cells. Expression of message for CCR7, a shared receptor for Exodus-2 and -3, was detected in activated polyclonal NK cells and NKL cells but not resting NK cells. Taken together, these results indicate that Exodus-2 and -3 can participate in the recruitment and proliferation of activated NK cells. Exodus-2 and -3 may regulate interactions between T cells and NK cells that are crucial for the generation of optimal immune responses.

  12. A cyclic-RGD-BioShuttle functionalized with TMZ by DARinv “Click Chemistry” targeted to αvβ3 integrin for therapy

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    Klaus Braun, Manfred Wiessler, Rüdiger Pipkorn, Volker Ehemann, Tobias Bäuerle, Heinz Fleischhacker, Gabriele Müller, Peter Lorenz, Waldemar Waldeck


    Full Text Available Clinical experiences often document, that a successful tumor control requires high doses of drug applications. It is widely believed that unavoidable adverse reactions could be minimized by using gene-therapeutic strategies protecting the tumor-surrounding healthy tissue as well as the bone-marrow. One new approach in this direction is the use of “Targeted Therapies” realizing a selective drug targeting to gain effectual amounts at the target site, even with drastically reduced application doses. MCF-7 breast cancer cells expressing the αvβ3 [alpha(vbeta(3] integrin receptor are considered as appropriate candidates for such a targeted therapy. The modularly composed BioShuttle carrier consisting of different units designed to facilitate the passage across the cell membranes and for subcellular addressing of diagnostic and/or therapeutic molecules could be considered as an eligible delivery platform. Here we used the cyclic RGD-BioShuttle as a carrier for temozolomide (TMZ at the αvβ3 integrin receptor realizing local TMZ concentrations sufficient for cell killing. The IC50 values are 12 µMol/L in the case of cRGD-BioShuttle-TMZ and 100 µMol/L for underivatized TMZ, which confirms the advantage of TMZ reformulation to realize local concentrations sufficient for cell killing.Our paper focuses on the design, synthesis and application of the cRGD-BioShuttle conjugate composed of the cyclic RGD, a αvβ3 integrin-ligand, ligated to the cytotoxic drug TMZ. The ligation was carried out by the Diels Alder Reaction with inverse electron demand (DARinv.

  13. Detection and identification of plasma progesterone metabolites in the female Florida manatee (Trichechus manatus latirostris) using GC/MS/MS. (United States)

    Tripp, K M; Dubois, M; Delahaut, P; Verstegen, J P


    Florida manatees (Trichechus manatus latirostris) have relatively low peripheral concentrations of progesterone (P4). The objective of this study was to determine if these relatively low P4 concentrations are associated with a high ratio of progestin metabolites and to document metabolite concentrations from individual blood samples obtained from manatees during diestrus or pregnancy. Metabolites known to exist in elephants-terrestrial manatee relatives-were targeted. These included 5alpha-reduced progestins (5alpha-pregnane-3,20-dione [5alpha-DHP] and 3alpha-hydroxy-5alpha-pregnan-20-one [5alpha-P3-OH]) and 17alpha-hydroxyprogesterone (17alpha-OHP), which occurs in Asian elephants. An additional, inactive metabolite, 20alpha-hydroxyprogesterone (20alpha-OHP), indicative of P4 overproduction, was also targeted. Progesterone itself was the predominant progestin detected in pregnant and nonpregnant manatee plasma (n = 10) using gas chromatography-mass spectrometry with tandem quadrupole detectors (GC/MS/MS). Progesterone concentrations in pregnant females varied from early (moderate to high) through mid and late (low) pregnancy. Progesterone concentrations ranged from low to high in nonpregnant, nonlactating females. The most commonly detected metabolite was 5alpha-P3-OH (n = 7), which occurred in pregnant (lower limit of detection [LLOD] to high) and nonpregnant (trace to high) females. The 5alpha-DHP metabolite was also detected in pregnant (LLOD to moderate) and nonpregnant (low) females. The 17alpha-OHP metabolite was not detected in any tested female. The 20alpha-OHP metabolite was detected in one nonpregnant, nonlactating, captive female (LLOD). Metabolites were most prevalent during early pregnancy, concurrent with maximum P4 concentrations. Based on their concentrations in peripheral circulation, we inferred that these metabolites may have, opposite to elephants, a limited physiologic role during luteal, pregnant, and nonpregnant phases in the manatee.

  14. Interactions between alpha-latrotoxin and trivalent cations in rat striatal synaptosomal preparations

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    Scheer, H.W.


    The interactions between alpha-latrotoxin (alpha-LTx), a neurosecretagogue purified from the venom of the black widow spider, and the trivalent cations Al3+, Y3+, La3+, Gd3+, and Yb3+ were investigated in rat striatal synaptosomal preparations. All trivalent cations tested were inhibitors of alpha-LTx-induced (/sup 3/H)dopamine ((/sup 3/H)DA) release (order of potency: Yb3+ greater than Gd3+ approximately Y3+ greater than La3+ greater than Al3+). Only with Al3+ could inhibition of (/sup 3/H)DA release be attributed to a block of /sup 125/I-alpha-LTx specific binding to synaptosomal preparations. The inhibitory effect of trivalent ions was reversible provided synaptosomes were washed with buffer containing EDTA. Trivalent ions also inhibited alpha-LTx-induced (/sup 3/H)DA release at times when alpha-LTx-stimulated release was already evident. alpha-LTx-induced synaptosomal membrane depolarization was blocked by La3+, but not affected by Gd3+, Y3+, and Yb3+. alpha-LTx-stimulated uptake of /sup 45/Ca/sup 2 +/ was inhibited by all trivalent cations tested. These results demonstrate that there exist at least three means by which trivalent cations can inhibit alpha-LTx action in rat striatal synaptosomal preparations: (1) inhibition of alpha-LTx binding (Al3+); (2) inhibition of alpha-LTx-induced depolarization (La3+); and (3) inhibition of alpha-LTx-induced /sup 45/Ca/sup 2 +/ uptake (Gd3+, Y3+, Yb3+, La3+).

  15. KDN-containing glycoprotein from loach skin mucus. (United States)

    Nakagawa, H; Hama, Y; Sumi, T; Li, S C; Li, Y T


    It has been widely recognized that the mucus coat of fish plays a variety of important physical, chemical, and physiological functions. One of the major constituents of the mucus coat is mucus glycoprotein. We found that sialic acids in the skin mucus of the loach, Misgurnus anguillicaudatus, consisted predominantly of KDN. Subsequently, we isolated KDN-containing glycoprotein from loach skin mucus and characterized its chemical nature and structure. Loach mucus glycoprotein was purified from the Tris-HCl buffer extract of loach skin mucus by DEAE-cellulose chromatography, Nuclease P1 treatment, and Sepharose CL-6B gel filtration. The purified mucus glycoprotein was found to contain 38.5 KDN, 0.5% NeuAc, 25.0% GalNAc, 3.5% Gal, 0.5% GlcNAc and 28% amino acids. Exhaustive Actinase digestion of the glycoprotein yielded a glycopeptide with a higher sugar content and higher Thr and Ser contents. The molecular size of this glycopeptide was approximately 1/12 of the intact glycoprotein. These results suggest that approximately 11 highly glycosylated polypeptide units are linked in tandem through nonglycosylated peptides to form the glycoporotein molecule. The oligosaccharide alditols liberated from the loach mucus glycoprotein by alkaline borohydride treatment were separated by Sephadex G-25 gel filtration and HPLC. The purified sugar chains were analyzed b --> 6GalNAc-ol, KDNalpha2 --> 3(GalNAcbeta1 --> 14)GalNAc-ol, KDNalpha2 --> 6(GalNAcalpha1 --> 3)GalNAc-ol, KDNalpha2 --> 6(Gal3alpha1--> 3)GalNAc-ol, and NeuAcalpha2 --> 6Gal NAc-ol. It is estimated that one loach mucus glycoprotein molecule contains more than 500 KDN-containing sugar chains that are linked to Thr and Ser residues of the protein core through GalNAc.

  16. T-type Ca(2+) channel modulation by otilonium bromide. (United States)

    Strege, Peter R; Sha, Lei; Beyder, Arthur; Bernard, Cheryl E; Perez-Reyes, Edward; Evangelista, Stefano; Gibbons, Simon J; Szurszewski, Joseph H; Farrugia, Gianrico


    Antispasmodics are used clinically to treat a variety of gastrointestinal disorders by inhibition of smooth muscle contraction. The main pathway for smooth muscle Ca(2+) entry is through L-type channels; however, there is increasing evidence that T-type Ca(2+) channels also play a role in regulating contractility. Otilonium bromide, an antispasmodic, has previously been shown to inhibit L-type Ca(2+) channels and colonic contractile activity. The objective of this study was to determine whether otilonium bromide also inhibits T-type Ca(2+) channels. Whole cell currents were recorded by patch-clamp technique from HEK293 cells transfected with cDNAs encoding the T-type Ca(2+) channels, Ca(V)3.1 (alpha1G), Ca(V)3.2 (alpha1H), or Ca(V)3.3 (alpha1I) alpha subunits. Extracellular solution was exchanged with otilonium bromide (10(-8) to 10(-5) M). Otilonium bromide reversibly blocked all T-type Ca(2+) channels with a significantly greater affinity for Ca(V)3.3 than Ca(V)3.1 or Ca(V)3.2. Additionally, the drug slowed inactivation in Ca(V)3.1 and Ca(V)3.3. Inhibition of T-type Ca(2+) channels may contribute to inhibition of contractility by otilonium bromide. This may represent a new mechanism of action for antispasmodics and may contribute to the observed increased clinical effectiveness of antispasmodics compared with selective L-type Ca(2+) channel blockers.

  17. Profiles of circulating steroid hormones, gonadotropins, immunoreactive inhibin and prolactin during pregnancy in goats and immunolocalization of inhibin subunits, steroidogenic enzymes and prolactin in the corpus luteum and placenta. (United States)

    Kandiel, Mohamed M M; Watanabe, Gen; Sosa, Gamal A; Abou El-Roos, Mahmoud E A; Abdel-Ghaffar, Alaa E; Li, Jun Y; Manabe, Noboru; El Azab, Abd El Salam I; Taya, Kazuyoshi


    The current study was performed to follow up the circulating hormonal changes and to correlate the findings with the physiological activity of the corpus luteum (CL) and placenta during pregnancy in goats. Blood samples were collected weekly from five goats during pregnancy for measuring steroid and protein hormones. A gradual increase was observed in immunoreactive (ir-) inhibin, with maximal levels at the 17th week. The plasma concentrations of estradiol and prolactin (PRL) showed nearly similar patterns during pregnancy, where they declined to basal levels during the first 4 weeks post-breeding and then increased significantly, with the maximal concentration during late pregnancy. The plasma FSH and LH concentrations were maintained at basal levels throughout the gestation period. The plasma progesterone concentration abruptly increased in the first week post-breeding and remained at high values throughout the pregnancy period. Immunohistochemical localization of inhibin alpha, beta(A), beta(B) and steroidogenic enzymes cytochrome P450 aromatase, 3alpha-hydroxysteroid dehydrogenase (3betaHSD), cytochrome 17alpha-hydroxylase P450 and cholesterol side-chain cleavage cytochrome P450 in the cyclic and pregnant goat CL revealed positive immunoreactivity without affinity differences between the luteal and pregnancy stages. The placental syncytiotrophoblasts also showed positive staining, except for inhibin beta(A) and 3betaHSD. The giant binucleate cells of the placenta showed positive immunoreactions to PRL. These results suggest that the high concentrations of ir-inhibin, estradiol and PRL during late pregnancy are of placental origin and that the placenta may have a vital role in the maintenance of pregnancy, regulation of mammary growth and preparation for kidding and lactation in goats.

  18. Blockage of epithelial to mesenchymal transition and upregulation of let 7b are critically involved in ursolic acid induced apoptosis in malignant mesothelioma cell. (United States)

    Sohn, Eun Jung; Won, Gunho; Lee, Jihyun; Yoon, Sang Wook; Lee, Ilho; Kim, Hee Jeong; Kim, Sung-Hoon


    Malignant pleural mesothelioma (MPN), which is caused by asbestos exposure, is one of aggressive lung tumors. In the present study, we elucidated the anti-tumor mechanism of ursolic acid in malignant mesotheliomas. Ursolic acid significantly exerted cytotoxicity in a time and dose dependent manner in H28, H2452 and MSTO-211H mesothelioma cells and inhibited cell proliferation by colony formation assay in a dose-dependent fashion. Also, ursolic acid treatment accumulated the sub-G1 population, attenuated the expression of procapase 9, cyclin D1, pAKT, p-glycogen synthase kinase 3-alpha/beta (pGSK3α/β), β-catenin and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) and also cleaved caspase 3 and poly (ADP-ribose) polymerase (PARP) in mesothelioma cells. Furthermore, ursolic acid treatment blocked epithelial and mesenchymal transition (EMT) molecules by activating E-cadherin as an epithelial marker and attenuating Vimentin, and Twist as mesenchymal molecules. Interestingly, miRNA array revealed that 23 miRNAs (>2 folds) including let-7b and miRNA3613-5p, miRNA134 and miRNA196b were significantly upregulated while 33 miRNAs were downregulated in ursolic acid treated H2452 cells. Furthermore, overexpression of let 7b using let-7b mimics enhanced the antitumor effect of ursolic acid to attenuate the expression of procaspases 3, pro-PARP, pAKT, β-catenin and Twist and increase sub-G1 accumulation in H2452 mesothelioma cells. Overall, our findings suggest that ursolic acid induces apoptosis via inhibition of EMT and activation of let7b in mesothelioma cells as a potent chemotherapeutic agent for treatment of malignant mesotheliomas.

  19. Antibacterial Activity of Selected Standard Strains of Lactic Acid Bacteria Producing Bacteriocins – Pilot Study

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    Malgorzata Bodaszewska-Lubas


    Full Text Available  Introduction:In this paper, an attempt was made to evaluate the antibacterial potential of standard strains of lactic acid bacteria (LAB producing bacteriocins of various classes, thus demonstrating various mechanisms of cell membrane damages against the Streptococcus agalactiae strains (Group B Streptococcus, GBS, depending on surface polysaccharides and surface alpha-like protein genes.Materials/Methods:Antimicrobial property of the strains of L. plantarum C 11, L. sakei DSMZ 6333, and L. lactis ATCC 11454 producing bacteriocins: JK and EF plantaricins, sakacin and nisin, respectively, against the GBS strains was evaluated. The chosen to the study GBS strains were represented by serotypes Ia, Ib, II, III, V and they had bca, epsilon, rib, alp2 or alp3 alpha-like protein genes. The experiment was conducted by means of suspension culture and the bacteria count was determined using the serial dilution method.Results:A great ability of L. plantarum C 11 strain was proven to inhibit the GBS growth. The strain of L. sakei DSMZ 6333 did not demonstrate any ability to inhibit the growth of GBS, whereas L. lactis ATCC 11454 inhibited the growth of S. agalactiae indicator strains to a minor extent. Statistically significant differences were demonstrated between the GBS strains representing various serotypes against the antimicrobial activity of model LAB strains. The least sensitive to the activity of bacteriocins were the strains representing serotypes Ib and III, whereas the strains representing serotype II were the most sensitive. The sensitivity of the GBS strains to the antimicrobial activity of LAB was not dependent on alpha-like protein genes.Discussion:Among the LAB standard strains producing bacteriocins, the strongest antimicrobial property was observed in the strain of L. plantarum C 11. Because of the generally known and verified strong antagonistic property of the strains of L. plantarum species against indicator bacteria, it is necessary

  20. Heparin-binding Hemagglutinin of Mycobacterium tuberculosis Is an Inhibitor of Autophagy (United States)

    Zheng, Qing; Li, Zhi; Zhou, Shan; Zhang, Qian; Zhou, Lei; Fu, Xiaorui; Yang, Liu; Ma, Yueyun; Hao, Xiaoke


    Airway epithelial cell is often the initial site of attack by pathogens, and cell death is commonly caused by internalization of Mycobacterium tuberculosis (Mtb). However, the mechanism of interaction between epithelial cells and Mtb is not well understood. In this study, we investigated the role of the heparin-binding hemagglutinin (HBHA) protein of Mtb in the function of epithelial cells. In particular, the autophagy of A549 cells was determined based on microtubule-associated protein 1 light chain 3 alpha (LC3) activity. Autophagosome formation was detected by Monodansylcadaverine (MDC) staining and immune fluorescence staining of LC3. Autophagy could be significantly suppressed by HBHA protein. In addition, the LDH assay results showed that HBHA treatment could induce death on A549 cells. To explore the form of cell death, we detected the activity of caspase-3 and LDH release of A549 cells in the presence or absence of caspase inhibitor Z-VAD-FMK. Results demonstrated that HBHA treatment could induce apoptosis of A549 cells. To further confirm these results, we constructed the recombinant Mycobacterium smegmatis (MS) expressing HBHA (rMS-HBHA) and explored the influence of rMS-HBHA on the function of A549 cells. rMS-HBHA infection significantly inhibited LC3 expression and the maturation of autophagosomes in A549 cells. Subsequently, we infected A549 cells with MS and detected the viability of intracellular MS by CFU counts. rMS-HBHA showed higher survival and replication capacity in A549 cells than those of the wild-type MS. Finally, infection of A549 cells with rMS-HBHA caused further apoptosis. These findings suggested that rMS-HBHA could inhibit autophagy, promote its survival and replication within A549 cells, and subsequently induce apoptosis on infected cells to facilitate infection.

  1. Prostaglandin inhibitory and antioxidant components of Cistus laurifolius, a Turkish medicinal plant. (United States)

    Sadhu, Samir Kumar; Okuyama, Emi; Fujimoto, Haruhiro; Ishibashi, Masami; Yesilada, Erdem


    As Cistus laurifolius has been used traditionally to treat inflammatory and rheumatic disorders, its leaves were tested for prostaglandin (PG) inhibitory and antioxidant activities. The leaf extract showed both activities, i.e., inhibitory effect at 300 microg/ml on PGE1- and E2-induced contractions in guinea pig ileum and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect. The separation guided by the activities shown by these dual assays provided sixteen compounds, 1-16. Known compounds 1-12 and 15 were identified as 3-O-methyl quercetin (1), 3,7-O-dimethyl quercetin (2), genkwanin (3), 3,7-O-dimethyl kaempferol (4), 3,4'-O-dimethyl quercetin (5), apigenin (6), 3,4'-O-dimethyl kaempferol (7), ellagic acid (8), beta-sitosterol-3-O-beta-glucoside (9), quercetin 3-O-alpha-rhamnoside (10), 5-O-p-coumaroyl quinic acid methyl ester (11), 1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-alpha-l-rhamnopyranoxypropyl)-2-methoxyphenoxy]-1,3-propanediol (12) and 2,3-dihydro-2-(4'-alpha-l-rhamnopyranosyloxy-3'-methoxyphenyl)-3-hydroxymethyl-7-methoxy-5-benzofuranpropanol (15). New lignan glycosides 13 and 14 were determined to be olivil 9-O-beta-D-xyloside and berchemol 9-O-rhamnoside, respectively. Compound 16 was isolated as a 2:1 mixture of two diastereomers, the major one of which was determined to be (7S,8R)-dihydrodehydrodiconiferyl alcohol 9'-O-alpha-L-rhamnoside. The structures were determined by detailed 2D NMR analysis together with NOEDF and CD. PG inhibitory effect was observed in 1, 5, 10, 12 and 16 at 30 microg/ml and antioxidant activity, in 1, 2, 8, 10, 12-14 and 16.

  2. GSK3 influences social preference and anxiety-related behaviors during social interaction in a mouse model of fragile X syndrome and autism.

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    Marjelo A Mines

    Full Text Available BACKGROUND: Nearly 1% of children in the United States exhibit autism spectrum disorders, but causes and treatments remain to be identified. Mice with deletion of the fragile X mental retardation 1 (Fmr1 gene are used to model autism because loss of Fmr1 gene function causes Fragile X Syndrome (FXS and many people with FXS exhibit autistic-like behaviors. Glycogen synthase kinase-3 (GSK3 is hyperactive in brains of Fmr1 knockout mice, and inhibition of GSK3 by lithium administration ameliorates some behavioral impairment in these mice. We extended our studies of this association by testing whether GSK3 contributes to socialization behaviors. This used two mouse models with disrupted regulation of GSK3, Fmr1 knockout mice and GSK3 knockin mice, in which inhibitory serines of the two isoforms of GSK3, GSK3alpha and GSK3beta, are mutated to alanines, leaving GSK3 fully active. METHODOLOGY/PRINCIPAL FINDINGS: To assess sociability, test mice were introduced to a restrained stimulus mouse (S1 for 10 min, followed by introduction of a second restrained stimulus mouse (S2 for 10 min, which assesses social preference. Fmr1 knockout and GSK3 knockin mice displayed no deficit in sociability with the S1 mouse, but unlike wild-type mice neither demonstrated social preference for the novel S2 mouse. Fmr1 knockout mice displayed more anxiety-related behaviors during social interaction (grooming, rearing, and digging than wild-type mice, which was ameliorated by inhibition of GSK3 with chronic lithium treatment. CONCLUSIONS/SIGNIFICANCE: These results indicate that impaired inhibitory regulation of GSK3 in Fmr1 knockout mice may contribute to some socialization deficits and that lithium treatment can ameliorate certain socialization impairments. As discussed in the present work, these results suggest a role for GSK3 in social behaviors and implicate inhibition of GSK3 as a potential therapeutic.

  3. Effects of mode of administration (MOA on the measurement properties of the EORTC QLQ-C30: a randomized study

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    Aaronson Neil K


    Full Text Available Abstract Background While modern electronic data collection methods (e.g., computer touch-screen or web-based hold much promise, most current studies continue to make use of more traditional data collection techniques, including paper-and-pencil administration and telephone interviews. The present randomized trial investigated the measurement properties of the EORTC QLQ-C30 under three different modes of administration (MOA's. Methods A heterogeneous sample of 314 cancer patients undergoing treatment at a specialized treatment center in Amsterdam were randomized to one of three MOA's for the QLQ-C30: paper-and-pencil at home via the mail, telephone interview, and paper-and-pencil at the hospital clinic. Group differences in internal consistency reliabilities (Cronbach's alpha coefficient for the scale scores were compared. Differences in mean scale scores were also compared by means of ANOVA, with adjustment for potential confounders. Results Only one statistically significant, yet minor, difference in Cronbach's alpha between the MOA groups was observed for the Role Functioning scale (all 3 alphas >0.80. Significant differences in group means -after adjustment- were found for the Emotional Functioning (EF scale. Patients completing the written questionnaire at home had significantly lower levels of EF as compared to those interviewed via the telephone; EF scores of those completing the questionnaire at the clinic fell in-between those of the other two groups. These differences, however, were small in magnitude. Conclusions MOA had little effect on the reliability or the mean scores of the EORTC QLQ-C30, with the possible exception of the EF scale.

  4. Mediating effect of dopamine D3 receptors on Jak2 and GABAAα1 expression in mouse brains induced by cocaine

    Institute of Scientific and Technical Information of China (English)

    LIU Nu-yun; ZHANG Lu; ZHANG Lin; WANG Xiao-ning


    Background Cocaine addiction may involve complex neuroadaptations, including many changes of genes expression.Dopamine D3 receptors play an important role in cocaine addiction; however, its role in cocaine induced gene expression change is poorly understood. To identify the changes in gene expression induced by repeated cocaine exposure through D3 dopamine receptors, we compared the expression of four molecules: Janus kinase 2 (Jak2), g-aminobutanoic acid receptor subunit alpha 1 (GABAAα1), glutamate receptor AMPA3 alpha 3 (GluR 3) and stromal cell derived factor 1 (SDF1). These four have been implicated in mediating the actions of cocaine in the nucleus accumbens (NAc) and caudoputamen (CPu) in mice after acute and repeated cocaine exposure.Methods For the acute and repeated injections, the mice were divided into four groups: 30 mg/kg cocaine, nafadotride 0.5 mg/kg + cocaine 30 mg/kg, nafadotride 0.5 mg/kg, and saline as the basal group. The expression of Jak2, GABAAα1,GluR 3 and SDF1 were assayed by Western blot, quantitative real-time RT-PCR and immunohistochemistry.Results Twenty-four hours after seven consecutive days of repeated cocaine exposure, the expression of GABAAα1 decreased in cocaine group compared with basal line and further decreased in the cocaine + nafadotride group and remained at basal level in the nafadotride group. Similarly, the Jak2 expression decreased in cocaine group compared with base line. However, the levels of Jak2 increased in cocaine + nafadotride group compared with cocaine group, while remained at basal level in nafadotride group.Conclusions GABAAα1 and Jak2 may be involved in chronic cocaine induced neuroadaptations. D3 dopaminereceptors play an important role in the expression of these genes.

  5. Expression of {beta}{sub 1} integrins in human endometrial stromal and decidual cells

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    Shiokawa, Shigetatsu; Yoshimura, Yasunori; Nakamura, Yukio [Kyorin Univ. School of Medicine, Tokyo (Japan)] [and others


    The present study was undertaken to investigate the expression of {beta}{sub 1} integrins in human endometrium and decidua using flow cytometry, immunohistochemistry, and immunoprecipitation. Fluorescence-activated flow cytometry demonstrated the greater expression of the {beta}{sub 1}, {alpha}{sub 1}, {alpha}{sub 2}, and {alpha}{sub 5} subunits of the {beta}{sub 1} integrin family in cultured stromal cells from the midsecretory phase, than in those of the early proliferative phase. The addition of estradiol (E{sub 2}) and progesterone (P) to cultured stromal cells in the early proliferative phase increased the expression of {beta}{sub 1} integrins in vitro. Flow cytometry also demonstrated the expression of the {beta}{sub 1}, {alpha}{sub 1}, {alpha}{sub 2}, {alpha}{sub 3}, {alpha}{sub 5}, and {alpha}{sub 6} subunits of {beta}{sub 1} integrin family in cultured decidual cells, and the enriched-fraction of prolactin (PRL)-producing decidual cells isolated by Percoll gradients showed high levels of {beta}{sub 1} integrins expression. Immunohistochemistry confirmed the {beta}{sub 1} integrin cell surface phenotypes in cultured decidual cells observed by flow cytometry. In summary, the present study demonstrated that endometrial stromal and decidual cells expressed {beta}{sub 1} integrin subunits at their surfaces. The expression exhibited a variability throughout the menstrual cycles, being predominantly detected in the secretory phase, and was maintained highly in the decidua. Thus, {beta}{sub 1} integrins in human endometrium and decidua may be important in mediating the organization of extracellular matrix proteins derived from embryos during the early stage of implantation. 43 refs., 7 figs., 2 tabs.

  6. Recruitment of CCR6-expressing Th17 cells by CCL20 secreted from plasmin-stimulated macrophages

    Institute of Scientific and Technical Information of China (English)

    Qun Li; Yves Laumonnier; Tatiana Syrovets; Thomas Simmet


    In the present study,monocyte-derived human macrophages were differentiated from buffy coats.Na(i)ve CD4+ T-cells enriched from peripheral blood mononuclear cells using anti-CD4 magnetic beads and the autoMACS separation system were polarized under T-helper 17 (Th17)-promoting conditions for 6 days to get Th17 cells.The frequency of Th17 cell differentiation and the expression of C-C chemokine receptor type 6 (CCR6) on Th17 cells were investigated by flow cytometry.Plasmin-triggered induction of macrophage inflammatory protein-3alpha/C-C chemokine ligand 20 (CCL20) genes in macrophages was assessed by reverse transcription-polymerase chain reaction,and secreted protein levels were measured by enzymelinked immunosorbent assay.Th17 cell migration induced by CCL20 secreted from plasmin-stimulated macrophages was tested in vitro by chemotaxis using a transwell system.These results demonstrate that plasmin triggers the expression of chemokine CCL20 messenger RNA and the release of CCL20 protein in human monocyte-derived macrophages,which critically depend on the proteolytic activity of plasmin and activation of p38 mitogen-activated protein kinase and nuclear factor-kappaB signaling pathways.Expression of CCR6 was detected on 87.23 ± 8.6% of Th17 cells in vitro.Similar to chemotaxis triggered by recombinant human CCL20,supernatants collected from plasmin-stimulated macrophage-induced chemotactic migration of Th17 cells,which could be inhibited by an anti-CCL20 neutralizing antibody.These results suggest that plasmin generated in inflamed tissues might elicit production of chemokine CCL20 by human macrophages leading to the recruitmentof CCR6 positive Th17 cells to the inflammatory sites.

  7. Structural and functional characteristics of urinary tract in offspring of Balkan endemic nephropathy patients

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    Radisavljević Snežana


    Full Text Available Introduction. Balkan endemic nephropathy (BEN is a familial chronic progressive tubulointerstitial disease of unknown aetiology that occurs with high prevalence in endemic rural environments of Serbia, Bosnia and Herzegovina, Croatia, Bulgaria and Romania. It has been documented only in adults. Objective. The aim of this study was to examine clinical markers of BEN in children and adolescent offspring of BEN patients. Methods. Prospective clinical trial involved two groups of children and adolescents: I consisted of 30 offspring of BEN patients and II of 29 offspring of non-BEN dialysis patients, both of them living in the same South Morava region of Serbia. All of them were healthy at the time of the investigation, not receiving any drugs. The study included personal and family history, physical examination, comprehensive laboratory analyses and renal ultrasound. Blood pressure (BP was determined by using casual BP and 24 h ABPM in subjects older than 5 years. Urinary proteins were investigated by analysing microalbumin, alfa 1 microglobulin, beta 2 microglobulin and SDS-PAGE electrophoresis. GFR was measured by estimated creatinine clearance and by serum Cystatin C concentrations. Results. There were no statistically significant differences in age, gender, history of urinary tract infections or functional voiding disorders between these two groups. All of the studied subjects had normal BP and GFR. Renal ultrasound was abnormal only in BEN offspring (6.66% as well as increased urine concentrations of microalbumin (3.3%, alpha 1 microglobulin (10% and beta 2 microglobulin (13.3% while low molecular protein (<66,000 D was prevalent in BEN compared with non- BEN offspring (21.43% vs. 3.7%. Conclusion. Renal abnormalities in offspring of BEN patients may be an early marker of BEN. This has to be confirmed in long term follow-up of a greater number of BEN paediatric offspring.

  8. The depolarizing action of 5-hydroxytryptamine on rabbit vagal primary afferent and sympathetic neurones and its selective blockade by MDL 72222. (United States)

    Azami, J; Fozard, J R; Round, A A; Wallis, D I


    MDL 72222 (1 alpha H,3 alpha,5 alpha H-tropan-3-yl-3,5-dichlorobenzoate) is a novel compound with potent and selective blocking actions at certain excitatory 5-hydroxytryptamine (5-HT) receptors on mammalian peripheral neurones. In the present study, the sucrose-gap technique has been used to record depolarizing responses to 5-HT from the cells of the rabbit nodose and superior cervical ganglia and to investigate the potency and selectivity of MDL 72222 as an antagonist of these responses. On nodose ganglia, responses to 5-HT were inhibited surmountably by MDL 72222 at concentrations up to 100 nmol/l. The threshold for antagonism was 2-10 nmol/l and the apparent pA2 value (Schild 1947) was 7.7 +/- 0.2, n = 10. Blockade was selective since responses to GABA and noradrenaline were unaffected by MDL 72222, 100 nmol/l. With concentrations of MDL 72222 higher than 100 nmol/l, antagonism was concentration-related but not in a manner consistent with simple competitive antagonism and even a concentration of 1 mumol/l failed to abolish the response to 5-HT. The results from the superior cervical ganglion were essentially similar to those obtained from the nodose ganglion. The threshold concentration of MDL 72222 for inhibition of 5-HT was 1-10 nmol/l and blockade was selective in that depolarizing responses to dimethylphenyl-piperazinium (DMPP) was unaffected by a concentration of MDL 72222 of 1 mumol/l. The data provide direct evidence that MDL 72222 is a potent and selective antagonist of the receptors for 5-HT which mediate depolarizing responses in vagal primary afferent cell bodies and in sympathetic ganglion cells.

  9. The depolarizing action of 5-hydroxytryptamine on rabbit vagal afferent and sympathetic neurones in vitro and its selective blockade by ICS 205-930. (United States)

    Round, A; Wallis, D I


    Depolarizing responses to 5-hydroxytryptamine (5-HT) were recorded from rabbit nodose (NG) and superior cervical (SCG) ganglia using the sucrose-gap technique. The antagonist potency and selectivity of ICS 205-930 ([3 alpha-tropanyl]-1H-indole-3-carboxylic acid ester) were investigated. In NG, 5-HT (5 to 80 nmol) evoked depolarizations of graded amplitude. The ED50 was 18.2 (10.9-30.5) nmol (geometric mean, 95% confidence limits). Responses were blocked surmountably by ICS 205-930, 10(-11) and 10(-10) M, the threshold for blockade being below 10(-11) M. Parallel, rightward shifts in dose-response curves were seen with these concentrations of antagonist, but at higher concentrations (10(-9) and 10(-8) M) there was a further rightward shift with reduction in slope and maximum of the curves. In SCG, where 5-HT (20 to 320 nmol) evoked depolarizations of graded amplitude and the ED50 was 55.8 (22.3-139.6) nmol (geometric mean, 95% confidence limits), ICS 205-930 had a similar inhibitory effect to that observed in NG. The apparent pA2 values for the surmountable blockade produced by ICS 205-930 at concentrations of 10(-11) and 10(-10) M were 10.2 +/- 0.2 for NG and 10.4 +/- 0.1 for SCG (means +/- s.e. mean). ICS 205-930 was selective in its action since it had no effect on dimethylphenylpiperazinium (DMPP) responses in either ganglion or on GABA responses in NG. This study provides quantitative evidence on the blocking action of ICS 205-930 at neuronal 5-HT receptors using a technique that allows the depolarizing responses evoked by the amine to be directly recorded.

  10. A new proposal on the operational quantity H{sub p}(3): Monte Carlo and experimental results

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    Mariotti, F., E-mail: francesca.mariotti@bologna.enea.i [ENEA Radiation Protection Institute, Via dei Colli 16, 40136 Bologna (Italy); Gualdrini, G.; Fantuzzi, E.; Ferrari, P.; Monteventi, F. [ENEA Radiation Protection Institute, Via dei Colli 16, 40136 Bologna (Italy)


    The European Union is funding the ORAMED Contract (Optimization of RAdiation protection for MEDical staff) project that aims at developing methodologies for better assessing and reducing exposures to medical staff for procedures resulting in potentially large doses or complex radiation fields, such as interventional radiology, nuclear medicine and new developments. One of the ORAMED Working Tasks is addressed to the discussion and implementation in the radiation protection practice of the eye lens equivalent dose. The aim of this task group is to develop a personal dosemeter characterized in term of H{sub p}(3). Until now H{sub p}(3) conversion coefficients were not reported in the official recommendations and the available data were calculated for a 30 x 30 x 15 cm{sup 3} slab phantom that is far away to represent the head. A reduced slab phantom, for both calculating the quantities and type testing personal dosemeter in terms of the operational quantity, was previously proposed by ENEA Bologna team. The study demonstrated that a reduced slab phantom is better representative of a real situation, but the angular dependence of H{sub p}(3,{alpha}) due to the edges of the slab reduces its applicability. Therefore a better-suited phantom is proposed here. The dosimetric assessment in terms of this quantity is seldom performed in the various workplaces (e.g. hospitals) and therefore a question rises about its usefulness and practical implementation. The present work tries to introduce new elements in the discussion on the quantity H{sub p}(3) and to propose a more suitable theoretical cylindrical phantom (and a corresponding experimental one for the calibration procedures) to better approximate the head in which the eyes are placed.

  11. Tumor necrosis factor (TNF)-alpha-induced IL-8 expression in gastric epithelial cells: role of reactive oxygen species and AP endonuclease-1/redox factor (Ref)-1. (United States)

    O'Hara, Ann M; Bhattacharyya, Asima; Bai, Jie; Mifflin, Randy C; Ernst, Peter B; Mitra, Sankar; Crowe, Sheila E


    TNF-alpha contributes to oxidative stress via induction of reactive oxygen species (ROS) and pro-inflammatory cytokines. The molecular basis of this is not well understood but it is partly mediated through the inducible expression of IL-8. As redox factor-1 (Ref-1), is an important mediator of redox-regulated gene expression we investigated whether ROS and Ref-1 modulate TNF-alpha-induced IL-8 expression in human gastric epithelial cells. We found that TNF-alpha treatment of AGS cells enhanced nuclear expression of Ref-1 and potently induced IL-8 expression. Overexpression of Ref-1 enhanced IL-8 gene transcription at baseline and after TNF-alpha treatment whereas Ref-1 suppression and antioxidant treatment inhibited TNF-alpha-stimulated IL-8 expression. TNF-alpha-mediated enhancement of other pro-inflammatory chemokines like MIP-3 alpha and Gro-alpha was also regulated by Ref-1. Although TNF-alpha increased DNA binding activity of Ref-1-regulated transcription factors, AP-1 and NF-kappaB, to the IL-8 promoter, promoter activity was mainly mediated by NF-kappaB binding. Silencing of Ref-1 in AGS cells inhibited basal and TNF-alpha-induced AP-1 and NF-kappaB DNA binding activity, but not their nuclear accumulation. Collectively, we provide the first mechanistic evidence of Ref-1 involvement in TNF-alpha-mediated, redox-sensitive induction of IL-8 and other chemokines in human gastric mucosa. This has implications for understanding the pathogenesis of gastrointestinal inflammatory disorders.

  12. Inhibitory effect of polyunsaturated fatty acids on apoptosis induced by etoposide, okadaic acid and AraC in Neuro2a cells

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    Full Text Available Neuronal apoptosis is involved in neurodegenerative diseases such as Alzheimer's disease and Parkinson.s disease. An efficient means of preventing it remains to be found. Some n-3 polyunsaturated fatty acids (PUFAs such as docosahexaenoic acid (DHA, 22 : 6n-3 and eicosapentaenoic acid (EPA, 20 : 5n-3 have been reported to be protective against the neuronal apoptosis and neuronal degeneration seen after spinal cord injury (SCI [1]. However, it is unclear which kinds of PUFAs have the most potent ability to inhibit neuronal apoptosis and whether the simultaneous treatment of PUFAs inhibits the apoptosis. In the present study, we compared the abilities of various n-3- and n-6- PUFAs to inhibit the apoptosis induced after the administration of different apoptotic inducers, etoposide, okadaic acid, and AraC, in mouse neuroblastoma cells (Neuro2a. Preincubation with DHA (22 : 6n-3, eicosapentaenoic acid (EPA, 20 : 5n-3, alpha-linolenic acid (alpha-LNA, 18 : 3n-3, linoleic acid (LA, 18 : 2n-6, arachidonic acid (AA, 20 : 4n-3, and gamma-linolenic acid (gamma-LNA, 18 : 3n-6 significantly inhibited caspase-3 activity and LDH leakage but simultaneous treatment with the PUFAs had no effect on the apoptosis of Neuro2a cells. There were no significant differences of the anti-apoptotic eff ect among the PUFAs. These results suggest that PUFAs may not be effective for inhibiting neuronal cell death after acute and chronic neurodegenerative disorders. However, dietary supplementation with PUFAs may be beneficial as a potential means to delay the onset of the diseases and/or their rate of progression.

  13. Fluorescently tagged laminin subunits facilitate analyses of the properties, assembly and processing of laminins in live and fixed lung epithelial cells and keratinocytes. (United States)

    Hopkinson, Susan B; DeBiase, Phillip J; Kligys, Kristina; Hamill, Kevin; Jones, Jonathan C R


    Recent analyses of collagen, elastin and fibronectin matrix assembly, organization and remodeling have been facilitated by the use of tagged proteins that can be visualized without the need for antibody labeling. Here, we report the generation of C-terminal tagged, full-length and "processed" (alpha3DeltaLG4-5) human alpha3 as well as C-terminal tagged, full-length human beta3 laminin subunits in adenoviral vectors. Human epidermal keratinocytes (HEKs) and human bronchial epithelial (BEP2D) cells, which assemble laminin-332-rich matrices, as well as primary rat lung alveolar type II (ATII) cells, which elaborate a fibrous network rich in laminin-311, were infected with adenovirus encoding the tagged human laminin subunits. In HEKs and BEP2D cells, tagged, full-length alpha3, alpha3DeltaLG4-5 and beta3 laminin subunits incorporate into arrays of matrix organized into patterns that are comparable to those observed when such cells are stained using laminin-332 subunit antibody probes. Moreover, HEKs and BEP2Ds move over these tagged, laminin-332-rich matrix arrays. We have also used the tagged beta3 laminin subunit-containing matrices to demonstrate that assembled laminin-332 arrays influence laminin matrix secretion and/or assembly. In the case of rat ATII cells, although tagged alpha3 laminin subunits are not detected in the matrix of rat ATII cells infected with virus encoding full-length human alpha3 laminin protein, processed human alpha3 laminin subunits are incorporated into an extracellular fibrous array. We discuss how these novel laminin reagents can be used to study the organization, processing and assembly of laminin matrices and how they provide new insights into the potential functional importance of laminin fragments.

  14. Inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3+ regulatory T cells. (United States)

    Hübner, Marc P; Stocker, J Thomas; Mitre, Edward


    We sought to determine whether Litomosoides sigmodontis, a filarial infection of rodents, protects against type 1 diabetes in non-obese diabetic (NOD) mice. Six-week-old NOD mice were sham-infected or infected with either L3 larvae, adult male worms, or adult female worms. Whereas 82% of uninfected NOD mice developed diabetes by 25 weeks of age, no L. sigmodontis-infected mice developed disease. Although all mice had evidence of ongoing islet cell inflammation by histology, L. sigmodontis-infected mice had greater numbers of total islets and non-infiltrated islets than control mice. Protection against diabetes was associated with a T helper type 2 (Th2) shift, as interleukin-4 (IL-4) and IL-5 release from alpha-CD3/alpha-CD28-stimulated splenocytes was greater in L. sigmodontis-infected mice than in uninfected mice. Increased circulating levels of insulin-specific immunoglobulin G1, showed that this Th2 shift occurs in response to one of the main autoantigens in diabetes. Multicolour flow cytometry studies demonstrated that protection against diabetes in L. sigmodontis-infected NOD mice was associated with significantly increased numbers of splenic CD4(+) CD25(+) FoxP3(+) regulatory T cells. Interestingly, injection of crude worm antigen into NOD mice also resulted in protection against type 1 diabetes, though to a lesser degree than infection with live L. sigmodontis worms. In conclusion, these studies demonstrate that filarial worms can protect against the onset of type 1 diabetes in NOD mice. This protection is associated with a Th2 shift, as demonstrated by cytokine and antibody production, and with an increase in CD4(+) CD25(+) FoxP3(+) regulatory T cells.

  15. TEAD-1 overexpression in the mouse heart promotes an age-dependent heart dysfunction. (United States)

    Tsika, Richard W; Ma, Lixin; Kehat, Izhak; Schramm, Christine; Simmer, Gretchen; Morgan, Brandon; Fine, Deborah M; Hanft, Laurin M; McDonald, Kerry S; Molkentin, Jeffery D; Krenz, Maike; Yang, Steve; Ji, Juan


    TEA domain transcription factor-1 (TEAD-1) is essential for proper heart development and is implicated in cardiac specific gene expression and the hypertrophic response of primary cardiomyocytes to hormonal and mechanical stimuli, and its activity increases in the pressure-overloaded hypertrophied rat heart. To investigate whether TEAD-1 is an in vivo modulator of cardiac specific gene expression and hypertrophy, we developed transgenic mice expressing hemagglutinin-tagged TEAD-1 under the control of the muscle creatine kinase promoter. We show that a sustained increase in TEAD-1 protein leads to an age-dependent dysfunction. Magnetic resonance imaging revealed decreases in cardiac output, stroke volume, ejection fraction, and fractional shortening. Isolated TEAD-1 hearts revealed decreased left ventricular power output that correlated with increased betaMyHC protein. Histological analysis showed altered alignment of cardiomyocytes, septal wall thickening, and fibrosis, although electrocardiography displayed a left axis shift of mean electrical axis. Transcripts representing most members of the fetal heart gene program remained elevated from fetal to adult life. Western blot analyses revealed decreases in p-phospholamban, SERCA2a, p-CX43, p-GSK-3alpha/beta, nuclear beta-catenin, GATA4, NFATc3/c4, and increased NCX1, nuclear DYKR1A, and Pur alpha/beta protein. TEAD-1 mice did not display cardiac hypertrophy. TEAD-1 mice do not tolerate stress as they die over a 4-day period after surgical induction of pressure overload. These data provide the first in vivo evidence that increased TEAD-1 can induce characteristics of cardiac remodeling associated with cardiomyopathy and heart failure.

  16. The MUSES-C, mission description and its status (United States)

    Kawaguchi, Jun'ichiro; Uesugi, Kuninori T.; Fujiwara, Akira; Saitoh, Hirobumi


    The MUSES-C mission is the world's first sample and return attempt to/from the near Earth asteroid Nereus (4660). It is the ISAS (The Institute of Space and Astronautical Science, Ministry of Education) which manages the mission that started in 1996 scheduling to be launched in January of 2002. The mission is built as a kind of technology demonstration, however, it is aiming at not only the in-situ observation but also the touch-down sampling of the surface fragments. The sample collected is returned to the Earth in January of 2006. The mission is a four year journey. The major purpose of it originally consists of the following four subjects: 1) The Ion thruster propulsion performed in interplanetary field as a primary means, 2) Autonomous guidance, navigation and control during the rendezvous and touch down phase, 3) The sample collection mechanism and 4) The hyperbolic reentry capsule with the asteroid sample contained inside it. The current primary objective is extended to carry the joint small rover with NASA/JPL, which is supposed to be placed on the surface and to look into the crater created by the sampling shot of the projectile. The rover is designated as the Small Science Vehicle (SSV) that weighs about 1 kg carrying three kinds of in-situ instruments: 1) A Visible Camera, 2) Near Infra-Red Spectrometer and potentially 3) Alpha-Proton X-ray Spectrometer (APXS) similar to that delivered on the Mars Path Finder. During the fiscal 1998, the spacecraft undergoes the PM tests and the FM fabrication starts from next year, 1999. The paper presents the latest mission description around the asteroid and shows the current status of the spacecraft as well as the instruments and so on. The mission will be the good example of an international collaboration in the small interplanetary exploration.

  17. ATPase center of bacteriophage lambda terminase involved in post-cleavage stages of DNA packaging: identification of ATP-interactive amino acids. (United States)

    Hang, J Q; Tack, B F; Feiss, M


    Terminase is the enzyme that mediates lambda DNA packaging into the viral prohead. The large subunit of terminase, gpA (641 amino acid residues), has a high-affinity ATPase activity (K(m)=5 microM). To directly identify gpA's ATP-interacting amino acids, holoterminase bearing a His(6)-tag at the C terminus of gpA was UV-crosslinked with 8-N(3)-[alpha-(32)P]ATP. Tryptic peptides from the photolabeled terminase were purified by affinity chromatography and reverse-phase HPLC. Two labeled peptides of gpA were identified. Amino acid sequencing failed to show the tyrosine residue of the first peptide, E(43)SAY(46)QEGR(50), or the lysine of the second peptide, V(80)GYSK(84)MLL(87), indicating that Y(46) and K(84) were the 8-N(3)-ATP-modified amino acids. To investigate their roles in lambda DNA packaging, Y(46) was changed to E, A, and F, and K(84) was changed to E and A. Purified His(6)-tagged terminases with changes at residues 46 and 84 lacked the gpA high-affinity ATPase activity, though the cos cleavage and cohesive end separation activities were near to those of the wild-type enzyme. In virion assembly reactions using virion DNA as a packaging substrate, the mutant terminases showed severe defects. In summary, the results indicate that Y(46) and K(84) are part of the high-affinity ATPase center of gpA, and show that this ATPase activity is involved in the post-cos cleavage stages of lambda DNA packaging.

  18. GSK-3 as a Target for Lithium-induced Neuroprotection against Excitotoxicity in Neuronal Cultures and Animal Models of Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    De-Maw eChuang


    Full Text Available The mood stabilizer lithium inhibits glycogen synthase kinase-3 (GSK-3 directly or indirectly by enhancing serine phosphorylation of both alpha and beta isoforms. Lithium robustly protected primary brain neurons from glutamate-induced excitotoxicity; these actions were mimicked by other GSK-3 inhibitors or silencing/inhibiting GSK-3alpha and/or beta isoforms. Lithium rapidly activated Akt to enhance GSK-3 serine phosphorylation and to block glutamate-induced Akt inactivation. Lithium also upregulated Bcl-2 and suppressed glutamate-induced p53 and Bax. Induction of BDNF was required for lithium’s neuroprotection to occur. BDNF promoter IV was activated by GSK-3 inhibition using lithium or other drugs, or through gene silencing/inactivation of either isoform. Further, lithium’s neuroprotective effects were associated with inhibition of NMDA receptor-mediated calcium influx and downstream signaling. In rodent ischemic models, post-insult treatment with lithium decreased infarct volume, ameliorated neurological deficits and improved functional recovery. Upregulation of heat shock protein 70 (HSP70 and Bcl-2 as well as downregulation of p53 likely contributed to lithium’s protective effects. Delayed treatment with lithium improved functional MRI responses, which was accompanied by enhanced angiogenesis. Two GSK-3-regulated pro-angiogenic factors, matrix metalloproteinase-9 (MMP-9 and vascular endothelial growth factor were induced by lithium. Finally, lithium promoted migration of mesenchymal stem cells (MSCs by upregulation of MMP-9 through GSK-3beta inhibition. Notably, transplantation of lithium-primed MSCs into ischemic rats enhanced MSC migration to the injured brain regions and improved the neurological performance. Several other GSK-3 inhibitors have also been reported to be beneficial in rodent ischemic models. Together, GSK-3 inhibition is a rational strategy to combat ischemic stroke and other excitotoxicity-related brain disorders.

  19. Structure-activity relationships of 111In- and 99mTc-labeled quinolin-4-one peptidomimetics as ligands for the vitronectin receptor: potential tumor imaging agents. (United States)

    Harris, Thomas D; Kalogeropoulos, Shirley; Nguyen, Tiffany; Dwyer, Gregory; Edwards, D Scott; Liu, Shuang; Bartis, Judit; Ellars, Charles; Onthank, Dave; Yalamanchili, Padmaja; Heminway, Stuart; Robinson, Simon; Lazewatsky, Joel; Barrett, John


    The integrin receptor alpha(v)beta(3) is overexpressed on the endothelial cells of growing tumors and on some tumor cells themselves. Radiolabeled alpha(v)beta(3) antagonists have demonstrated potential application as tumor imaging agents and as radiotherapeutic agents. This report describes the total synthesis of eight new HYNIC and DOTA conjugates of receptor alpha(v)beta(3) antagonists belonging to the quinolin-4-one class of peptidomimetics, and their radiolabeling with (99m)Tc (for HYNIC) and (111)In (for DOTA). Tethering of the radionuclide-chelator complexes was achieved at two different sites on the quinolin-4-one molecule. All such derivatives maintained high affinity for receptor alpha(v)beta(3) and high selectivity versus receptors alpha(IIb)beta(3), alpha(v)beta(5), alpha(5)beta(1). Biodistribution of the radiolabeled compounds was evaluated in the c-neu Oncomouse mammary adenocarcinoma model. DOTA conjugate (111)In-TA138 presented the best biodistribution profile. Tumor uptake at 2 h postinjection was 9.39% of injected dose/g of tissue (%ID/g). Activity levels in selected organs was as follows: blood, 0.54% ID/g; liver, 1.94% ID/g; kidney, 2.33% ID/g; lung, 2.74% ID/g; bone, 1.56% ID/g. A complete biodistribution analysis of (111)In-TA138 and the other radiolabeled compounds of this study are presented and discussed. A scintigraphic imaging study with (111)In-TA138 showed a clear delineation of the tumors and rapid clearance of activity from nontarget tissues.

  20. Paleomagnetic evidence for Late Miocene counterclockwise rotation of north coast carbonate sequence, Puerto Rico

    Energy Technology Data Exchange (ETDEWEB)

    Reid, J.A.; Plumley, P.W. (Syracuse Univ., NY (United States)); Schellekens, J.H. (Univ. of Puerto Rico, Mayaguez (Puerto Rico))


    A paleomagnetic study of the essentially undeformed middle Tertiary carbonate sequence along the north coast of Puerto Rico reveals statistically significant pre-Pliocene discordance of characteristic component directions against those expected from cratonic North America for much of the section. Despite generally weak to moderately weak magnetic intensities, confirmation of the magnetization as primary in origin comes from the presence of two distinct components of magnetization, intrasite bipolarity, and/or the reproducibility of measurements. The mean geographic direction for the upper Oligocene to middle Miocene strata is 335.2{degree}/32.9{degree} and the corrected mean paleomagnetic pole is 207.6{degree}/66.5{degree}, (N = 3, {alpha}95 = 4.3{degree}). This suggests a counter-clockwise (CCW) block rotation of Puerto Rico and its microplate of 24.5{degrees} ({plus minus} 5.8{degrees}) during the late Miocene. Using a width of 250 km for the Northern Caribbean Plate Boundary Zone (NCPBZ) between the North American Plate and Caribbean Plate, the mean left lateral displacement implied is 1.8 to 2.4 cm/yr, which agrees fairly well with published relative motion rates for the two plates. Average rotation rate for 50 Ma to 20 Ma was 0.7{degree}/my but perhaps as great as 4{degree}/my in the Miocene. Resolution of mean paleolatitude indicates northward motion of a degree or less during the period of rotation. Causes of this short-lived rotation may include (1) tectonic escape from the inhibiting presence of the Bahama Banks and Beata Ridge during eastward motion of Puerto Rico along the sinistral transpressive Puerto Rico Trench and Muertos Trough fault systems or (2) changes in relative plate motions of the Caribbean and North American Plate during the late Miocene.

  1. The Conoid Associated Motor MyoH Is Indispensable for Toxoplasma gondii Entry and Exit from Host Cells. (United States)

    Graindorge, Arnault; Frénal, Karine; Jacot, Damien; Salamun, Julien; Marq, Jean Baptiste; Soldati-Favre, Dominique


    Many members of the phylum of Apicomplexa have adopted an obligate intracellular life style and critically depend on active invasion and egress from the infected cells to complete their lytic cycle. Toxoplasma gondii belongs to the coccidian subgroup of the Apicomplexa, and as such, the invasive tachyzoite contains an organelle termed the conoid at its extreme apex. This motile organelle consists of a unique polymer of tubulin fibres and protrudes in both gliding and invading parasites. The class XIV myosin A, which is conserved across the Apicomplexa phylum, is known to critically contribute to motility, invasion and egress from infected cells. The MyoA-glideosome is anchored to the inner membrane complex (IMC) and is assumed to translocate the components of the circular junction secreted by the micronemes and rhoptries, to the rear of the parasite. Here we comprehensively characterise the class XIV myosin H (MyoH) and its associated light chains. We show that the 3 alpha-tubulin suppressor domains, located in MyoH tail, are necessary to anchor this motor to the conoid. Despite the presence of an intact MyoA-glideosome, conditional disruption of TgMyoH severely compromises parasite motility, invasion and egress from infected cells. We demonstrate that MyoH is necessary for the translocation of the circular junction from the tip of the parasite, where secretory organelles exocytosis occurs, to the apical position where the IMC starts. This study attributes for the first time a direct function of the conoid in motility and invasion, and establishes the indispensable role of MyoH in initiating the first step of motility along this unique organelle, which is subsequently relayed by MyoA to enact effective gliding and invasion.

  2. The Conoid Associated Motor MyoH Is Indispensable for Toxoplasma gondii Entry and Exit from Host Cells.

    Directory of Open Access Journals (Sweden)

    Arnault Graindorge


    Full Text Available Many members of the phylum of Apicomplexa have adopted an obligate intracellular life style and critically depend on active invasion and egress from the infected cells to complete their lytic cycle. Toxoplasma gondii belongs to the coccidian subgroup of the Apicomplexa, and as such, the invasive tachyzoite contains an organelle termed the conoid at its extreme apex. This motile organelle consists of a unique polymer of tubulin fibres and protrudes in both gliding and invading parasites. The class XIV myosin A, which is conserved across the Apicomplexa phylum, is known to critically contribute to motility, invasion and egress from infected cells. The MyoA-glideosome is anchored to the inner membrane complex (IMC and is assumed to translocate the components of the circular junction secreted by the micronemes and rhoptries, to the rear of the parasite. Here we comprehensively characterise the class XIV myosin H (MyoH and its associated light chains. We show that the 3 alpha-tubulin suppressor domains, located in MyoH tail, are necessary to anchor this motor to the conoid. Despite the presence of an intact MyoA-glideosome, conditional disruption of TgMyoH severely compromises parasite motility, invasion and egress from infected cells. We demonstrate that MyoH is necessary for the translocation of the circular junction from the tip of the parasite, where secretory organelles exocytosis occurs, to the apical position where the IMC starts. This study attributes for the first time a direct function of the conoid in motility and invasion, and establishes the indispensable role of MyoH in initiating the first step of motility along this unique organelle, which is subsequently relayed by MyoA to enact effective gliding and invasion.

  3. Inositol hexaphosphate suppresses growth and induces apoptosis in prostate carcinoma cells in culture and nude mouse xenograft: PI3K-Akt pathway as potential target. (United States)

    Gu, Mallikarjuna; Roy, Srirupa; Raina, Komal; Agarwal, Chapla; Agarwal, Rajesh


    Constitutive activation of phosphoinositide 3-kinase (PI3K)-Akt pathway transmits growth-regulatory signals that play a central role in promoting survival, proliferation, and angiogenesis in human prostate cancer cells. Here, we assessed the efficacy of inositol hexaphosphate (IP6) against invasive human prostate cancer PC-3 and C4-2B cells and regulation of PI3K-Akt pathway. IP6 treatment of cells suppressed proliferation, induced apoptosis along with caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage, and inhibited constitutive activation of Akt and its upstream regulators PI3K, phosphoinositide-dependent kinase-1 and integrin-linked kinase-1 (ILK1). Downstream of Akt, IP6 inhibited the phosphorylation of glycogen synthase kinase-3alpha/beta at Ser(21/9) and consequently reduced cyclin D1 expression. Efficacy studies employing PC-3 tumor xenograft growth in nude mice showed that 2% (w/v) IP6 feeding in drinking water inhibits tumor growth and weight by 52% to 59% (P IP6 significantly reduces the expression of molecules associated with cell survival/proliferation (ILK1, phosphorylated Akt, cyclin D1, and proliferating cell nuclear antigen) and angiogenesis (platelet endothelial cell adhesion molecule-1 or CD31, vascular endothelial growth factor, endothelial nitric oxide synthase, and hypoxia-inducible factor-1alpha) together with an increase in apoptotic markers (cleaved caspase-3 and PARP). These findings suggest that, by targeting the PI3K-ILK1-Akt pathway, IP6 suppresses cell survival, proliferation, and angiogenesis but induces death in prostate cancer cells, which might have translational potential in preventing and controlling the growth of advanced and aggressive prostate cancer for which conventional chemotherapy is not effective.

  4. Tirucallic acids are novel pleckstrin homology domain-dependent Akt inhibitors inducing apoptosis in prostate cancer cells. (United States)

    Estrada, Aydee C; Syrovets, Tatiana; Pitterle, Kai; Lunov, Oleg; Büchele, Berthold; Schimana-Pfeifer, Judith; Schmidt, Thomas; Morad, Samy A F; Simmet, Thomas


    Activation of the serine/threonine kinase Akt is associated with aggressive clinical behavior of prostate cancer. We found that the human prostate cancer cell lines LNCaP and PC-3 express predominantly Akt1 and Akt2. Selective down-regulation of Akt1, but not Akt2, by short-hairpin RNA reduced the viability of prostate cancer cells. In addition, structurally different Akt inhibitors were cytotoxic for the prostate cancer cells, confirming that the Akt pathway is indispensable for their viability. We have purified the tetracyclic triterpenoids 3-oxo-tirucallic acid, 3-alpha-acetoxy-tirucallic acid, and 3-beta-acetoxy-tirucallic acid from the oleogum resin of Boswellia carterii to chemical homogeneity. The acetoxy-derivatives in particular potently inhibited the activities of human recombinant Akt1 and Akt2 and of constitutively active Akt immunoprecipitated from PC-3 cells, whereas inhibitor of nuclear factor-kappaB kinases remained unaffected. Docking data indicated that these tetracyclic triterpenoids form hydrogen bonds within the phosphatidylinositol binding pocket of the Akt pleckstrin homology domain. Accordingly, 3-beta-acetoxy-tirucallic acid did not inhibit the activity of Akt1 lacking the pleckstrin homology domain. In the prostate cancer cell lines investigated, these compounds inhibited the phosphorylation of cellular Akt and the Akt signaling pathways, including glycogen synthase kinase-3beta and BAD phosphorylation, nuclear accumulation of p65, the androgen receptor, beta-catenin, and c-Myc. These events culminated in the induction of apoptosis in prostate cancer, but not in nontumorigenic cells. The tirucallic acid derivatives inhibited proliferation and induced apoptosis in tumors xenografted onto chick chorioallantoic membranes and decreased the growth of pre-established prostate tumors in nude mice without overt systemic toxicity. Thus, tirucallic acid derivatives represent a new class of Akt inhibitors with antitumor properties.

  5. Use of secondary structural information and C-C distance restraints to model protein structures with MODELLER

    Indian Academy of Sciences (India)

    Boojala V B Reddy; Yiannis N Kaznessis


    Protein secondary structure predictions and amino acid long range contact map predictions from primary sequence of proteins have been explored to aid in modelling protein tertiary structures. In order to evaluate the usefulness of secondary structure and 3D-residue contact prediction methods to model protein structures we have used the known Q3 (alpha-helix, beta-strands and irregular turns/loops) secondary structure information, along with residue-residue contact information as restraints for MODELLER. We present here results of our modelling studies on 30 best resolved single domain protein structures of varied lengths. The results shows that it is very difficult to obtain useful models even with 100% accurate secondary structure predictions and accurate residue contact predictions for up to 30% of residues in a sequence. The best models that we obtained for proteins of lengths 37, 70, 118, 136 and 193 amino acid residues are of RMSDs 4.17, 5.27, 9.12, 7.89 and 9.69, respectively. The results show that one can obtain better models for the proteins which have high percent of alpha-helix content. This analysis further shows that MODELLER restrain optimization program can be useful only if we have truly homologous structure(s) as a template where it derives numerous restraints, almost identical to the templates used. This analysis also clearly indicates that even if we satisfy several true residue-residue contact distances, up to 30% of their sequence length with fully known secondary structural information, we end up predicting model structures much distant from their corresponding native structures.

  6. New pyrazole derivative 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole: synthesis and assessment of some biological activities. (United States)

    de Oliveira, Lanussy Porfiro; da Silva, Daiany Priscilla Bueno; Florentino, Iziara Ferreira; Fajemiroye, James Oluwagbamigbe; de Oliveira, Thiago Sardinha; Marcelino, Renato Ivan de Ávila; Pazini, Francine; Lião, Luciano Morais; Ghedini, Paulo César; de Moura, Soraia Santana; Valadares, Marize Campos; de Carvalho, Verônica Vale; Vaz, Boniek Gontijo; Menegatti, Ricardo; Costa, Elson Alves


    The molecular modification and synthesis of compounds is vital to discovering drugs with desirable pharmacological and toxicity profiles. In response to pyrazole compounds' antipyretic, analgesic, and anti-inflammatory effects, this study sought to evaluate the analgesic, anti-inflammatory, and vasorelaxant effects, as well as the mechanisms of action, of a new pyrazole derivative, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole. During the acetic acid-induced abdominal writhing test, treatments with 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced abdominal writhing, while during the formalin test, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced licking times in response to both neurogenic pain and inflammatory pain, all without demonstrating any antinociceptive effects, as revealed during the tail flick test. 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole also reduced carrageenan-induced paw edema and cell migration during the carrageenan-induced pleurisy test. As demonstrated by the model of the isolated organ, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole exhibits a vasorelaxant effect attenuated by Nω-nitro-l-arginine methyl ester, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one, tetraethylammonium or glibenclamide. 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole also blocked CaCl2 -induced contraction in a dose-dependent manner. Suggesting a safe toxicity profile, 5-[1-(4-fluorophenyl)-1H-pyrazol-4-yl]-2H-tetrazole reduced the viability of 3T3 cells at higher concentrations and was orally tolerated, despite signs of toxicity in doses of 2000 mg/kg. Lastly, the compounds' analgesic activity might be attributed to the involvement of the NO/cGMP pathway and K(+) channels observed in the vasorelaxant effect.

  7. Autophagy in periodontitis patients and gingival fibroblasts: unraveling the link between chronic diseases and inflammation

    Directory of Open Access Journals (Sweden)

    Bullon Pedro


    Full Text Available Abstract Background Periodontitis, the most prevalent chronic inflammatory disease, has been related to cardiovascular diseases. Autophagy provides a mechanism for the turnover of cellular organelles and proteins through a lysosome-dependent degradation pathway. The aim of this research was to study the role of autophagy in peripheral blood mononuclear cells from patients with periodontitis and gingival fibroblasts treated with a lipopolysaccharide of Porphyromonas gingivalis. Autophagy-dependent mechanisms have been proposed in the pathogenesis of inflammatory disorders and in other diseases related to periodontitis, such as cardiovascular disease and diabetes. Thus it is important to study the role of autophagy in the pathophysiology of periodontitis. Methods Peripheral blood mononuclear cells from patients with periodontitis (n = 38 and without periodontitis (n = 20 were used to study autophagy. To investigate the mechanism of autophagy, we evaluated the influence of a lipopolysaccharide from P. gingivalis in human gingival fibroblasts, and autophagy was monitored morphologically and biochemically. Autophagosomes were observed by immunofluorescence and electron microscopy. Results We found increased levels of autophagy gene expression and high levels of mitochondrial reactive oxygen species production in peripheral blood mononuclear cells from patients with periodontitis compared with controls. A significantly positive correlation between both was observed. In human gingival fibroblasts treated with lipopolysaccharide from P. gingivalis, there was an increase of protein and transcript of autophagy-related protein 12 (ATG12 and microtubule-associated protein 1 light chain 3 alpha LC3. A reduction of mitochondrial reactive oxygen species induced a decrease in autophagy whereas inhibition of autophagy in infected cells increased apoptosis, showing the protective role of autophagy. Conclusion Results from the present study suggest that autophagy

  8. Ozone-induced inflammation in the lower airways of human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Koren, H.S.; Devlin, R.B.; Graham, D.E.; Mann, R.; McGee, M.P.; Horstman, D.H.; Kozumbo, W.J.; Becker, S.; House, D.E.; McDonnell, W.F.


    Although ozone (O3) has been shown to induce inflammation in the lungs of animals, very little is known about its inflammatory effects on humans. In this study, 11 healthy nonsmoking men, 18 to 35 yr of age (mean, 25.4 +/- 3.5), were exposed once to 0.4 ppm O3 and once to filtered air for 2 h with intermittent exercise. Eighteen hours later, bronchoalveolar lavage (BAL) was performed and the cells and fluid were analyzed for various indicators of inflammation. There was an 8.2-fold increase in the percentage of polymorphonuclear leukocytes (PMN) in the total cell population, and a small but significant decrease in the percentage of macrophages after exposure to O3. Immunoreactive neutrophil elastase often associated with inflammation and lung damage increased by 3.8-fold in the fluid while its activity increased 20.6-fold in the lavaged cells. A 2-fold increase in the levels of protein, albumin, and IgG suggested increased vascular permeability of the lung. Several biochemical markers that could act as chemotactic or regulatory factors in an inflammatory response were examined in the BAL fluid (BALF). The level of complement fragment C3 alpha was increased by 1.7-fold. The chemotactic leukotriene B4 was unchanged while prostaglandin E2 increased 2-fold. In contrast, three enzyme systems of phagocytes with potentially damaging effects on tissues and microbes, namely, NADPH-oxidase and the lysosomal enzymes acid phosphatase and beta-glucuronidase, were increased neither in the lavaged fluid nor cells. In addition, the amounts of fibrogenic-related molecules were assessed in BALF.

  9. Photoaffinity labeling of rat liver microsomal morphine UDP-glucuronosyltransferase by ( sup 3 H)flunitrazepam

    Energy Technology Data Exchange (ETDEWEB)

    Thomassin, J.; Tephly, T.R. (Univ. of Iowa, Iowa City (USA))


    Benzodiazepines have been shown to competitively inhibit morphine glucuronidation in rat and human hepatic microsomes. Flunitrazepam exerted a potent competitive inhibition of rat hepatic morphine UDP-glucuronosyltransferase (UDPGT) activity (Ki = 130 microM). It has no effect on the activity of p-nitrophenol, 17 beta-hydroxysteroid, 3 alpha-hydroxysteroid, or 4-hydroxybiphenyl UDPGTs. Because flunitrazepam is an effective photoaffinity label for benzodiazepine receptors, studied were performed in solubilized rat hepatic microsomes and with partially purified preparations of morphine UDPGT to determine the enhancement of flunitrazepam inhibition and binding to morphine UDPGT promoted by exposure to UV light. Under UV light, flunitrazepam inhibition was markedly enhanced. UV light exposure also led to a marked increase in binding of (3H)flunitrazepam to microsomal protein, which was protected substantially by preincubation with morphine. Testosterone, androsterone, and UDP-glucuronic acid did not protect against UV-enhanced flunitrazepam binding, and morphine did not reverse flunitrazepam binding once binding had occurred. As morphine UDPGT was purified, a good correlation was found between the increases in specific activity of morphine UDPGT and flunitrazepam binding to protein. Chromatofocusing chromatography showed that flunitrazepam bound only to fractions containing active morphine UDPGT, and no binding to 4-hydroxybiphenyl UDPGT was observed. Fluorography of a sodium dodecyl sulfate-polyacrylamide electrophoresis gel of solubilized hepatic microsomes that had been treated with (3H) flunitrazepam under UV light revealed a band with a monomeric molecular weight between 54,000 and 58,000. This monomeric molecular weight compares favorably with the reported monomeric molecular weight of homogeneous morphine UDPGT (56,000).

  10. Na(v)1.7 and Na(v)1.3 are the only tetrodotoxin-sensitive sodium channels expressed by the adult guinea pig enteric nervous system. (United States)

    Sage, D; Salin, P; Alcaraz, G; Castets, F; Giraud, P; Crest, M; Mazet, B; Clerc, N


    The types of sodium channels that are expressed by neurons shape the rising phase of action potentials and influence patterns of action potential discharge. With regard to the enteric nervous system (ENS), there is uncertainty about which channels are expressed, and in particular it is unknown whether Na(v)1.7 is present. We designed specific probes for the guinea pig Na(v)1.7 alpha subunit as well as for the other tetrodotoxin (TTX)-sensitive alpha subunits (Na(v)1.1, Na(v)1.2, Na(v)1.3, and Na(v)1.6) in order to perform in situ hybridization (ISH) histochemistry on guinea pig myenteric ganglia. We established that only Na(v)1.7 mRNA and Na(v)1.3 mRNA are expressed in these ganglia. The ISH signal for Na(v)1.7 transcripts was found in seemingly all the myenteric neurons. The expression of the Na(v)1.3 alpha subunit was confirmed by immunohistochemistry in a large proportion (62%) of the myenteric neuron population. This population included enteric sensory neurons. Na(v)1.6 immunoreactivity, absent from myenteric neurons, was detected in glial cells only when a high anti-Na(v)1.6 antibody concentration was used. This suggests that the Na(v)1.6 alpha subunit and mRNA are present only at low levels, which is consistent with the fact that no Na(v)1.6 mRNA could be detected in the ENS by ISH. The fact that adult myenteric neurons are endowed with only two TTX-sensitive alpha subunits, namely, Na(v)1.3 and Na(v)1.7, emphasizes the singularity of the ENS. Both these subunits, known to have slow-inactivation kinetics, are well adapted for generating action potentials from slow excitatory postsynaptic potentials, a mode of synaptic transmission that applies to all ENS neuron types.


    Directory of Open Access Journals (Sweden)

    Amit Kumar


    Full Text Available Bright red hemoglobins, the most well-known paradigm in protein science, seem to be ubiquitous in nature. With advances in modern tools and techniques, discovery of new globins at a rapid pace has expanded this family. With every discovery, new insights emerged regarding their novel structure, function and several other characteristics previously not observed for hemoglobins. Even the classical function unanimously assigned to hemoglobins – oxygen transport and storage – needed re-evaluation. The ability of this class of proteins to show responses against various gaseous ligands, even the poisonous ones, indicate that it is obviously as ancient as life. As organisms evolved, hemoglobins also evolved, and accumulated a great degree of diversity in all aspects. The classical globin fold is very unique with 3-on-3 alpha helical bundle as observed in the traditional oxygen-transport hemoglobins like myoglobin, human blood hemoglobin and leghemoglobins in plants. However, a class of the newly discovered hemoglobins, which dominate the superfamily and appears ancient in origin mostly have 2-on-2 fold, commonly termed as “truncated” hemoglobins. These hemoglobins are phylogenetically distinct from their classical counterparts and are often shorter in their polypeptide length by 20-40 residues mainly due to a lack of short A helix, D helix and F helix. However, hemoglobins with 2-on-2 fold were also later found to have polypeptide chain lengths similar in size to classical globins. Disordered pre-F helix region, conserved glycine motifs and other key residues and apolar tunnels through their protein matrix for migration of ligands are some unique characteristics features of these truncated hemoglobins. Some of these are also hexacoordinated at heme iron where an amino acid from within the protein coordinates heme iron in absence of a ligand. These hemoglobins are well known for their high affinity towards ligand and have a diverse mechanism of

  12. Acyl-CoA:cholesterol acyltransferases (ACATs/SOATs): Enzymes with multiple sterols as substrates and as activators. (United States)

    Rogers, Maximillian A; Liu, Jay; Song, Bao-Liang; Li, Bo-Liang; Chang, Catherine C Y; Chang, Ta-Yuan


    Cholesterol is essential to the growth and viability of cells. The metabolites of cholesterol include: steroids, oxysterols, and bile acids, all of which play important physiological functions. Cholesterol and its metabolites have been implicated in the pathogenesis of multiple human diseases, including: atherosclerosis, cancer, neurodegenerative diseases, and diabetes. Thus, understanding how cells maintain the homeostasis of cholesterol and its metabolites is an important area of study. Acyl-coenzyme A:cholesterol acyltransferases (ACATs, also abbreviated as SOATs) converts cholesterol to cholesteryl esters and play key roles in the regulation of cellular cholesterol homeostasis. ACATs are most unusual enzymes because (i) they metabolize diverse substrates including both sterols and certain steroids; (ii) they contain two different binding sites for steroidal molecules. In mammals, there are two ACAT genes that encode two different enzymes, ACAT1 and ACAT2. Both are allosteric enzymes that can be activated by a variety of sterols. In addition to cholesterol, other sterols that possess the 3-beta OH at C-3, including PREG, oxysterols (such as 24(S)-hydroxycholesterol and 27-hydroxycholesterol, etc.), and various plant sterols, could all be ACAT substrates. All sterols that possess the iso-octyl side chain including cholesterol, oxysterols, various plant sterols could all be activators of ACAT. PREG can only be an ACAT substrate because it lacks the iso-octyl side chain required to be an ACAT activator. The unnatural cholesterol analogs epi-cholesterol (with 3-alpha OH in steroid ring B) and ent-cholesterol (the mirror image of cholesterol) contain the iso-octyl side chain but do not have the 3-beta OH at C-3. Thus, they can only serve as activators and cannot serve as substrates. Thus, within the ACAT holoenzyme, there are site(s) that bind sterol as substrate and site(s) that bind sterol as activator; these sites are distinct from each other. These features form

  13. Millisecond autothermal catalytic reforming of carbohydrates for synthetic fuels by reactive flash volatilization (United States)

    Dauenhauer, Paul Jakob

    Carbohydrates including glucose, cellulose, starch and polyols including glycerol, ethylene glycol and methanol produced in large quantities from biomass are considered as a carbon-based feedstock for high temperature catalytic reforming by catalytic partial oxidation. Autothermal catalytic partial oxidation of methanol, ethylene glycol, and glycerol with Rh and Pt-based catalysts with ceria on alumina foam supports at residence times less than ten milliseconds produced equilibrium selectivity to synthesis gas. The addition of steam at S/C>4 produced selectivity to H2 higher than 80% with little or no selectivity to minor products. In a new process referred to as 'reactive flash volatilization,' catalytic partial oxidation was combined with pyrolysis of biomass by directly impinging particles of cellulose, starch, polyethylene, soy oil, or Aspen (Populous Tremuloides) on an operating Rh-based reforming catalyst at 700-800°C. Solid particles endothermically pyrolyzed to volatile organic compounds which mixed with air and reformed on the catalyst exothermically generating heat to drive the overall process. Particles of ˜250 mum microcrystalline cellulose processed at the conditions of C/O=1.0 on a RhCe/gamma-Al2O3/alpha-Al 2O3 at a residence time of ˜70 milliseconds produced a gaseous effluent stream selecting for 50% H2 and 50% CO with no observable side products other than H2O and CO2, and feed ratio of N2/O2, the temperature of the feed gas, the total particle feed rate, and the addition of steam permitting cellulose conversion with ˜75% fuel efficiency. Cellulose, sucrose, and glycerol particle conversion was examined with high-speed photography (1000 frames/second) revealing the formation of a liquid intermediate from cellulose permitting extremely high heat flux (˜1 MW/m 2). Finally, large cellulose rods (7x7x500 mm) were directly pressed against a Rh-based reforming catalyst co-reforming methane with air to examine the processing speed as a function of

  14. Reduced bone breakage and increased bone strength in free range laying hens fed omega-3 polyunsaturated fatty acid supplemented diets. (United States)

    Tarlton, John F; Wilkins, Lindsay J; Toscano, Michael J; Avery, Nick C; Knott, Lynda


    The omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are the immediate precursors to a number of important mediators of immunity, inflammation and bone function, with products of omega-6 generally thought to promote inflammation and favour bone resorption. Western diets generally provide a 10 to 20-fold deficit in omega-3 PUFAs compared with omega-6, and this is thought to have contributed to the marked rise in incidence of disorders of modern human societies, such as heart disease, colitis and perhaps osteoporosis. Many of our food production animals, fed on grains rich in omega-6, are also exposed to a dietary deficit in omega-3, with perhaps similar health consequences. Bone fragility due to osteoporotic changes in laying hens is a major economic and welfare problem, with our recent estimates of breakage rates indicating up to 95% of free range hens suffer breaks during lay. Free range hens housed in full scale commercial systems were provided diets supplemented with omega-3 alpha linolenic acid, and the skeletal benefits were investigated by comparison to standard diets rich in omega-6. There was a significant 40-60% reduction in keel bone breakage rate, and a corresponding reduction in breakage severity in the omega-3 supplemented hens. There was significantly greater bone density and bone mineral content, alongside increases in total bone and trabecular volumes. The mechanical properties of the omega-3 supplemented hens were improved, with strength, energy to break and stiffness demonstrating significant increases. Alkaline phosphatase (an osteoblast marker) and tartrate-resistant acid phosphatase (an osteoclast marker) both showed significant increases with the omega-3 diets, indicating enhanced bone turnover. This was corroborated by the significantly lower levels of the mature collagen crosslinks, hydroxylysyl pyridinoline, lysyl pyridinoline and histidinohydroxy-lysinonorleucine, with a corresponding significant shift in the mature

  15. Platypus globin genes and flanking loci suggest a new insertional model for beta-globin evolution in birds and mammals. (United States)

    Patel, Vidushi S; Cooper, Steven J B; Deakin, Janine E; Fulton, Bob; Graves, Tina; Warren, Wesley C; Wilson, Richard K; Graves, Jennifer A M


    Vertebrate alpha (alpha)- and beta (beta)-globin gene families exemplify the way in which genomes evolve to produce functional complexity. From tandem duplication of a single globin locus, the alpha- and beta-globin clusters expanded, and then were separated onto different chromosomes. The previous finding of a fossil beta-globin gene (omega) in the marsupial alpha-cluster, however, suggested that duplication of the alpha-beta cluster onto two chromosomes, followed by lineage-specific gene loss and duplication, produced paralogous alpha- and beta-globin clusters in birds and mammals. Here we analyse genomic data from an egg-laying monotreme mammal, the platypus (Ornithorhynchus anatinus), to explore haemoglobin evolution at the stem of the mammalian radiation. The platypus alpha-globin cluster (chromosome 21) contains embryonic and adult alpha- globin genes, a beta-like omega-globin gene, and the GBY globin gene with homology to cytoglobin, arranged as 5'-zeta-zeta'-alphaD-alpha3-alpha2-alpha1-omega-GBY-3'. The platypus beta-globin cluster (chromosome 2) contains single embryonic and adult globin genes arranged as 5'-epsilon-beta-3'. Surprisingly, all of these globin genes were expressed in some adult tissues. Comparison of flanking sequences revealed that all jawed vertebrate alpha-globin clusters are flanked by MPG-C16orf35 and LUC7L, whereas all bird and mammal beta-globin clusters are embedded in olfactory genes. Thus, the mammalian alpha- and beta-globin clusters are orthologous to the bird alpha- and beta-globin clusters respectively. We propose that alpha- and beta-globin clusters evolved from an ancient MPG-C16orf35-alpha-beta-GBY-LUC7L arrangement 410 million years ago. A copy of the original beta (represented by omega in marsupials and monotremes) was inserted into an array of olfactory genes before the amniote radiation (>315 million years ago), then duplicated and diverged to form orthologous clusters of beta-globin genes with different expression

  16. Nitric oxide, cholesterol oxides and endothelium-dependent vasodilation in plasma of patients with essential hypertension

    Directory of Open Access Journals (Sweden)

    P. Moriel


    Full Text Available The objective of the present study was to identify disturbances of nitric oxide radical (·NO metabolism and the formation of cholesterol oxidation products in human essential hypertension. The concentrations of·NO derivatives (nitrite, nitrate, S-nitrosothiols and nitrotyrosine, water and lipid-soluble antioxidants and cholesterol oxides were measured in plasma of 11 patients with mild essential hypertension (H: 57.8 ± 9.7 years; blood pressure, 148.3 ± 24.8/90.8 ± 10.2 mmHg and in 11 healthy subjects (N: 48.4 ± 7.0 years; blood pressure, 119.4 ± 9.4/75.0 ± 8.0 mmHg.Nitrite, nitrate and S-nitrosothiols were measured by chemiluminescence and nitrotyrosine was determined by ELISA. Antioxidants were determined by reverse-phase HPLC and cholesterol oxides by gas chromatography. Hypertensive patients had reduced endothelium-dependent vasodilation in response to reactive hyperemia (H: 9.3 and N: 15.1% increase of diameter 90 s after hyperemia, and lower levels of ascorbate (H: 29.2 ± 26.0, N: 54.2 ± 24.9 µM, urate (H: 108.5 ± 18.9, N: 156.4 ± 26.3 µM, ß-carotene (H: 1.1 ± 0.8, N: 2.5 ± 1.2 nmol/mg cholesterol, and lycopene (H: 0.4 ± 0.2, N: 0.7 ± 0.2 nmol/mg cholesterol, in plasma, compared to normotensive subjects. The content of 7-ketocholesterol, 5alpha-cholestane-3ß,5,6ß-triol and 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol in LDL, and the concentration of endothelin-1 (H: 0.9 ± 0.2, N: 0.7 ± 0.1 ng/ml in plasma were increased in hypertensive patients. No differences were found for ·NO derivatives between groups. These data suggest that an increase in cholesterol oxidation is associated with endothelium dysfunction in essential hypertension and oxidative stress, although ·NO metabolite levels in plasma are not modified in the presence of elevated cholesterol oxides.

  17. The Saccharomyces cerevisiae Leu3 protein activates expression of GDH1, a key gene in nitrogen assimilation. (United States)

    Hu, Y; Cooper, T G; Kohlhaw, G B


    The Leu3 protein of Saccharomyces cerevisiae has been shown to be a transcriptional regulator of genes encoding enzymes of the branched-chain amino acid biosynthetic pathways. Leu3 binds to upstream activating sequences (UASLEU) found in the promoters of LEU1, LEU2, LEU4, ILV2, and ILV5. In vivo and in vitro studies have shown that activation by Leu3 requires the presence of alpha-isopropylmalate. In at least one case (LEU2), Leu3 actually represses basal-level transcription when alpha-isopropylmalate is absent. Following identification of a UASLEU-homologous sequence in the promoter of GDH1, the gene encoding NADP(+)-dependent glutamate dehydrogenase, we demonstrate that Leu3 specifically interacts with this UASLEU element. We then show that Leu3 is required for full activation of the GDH1 gene. First, the expression of a GDH1-lacZ fusion gene is three- to sixfold lower in a strain lacking the LEU3 gene than in an isogenic LEU3+ strain. Expression is restored to near-normal levels when the leu3 deletion cells are transformed with a LEU3-bearing plasmid. Second, a significant decrease in GDH1-lacZ expression is also seen when the UASLEU of the GDH1-lacZ construct is made nonfunctional by mutation. Third, the steady-state level of GDH1 mRNA decreases about threefold in leu3 null cells. The decrease in GDH1 expression in leu3 null cells is reflected in a diminished specific activity of NADP(+)-dependent glutamate dehydrogenase. We also demonstrate that the level of GDH1-lacZ expression correlates with the cells' ability to generate alpha-isopropylmalate and is lowest in cells unable to produce alpha-isopropylmalate. We conclude that GDH1, which plays an important role in the assimilation of ammonia in yeast cells, is, in part, activated by a Leu3-alpha-isopropylmalate complex. This conclusion suggests that Leu3 participates in transcriptional regulation beyond the branched-chain amino acid biosynthetic pathways.

  18. Noninvasive visualization and quantification of tumor {alpha}{sub V{beta}3} integrin expression using a novel positron emission tomography probe, {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Zhao-Hui [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Furukawa, Takako, E-mail: tfuru@nirs.go.j [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan); Galibert, Mathieu; Boturyn, Didier [Departement de Chimie Moleculaire, UMR 5250, CNRS-Universite Joseph Fourier, 38041 Grenoble Cedex 9 (France); Coll, Jean-Luc [INSERM U823, Institut Albert Bonniot and Universite Joseph Fourier, 38706 La Tronche Cedex, Grenoble (France); Fukumura, Toshimitsu; Saga, Tsuneo [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Dumy, Pascal [Departement de Chimie Moleculaire, UMR 5250, CNRS-Universite Joseph Fourier, 38041 Grenoble Cedex 9 (France); Fujibayashi, Yasuhisa [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Biomedical Imaging Research Center, University of Fukui, Fukui 910-1193 (Japan)


    Introduction: The {alpha}{sub V{beta}3} integrin is a well-known transmembrane receptor involved in tumor invasion, angiogenesis and metastasis. Our aim was to evaluate a novel positron emission tomography (PET) probe, {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4}, for noninvasive visualization and quantification of {alpha}{sub V{beta}3} integrin expression. Methods: RAFT-c(-RGDfK-){sub 4}, a tetrameric cyclic Arg-Gly-Asp (RGD)-based peptide, was conjugated with a bifunctional chelator, 1,4,8,11-tetraazacyclotetradecane (cyclam), radiolabeled with the positron emitter {sup 64}Cu and evaluated in vitro by cell binding and competitive inhibition assays and in vivo by biodistribution and receptor blocking studies, and PET imaging. The following cell lines, human embryonic kidney HEK293({beta}{sub 1}) [{alpha}{sub V{beta}3}-negative] and HEK293({beta}{sub 3}) [{alpha}{sub V{beta}3}-overexpressing] and human glioblastoma U87MG [naturally expressing {alpha}{sub V{beta}3}], together with their subcutaneous xenografts in athymic nude mice, were used for the present study. The expression levels of {alpha}{sub V{beta}3} on these cell lines and tumor xenografts were analyzed by flow cytometry and sodium dodecyl sulfate-polyacrylamide gel electrophoresis/autoradiography, respectively. Results: {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4} demonstrated the in vitro and in vivo specificity for the {alpha}{sub V{beta}3} integrin and displayed rapid blood clearance, predominantly renal excretion and low uptake in nontumor tissues. Tumor uptake of {sup 64}Cu-cyclam-RAFT-c(-RGDfK-){sub 4} (3 h postinjection) in HEK293({beta}{sub 3}) (high levels of {alpha}{sub V{beta}3}), U87MG (moderate levels of {alpha}{sub V{beta}3}) and HEK293({beta}{sub 1}) (undetectable levels of {alpha}{sub V{beta}3}) tumors was 9.35%{+-}1.19%, 3.46%{+-}0.45% and 1.18%{+-}0.30% injected dose per gram, respectively, with a strong and positive correlation with the tumor {alpha}{sub V{beta}3} expression levels

  19. A high-throughput, nonisotopic, competitive binding assay for kinases using nonselective inhibitor probes (ED-NSIP). (United States)

    Vainshtein, Inna; Silveria, Scott; Kaul, Poonam; Rouhani, Riaz; Eglen, Richard M; Wang, John


    A novel competitive binding assay for protein kinase inhibitors has been developed for high-throughput screening (HTS). Unlike functional kinase assays, which are based on detection of substrate phosphorylation by the enzyme, this novel method directly measures the binding potency of compounds to the kinase ATP binding site through competition with a conjugated binding probe. The binding interaction is coupled to a signal amplification system based on complementation of beta-galactosidase enzyme fragments, a homogeneous, nonisotopic assay technology platform developed by DiscoveRx Corp. In the present study, staurosporine, a potent, nonselective kinase inhibitor, was chemically conjugated to a small fragment of beta-galactosidase (termed ED-SS). This was used as the binding probe to the kinase ATP binding pocket. The binding potencies of several inhibitors with diverse structures were assessed by displacement of ED-SS from the kinase. The assay format was specifically evaluated with GSK3alpha, an enzyme previously screened in a radioactive kinase assay (i.e., measurement of [(33)P]-gamma-ATP incorporation into the kinase peptide substrate). Under optimized assay conditions, nonconjugated staurosporine inhibited ED-SS binding in a concentration-dependent manner with an apparent potency (IC(50)) of 11 nM, which was similar to the IC(50) value determined in a radioactive assay. Furthermore, 9 kinase inhibitors with diverse structures, previously identified from chemical compound library screening, were screened using the competitive binding assay. The potencies in the binding assay were in very good agreement with those obtained previously in the isotopic functional activity assay. The binding assay was adapted for automated HTS using selected compound libraries in a 384-well microtiter plate format. The HTS assay was observed to be highly robust and reproducible (Z' factors > 0.7) with high interassay precision (R(2) > 0.96). Interference of compounds with the beta

  20. Principles of the bark of Amphipterygium adstringens (Julianaceae) with anti-inflammatory activity. (United States)

    Oviedo-Chávez, I; Ramírez-Apan, T; Soto-Hernández, M; Martínez-Vázquez, M


    Despite the fact that Amphipterygium adstringens (usually known as "cuachalalate") is used intensively in traditional medicine throughout México, there are, to our knowledge, no previous studies concerning the actual therapeutic, anti-inflammatory properties of this species. This lack of data prompted us to evaluate the aqueous (AE) and hexane (HE) extracts from A. adstringens in two models of acute inflammation: 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema and carrageenan-induced paw edema. The results showed that HE possesses dose-dependent activity, while AE showed no anti-inflammatory effect on TPA-induced edema. Reverse effects were found in the carrageenan test, wherein AE showed a 73.5% of inhibition of edema, while HE showed only a 14.4% activity at 100 mg/kg body weight. These results could indicate that AE and HE possess different anti-inflammatory mechanisms of action. On the other hand, it is known that masticadienonic (1) and 3alpha-hydroxymasticadienonic (2) acids are the main constituents of the organic extract of A. adstringens bark. Because of this knowledge, we tested 1 and 2 in the same experimental models. The results showed that 2 possesses a dose-dependent effect, while 1 does not show a dose-dependent response in TPA-induced edema. In carrageenan-induced edema tests, both 1 and 2 showed almost the same activity (approximately 44% inhibition at 100 mg/kg body weight). In order to determine whether the anti-inflammatory activities of AE, HE, 1 and 2 are involved in the alteration of inducible nitric oxide synthase (iNOS) activity, we evaluated these substances by examining nitric oxide generation in lipopolysaccharide (LPS)-activated peritoneal macrophages. The results showed that 1 presented the highest activity (93.3%), followed by 2 (86.5%), while AE (57%) and HE (33.6%) showed the lowest. In the cytotoxic MTT assay, however only 1 and 2 showed any activity whatsoever.

  1. The immune function of MHC class II molecules mutated in the putative superdimer interface. (United States)

    Hayball, John D; Lake, Richard A


    Analysis of the crystal structure of human class II (HLA-DR1) molecules suggests that the alphabeta heterodimer may be further ordered as a dimer of heterodimers (superdimer), leading to the hypothesis that T cell receptor dimerisation is a mechanism for initiating signaling events preceding T cell activation. The interface between pairs of molecules is stabilised by both salt bridges, polar and hydrophobic interactions. The residues that form the superdimer interface occur in three areas distinct from the antigen-binding groove. They can be defined as follows: region 1, beta-beta contacts in the helix of the beta1 domain; region 2, alpha-alpha contacts near the alpha 1/alpha2 domain junction and region 3; alpha-beta contacts in the alpha2/beta2 domains adjacent to the plasma membrane. To determine whether salt bridges and polar interactions formed within these regions are involved in the immune function of the murine MHC class II molecule, I-A(b), appropriate residues in both the alpha and beta chain were identified and mutated to uncharged alanine. Cell lines transfected with different combinations of mutated alpha and beta chains were generated and tested for MHC class II expression, peptide binding capabilities, and ability to present antigenic peptide to an OVA-specific T cell hybridoma. With the exception of two residues in region 2, the substitutions tested did not modulate MHC class II expression, or peptide binding function. When tested for ability to present peptide to an antigen-specific T cell hybridoma, with the exception of mutations in region 2, the substitutions did not appear to abrogate the ability of I-A(b) to stimulate the T cells. These results suggest that mutation of residues in region 2 of the putative superdimer interface have a gross effect on the ability of I-A(b) to be expressed on the cell surface. However, abrogation of salt bridges in region 1 and 3 do not influence I-A(b) cell surface expression, peptide binding or ability to

  2. Conversion of Human Steroid 5[beta]-Reductase (AKR1D1) into 3[beta]-Hydroxysteroid Dehydrogenase by Single Point Mutation E120H: Example of Perfect Enzyme Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Mo; Drury, Jason E.; Christianson, David W.; Penning, Trevor M. (UPENN)


    Human aldo-keto reductase 1D1 (AKR1D1) and AKR1C enzymes are essential for bile acid biosynthesis and steroid hormone metabolism. AKR1D1 catalyzes the 5{beta}-reduction of {Delta}{sup 4}-3-ketosteroids, whereas AKR1C enzymes are hydroxysteroid dehydrogenases (HSDs). These enzymes share high sequence identity and catalyze 4-pro-(R)-hydride transfer from NADPH to an electrophilic carbon but differ in that one residue in the conserved AKR catalytic tetrad, His120 (AKR1D1 numbering), is substituted by a glutamate in AKR1D1. We find that the AKR1D1 E120H mutant abolishes 5{beta}-reductase activity and introduces HSD activity. However, the E120H mutant unexpectedly favors dihydrosteroids with the 5{alpha}-configuration and, unlike most of the AKR1C enzymes, shows a dominant stereochemical preference to act as a 3{beta}-HSD as opposed to a 3{alpha}-HSD. The catalytic efficiency achieved for 3{beta}-HSD activity is higher than that observed for any AKR to date. High resolution crystal structures of the E120H mutant in complex with epiandrosterone, 5{beta}-dihydrotestosterone, and {Delta}{sup 4}-androstene-3,17-dione elucidated the structural basis for this functional change. The glutamate-histidine substitution prevents a 3-ketosteroid from penetrating the active site so that hydride transfer is directed toward the C3 carbonyl group rather than the {Delta}{sup 4}-double bond and confers 3{beta}-HSD activity on the 5{beta}-reductase. Structures indicate that stereospecificity of HSD activity is achieved because the steroid flips over to present its {alpha}-face to the A-face of NADPH. This is in contrast to the AKR1C enzymes, which can invert stereochemistry when the steroid swings across the binding pocket. These studies show how a single point mutation in AKR1D1 can introduce HSD activity with unexpected configurational and stereochemical preference.

  3. Visceral adiposity syndrome. (United States)

    Lopes, Heno F; Corrêa-Giannella, Maria Lúcia; Consolim-Colombo, Fernanda M; Egan, Brent M


    The association of anthropometric (waist circumference) and hemodynamic (blood pressure) changes with abnormalities in glucose and lipid metabolism has been motivation for a lot of discussions in the last 30 years. Nowadays, blood pressure, body mass index/abdominal circumference, glycemia, triglyceridemia, and HDL-cholesterol concentrations are considered in the definition of Metabolic syndrome, referred as Visceral adiposity syndrome (VAS) in the present review. However, more than 250 years ago an association between visceral and mediastinal obesity with hypertension, gout, and obstructive apnea had already been recognized. Expansion of visceral adipose tissue secondary to chronic over-consumption of calories stimulates the recruitment of macrophages, which assume an inflammatory phenotype and produce cytokines that directly interfere with insulin signaling, resulting in insulin resistance. In turn, insulin resistance (IR) manifests itself in various tissues, contributing to the overall phenotype of VAS. For example, in white adipose tissue, IR results in lipolysis, increased free fatty acids release and worsening of inflammation, since fatty acids can bind to Toll-like receptors. In the liver, IR results in increased hepatic glucose production, contributing to hyperglycemia; in the vascular endothelium and kidney, IR results in vasoconstriction, sodium retention and, consequently, arterial hypertension. Other players have been recognized in the development of VAS, such as genetic predisposition, epigenetic factors associated with exposure to an unfavourable intrauterine environment and the gut microbiota. More recently, experimental and clinical studies have shown the autonomic nervous system participates in modulating visceral adipose tissue. The sympathetic nervous system is related to adipose tissue function and differentiation through beta1, beta2, beta3, alpha1, and alpha2 adrenergic receptors. The relation is bidirectional: sympathetic denervation of

  4. Consumo e padronização de fármacos antihipertensivos na farmácia-ensino da Universidade Estadual de Maringá (FEN-UEM Distribution and standardization of antihypertensive medications in the pharmacy of State University of Maringá (FEN-UEM

    Directory of Open Access Journals (Sweden)

    Roberto Kenji Nakamura Cuman


    Full Text Available Com o objetivo de padronizar fármacos anti-hipertensivos na FEN-UEM, foram analisados a aquisição e o consumo desses fármacos. Os dados foram coletados a partir das notas fiscais de compra das especialidades farmacêuticas anti-hipertensivas (EAH pela referida farmácia. O estudo foi realizado no período de primeiro de janeiro de 1990 a trinta e um de dezembro de 1994. Foram analisados a quantidade de EAH adquirida, o princípio ativo e a classe farmacológica. A FEN - UEM adquiriu 4.751 EAH nesse período. Houve aumento na aquisição de inibidores da enzima conversora de angiotensina (63,6% e redução na de diuréticos (54,2%, bloqueadores beta-adrenérgicos (36,3%, agonistas alfa centrais (64,3% e associações (28,2%. A aquisição de bloqueadores de canais de cálcio foi constante nesse período. Os dados sugerem que a aquisição e a dispensação desses medicamentos estão correlacionadas com a terapêutica atual, permitindo avaliar o perfil de fármacos anti-hipertensivos na Farmácia-Ensino da UEM e padronizar as EAH a serem dispensadas pelas farmácias.With the objective of standardizing antihypertensive drugs in FEN-UEM, the acquisition and consumption of these drugs were analyzed. The data were collected starting from the invoices of purchase of the pharmaceutical antihypertensives specialties (EAH for the referred pharmacy. The study was carried out in the period of January 1st, 1990 trough December 31st 1994. The amount of acquired EAH, active substance and pharmacological class were analyzed. The FEN-UEM acquired 4,751 EAH in this period. There was increased in the acquisition of angiotensin-converting enzyme inhibitors (63,6% and reduction for diuretics (54,2%, beta-blockers (36,3%, alpha central agonists (64,3% and associations (28,2%. The acquisition of calcium antagonists was constant in this period. The data suggest that the acquisition and distribution of these medications are correlated with the current therapeutics

  5. The specificity of viral sialidases. The use of oligosaccharide substrates to probe enzymic characteristics and strain-specific differences. (United States)

    Corfield, A P; Wember, M; Schauer, R; Rott, R


    1. The action of sialidases from Newcastle disease virus (NDV), influenza A2 virus (IA2V) and fowl plague virus (FPV) on sialyloligosaccharide substrates containing alpha 2-3, alpha 2-6 or alpha 2-8 linkages was studied. 2. In all cases 2-3-linked sialic acids were preferentially released. Compared with II6Neu5AcLac, all 2-6-linked substrates, including sialyl-N-acetyllactosamine and its asparaginyl derivative, a urinary hexasaccharide and Neu5Ac(2-6)GalNAc were cleaved at improved rates by NDV and less by FPV sialidases. In the case of IA2V sialidase the asparaginyl oligosaccharide was very poorly cleaved, illustrating a variation in viral strain specificity. 3. A decrease in relative rates was observed in the order NDV greater than IA2V greater than FPV for substrates with 2-3 linkages relative to II6Neu5AcLac. The greatest relative rate was 470-fold higher. The 2-3-linked sialyl-N-acetyllactosaminylasparagine and IV3Neu5AcLcOse4 were poor substrates for the IA2V sialidase, but the rates were greater than with the 2-6 linked substrates. 4. The ganglioside substrate II3Neu5AcLacCer showed lower activity than its oligosaccharide analogue, but neither II3Neu5AcGgOse4Cer nor its oligosaccharide were substrates. 5. The Km values for 2-6-linked substrates were generally of the order 10 mM while those for the 2-3-linked substrates were approximately 1 mM. The V values were consistently higher for the 2-3-linked substrates. IV3Neu5AcLcOse4 showed high Km and very high V values, while the 2-8-linked disialyllactose showed this trend only with NDV enzyme, the IA2V and FPV sialidases exhibiting high Km and low V values. 6. The results are discussed in the light of the current knowledge of viral sialidase specificity and relative to the binding of virus particles to cell surfaces.

  6. Estimating index of population trend by re-sampling techniques (jackknife and bootstrap) and its application to the life table study of rice leaf roller, Cnaphalocrocis medinalis(Lepidoptera: Pyralidae)

    Institute of Scientific and Technical Information of China (English)

    Fang-Ling Tao; Shi-Fan Min; Wei-Jian Wu; Guang-Wen Liang; Ling Zeng


    Taking a published natural population life table office leaf roller, Cnaphalocrocis medinalis (Lepidoptera: Pyralidae), as an example, we estimated the population trend index,I, via re-sampling methods (jackknife and bootstrap), determined its statistical properties and illustrated the application of these methods in determining the control effectiveness of bio-agents and chemical insecticides. Depending on the simulation outputs, the smoothed distribution pattern of the estimates of I by delete-1 jackknife is visually distinguishable from the normal density, but the smoothed pattern produced by delete-d jackknife, and logarithm-transformed smoothed patterns produced by both empirical and parametric bootstraps,matched well the corresponding normal density. Thus, the estimates of I produced by delete-1 jackknife were not used to determine the suppressive effect of wasps and insecticides. The 95% percent confidence intervals or the narrowest 95 percentiles and Z-test criterion were employed to compare the effectiveness of Trichogrammajaponicum Ashmead and insecti-cides (powder, 1.5% mevinphos + 3% alpha-hexachloro cyclohexane) against the rice leaf roller based on the estimates of I produced by delete-d jackknife and bootstrap techniques.At α= 0.05 level, there were statistical differences between wasp treatment and control, and between wasp and insecticide treatments, if the normality is ensured, or by the narrowest 95 percentiles. However, there is still no difference between insecticide treatment and control.By Z-test criterion, wasp treatment is better than control and insecticide treatment with P-value<0.01. Insecticide treatment is similar to control with P-value > 0.2 indicating that 95% confidence intervals procedure is more conservative. Although similar conclusions may be drawn by re-sampling techniques, such as the delta method, about the suppressive effect of trichogramma and insecticides, the normality of the estimates can be checked and guaranteed

  7. Comparison of triple-risk assessment of fetal trisomy 21 including total human choriogonadotropin (hCG) or its free beta-subunit (free beta hCG). (United States)

    Sancken, U; Bahner, D


    Second trimester total hCG and free betahCG levels in maternal serum samples of 33 pregnancies affected by fetal trisomy 21 and of 188 matched controls were compared in a retrospective study. To find out differences of discriminating efficacy by using one of these markers a multivariate discriminant analysis was performed. Statistical evaluation was performed for hCG/free betahCG frequency distributions. Discriminant analysis was carried out using the status 'affected' or 'unaffected' as the group variable and the serum markers unconjugated estriol (uE3), alpha-fetoprotein (AFP), and alternatively, hCG or free betahCG, as discriminant variables. The median of free betahCG MoM values in affected pregnancies was slightly higher (1.90 MoM) than the median of total hCG MoM values (1.72 MoM) but a lower standard deviation was stated for the logarithmic hCG MoM values (SD = 0.49) compared with free betahCG MoM values (SD = 0.51). A two-tailed Student's t test revealed no significant differences of hCG and free betahCG MoM values in both the affected and unaffected pregnancies. By inclusion of free betahCG the discriminant analysis classified 26 out of 33 affected cases correctly and 45 out of 188 unaffected cases incorrectly. For the inclusion of hCG these ratios were 25/33 and 41/188, respectively. Taking in account the individual maternal age risks at a defined false-positive rate of 5% including free betahCG yielded a higher detection rate than including hCG. However, using 1:380 (age-related at-term risk of a 35-year-old woman) as a cut-off risk including hCG yielded a higher detection rate than including free betahCG. For the observed cases none of the markers, hCG or free betahCG, was superior in Down syndrome screening. Copyright 2003 S. Karger AG, Basel

  8. Crystal structures and topological aspects of the high-temperature phases and decomposition products of the alkali-metal oxalates M2[C2O4] (M=K, Rb, Cs). (United States)

    Dinnebier, Robert E; Vensky, Sascha; Jansen, Martin; Hanson, Jonathan C


    The high-temperature phases of the alkali-metal oxalates M2[C2O4] (M = K, Rb, Cs), and their decomposition products M2[CO3] (M = K, Rb, Cs), were investigated by fast, angle-dispersive X-ray powder diffraction with an image-plate detector, and also by simultaneous differential thermal analysis (DTA)/thermogravimetric analysis (TGA)/mass spectrometry (MS) and differential scanning calorimetry (DSC) techniques. The following phases, in order of decreasing temperature, were observed and crystallographically characterized (an asterisk denotes a previously unknown modification): *alpha-K2[C2O4], *alpha-Rb2[C2O4], *alpha-Cs2[C2O4], alpha-K2[CO3], *alpha-Rb2[CO3], and *alpha-Cs2[CO3] in space group P6(3)/mmc; *beta-Rb2[C2O4], *beta-Cs2[C2O4], *beta-Rb2[CO3], and *beta-Cs2[CO3] in Pnma; gamma-Rb2[C2O4], gamma-Cs[C2O4], gamma-Rb2[CO3], and gamma-Cs2[CO3] in P2(1)/c; and delta-K2[C2O4] and delta-Rb2[C2O4] in Pbam. With respect to the centers of gravity of the oxalate and carbonate anions, respectively, the crystal structures of all known alkali-metal oxalates and carbonates belong to the AlB2 family, and adopt either the AlB2 or the Ni2In arrangement depending on the size of the cation and the temperature. Despite the different sizes and constitutions of the carbonate and oxalate anions, the high-temperature phases of the alkali-metal carbonates M2[CO3] (M = K, Rb, Cs), exhibit the same sequence of basic structures as the corresponding alkali-metal oxalates. The topological aspects and order-disorder phenomena at elevated temperature are discussed.

  9. Crystal Structure and Topological Aspects of the High-Temperature Phases of the Alkali-metal Oxalates M-2 C2O4(M= K,Rb, Cs)

    Energy Technology Data Exchange (ETDEWEB)

    Dinnebier,R.; Vensky, S.; Jensen, M.; Hanson, J.


    The high-temperature phases of the alkali-metal oxalates M{sub 2}[C{sub 2}O{sub 4}] (M=K, Rb, Cs), and their decomposition products M{sub 2}[CO{sub 3}] (M=K, Rb, Cs), were investigated by fast, angle-dispersive X-ray powder diffraction with an image-plate detector, and also by simultaneous differential thermal analysis (DTA)/thermogravimetric analysis (TGA)/mass spectrometry (MS) and differential scanning calorimetry (DSC) techniques. The following phases, in order of decreasing temperature, were observed and crystallographically characterized (an asterisk denotes a previously unknown modification): *{alpha}-K{sub 2}[C{sub 2}O{sub 4}], *{alpha}-Rb{sub 2}[C{sub 2}O{sub 4}], *{alpha}-Cs{sub 2}[C{sub 2}O{sub 4}], {alpha}-K{sub 2}[CO{sub 3}], *{alpha}-Rb{sub 2}[CO{sub 3}], and *{alpha}-Cs{sub 2}[CO{sub 3}] in space group P6{sub 3}/mmc; *{beta}-Rb{sub 2}[C{sub 2}O{sub 4}], *{beta}-Cs{sub 2}[C{sub 2}O{sub 4}], *{beta}-Rb{sub 2}[CO{sub 3}], and *{beta}-Cs{sub 2}[CO{sub 3}] in Pnma; {gamma}-Rb{sub 2}[C{sub 2}O{sub 4}], {gamma}-Cs[C{sub 2}O{sub 4}], {gamma}-Rb{sub 2}[CO{sub 3}], and {gamma}-Cs{sub 2}[CO{sub 3}] in P2{sub 1}/c; and {delta}-K{sub 2}[C{sub 2}O{sub 4}] and {delta}-Rb{sub 2}[C{sub 2}O{sub 4}] in Pbam. With respect to the centers of gravity of the oxalate and carbonate anions, respectively, the crystal structures of all known alkali-metal oxalates and carbonates belong to the AlB{sub 2} family, and adopt either the AlB{sub 2} or the Ni{sub 2}In arrangement depending on the size of the cation and the temperature. Despite the different sizes and constitutions of the carbonate and oxalate anions, the high-temperature phases of the alkali-metal carbonates M{sub 2}[CO{sub 3}] (M=K, Rb, Cs), exhibit the same sequence of basic structures as the corresponding alkali-metal oxalates. The topological aspects and order-disorder phenomena at elevated temperature are discussed.

  10. Expression profiling and Ingenuity biological function analyses of interleukin-6- versus nerve growth factor-stimulated PC12 cells

    Directory of Open Access Journals (Sweden)

    Dimitriades-Schmutz Beatrice


    Full Text Available Abstract Background The major goal of the study was to compare the genetic programs utilized by the neuropoietic cytokine Interleukin-6 (IL-6 and the neurotrophin (NT Nerve Growth Factor (NGF for neuronal differentiation. Results The designer cytokine Hyper-IL-6 in which IL-6 is covalently linked to its soluble receptor s-IL-6R as well as NGF were used to stimulate PC12 cells for 24 hours. Changes in gene expression levels were monitored using Affymetrix GeneChip technology. We found different expression for 130 genes in IL-6- and 102 genes in NGF-treated PC12 cells as compared to unstimulated controls. The gene set shared by both stimuli comprises only 16 genes. A key step is upregulation of growth factors and functionally related external molecules known to play important roles in neuronal differentiation. In particular, IL-6 enhances gene expression of regenerating islet-derived 3 alpha (REG3A; 1084-fold, regenerating islet-derived 3 beta (REG3B/PAPI; 672-fold, growth differentiation factor 15 (GDF15; 80-fold, platelet-derived growth factor alpha (PDGFA; 69-fold, growth hormone releasing hormone (GHRH; 30-fold, adenylate cyclase activating polypeptide (PACAP; 20-fold and hepatocyte growth factor (HGF; 5-fold. NGF recruits GDF15 (131-fold, transforming growth factor beta 1 (TGFB1; 101-fold and brain-derived neurotrophic factor (BDNF; 89-fold. Both stimuli activate growth-associated protein 43 (GAP-43 indicating that PC12 cells undergo substantial neuronal differentiation. Moreover, IL-6 activates the transcription factors retinoic acid receptor alpha (RARA; 20-fold and early growth response 1 (Egr1/Zif268; 3-fold known to play key roles in neuronal differentiation. Ingenuity biological function analysis revealed that completely different repertoires of molecules are recruited to exert the same biological functions in neuronal differentiation. Major sub-categories include cellular growth and differentiation, cell migration, chemotaxis, cell

  11. Cellular growth and survival are mediated by beta 1 integrins in normal human breast epithelium but not in breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Howlett, Anthony R; Bailey, Nina; Damsky, Caroline; Petersen, Ole W; Bissell, Mina J


    We previously established a rapid three-dimensional assay for discrimination of normal and malignant human breast epithelial cells using a laminin-rich reconstituted basement membrane. In this assay, normal epithelial cells differentiate into well-organized acinar structures whereas tumor cells fail to recapitulate this process and produce large, disordered colonies. The data suggest that breast acinar morphogenesis and differentiation is regulated by cell-extracellular matrix (ECM) interactions and that these interactions are altered in malignancy. Here, we investigated the role of ECM receptors (integrins) in these processes and report on the expression and function of potential laminin receptors in normal and tumorigenic breast epithelial cells. Immmunocytochemical analysis showed that normal and carcinoma cells in a three-dimensional substratum express profiles of integrins similar to normal and malignant breast tissues in situ. Normal cells express {alpha}1, {alpha}2, {alpha}3, {alpha}6, {beta}1 and {beta}4 integrin subunits, whereas breast carcinoma cells show variable losses, disordered expression, or down regulation of these subunits. Function-blocking experiments using inhibitory antiintegrin subunit antibodies showed a >5-fold inhibition of the formation of acinar structures by normal cells in the presence of either anti-{beta}1 or anti-{alpha}3 antibodies, whereas anti-{alpha}2 or -{alpha}6 had little or no effect. In experiments where collagen type I gels were used instead of basement membrane, acinar morphogenesis was blocked by anti-{beta}1 and -{alpha}2 antibodies but not by anti-{alpha}3. These data suggest a specificity of integrin utilization dependent on the ECM ligands encountered by the cell. The interruption of normal acinar morphogenesis by anti-integrin antibodies was associated with an inhibition of cell growth and induction of apoptosis. Function-blocking antibodies had no inhibitory effect on the rate of tumor cell growth, survival or

  12. Volatility mechanisms of borosilicate glasses and molten glasses of nuclear interest structural effects; Mecanismes de volatilite des verres et des fontes borosilicates d'interet nucleaire influence de la structure

    Energy Technology Data Exchange (ETDEWEB)

    Delorme, L


    This work is devoted to the study of the mechanisms which control the volatility of the reference glass used for the confinement of radioactive waste. It was conducted on simplified compositions, in the SiO{sub 2}-B{sub 2}O{sub 3}-Al{sub 2}O{sub 3}-{alpha}Na{sub 2}O-(1-alpha)Li{sub 2}O-CaO system.The structural approach carried out by NMR, from room temperature up to 1500 deg.C, shows a strong increase in the mobility of alkalis above Tg. A rapid exchange between B{sup III} and B{sup IV} sites near 700 deg.C, and the change of coordination number B{sup IV-} B{sup III} near 1100 deg.C, also seem to take place. The analysis of the vapor phase, carried out by High Temperature Mass Spectrometry coupled to Knudsen cells, reveals the presence between 780 deg.C and 830 deg.C of NaBO{sub 2}(g), LiBO{sub 2}(g) and Na{sub 2}(BO{sub 2})2(g). The calculation of the partial pressure of each species shows that the total pressure of simplified glasses is dominated by the contribution of sodium. To study the volatility of glasses at higher temperature, equipment using the Transpiration method was used. The analysis of the deposits indicate the presence at 1060 deg.C of the species quoted previously. The vaporization rate and the vapor density were determined for each composition studied in a saturated state. Thus, we show that the volatility of the reference glass can be simulated by that of a simplified glass. For {alpha}=1, the kinetic of vaporization between 1060 deg.C and 1200 deg.C reveals an evaporation from the surface associated with a mechanism of diffusion in the molten glass. This is similar to the volatility of the reference glass at 1060 deg.C. To finally explain these mechanisms on a microscopic basis, we develop a model of molecular interactions. Between 780 deg.C and 830 deg.C, these mechanisms are controlled by a strong attraction between Na{sub 2}O and Li{sub 2}O, which maintains the total vapor pressure on a quasi-constant lever up to {alpha}=0.27. (author)

  13. Effects of erythropoietin and vitamin E-modified membrane on plasma oxidative stress markers and anemia of hemodialyzed patients. (United States)

    Usberti, Mario; Gerardi, GianMario; Bufano, Giuseppe; Tira, Paola; Micheli, Annamaria; Albertini, Alberto; Floridi, Ardesio; Di Lorenzo, Diego; Galli, Francesco


    Oxidant stress has a pathogenic role in uremic anemia, possibly interfering with erythropoietin (EPO) function and red blood cell (RBC) survival. Therefore, it is expected that antioxidant therapy might exert a beneficial effect on these parameters. To test this hypothesis, we investigated some oxidant stress indices, anemia levels, and RBC survival in 47 hemodialysis (HD) patients randomly assigned to three groups. Patients in groups A (n = l8) and B (n = 20) were on dialysis therapy using conventional cellulosic and synthetic membranes and were administered high and low doses of recombinant human EPO (rHuEPO), respectively. Patients in group C (n = 9) were dialyzed with vitamin E-modified membranes (CL-Es) and investigated in a two-step prospective study. In step Cl, patients were administered rHuEPO doses similar to those of group A. In step C2, rHuEPO doses were reduced to those of group B. As oxidant stress markers, we determined in plasma the susceptibility of lipids to undergo iron-catalyzed oxidation (reactive oxygen molecules [ROMs] test) and malondialdehyde-4-hydroxynonenal (MDA-4HNE), alpha-tocopherol (alpha-T), total thiol (-SH), and total antioxidant activity. RBC survival was measured using the chromium 51 T/2 technique in 22 patients. Results show that: (1) high rHuEPO doses (groups A and C1) were associated with decreased ROM production, low alpha-T levels, and slightly increased -SH levels compared with corresponding groups on low rHuEPO doses (groups B and C2); (2) treatment with CL-Es (group C) increased plasma alpha-T and decreased -SH levels; these data were associated with decreased indices of lipid peroxidation, particularly MDA-4HNE 1evels, only in patients administered low rHuEPO doses; (3) alpha-T concentration influenced RBC survival, which was remarkably decreased in HD patients; patients treated with CL-Es showed a better degree of anemia correction; and (4) alpha-T level correlated negatively with -SH level and seemed to be independent

  14. Plasma 25-hydroxyvitamin D, more so than its epimer, has a linear relationship to leaner body composition across infancy in healthy term infants. (United States)

    Hazell, Tom J; Gallo, Sina; Berzina, Ilze; Vanstone, Catherine A; Rodd, Celia; Weiler, Hope A


    Vitamin D status positively associates with skeletal muscle mass and function in adolescents. The C-3 alpha epimer of 25-hydroxyvitamin D3 (3-epi-25(OH)D3) is high in infants, yet the potential impacts of 25-hydroxyvitamin D3 (25(OH)D3) and 3-epi-25(OH)D3 on skeletal muscle development are largely unexplored. The objective of this study was (i) to explore how the concentrations of 25(OH)D3 and 3-epi-25(OH)D3 track with body composition (lean mass (LM) and fat mass (FM)) and (ii) to determine the association between 25(OH)D3 and 3-epi-25(OH)D3 in infancy. Healthy breastfed infants (n = 132) were followed from 1 to 12 months of age as part of a vitamin D dose-response study (NCT00381914). Anthropometry and diet were assessed. Body composition was measured with dual-energy X-ray absorptiometry. Plasma 25(OH)D3 and 3-epi-25(OH)D3 concentrations were evaluated using liquid chromatography tandem mass spectrometry. Plasma 25(OH)D3 and 3-epi-25(OH)D3 increased from 1 to 3 months of age and decreased thereafter (p 0.273) than those below this cutoff. LM was not associated with 25(OH)D3, whereas LM% was positively associated with 25(OH)D3 (β = 0.03; CI: 0.01 to 0.06; p = 0.006), while accounting for sex, weight-for-age Z-score, protein and fat intake, and age. For FM, the variables accounting for a significant amount of the variation were plasma 25(OH)D3 concentration (β = -2.38; CI: -4.35, -0.41; p = 0.019), weight-for-age Z-score, protein and fat intake, and time. In healthy infants, higher vitamin D status associates with leaner body composition, though the effect is smaller in magnitude relative to growth.

  15. The seed's protein and oil content, fatty acid composition, and growing cycle length of a single genotype of chia (Salvia hispanica L.) as affected by environmental factors. (United States)

    Ayerza, Ricardo


    As a botanical source, variability in chia seed composition could be expected between growing locations, and between years within a location, due to genotype and environment effects as well genetic x environment's interactions. The objective of the present study was to determine the location effect on the growing cycle length, and seed's protein content, lipid content, and fatty acid profiles, of a single chia genotype. Seeds of chia genotype Tzotzol grown on eight sites in five different ecosystems were tested. One site was in Argentina, in the Semi-Arid Chaco ecosystem (T(5)); one was in Bolivia, in the Sub-Humid Chaco ecosystem (T(4)); and six in Ecuador, one in the Coastal Desert (T(3)), two on the Tropical Rain Forest (T(2)), and three in the Inter-Andean Dry Valley ecosystem (T(1)). Seeds from plants grown in T(4) and in T(3) contained significantly (P <0.05) more protein percentage than did seeds from the other three ecosystems. No significant (P <0.05) differences in protein content were found between T(3) and T(4), and between T(1), T(2), and T(5). Seeds from T(1) and T(5) ecosystems, with 33.5 and 32.2%, respectively, were the numerically highest oil content producers, but their results were only significantly (P <0.05) higher when compared with the T(2) seeds. Significant (P <0.05) differences in palmitic, stearic, oleic, linoleic and alpha-linolenic fatty acids between oils from seeds grown in different ecosystems were detected, however. Oil of seeds grown in the T(3) ecosystem had the palmitic, stearic and oleic fatty acids' highest contents. Palmitic and oleic fatty acid levels were significantly (P <0.05) higher when were compared to that of seeds grown in the T(1) ecosystem, and stearic when was compared to that of seeds grown in the T(5) ecosystem; omega-6 linoleic fatty acid content was significantly (P <0.05) lower in oils of seeds produced in T(1), and T(2) than in those produced in T(3), T(4), and T(5) ecosystems; omega-3 alpha-linolenic fatty

  16. Angiotensin II inhibits insulin-stimulated GLUT4 translocation and Akt activation through tyrosine nitration-dependent mechanisms.

    Directory of Open Access Journals (Sweden)

    Alfredo Csibi

    Full Text Available Angiotensin II (Ang II plays a major role in the pathogenesis of insulin resistance and diabetes by inhibiting insulin's metabolic and potentiating its trophic effects. Whereas the precise mechanisms involved remain ill-defined, they appear to be associated with and dependent upon increased oxidative stress. We found Ang II to block insulin-dependent GLUT4 translocation in L6 myotubes in an NO- and O(2(*--dependent fashion suggesting the involvement of peroxynitrite. This hypothesis was confirmed by the ability of Ang II to induce tyrosine nitration of the MAP kinases ERK1/2 and of protein kinase B/Akt (Akt. Tyrosine nitration of ERK1/2 was required for their phosphorylation on Thr and Tyr and their subsequent activation, whereas it completely inhibited Akt phosphorylation on Ser(473 and Thr(308 as well as its activity. The inhibitory effect of nitration on Akt activity was confirmed by the ability of SIN-1 to completely block GSK3alpha phosphorylation in vitro. Inhibition of nitric oxide synthase and NAD(PHoxidase and scavenging of free radicals with myricetin restored insulin-stimulated Akt phosphorylation and GLUT4 translocation in the presence of Ang II. Similar restoration was obtained by inhibiting the ERK activating kinase MEK, indicating that these kinases regulate Akt activation. We found a conserved nitration site of ERK1/2 to be located in their kinase domain on Tyr(156/139, close to their active site Asp(166/149, in agreement with a permissive function of nitration for their activation. Taken together, our data show that Ang II inhibits insulin-mediated GLUT4 translocation in this skeletal muscle model through at least two pathways: first through the transient activation of ERK1/2 which inhibit IRS-1/2 and second through a direct inhibitory nitration of Akt. These observations indicate that not only oxidative but also nitrative stress play a key role in the pathogenesis of insulin resistance. They underline the role of protein

  17. Long-chain polyunsaturated fatty acid (LCPUFA requirement for brain development: A personal view

    Directory of Open Access Journals (Sweden)

    Gibson Robert A


    Full Text Available Dietary docosahexaenoic acid (DHA is known to accumulate in the infant brain and clinical trials have established that dietary DHA is associated with improvements in visual and neural function in preterm infants. Thus, an elevated DHA status is considered to be important throughout infancy for brain development. While DHA can be added directly to infant foods, there have been important studies to show that infants can partially meet their own DHA requirements by consuming adequate levels of omega 3 alpha linolenic acid (ALA. A key requirement to allow for the conversion of ALA to DHA and to maximise its incorporation into tissues is a diet that is also low in omega 6 linoleic acid (LA. Such diets are hard to find commercially because dietary guidelines dictate that ~3% energy of infant diets should be in the form of LA. These estimates were based on early animal experiments in which basal diets were devoid of both LA and ALA. However, recent animal experiments have indicated that the level of LA required to avoid essential fatty acid deficiency is much lower when ALA is also present in the diet. When a wide range diets are evaluated in animal systems, it is possible to see that the level of DHA found in the blood of animals fed diets containing only LA and ALA can reach levels similar to that of animals fed diets rich in fish oil, but only when the ALA:LA ratio is high and the total amount of dietary polyunsaturated fatty acids (PUFA is low. Diets that are rich in either monounsaturates or saturates meet these requirements. Importantly, there are human infant studies that have tested such diets and demonstrated that human infants accumulate greater amounts of DHA than when diets are high in LA. It might be time to reconsider the dietary requirement of the two essential fatty acids LA and ALA in human infants in terms of their ability to enhance endogenous synthesis of DHA rather than more adult biomarkers like cholesterol levels.

  18. Role of canine basal cells in postnatal prostatic development, induction of hyperplasia, and sex hormone-stimulated growth; and the ductal origin of carcinoma. (United States)

    Leav, I; Schelling, K H; Adams, J Y; Merk, F B; Alroy, J


    The canine prostate has often been proposed as a model for abnormal growth of the human gland. Hyperplasia of the prostate is common in aging men and has been estimated to be present in 100% of old intact dogs. While prostatic carcinoma is common in older men, it appears to be rare in dogs and unlike the disease in humans, it occurs with relatively high frequency in castrated animals. Since basal cells are thought to be key participants in normal and abnormal growth of the human gland, we used immunohistochemistry to investigate the role that they may play in canine prostatic development, the evolution of hyperplasia and carcinoma, and the effects of sex hormones on these cells. Prostate specimens were obtained at autopsy from seven sexually immature dogs, autopsy and biopsy samples from 14 sexually mature intact animals, from four castrates, and from19 dogs with prostatic carcinoma. In addition, we also studied the prostates from two intact dogs treated with 5alpha-dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5alpha-androstane-3alpha diol and estradiol-17alpha, as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cytokeratin (HMC), pancytokeratin, androgen receptor (AR), and the proliferative marker KI-67. We find that basal cells are the major proliferative cell type in the neonatal and adult canine prostate and that the expression of HMC staining, which defines these cells, may be regulated by androgens. In the adult gland, ductal basal cells formed a contiguous layer, whereas those lining acini were discontinuous. Populations of both basal cell types were variably AR positive, but while HMC immunostaining was abolished in acinar cells following long-term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal cell population increased with age and

  19. 黑壳楠叶片精油挥发性成分的GC/MS 鉴定与应用分析%GC/MS Analysis of Volatile Substances in Essential Oil of Lindera megaphylla Blade and Its Application

    Institute of Scientific and Technical Information of China (English)

    卞京军; 程密密; 罗思源; 陈思伶; 刘世尧; 白志川


    The essential oil was extracted from the leaves of the Lauraceae plant L indera megaphylla with steam distillation, and the volatile substances in it were analyzed and identified with GC-MS. A total of 87 volatile aromatic substances were separated and identified, accounting for 95.6% of the total essential oil, hydrocarbons (37% ) and alcohols (34.74% ) being the principal components. The first ten kinds of volatile components were Phytol (14.3% ), n-Hexadecanoic acid (6.09% ), D-Limonene (4.67% ), 2H-Pyran, 2-(2-heptadecynyloxy)tetrahydro-(4.65% ), Copaene (4.3% ), alpha-Cadinol (4.23% ), Caryophyllene ox-ide (4.11% ), 1, 6, 10-Dodecatrien-3-ol, 3, 7, 11-trimethyl-(3.32% ), Cyclohexane, 1-ethenyl-1-methyl-2, 4-bis (1-methyle thenyl)-, [1S-(1.alpha., 2. beta., 4. beta. )]-(3.24% ), Bicyclo[2.2.1]heptan-2-ol, 1, 7, 7-trimethyl-, acetate, (1S-endo)-(2.62% ), of which Phytol, n-Hexadecanoic acid and D-Limonene might be of considerable value of development and utilization.%采用水蒸气蒸馏法对樟科植物黑壳楠叶片进行精油提取,并对其挥发性成分进行气相色谱质谱联用仪(GC/MS)分离鉴定与应用分析.结果表明:在重庆黑壳楠叶片中分离鉴定出挥发性成分87种,占精油总量的95.6%,以烃类(37%)、醇类(34.74%)化合物为主.前10种挥发性成分分别为:植物醇(14.3%)、棕榈酸(6.09%)、右旋柠檬烯(4.67%)、2H-Pyran ,2-(2-heptadecynyloxy)tetrahydro-(4.65%)、古巴烯(4.3%)、荜茄醇(4.23%)、氧化石竹烯(4.11%)、反式橙花叔醇(3.32%)、β榄香烯(3.24%)、乙酸龙脑酯(2.62%),其中植物醇、棕榈酸、右旋柠檬烯等有较大开发利用价值.

  20. A SELDI mass spectrometry study of experimental autoimmune encephalomyelitis: sample preparation, reproducibility, and differential protein expression patterns. (United States)

    Azzam, Sausan; Broadwater, Laurie; Li, Shuo; Freeman, Ernest J; McDonough, Jennifer; Gregory, Roger B


    Experimental autoimmune encephalomyelitis (EAE) is an autoimmune, inflammatory disease of the central nervous system that is widely used as a model of multiple sclerosis (MS). Mitochondrial dysfunction appears to play a role in the development of neuropathology in MS and may also play a role in disease pathology in EAE. Here, surface enhanced laser desorption ionization mass spectrometry (SELDI-MS) has been employed to obtain protein expression profiles from mitochondrially enriched fractions derived from EAE and control mouse brain. To gain insight into experimental variation, the reproducibility of sub-cellular fractionation, anion exchange fractionation as well as spot-to-spot and chip-to-chip variation using pooled samples from brain tissue was examined. Variability of SELDI mass spectral peak intensities indicates a coefficient of variation (CV) of 15.6% and 17.6% between spots on a given chip and between different chips, respectively. Thinly slicing tissue prior to homogenization with a rotor homogenizer showed better reproducibility (CV = 17.0%) than homogenization of blocks of brain tissue with a Teflon® pestle (CV = 27.0%). Fractionation of proteins with anion exchange beads prior to SELDI-MS analysis gave overall CV values from 16.1% to 18.6%. SELDI mass spectra of mitochondrial fractions obtained from brain tissue from EAE mice and controls displayed 39 differentially expressed proteins (p≤ 0.05) out of a total of 241 protein peaks observed in anion exchange fractions. Hierarchical clustering analysis showed that protein fractions from EAE animals with severe disability clearly segregated from controls. Several components of electron transport chain complexes (cytochrome c oxidase subunit 6b1, subunit 6C, and subunit 4; NADH dehydrogenase flavoprotein 3, alpha subcomplex subunit 2, Fe-S protein 4, and Fe-S protein 6; and ATP synthase subunit e) were identified as possible differentially expressed proteins. Myelin Basic Protein isoform 8 (MBP8) (14.2 k

  1. Further studies on the blockade of 5-HT depolarizations of rabbit vagal afferent and sympathetic ganglion cells by MDL 72222 and other antagonists. (United States)

    Round, A; Wallis, D I


    The blocking action of MDL 72222 (1 alpha H, 3 alpha, 5 alpha H-tropan-3-yl-3, 5-dichlorobenzoate at 5-hydroxytryptamine (5-HT) receptors on nodose (NG) and superior cervical ganglia (SCG) has been investigated further. The sucrose-gap technique was used to record potential changes from populations of neurones. The surmountable blockade induced by small concentrations of the antagonist was quantified and the blocking potency compared with that of a number of other compounds. In nodose ganglia three 4-5 point dose-response (DR) curves were established, using bolus injections of 5-HT (5-80 nmol). The mean amplitude of the response to 80 nmol was 4.18 +/- 0.53 mV and the ED50 was 18.2 nmol. Second and 3rd dose-response curves showed small displacements to the right, indicating a slight reduction in sensitivity. In superior cervical ganglia responsiveness was less. Amounts of 5-HT ranging from 20 to 320 nmol evoked dose-related depolarizations. The mean amplitude of the response evoked by 320 nmol 5-HT was 1.7 +/- 0.14 mV. Three 4-5 point dose-response curves could be elicited from a single ganglion. The ED50 was 55.8 nmol. Initial, 2nd and 3rd dose-response curves could be superimposed, there being no significant rightward shift. The results confirm that MDL 72222 is a potent, selective antagonist at 5-HT receptors in nodose and superior cervical ganglia. In the nodose ganglion, after equilibration for 1 hr with 10(-8) or 10(-7) M MDL 72222, dose-response curves for 5-HT showed rightward, parallel shifts. In contrast, 10(-6) M MDL 72222 or prolonged exposure (3-4 hr) to 10(-8), 10(-7) or 10(-6) M caused larger rightward shifts of the dose-response curves and depressed the maximum responses. In the superior cervical ganglion, equilibration for 1 hr with concentrations of 10(-8) or 10(-7) M produced effects on the dose-response curves similar to those seen in the nodose ganglion, but longer exposures (3-4 hr) did not depress the maximum. Apparent pA2 values were

  2. Estrogen and prostate cancer: an eclipsed truth in an androgen-dominated scenario. (United States)

    Carruba, Giuseppe


    Prostate cancer is the commonest non-skin cancer in men. Incidence and mortality rates of this tumor vary strikingly throughout the world. Although several factors have been implicated to explain this remarkable variation, lifestyle and dietary factors may play a dominant role, with sex hormones behaving as intermediaries between exogenous factors and molecular targets in development and progression of prostate cancer. Human prostate cancer is generally considered a paradigm of androgen-dependent tumor; however, estrogen role in both normal and malignant prostate appears to be equally important. The association between plasma androgens and prostate cancer remains contradictory and mostly not compatible with the androgen hypothesis. Similar evidence apply to estrogens, although the ratio of androgen to estrogen in plasma declines with age. Apart from methodological problems, a major issue is to what extent circulating hormones can be considered representative of their intraprostatic levels. Both nontumoral and malignant human prostate tissues and cells are endowed with key enzymes of steroid metabolism, including 17betahydroxysteroid dehydrogenase (17betaHSD), 5beta-reductase, 3alpha/3betaHSD, and aromatase. A divergent expression and/or activity of these enzymes may eventually lead to a differential prostate accumulation of steroid derivatives having distinct biological activities, as it occurs for hydroxylated estrogens in the human breast. Locally produced or metabolically transformed estrogens may differently affect proliferative activity of prostate cancer cells. Aberrant aromatase expression and activity has been reported in prostate tumor tissues and cells, implying that androgen aromatization to estrogens may play a role in prostate carcinogenesis or tumor progression. Interestingly, many genes encoding for steroid enzymes are polymorphic, although only a few studies have supported their relation with risk of prostate cancer. In animal model systems

  3. Production and use of mutanase from Trichoderma harzianum for effective degradation of streptococcal mutans Produção e utilização da mutanase de Trichoderma harzianum para a degradação efetiva dos mutans estreptocócicos de estreptococos mutans

    Directory of Open Access Journals (Sweden)

    Adrian Wiater


    Full Text Available Basic cultural parameters affecting mutanase production by Trichoderma harzianum F-340 in shaken flasks and aerated fermenter cultures have been standardized. The best medium for enzyme production was Mandels medium A with initial pH 5.3, supplemented with 0.3% mutan and 0.05% peptone and inoculated with 20% of the 72-h mycelium as inoculum. It was shown that mycelial mass, used in the culture medium as a sole carbon source, induced mutanase synthesis and could be utilized as an inexpensive and easily available substitute for bacterial mutan. Application of optimized medium and cultural conditions enabled us to obtain a high mutanase yield (0.6-0.7 U/mL, 2.0-2.5 U/mg protein in a short period of time (3-5 days, which was much higher than the best reported in literature. The enzyme in crude state was stable in the pH range of 4.5-6.0, and at temperatures of up to 40ºC; its maximum activity was recorded at 45ºC and at pH 5.5. The mutanase preparation obtained from the T. harzianum fungus was relatively stable under storage conditions, and showed a high hydrolytic potential in reaction with a mixed-linkage (alpha-1,3, alpha-1,6 water-insoluble mutan of streptococcal origin (hydrolysis yield reached a value of 69% in 24 h. Steady-state measurement of the enzymic reaction products during the hydrolysis revealed that mutanase exhibited an exo type of action on mutan. Thin-layer chromatographic analysis showed that glucose was the primary final product of mutan hydrolysis with mutanase. The potential application of mutanase in dentistry is discussed.Os parâmetros básicos que afetam a produção da mutanase por Trichoderma harzianum F-340 em frascos agitados e em fermentadores foram estabelecidos. O melhor meio para produção da enzima foi o meio Mandels com pH inicial de 5,3, suplementado com 0,3% de mutana e 0,05% de peptona e inoculado com 20% de um micélio de 72h. Demonstrou-se que a massa micelial, usada como única fonte de carbono no meio

  4. Ugan古河道胡杨可培养内生细菌的多样性%Phylogenetic diversity of culturable endophytic bacteria Isolated from the Populus euphratica at the disused ancient Ugan River

    Institute of Scientific and Technical Information of China (English)

    卡依尔·玉素甫; 谢仁娜依·甫拉提; 玛丽帕·吐达洪1; 马丽艳木·阿木东; 艾尼江·尔斯曼; 祖母拉提·阿布都热依木; 艾尔肯·热合曼


    according to their 16S rDNA sequence similarities to type strains of described organisms, they have been placed into four phylogenetic groups ( 1 , Firmicutes; 2 , Actinobacteria; 3 , Alpha Proteobacteria and 4,Gamma Proteobacteria) ,18 genera and 32 species.Among them,Bacillus and pseudomonas were the most widely distributed and predominant, occupied the majority of isolates 40.32% and 16.13% , respectively.Isolate KTH-63 ( HM371419 ) formed a distinct clade with Macrococcus brunensis in phylogenetic tree based on 16S rDNA sequence among the family Staphylococcaceae, so it was demonstrated that the KTH-63 represents a potential novel genus and novel species within the family Staphylococcaceae with 92.491% sequence similarity with the described species Macrococcus brunensis of this family.Isolates KLH-1, KLH-21, KLH-18 , KLH-25 , KNA-3 , KTH-8 , KTH-14, KTH-20 and KNA-26 with 96.089% -97.769% sequence similarities to their closely related members were presumed to be potential novel species, and the discovery rate of potential novel species in the endophytic bacterial community of Populus euphratica was reach up to 16.13%.Furthermore, 10 genera and 18 species have been added to the plant endophytic bacterial categoria by the data obtained in this work.[Conclusion]The result showed that the cultivable endophytic bacterial diversity in Populus euphratica at Ugan river was very abundant and have high percentage of potential novel species, and it have greatly refreshed the plant endophytic bacterial records.The community structure obtained in this study also may be presumed as a miniature of the endophytic bacterial flora in the Populus euphratica during the recent ages before the affect of modern civilization prossessing to Tarim river valley,which deserve further study and exploitation.

  5. 血清甲胎蛋白异质体、高尔基体糖蛋白-73及甲胎蛋白检测在老年人原发性肝癌的诊断价值%Assessment of serum golgi protein 73, alpha-fetoprotein variants, alpha fetoprotein detection in the ;diagnosis of elderly hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    周文瑞; 李新丰; 林奇忆; 王高雄; 黄天从


    ;AFP与GP73联合检测后敏感度为96.3%,特异度为95.5%;AFP⁃L3与 GP73联合检测后敏感度为97.0%,特异度为93.3%。结论 GP73、AFP⁃L3有望成为新的诊断原发性肝癌的血清标志物,血清AFP⁃L3、GP73、AFP联合检测联合应用能弥补单项血清标志物的不足,对提高老年HCC的诊断具有一定价值。%Objective To explore the clinical application values of the detection of golgi protein⁃73 (GP73), alpha⁃fetoprotein variants ( AFP⁃L3 ), alpha fetoprotein ( AFP ) in the diagnosis of elderly hepatocellular carcinoma(HCC).Methods Forty cases of HCC patients(HCC group),21 cases with benign tumor of liver ( benign tumor of liver group) and 19 cases with cirrhotic patients ( liver cirrhosis group) were enrolled. GP73 was detected by double antibody sandwich enzyme linked immunosorbent lenscu⁃linaris ( ELISA) ,AFP and AFP⁃L3 were examined with electrochemiluminescence immunoassay ( ECLIA) ,AFP⁃L3 was isolated with agglutinin⁃coupled spin cloumn ( ACSC). Results The differences of AFP, AFP⁃L3, AFP⁃L3%,GP73 among groups were statistically significant ( F =213. 04, 151. 98, 231. 80, 657. 04; P 0. 05). The areas of AFP, AFP⁃L3, AFP⁃L3% and GP73 under the receiver operating characteristic (ROC) curves in the differential diagnosis of primary hepatic carcinoma (PHC) were 0.744, 0.799,0.720,0.875,and the area of GP73 was the largest. The sensitivity and specificity of AFP were 62.5%and 80. 0%, AFP⁃L3 were 70.0% and 77. 5%, GP73 were 90. 0% and 70. 0%. Compared with the single detection,the sensitivity and specificity of AFP and AFP⁃L3 parallel testing were 86.7% and 95.5%,AFP and GP73 parallel testing were 96. 3% and 95. 5%, AFP⁃L3 and GP73 parallel testing were 97.0% and 93.3%. Conclusions GP73 and AFP⁃L3 are expected to become new serum markers for diagnosis of primary liver cancer.The allied combination of serum GP73,AFP⁃L3 and AFP makes up for the insufficient clinical applications